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SALT LAKE CITY, buy lasix usa Aug. 31, 2021 /PRNewswire/ -- August 31, 2021 – Health Catalyst, Inc. ("Health Catalyst," buy lasix usa Nasdaq. HCAT), a leading provider of data and analytics technology and services to healthcare organizations, today announced Matt Revis will join the Health Catalyst leadership team.

Revis will report directly to Health buy lasix usa Catalyst Chief Operating Officer Paul Horstmeier. Revis will continue to lead the Twistle business, a role he is familiar with, having served as Twistle's President and Chief Operating Officer prior to the acquisition of the patient engagement technology company by Health Catalyst in July 2021."Given the opportunity for patient engagement technology to transform healthcare, it is an incredible time to lead Twistle by Health Catalyst. As we enter the next stage of our journey, it's my aim to drive even greater care outcomes buy lasix usa for our healthcare clients and their patients," said Revis. "I look forward to working with my fellow team members across the Health Catalyst organization to ensure Twistle reaches its full potential and delivers on our mission of massive, measurable healthcare improvement."Prior to joining Twistle in 2019, Revis served as a Head of Product at Jibo, where he was responsible for the full product development lifecycle of the world's first social robot for the home.

Jibo was named the 2017 buy lasix usa Product of the Year by Time Magazine. Revis also served in leadership roles at Nuance Communications where he helped build the company's healthcare strategy through a mix of product innovation, M&A, and strategic partnership development."Matt's experience driving healthcare strategy and growth through product innovation and strategic partnerships will no doubt help further our global mission of healthcare improvement," said Dan Burton, CEO of Health Catalyst. "We are grateful for his leadership and dedication to Twistle by Health Catalyst and are excited to have him as member of our world class leadership team."About Health CatalystHealth Catalyst is a leading provider of data and analytics technology and services to buy lasix usa healthcare organizations committed to being the catalyst for massive, measurable, data-informed healthcare improvement. Its customers leverage the cloud-based data platform—powered by data from more than 100 million patient records and encompassing trillions of facts—as well as its analytics software and professional services expertise to make data-informed decisions and realize measurable clinical, financial, and operational improvements.

Health Catalyst envisions a future in which all healthcare decisions are data informed.Media Contact:Amanda Hundtamanda.hundt@healthcatalyst.com buy lasix usa 575-491-0974 View original content to download multimedia:https://www.prnewswire.com/news-releases/matt-revis-joins-health-catalyst-leadership-team-301364818.htmlSOURCE Health CatalystALBUQUERQUE, N.M. And SALT LAKE CITY, Aug. 24, 2021 /PRNewswire/ -- Twistle buy lasix usa by Health Catalyst, Inc. (Nasdaq.

HCAT) ("Twistle"), a leader in patient engagement technology, is now being buy lasix usa used to support obstetric services for patients in Northeastern New Mexico. Rural OB Access &. Maternal Services (ROAMS), a federally funded four-year grant from the Health Resources and Services Administration, has deployed Twistle across its network of care, which links patients to caregivers across five buy lasix usa rural communities in New Mexico, including Taos, Colfax, Union, Harding, and Mora Counties. "Our goal with ROAMS is to improve maternal access to care in a safe and financially viable model.

We support mothers with holistic services, including education and care navigation, and make OB services for our rural communities buy lasix usa sustainable. Preventing unnecessary travel, especially for specialty care, is key to the success of this program," said Dr. Timothy Brininger MD, FP/OB, Medical Director of ROAMS.Dr. Brininger continued, "With Twistle, buy lasix usa we connect women directly to their care teams through their mobile phones or a tablet.

This technology allows us to reach women wherever they are. We are aiming to improve access, reduce long travel to clinics/specialty care and enhance detection of antepartum and postpartum problems buy lasix usa. We know that early intervention prevents a lot of complications."Twistle's HIPAA-compliant, personalized text-based software supports pre- and post-partum patients with access to supportive messages such has detailed care plan information, educational materials, and reminders about appointments. In addition, the platform buy lasix usa can be used to collect assessments and enable providers to communicate with patients to monitor health and allow patients to request assistance.

As a result, conditions such as worsening gestational diabetes or hypertension during pregnancy and after delivery may be detected early and managed more safely with better provider-patient engagement."In our experience, we have been able to improve access and reduce health inequities by connecting patients to digital care and services and alleviating barriers like transportation issues, inflexible work schedules, and childcare challenges," said Twistle Medical Director Dr. Rameet Singh, buy lasix usa MD, MPH. "I am excited to play a role in this important women's health initiative not only through my role at Twistle but also as a practicing OB-GYN in New Mexico."Twistle's work with ROAMS highlights the value of patient engagement in improving the health of a population and underscores the opportunity for Twistle, together with data and analytics technology and services company Health Catalyst, to deliver massive, measurable, data-informed healthcare improvements.To learn more about ROAMS, visit https://roamsnm.org/. About Twistle by Health CatalystTwistle helps care teams transform the patient experience, improve quality, buy lasix usa and reduce costs through patient-centered, HIPAA-compliant communication.

We offer "turn-by-turn" guidance as patients navigate their health journey - before, during, and after a care episode. A rich library of clinical content and best practices buy lasix usa optimizes patient engagement to improve care plan compliance. In addition, Twistle delivers education, coaching, remote patient monitoring, and assessment forms to regularly connect patients and care teams, delivering a more comprehensive patient experience that saves valuable staff time, improves patient satisfaction and clinical outcomes, decreases avoidable readmissions and ED visits, and reduces the length of stay.About Health CatalystHealth Catalyst is a leading provider of data and analytics technology and services to healthcare organizations committed to being the catalyst for massive, measurable, data-informed healthcare improvement. Its customers leverage the cloud-based data platform—powered buy lasix usa by data from more than 100 million patient records and encompassing trillions of facts—as well as its analytics software and professional services expertise to make data-informed decisions and realize measurable clinical, financial, and operational improvements.

Health Catalyst envisions a future in which all healthcare decisions are data informed.About Rural OB Access &. Maternal Services Project (ROAMS)ROAMS, the Rural buy lasix usa Ob Access &. Maternal Service, is a collaboration between Holy Cross Medical Center (HCMC) in Taos, Miner's Colfax Medical Center (MCMC) in Raton, Union County General Hospital (UCGH) in Clayton, Presbyterian Medical Services Questa Health Center (PMS/QHC), and the First Steps program in Taos. Its goal is to improve maternal buy lasix usa health outcomes in Northeastern New Mexico.

ROAMS is improving maternal access to care in the northeast region of New Mexico by setting up two new prenatal clinics, one at the Questa Health Center and the other at UCGH in Clayton. This will enable coordinated communication between the four hospitals buy lasix usa and clinics and will establish telehealth communication with expectant mothers from their own homes. When fully functional it is expected that a patient will be able to engage with her OB providers as well as Maternal-Fetal medicine experts from their own home or their local hospital or clinic. View original content to download multimedia:https://www.prnewswire.com/news-releases/twistle-and-roams-partner-to-improve-access-to-prenatal-care-301361327.htmlSOURCE Twistle by Health Catalyst Amanda Hundt, amanda.hundt@healthcatalyst.com, 575-491-0974.

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The Banff Classification of Allograft Pathology systematically categorizes histologic injury on the basis of this hyperlink acute and chronic renal compartment lithium and lasix interaction lesions. The Banff schema was developed by an iterative process involving expert consensus, mainly incorporating data from studies that mapped intercorrelated individual lesion scores to known diagnoses, such as T cell–mediated rejection or antibody-mediated rejection (ABMR).1 Although the Banff classification has served as a major advance in the management of allograft recipients, it exhibits some intrinsic limitations. Current Banff diagnoses are composites of categoric lesion scores associated with a lithium and lasix interaction diagnosis from a histologic standpoint alone. Underlying pathogenetic mechanisms are woven into existing Banff diagnoses only in a few instances, such as the inclusion of anti-HLA donor-specific antibody (HLA-DSA) assays and/or C4d staining for ABMR, or the incorporation of SV40 staining for polyomalasix nephropathy. Moreover, demonstrable prognostic heterogeneity exists within the same Banff diagnostic group, which is frequently identified in newer data.2 Sequential Banff classification updates3 have therefore aimed to address these limitations by incorporating unbiased or multidimensional data.4 Nonetheless, this lithium and lasix interaction remains an ongoing challenge.In this issue of JASN, Vaulet et al.5 used a semi-supervised clustering approach to retrospectively evaluate a large dataset (3622 biopsies from 949 patients).

The authors used individual Banff acute lesion scores coupled with death-censored graft survival data to identify diagnostic clusters with prognostic relevance among these biopsies with histologic diagnoses of rejection. Acute lesion scores were lithium and lasix interaction incorporated in the modeling in a weighted manner on the basis of their individual associations with graft survival. Information regarding the presence or absence of DSA at the time of biopsy was also utilized. In addition, the authors lithium and lasix interaction expertly identified and minimized biases arising from the inclusion of both protocol and indication biopsies and multiple biopsies within the same patient (with varying lesion scores). Cluster stability was assessed and confirmed in a majority of biopsies.In this manner, they identified six novel clusters with an acceptable level of diagnostic accuracy compared with the original Banff diagnoses (adjusted Rand index, 0.48).

Clusters 1–3 were not lithium and lasix interaction associated with DSA, whereas clusters 4–6 were DSA positive. Cluster 1 (the “no rejection” cluster) had limited inflammation and was associated with a 10-year graft survival of 54.6%. Cluster 2 lithium and lasix interaction represented moderate to severe glomerulitis, with limited tubulointerstitial inflammation, whereas cluster 3 was characterized by moderate to severe degrees of tubulointerstitial inflammation (resembling T cell–mediated rejection). Compared with cluster 1, clusters 2 and 3 associated with poor graft outcomes (with 10-year graft survival of 33.3% and 39.8%, respectively). Among DSA-positive clusters, cluster 4 exhibited C4d activity and minimal inflammation, but associated with lithium and lasix interaction a markedly low graft survival rates (28.6%) when compared with cluster 1, despite sharing similar Banff scores.

Although biopsies in cluster 5 had high glomerulitis g scores, reflective of the predominant microvascular inflammation in ABMR, they also had lower interstitial inflammation i and tubulitis t scores (and were thus categorized as “mixed borderline rejection”). Biopsies in cluster 6 had higher t and i scores, representing actual mixed lithium and lasix interaction rejection. Interestingly, both cluster 5 and cluster 6 had similar 10-year graft survival rates (6.1% and 6.2%, respectively), despite variable i and t scores. The association between these novel clusters and graft loss was validated in an external cohort comprising 5191 biopsies, which exhibited an adjusted Rand index of 0.35 (versus 0.48 in the training lithium and lasix interaction set). The lower agreement with Banff scores in the validation set as compared to the training set may have resulted from intrinsic differences between the cohorts, including a significantly higher proportion of patients allocated to cluster 4 as a result of a higher C4d prevalence in the validation set (26% versus 8.7%, P<0.001).

Nevertheless, this study’s clinical applicability could be synthesized as shown in Figure 1 (adapted from Supplemental Figure 4 in Vaulet et al.5), demonstrating the potential for these results to be incorporated into routine patient care.A simplified schema depicting lithium and lasix interaction the potential clinical utility of clustering approach (adapted from Supplemental Figure 4 in reference 5). Analyses of year-1 biopsies without any definite nonrejection diagnosis would start with DSA assessment. DSA-negative biopsies could be subdivided lithium and lasix interaction as shown into “no rejection,” predominant glomerulitis, or predominant tubulo-interstitial inflammation clusters (clusters 1, 2, and 3, respectively). Similarly, DSA-positive biopsies could be subdivided as shown into quiescent, glomerulitis predominant “mixed-borderlines,” or inflammation predominant (clusters 4, 5, and 6, respectively). The prognostic relevance of these lithium and lasix interaction clusters from Vaulet et al.

Are shown as 10-year graft survival rates. I, inflammation lithium and lasix interaction. G, glomerulitis. T, tubulitis lithium and lasix interaction. PVAN, Polyoma lasix-associated nephropathy." data-icon-position data-hide-link-title="0">Figure 1.

A simplified schema depicting the potential clinical utility of clustering approach (adapted from Supplemental Figure 4 in reference 5). Analyses of year-1 biopsies without lithium and lasix interaction any definite nonrejection diagnosis would start with DSA assessment. DSA-negative biopsies could be subdivided as shown into “no rejection,” predominant glomerulitis, or predominant tubulo-interstitial inflammation clusters (clusters 1, 2, and 3, respectively). Similarly, DSA-positive biopsies could be subdivided as shown into lithium and lasix interaction quiescent, glomerulitis predominant “mixed-borderlines,” or inflammation predominant (clusters 4, 5, and 6, respectively). The prognostic relevance of these clusters from Vaulet et al.

Are shown lithium and lasix interaction as 10-year graft survival rates. I, inflammation. G, glomerulitis lithium and lasix interaction. T, tubulitis. PVAN, Polyoma lasix-associated lithium and lasix interaction nephropathy.Although Vaulet et al.

Provide a novel and comprehensive analysis, there are important considerations that could affect the interpretation of the study results. First, only those who completed a 5-year follow-up were included, adding a potential lithium and lasix interaction selection bias by missing patients with the highest all-cause graft loss rates after transplant. Second, most biopsies included in the dataset were obtained within the first year (83.3%), and it is unknown whether cluster designation may be affected by late-rejection biopsies with late ABMR or predominantly interstitial fibrosis and tubular atrophy. Although the authors focused on acute lesions only, future clustering approaches must include lithium and lasix interaction data from chronic lesion scores, because these are reported6 to associate with graft loss. In this regard, despite differing in inflammation, clusters 5 and 6 had similar graft survival rates, a finding that may point to a role for unmapped chronic scores.

In the absence of additional pathogenetic differences between clusters 5 and 6, treatment strategies for both these clusters would be similar in most centers, limiting the utility of lithium and lasix interaction these two clusters in particular.In addition, diagnostic and prognostic heterogeneity needs to be considered within the glomerulitis clusters as there was no evaluation of non–HLA-DSA. Similar heterogeneity may exist in the “no-rejection” cluster 1 because the graft loss rate was higher than nationally reported estimates in the United States.7 This represents a downside of clustering approaches, which may oversimplify the heterogeneity of many characteristics into a limited number of profiles.8 It also remains necessary to evaluate in greater depth underlying clinical risk factors within each cluster. For example, although cluster 1 and cluster 4 were histologically similar and lithium and lasix interaction differed only in the presence of HLA-DSA, 10-year graft survival rates were markedly worse in the latter (54.6% versus 28.6%). We conjecture that cluster 4 may be capturing an unmeasured parameter within patients, such as nonadherence, which has been associated with both DSA and graft loss.9 Finally, as the authors caution, this approach should not replace comprehensive evaluation of individual biopsies by transplant physicians and pathologists.Despite such limitations, this novel dataset from an expert group of investigators highlights the advantage of using semisupervised clustering that incorporates biopsy scores as high-dimensional continuous variables, guided by nonbiopsy-related information (in this case graft survival). The findings show this approach has the ability to relay meaningful clinical data and reduce noninformative factors from preexisting lithium and lasix interaction diagnostic clusters.

Such innovative tools, enabled by machine learning, could also offer guidance for patients with overlapping histologic patterns on allograft biopsy, helping to reclassify them. In future studies of patients with serial biopsies, it would be particularly interesting to assess the prognostic relevance of dynamic clustering lithium and lasix interaction trends, namely, cluster reclassification within the same patient, to further assertain the utility of this approach. Post hoc analysis of previously completed trials using similar “big data” approaches could reveal novel means to stratify participants and facilitate cluster-based targeted therapeutics when planning interventional trials in transplantation.DisclosuresG. Vasquez-Rios has nothing to disclose lithium and lasix interaction. M.

Menon reports having an lithium and lasix interaction ownership interest in Renalytix AI. Reports being a scientific advisor or member of JASN Editorial board as Editorial fellow, Journal of Clinical Medicine Editorial board, and Clinical Transplantation Associate Editor.AcknowledgmentsThe content of this article reflects the personal experience and views of the author(s) and should not be considered medical advice or recommendations. The content does not reflect the views or opinions of the American Society lithium and lasix interaction of Nephrology (ASN) or JASN. Responsibility for the information and views expressed herein lies entirely with the author(s).FootnotesPublished online ahead of print. Publication date available at www.jasn.org.See related article, “Data-driven Derivation and Validation of Novel Phenotypes for Acute Kidney Transplant Rejection using Semi-supervised Clustering” on pages 1084–1096.Copyright © 2021 by the American Society of Nephrology.

The Banff Classification of Allograft Pathology systematically categorizes histologic injury on the basis of acute and chronic renal buy lasix usa compartment lesions. The Banff schema was developed by an iterative process involving expert consensus, mainly incorporating data from studies that mapped intercorrelated individual lesion scores to known diagnoses, such as T cell–mediated rejection or antibody-mediated rejection (ABMR).1 Although the Banff classification has served as a major advance in the management of allograft recipients, it exhibits some intrinsic limitations. Current Banff diagnoses are composites of categoric lesion scores associated with buy lasix usa a diagnosis from a histologic standpoint alone. Underlying pathogenetic mechanisms are woven into existing Banff diagnoses only in a few instances, such as the inclusion of anti-HLA donor-specific antibody (HLA-DSA) assays and/or C4d staining for ABMR, or the incorporation of SV40 staining for polyomalasix nephropathy.

Moreover, demonstrable prognostic heterogeneity exists within the same Banff diagnostic group, which is frequently identified in newer data.2 Sequential Banff classification updates3 have therefore aimed to address these buy lasix usa limitations by incorporating unbiased or multidimensional data.4 Nonetheless, this remains an ongoing challenge.In this issue of JASN, Vaulet et al.5 used a semi-supervised clustering approach to retrospectively evaluate a large dataset (3622 biopsies from 949 patients). The authors used individual Banff acute lesion scores coupled with death-censored graft survival data to identify diagnostic clusters with prognostic relevance among these biopsies with histologic diagnoses of rejection. Acute lesion scores were incorporated in the modeling in a weighted manner on the basis of buy lasix usa their individual associations with graft survival. Information regarding the presence or absence of DSA at the time of biopsy was also utilized.

In addition, the authors expertly buy lasix usa identified and minimized biases arising from the inclusion of both protocol and indication biopsies and multiple biopsies within the same patient (with varying lesion scores). Cluster stability was assessed and confirmed in a majority of biopsies.In this manner, they identified six novel clusters with an acceptable level of diagnostic accuracy compared with the original Banff diagnoses (adjusted Rand index, 0.48). Clusters 1–3 were not associated with DSA, whereas clusters 4–6 were DSA buy lasix usa positive. Cluster 1 (the “no rejection” cluster) had limited inflammation and was associated with a 10-year graft survival of 54.6%.

Cluster 2 represented moderate to severe glomerulitis, with limited tubulointerstitial inflammation, whereas cluster 3 was characterized by moderate to severe degrees of buy lasix usa tubulointerstitial inflammation (resembling T cell–mediated rejection). Compared with cluster 1, clusters 2 and 3 associated with poor graft outcomes (with 10-year graft survival of 33.3% and 39.8%, respectively). Among DSA-positive clusters, cluster 4 exhibited C4d activity and minimal inflammation, but associated buy lasix usa with a markedly low graft survival rates (28.6%) when compared with cluster 1, despite sharing similar Banff scores. Although biopsies in cluster 5 had high glomerulitis g scores, reflective of the predominant microvascular inflammation in ABMR, they also had lower interstitial inflammation i and tubulitis t scores (and were thus categorized as “mixed borderline rejection”).

Biopsies in cluster 6 had higher t and buy lasix usa i scores, representing actual mixed rejection. Interestingly, both cluster 5 and cluster 6 had similar 10-year graft survival rates (6.1% and 6.2%, respectively), despite variable i and t scores. The association between these novel clusters and buy lasix usa graft loss was validated in an external cohort comprising 5191 biopsies, which exhibited an adjusted Rand index of 0.35 (versus 0.48 in the training set). The lower agreement with Banff scores in the validation set as compared to the training set may have resulted from intrinsic differences between the cohorts, including a significantly higher proportion of patients allocated to cluster 4 as a result of a higher C4d prevalence in the validation set (26% versus 8.7%, P<0.001).

Nevertheless, this study’s clinical applicability could be buy lasix usa synthesized as shown in Figure 1 (adapted from Supplemental Figure 4 in Vaulet et al.5), demonstrating the potential for these results to be incorporated into routine patient care.A simplified schema depicting the potential clinical utility of clustering approach (adapted from Supplemental Figure 4 in reference 5). Analyses of year-1 biopsies without any definite nonrejection diagnosis would start with DSA assessment. DSA-negative biopsies could be subdivided as shown into “no rejection,” predominant glomerulitis, or predominant tubulo-interstitial inflammation clusters (clusters 1, 2, and 3, buy lasix usa respectively). Similarly, DSA-positive biopsies could be subdivided as shown into quiescent, glomerulitis predominant “mixed-borderlines,” or inflammation predominant (clusters 4, 5, and 6, respectively).

The prognostic relevance of these clusters from Vaulet buy lasix usa et al. Are shown as 10-year graft survival rates. I, inflammation buy lasix usa. G, glomerulitis.

T, tubulitis buy lasix usa. PVAN, Polyoma lasix-associated nephropathy." data-icon-position data-hide-link-title="0">Figure 1. A simplified schema depicting the potential clinical utility of clustering approach (adapted from Supplemental Figure 4 in reference 5). Analyses of year-1 biopsies without any definite buy lasix usa nonrejection diagnosis would start with DSA assessment.

DSA-negative biopsies could be subdivided as shown into “no rejection,” predominant glomerulitis, or predominant tubulo-interstitial inflammation clusters (clusters 1, 2, and 3, respectively). Similarly, DSA-positive biopsies buy lasix usa could be subdivided as shown into quiescent, glomerulitis predominant “mixed-borderlines,” or inflammation predominant (clusters 4, 5, and 6, respectively). The prognostic relevance of these clusters from Vaulet et al. Are shown buy lasix usa as 10-year graft survival rates.

I, inflammation. G, glomerulitis buy lasix usa. T, tubulitis. PVAN, Polyoma buy lasix usa lasix-associated nephropathy.Although Vaulet et al.

Provide a novel and comprehensive analysis, there are important considerations that could affect the interpretation of the study results. First, only those who completed a 5-year buy lasix usa follow-up were included, adding a potential selection bias by missing patients with the highest all-cause graft loss rates after transplant. Second, most biopsies included in the dataset were obtained within the first year (83.3%), and it is unknown whether cluster designation may be affected by late-rejection biopsies with late ABMR or predominantly interstitial fibrosis and tubular atrophy. Although the authors focused on acute lesions only, future clustering approaches must include data from chronic lesion scores, because buy lasix usa these are reported6 to associate with graft loss.

In this regard, despite differing in inflammation, clusters 5 and 6 had similar graft survival rates, a finding that may point to a role for unmapped chronic scores. In the absence of additional pathogenetic differences between clusters 5 and 6, treatment strategies for both these clusters would be buy lasix usa similar in most centers, limiting the utility of these two clusters in particular.In addition, diagnostic and prognostic heterogeneity needs to be considered within the glomerulitis clusters as there was no evaluation of non–HLA-DSA. Similar heterogeneity may exist in the “no-rejection” cluster 1 because the graft loss rate was higher than nationally reported estimates in the United States.7 This represents a downside of clustering approaches, which may oversimplify the heterogeneity of many characteristics into a limited number of profiles.8 It also remains necessary to evaluate in greater depth underlying clinical risk factors within each cluster. For example, although cluster buy lasix usa 1 and cluster 4 were histologically similar and differed only in the presence of HLA-DSA, 10-year graft survival rates were markedly worse in the latter (54.6% versus 28.6%).

We conjecture that cluster 4 may be capturing an unmeasured parameter within patients, such as nonadherence, which has been associated with both DSA and graft loss.9 Finally, as the authors caution, this approach should not replace comprehensive evaluation of individual biopsies by transplant physicians and pathologists.Despite such limitations, this novel dataset from an expert group of investigators highlights the advantage of using semisupervised clustering that incorporates biopsy scores as high-dimensional continuous variables, guided by nonbiopsy-related information (in this case graft survival). The findings show this approach has the ability to relay meaningful clinical data and reduce noninformative factors from preexisting diagnostic buy lasix usa clusters. Such innovative tools, enabled by machine learning, could also offer guidance for patients with overlapping histologic patterns on allograft biopsy, helping to reclassify them. In future studies of patients with serial biopsies, it would be particularly interesting to assess the prognostic relevance of dynamic clustering trends, namely, cluster reclassification within the same patient, to further assertain the buy lasix usa utility of this approach.

Post hoc analysis of previously completed trials using similar “big data” approaches could reveal novel means to stratify participants and facilitate cluster-based targeted therapeutics when planning interventional trials in transplantation.DisclosuresG. Vasquez-Rios has nothing to buy lasix usa disclose. M. Menon reports having an buy lasix usa ownership interest in Renalytix AI.

Reports being a scientific advisor or member of JASN Editorial board as Editorial fellow, Journal of Clinical Medicine Editorial board, and Clinical Transplantation Associate Editor.AcknowledgmentsThe content of this article reflects the personal experience and views of the author(s) and should not be considered medical advice or recommendations. The content does not reflect the views or opinions of the American Society of buy lasix usa Nephrology (ASN) or JASN. Responsibility for the information and views expressed herein lies entirely with the author(s).FootnotesPublished online ahead of print. Publication date available at www.jasn.org.See related article, “Data-driven Derivation and Validation of Novel Phenotypes for Acute Kidney Transplant Rejection using Semi-supervised Clustering” on pages 1084–1096.Copyright © 2021 by the American Society of Nephrology.

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Visit your doctor or health care professional for regular checks on your progress. Check your blood pressure regularly. Ask your doctor or health care professional what your blood pressure should be, and when you should contact him or her. If you are a diabetic, check your blood sugar as directed.

You may need to be on a special diet while taking Lasix. Check with your doctor. Also, ask how many glasses of fluid you need to drink a day. You must not get dehydrated.

You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how this drug affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol can make you more drowsy and dizzy. Avoid alcoholic drinks.

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Can lasix be given im

How to find out here now cite can lasix be given im this article:Singh O P. Aftermath of celebrity suicide – Media coverage and role of psychiatrists. Indian J Psychiatry 2020;62:337-8Celebrity suicide can lasix be given im is one of the highly publicized events in our country. Indians got a glimpse of this following an unfortunate incident where a popular Hindi film actor died of suicide. As expected, the media went into a frenzy as newspapers, can lasix be given im news channels, and social media were full of stories providing minute details of the suicidal act.

Some even going as far as highlighting the color of the cloth used in the suicide as well as showing the lifeless body of the actor. All kinds of personal details were dug up, and speculations and hypotheses became the order of the day in the next few days that followed. In the process, reputations of many people associated with the actor were besmirched and their private and personal details were freely and blatantly can lasix be given im broadcast and discussed on electronic, print, and social media. We understand that media houses have their own need and duty to report and sensationalize news for increasing their visibility (aka TRP), but such reporting has huge impacts on the mental health of the vulnerable population.The impact of this was soon realized when many incidents of copycat suicide were reported from all over the country within a few days of the incident. Psychiatrists suddenly started can lasix be given im getting distress calls from their patients in despair with increased suicidal ideation.

This has become a major area of concern for the psychiatry community.The Indian Psychiatric Society has been consistently trying to engage with media to promote ethical reporting of suicide. Section 24 (1) of Mental Health Care Act, 2017, forbids publication of photograph of mentally ill can lasix be given im person without his consent.[1] The Press Council of India has adopted the guidelines of World Health Organization report on Preventing Suicide. A resource for media professionals, which came out with an advisory to be followed by media in reporting cases of suicide. It includes points forbidding them from putting stories in prominent positions and unduly repeating them, explicitly describing the method used, providing details about the site/location, using sensational headlines, or using photographs and video footage of the incident.[2] Unfortunately, the advisory seems to have little effect in the aftermath of celebrity suicides. Channels were can lasix be given im full of speculations about the person's mental condition and illness and also his relationships and finances.

Many fictional accounts of his symptoms and illness were touted, which is not only against the ethics but is also contrary to MHCA, 2017.[1]It went to the extent that the name of his psychiatrist was mentioned and quotes were attributed to him without taking any account from him. The Indian Psychiatric Society has written to the Press Council of India underlining this concern and asking for measures to ensure ethics in reporting suicide.While there is a need for engagement with media to make them aware of the grave impact of negative suicide reporting on the can lasix be given im lives of many vulnerable persons, there is even a more urgent need for training of psychiatrists regarding the proper way of interaction with media. This has been amply brought out in the aftermath of this incident. Many psychiatrists and mental health professionals can lasix be given im were called by media houses to comment on the episode. Many psychiatrists were quoted, or “misquoted,” or “quoted out of context,” commenting on the life of a person whom they had never examined and had no “professional authority” to do so.

There were even stories with byline of a psychiatrist where the content provided was not only unscientific but also way beyond the expertise of a psychiatrist. These types of viewpoints perpetuate stigma, myths, and “misleading concepts” about psychiatry and are detrimental to the image of psychiatry in addition to doing harm and injustice to our patients can lasix be given im. Hence, the need to formulate a guideline for interaction of psychiatrists with the media is imperative.In the infamous Goldwater episode, 12,356 psychiatrists were asked to cast opinion about the fitness of Barry Goldwater for presidential candidature. Out of 2417 respondents, 1189 psychiatrists reported him to be mentally unfit while none had actually examined him.[3] This led to the formulation of “The Goldwater Rule” by the American Psychiatric Association in 1973,[4] but we have witnessed the same phenomenon at the time of presidential candidature of Donald Trump.Psychiatrists should be encouraged to interact with media to provide scientific information about mental illnesses and reduction of stigma, but “statements to the media” can be a double-edged can lasix be given im sword, and we should know about the rules of engagements and boundaries of interactions. Methods and principles of interaction with media should form a part of our training curriculum.

Many professional societies have guidelines and can lasix be given im resource books for interacting with media, and psychiatrists should familiarize themselves with these documents. The Press Council guideline is likely to prompt reporters to seek psychiatrists for their expert opinion. It is useful for them to have a template ready with suicide rates, emphasizing multicausality of suicide, role of mental disorders, as well as help available.[5]It is about time that the Indian Psychiatric Society formulated its own guidelines laying down the broad principles and boundaries governing the interaction of Indian psychiatrists with the media. Till then, it is desirable to be guided by the following broad principles:It should be assumed that no statement goes “off the record” as the media person is most likely recording the interview, and can lasix be given im we should also record any such conversation from our endIt should be clarified in which capacity comments are being made – professional, personal, or as a representative of an organizationOne should not comment on any person whom he has not examinedPsychiatrists should take any such opportunity to educate the public about mental health issuesThe comments should be justified and limited by the boundaries of scientific knowledge available at the moment. References Correspondence Address:Dr.

O P SinghAA 304, Ashabari Apartments, O/31, Baishnabghata, Patuli Township, can lasix be given im Kolkata - 700 094, West Bengal IndiaSource of Support. None, Conflict of Interest. NoneDOI. 10.4103/psychiatry.IndianJPsychiatry_816_20Abstract Electroconvulsive therapy (ECT) is an effective modality of treatment for a variety of psychiatric disorders. However, it has always been accused of being a coercive, unethical, and dangerous modality of treatment.

The dangerousness of ECT has been mainly attributed to its claimed ability to cause brain damage. This narrative review aims to provide an update of the evidence with regard to whether the practice of ECT is associated with damage to the brain. An accepted definition of brain damage remains elusive. There are also ethical and technical problems in designing studies that look at this question specifically. Thus, even though there are newer technological tools and innovations, any review attempting to answer this question would have to take recourse to indirect methods.

These include structural, functional, and metabolic neuroimaging. Body fluid biochemical marker studies. And follow-up studies of cognitive impairment and incidence of dementia in people who have received ECT among others. The review of literature and present evidence suggests that ECT has a demonstrable impact on the structure and function of the brain. However, there is a lack of evidence at present to suggest that ECT causes brain damage.Keywords.

Adverse effect, brain damage, electroconvulsive therapyHow to cite this article:Jolly AJ, Singh SM. Does electroconvulsive therapy cause brain damage. An update. Indian J Psychiatry 2020;62:339-53 Introduction Electroconvulsive therapy (ECT) as a modality of treatment for psychiatric disorders has existed at least since 1938.[1] ECT is an effective modality of treatment for various psychiatric disorders. However, from the very beginning, the practice of ECT has also faced resistance from various groups who claim that it is coercive and harmful.[2] While the ethical aspects of the practice of ECT have been dealt with elsewhere, the question of harmfulness or brain damage consequent upon the passage of electric current needs to be examined afresh in light of technological advances and new knowledge.[3]The question whether ECT causes brain damage was reviewed in a holistic fashion by Devanand et al.

In the mid-1990s.[4],[5] The authors had attempted to answer this question by reviewing the effect of ECT on the brain in various areas – cognitive side effects, structural neuroimaging studies, neuropathologic studies of patients who had received ECT, autopsy studies of epileptic patients, and finally animal ECS studies. The authors had concluded that ECT does not produce brain damage.This narrative review aims to update the evidence with regard to whether ECT causes brain damage by reviewing relevant literature from 1994 to the present time. Framing the Question The Oxford Dictionary defines damage as physical harm that impairs the value, usefulness, or normal function of something.[6] Among medical dictionaries, the Peter Collins Dictionary defines damage as harm done to things (noun) or to harm something (verb).[7] Brain damage is defined by the British Medical Association Medical Dictionary as degeneration or death of nerve cells and tracts within the brain that may be localized to a particular area of the brain or diffuse.[8] Going by such a definition, brain damage in the context of ECT should refer to death or degeneration of brain tissue, which results in the impairment of functioning of the brain. The importance of precisely defining brain damage shall become evident subsequently in this review.There are now many more tools available to investigate the structure and function of brain in health and illness. However, there are obvious ethical issues in designing human studies that are designed to answer this specific question.

Therefore, one must necessarily take recourse to indirect evidences available through studies that have been designed to answer other research questions. These studies have employed the following methods:Structural neuroimaging studiesFunctional neuroimaging studiesMetabolic neuroimaging studiesBody fluid biochemical marker studiesCognitive impairment studies.While the early studies tended to focus more on establishing the safety of ECT and finding out whether ECT causes gross microscopic brain damage, the later studies especially since the advent of advanced neuroimaging techniques have been focusing more on a mechanistic understanding of ECT. Hence, the primary objective of the later neuroimaging studies has been to look for structural and functional brain changes which might explain how ECT acts rather than evidence of gross structural damage per se. However, put together, all these studies would enable us to answer our titular question to some satisfaction. [Table 1] and [Table 2] provide an overview of the evidence base in this area.

Structural and Functional Neuroimaging Studies Devanand et al. Reviewed 16 structural neuroimaging studies on the effect of ECT on the brain.[4] Of these, two were pneumoencephalography studies, nine were computed tomography (CT) scan studies, and five were magnetic resonance imaging (MRI) studies. However, most of these studies were retrospective in design, with neuroimaging being done in patients who had received ECT in the past. In the absence of baseline neuroimaging, it would be very difficult to attribute any structural brain changes to ECT. In addition, pneumoencephalography, CT scan, and even early 0.3 T MRI provided images with much lower spatial resolution than what is available today.

The authors concluded that there was no evidence to show that ECT caused any structural damage to the brain.[4] Since then, at least twenty more MRI-based structural neuroimaging studies have studied the effect of ECT on the brain. The earliest MRI studies in the early 1990s focused on detecting structural damage following ECT. All of these studies were prospective in design, with the first MRI scan done at baseline and a second MRI scan performed post ECT.[9],[11],[12],[13],[41] While most of the studies imaged the patient once around 24 h after receiving ECT, some studies performed multiple post ECT neuroimaging in the first 24 h after ECT to better capture the acute changes. A single study by Coffey et al. Followed up the patients for a duration of 6 months and repeated neuroimaging again at 6 months in order to capture any long-term changes following ECT.[10]The most important conclusion which emerged from this early series of studies was that there was no evidence of cortical atrophy, change in ventricle size, or increase in white matter hyperintensities.[4] The next major conclusion was that there appeared to be an increase in the T1 and T2 relaxation time immediately following ECT, which returned to normal within 24 h.

This supported the theory that immediately following ECT, there appears to be a temporary breakdown of the blood–brain barrier, leading to water influx into the brain tissue.[11] The last significant observation by Coffey et al. In 1991 was that there was no significant temporal changes in the total volumes of the frontal lobes, temporal lobes, or amygdala–hippocampal complex.[10] This was, however, something which would later be refuted by high-resolution MRI studies. Nonetheless, one inescapable conclusion of these early studies was that there was no evidence of any gross structural brain changes following administration of ECT. Much later in 2007, Szabo et al. Used diffusion-weighted MRI to image patients in the immediate post ECT period and failed to observe any obvious brain tissue changes following ECT.[17]The next major breakthrough came in 2010 when Nordanskog et al.

Demonstrated that there was a significant increase in the volume of the hippocampus bilaterally following a course of ECT in a cohort of patients with depressive illness.[18] This contradicted the earlier observations by Coffey et al. That there was no volume increase in any part of the brain following ECT.[10] This was quite an exciting finding and was followed by several similar studies. However, the perspective of these studies was quite different from the early studies. In contrast to the early studies looking for the evidence of ECT-related brain damage, the newer studies were focused more on elucidating the mechanism of action of ECT. Further on in 2014, Nordanskog et al.

In a follow-up study showed that though there was a significant increase in the volume of the hippocampus 1 week after a course of ECT, the hippocampal volume returned to the baseline after 6 months.[19] Two other studies in 2013 showed that in addition to the hippocampus, the amygdala also showed significant volume increase following ECT.[20],[21] A series of structural neuroimaging studies after that have expanded on these findings and as of now, gray matter volume increase following ECT has been demonstrated in the hippocampus, amygdala, anterior temporal pole, subgenual cortex,[21] right caudate nucleus, and the whole of the medial temporal lobe (MTL) consisting of the hippocampus, amygdala, insula, and the posterosuperior temporal cortex,[24] para hippocampi, right subgenual anterior cingulate gyrus, and right anterior cingulate gyrus,[25] left cerebellar area VIIa crus I,[29] putamen, caudate nucleus, and nucleus acumbens [31] and clusters of increased cortical thickness involving the temporal pole, middle and superior temporal cortex, insula, and inferior temporal cortex.[27] However, the most consistently reported and replicated finding has been the bilateral increase in the volume of the hippocampus and amygdala. In light of these findings, it has been tentatively suggested that ECT acts by inducing neuronal regeneration in the hippocampus – amygdala complex.[42],[43] However, there are certain inconsistencies to this hypothesis. Till date, only one study – Nordanskog et al., 2014 – has followed study patients for a long term – 6 months in their case. And significantly, the authors found out that after increasing immediately following ECT, the hippocampal volume returns back to baseline by 6 months.[19] This, however, was not associated with the relapse of depressive symptoms. Another area of significant confusion has been the correlation of hippocampal volume increase with improvement of depressive symptoms.

Though almost all studies demonstrate a significant increase in hippocampal volume following ECT, a majority of studies failed to demonstrate a correlation between symptom improvement and hippocampal volume increase.[19],[20],[22],[24],[28] However, a significant minority of volumetric studies have demonstrated correlation between increase in hippocampal and/or amygdala volume and improvement of symptoms.[21],[25],[30]Another set of studies have used diffusion tensor imaging, functional MRI (fMRI), anatomical connectome, and structural network analysis to study the effect of ECT on the brain. The first of these studies by Abbott et al. In 2014 demonstrated that on fMRI, the connectivity between right and left hippocampus was significantly reduced in patients with severe depression. It was also shown that the connectivity was normalized following ECT, and symptom improvement was correlated with an increase in connectivity.[22] In a first of its kind DTI study, Lyden et al. In 2014 demonstrated that fractional anisotropy which is a measure of white matter tract or fiber density is increased post ECT in patients with severe depression in the anterior cingulum, forceps minor, and the dorsal aspect of the left superior longitudinal fasciculus.

The authors suggested that ECT acts to normalize major depressive disorder-related abnormalities in the structural connectivity of the dorsal fronto-limbic pathways.[23] Another DTI study in 2015 constructed large-scale anatomical networks of the human brain – connectomes, based on white matter fiber tractography. The authors found significant reorganization in the anatomical connections involving the limbic structure, temporal lobe, and frontal lobe. It was also found that connection changes between amygdala and para hippocampus correlated with reduction in depressive symptoms.[26] In 2016, Wolf et al. Used a source-based morphometry approach to study the structural networks in patients with depression and schizophrenia and the effect of ECT on the same. It was found that the medial prefrontal cortex/anterior cingulate cortex (ACC/MPFC) network, MTL network, bilateral thalamus, and left cerebellar regions/precuneus exhibited significant difference between healthy controls and the patient population.

It was also demonstrated that administration of ECT leads to significant increase in the network strength of the ACC/MPFC network and the MTL network though the increase in network strength and symptom amelioration were not correlated.[32]Building on these studies, a recently published meta-analysis has attempted a quantitative synthesis of brain volume changes – focusing on hippocampal volume increase following ECT in patients with major depressive disorder and bipolar disorder. The authors initially selected 32 original articles from which six articles met the criteria for quantitative synthesis. The results showed significant increase in the volume of the right and left hippocampus following ECT. For the rest of the brain regions, the heterogeneity in protocols and imaging techniques did not permit a quantitative analysis, and the authors have resorted to a narrative review similar to the present one with similar conclusions.[44] Focusing exclusively on hippocampal volume change in ECT, Oltedal et al. In 2018 conducted a mega-analysis of 281 patients with major depressive disorder treated with ECT enrolled at ten different global sites of the Global ECT-MRI Research Collaboration.[45] Similar to previous studies, there was a significant increase in hippocampal volume bilaterally with a dose–response relationship with the number of ECTs administered.

Furthermore, bilateral (B/L) ECT was associated with an equal increase in volume in both right and left hippocampus, whereas right unilateral ECT was associated with greater volume increase in the right hippocampus. Finally, contrary to expectation, clinical improvement was found to be negatively correlated with hippocampal volume.Thus, a review of the current evidence amply demonstrates that from looking for ECT-related brain damage – and finding none, we have now moved ahead to looking for a mechanistic understanding of the effect of ECT. In this regard, it has been found that ECT does induce structural changes in the brain – a fact which has been seized upon by some to claim that ECT causes brain damage.[46] Such statements should, however, be weighed against the definition of damage as understood by the scientific medical community and patient population. Neuroanatomical changes associated with effective ECT can be better described as ECT-induced brain neuroplasticity or ECT-induced brain neuromodulation rather than ECT-induced brain damage. Metabolic Neuroimaging Studies.

Magnetic Resonance Spectroscopic Imaging Magnetic resonance spectroscopic imaging (MRSI) uses a phase-encoding procedure to map the spatial distribution of magnetic resonance (MR) signals of different molecules. The crucial difference, however, is that while MRI maps the MR signals of water molecules, MRSI maps the MR signals generated by different metabolites – such as N-acetyl aspartate (NAA) and choline-containing compounds. However, the concentration of these metabolites is at least 10,000 times lower than water molecules and hence the signal strength generated would also be correspondingly lower. However, MRSI offers us the unique advantage of studying in vivo the change in the concentration of brain metabolites, which has been of great significance in fields such as psychiatry, neurology, and basic neuroscience research.[47]MRSI studies on ECT in patients with depression have focused largely on four metabolites in the human brain – NAA, choline-containing compounds (Cho) which include majorly cell membrane compounds such as glycerophosphocholine, phosphocholine and a miniscule contribution from acetylcholine, creatinine (Cr) and glutamine and glutamate together (Glx). NAA is located exclusively in the neurons, and is suggested to be a marker of neuronal viability and functionality.[48] Choline-containing compounds (Cho) mainly include the membrane compounds, and an increase in Cho would be suggestive of increased membrane turnover.

Cr serves as a marker of cellular energy metabolism, and its levels are usually expected to remain stable. The regions which have been most widely studied in MRSI studies include the bilateral hippocampus and amygdala, dorsolateral prefrontal cortex (DLPFC), and ACC.Till date, five MRSI studies have measured NAA concentration in the hippocampus before and after ECT. Of these, three studies showed that there is no significant change in the NAA concentration in the hippocampus following ECT.[33],[38],[49] On the other hand, two recent studies have demonstrated a statistically significant reduction in NAA concentration in the hippocampus following ECT.[39],[40] The implications of these results are of significant interest to us in answering our titular question. A normal level of NAA following ECT could signify that there is no significant neuronal death or damage following ECT, while a reduction would signal the opposite. However, a direct comparison between these studies is complicated chiefly due to the different ECT protocols, which has been used in these studies.

It must, however, be acknowledged that the three older studies used 1.5 T MRI, whereas the two newer studies used a higher 3 T MRI which offers betters signal-to-noise ratio and hence lesser risk of errors in the measurement of metabolite concentrations. The authors of a study by Njau et al.[39] argue that a change in NAA levels might reflect reversible changes in neural metabolism rather than a permanent change in the number or density of neurons and also that reduced NAA might point to a change in the ratio of mature to immature neurons, which, in fact, might reflect enhanced adult neurogenesis. Thus, the authors warn that to conclude whether a reduction in NAA concentration is beneficial or harmful would take a simultaneous measurement of cognitive functioning, which was lacking in their study. In 2017, Cano et al. Also demonstrated a significant reduction in NAA/Cr ratio in the hippocampus post ECT.

More significantly, the authors also showed a significant increase in Glx levels in the hippocampus following ECT, which was also associated with an increase in hippocampal volume.[40] To explain these three findings, the authors proposed that ECT produces a neuroinflammatory response in the hippocampus – likely mediated by Glx, which has been known to cause inflammation at higher concentrations, thereby accounting for the increase in hippocampal volume with a reduction in NAA concentration. The cause for the volume increase remains unclear – with the authors speculating that it might be due to neuronal swelling or due to angiogenesis. However, the same study and multiple other past studies [21],[25],[30] have demonstrated that hippocampal volume increase was correlated with clinical improvement following ECT. Thus, we are led to the hypothesis that the same mechanism which drives clinical improvement with ECT is also responsible for the cognitive impairment following ECT. Whether this is a purely neuroinflammatory response or a neuroplastic response or a neuroinflammatory response leading to some form of neuroplasticity is a critical question, which remains to be answered.[40]Studies which have analyzed NAA concentration change in other brain areas have also produced conflicting results.

The ACC is another area which has been studied in some detail utilizing the MRSI technique. In 2003, Pfleiderer et al. Demonstrated that there was no significant change in the NAA and Cho levels in the ACC following ECT. This would seem to suggest that there was no neurogenesis or membrane turnover in the ACC post ECT.[36] However, this finding was contested by Merkl et al. In 2011, who demonstrated that NAA levels were significantly reduced in the left ACC in patients with depression and that these levels were significantly elevated following ECT.[37] This again is contested by Njau et al.

Who showed that NAA levels are significantly reduced following ECT in the left dorsal ACC.[39] A direct comparison of these three studies is complicated by the different ECT and imaging parameters used and hence, no firm conclusion can be made on this point at this stage. In addition to this, one study had demonstrated increased NAA levels in the amygdala following administration of ECT,[34] with a trend level increase in Cho levels, which again is suggestive of neurogenesis and/or neuroplasticity. A review of studies on the DLPFC reveals a similarly confusing picture with one study, each showing no change, reduction, and elevation of concentration of NAA following ECT.[35],[37],[39] Here, again, a direct comparison of the three studies is made difficult by the heterogeneous imaging and ECT protocols followed by them.A total of five studies have analyzed the concentration of choline-containing compounds (Cho) in patients undergoing ECT. Conceptually, an increase in Cho signals is indicative of increased membrane turnover, which is postulated to be associated with synaptogenesis, neurogenesis, and maturation of neurons.[31] Of these, two studies measured Cho concentration in the B/L hippocampus, with contrasting results. Ende et al.

In 2000 demonstrated a significant elevation in Cho levels in B/L hippocampus after ECT, while Jorgensen et al. In 2015 failed to replicate the same finding.[33],[38] Cho levels have also been studied in the amygdala, ACC, and the DLPFC. However, none of these studies showed a significant increase or decrease in Cho levels before and after ECT in the respective brain regions studied. In addition, no significant difference was seen in the pre-ECT Cho levels of patients compared to healthy controls.[34],[36],[37]In review, we must admit that MRSI studies are still at a preliminary stage with significant heterogeneity in ECT protocols, patient population, and regions of the brain studied. At this stage, it is difficult to draw any firm conclusions except to acknowledge the fact that the more recent studies – Njau et al., 2017, Cano, 2017, and Jorgensen et al., 2015 – have shown decrease in NAA concentration and no increase in Cho levels [38],[39],[40] – as opposed to the earlier studies by Ende et al.[33] The view offered by the more recent studies is one of a neuroinflammatory models of action of ECT, probably driving neuroplasticity in the hippocampus.

This would offer a mechanistic understanding of both clinical response and the phenomenon of cognitive impairment associated with ECT. However, this conclusion is based on conjecture, and more work needs to be done in this area. Body Fluid Biochemical Marker Studies Another line of evidence for analyzing the effect of ECT on the human brain is the study of concentration of neurotrophins in the plasma or serum. Neurotrophins are small protein molecules which mediate neuronal survival and development. The most prominent among these is brain-derived neurotrophic factor (BDNF) which plays an important role in neuronal survival, plasticity, and migration.[50] A neurotrophic theory of mood disorders was suggested which hypothesized that depressive disorders are associated with a decreased expression of BDNF in the limbic structures, resulting in the atrophy of these structures.[51] It was also postulated that antidepressant treatment has a neurotrophic effect which reverses the neuronal cell loss, thereby producing a therapeutic effect.

It has been well established that BDNF is decreased in mood disorders.[52] It has also been shown that clinical improvement of depression is associated with increase in BDNF levels.[53] Thus, serum BDNF levels have been tentatively proposed as a biomarker for treatment response in depression. Recent meta-analytic evidence has shown that ECT is associated with significant increase in serum BDNF levels in patients with major depressive disorder.[54] Considering that BDNF is a potent stimulator of neurogenesis, the elevation of serum BDNF levels following ECT lends further credence to the theory that ECT leads to neurogenesis in the hippocampus and other limbic structures, which, in turn, mediates the therapeutic action of ECT. Cognitive Impairment Studies Cognitive impairment has always been the single-most important side effect associated with ECT.[55] Concerns regarding long-term cognitive impairment surfaced soon after the introduction of ECT and since then has grown to become one of the most controversial aspects of ECT.[56] Anti-ECT groups have frequently pointed out to cognitive impairment following ECT as evidence of ECT causing brain damage.[56] A meta-analysis by Semkovska and McLoughlin in 2010 is one of the most detailed studies which had attempted to settle this long-standing debate.[57] The authors reviewed 84 studies (2981 participants), which had used a combined total of 22 standardized neuropsychological tests assessing various cognitive functions before and after ECT in patients diagnosed with major depressive disorder. The different cognitive domains reviewed included processing speed, attention/working memory, verbal episodic memory, visual episodic memory, spatial problem-solving, executive functioning, and intellectual ability. The authors concluded that administration of ECT for depression is associated with significant cognitive impairment in the first few days after ECT administration.

However, it was also seen that impairment in cognitive functioning resolved within a span of 2 weeks and thereafter, a majority of cognitive domains even showed mild improvement compared to the baseline performance. It was also demonstrated that not a single cognitive domain showed persistence of impairment beyond 15 days after ECT.Memory impairment following ECT can be analyzed broadly under two conceptual schemes – one that classifies memory impairment as objective memory impairment and subjective memory impairment and the other that classifies it as impairment in anterograde memory versus impairment in retrograde memory. Objective memory can be roughly defined as the ability to retrieve stored information and can be measured by various standardized neuropsychological tests. Subjective memory or meta-memory, on the other hand, refers to the ability to make judgments about one's ability to retrieve stored information.[58] As described previously, it has been conclusively demonstrated that anterograde memory impairment does not persist beyond 2 weeks after ECT.[57] However, one of the major limitations of this meta-analysis was the lack of evidence on retrograde amnesia following ECT. This is particularly unfortunate considering that it is memory impairment – particularly retrograde amnesia which has received the most attention.[59] In addition, reports of catastrophic retrograde amnesia have been repeatedly held up as sensational evidence of the lasting brain damage produced by ECT.[59] Admittedly, studies on retrograde amnesia are fewer and less conclusive than on anterograde amnesia.[60],[61] At present, the results are conflicting, with some studies finding some impairment in retrograde memory – particularly autobiographical retrograde memory up to 6 months after ECT.[62],[63],[64],[65] However, more recent studies have failed to support this finding.[66],[67] While they do demonstrate an impairment in retrograde memory immediately after ECT, it was seen that this deficit returned to pre-ECT levels within a span of 1–2 months and improved beyond baseline performance at 6 months post ECT.[66] Adding to the confusion are numerous factors which confound the assessment of retrograde amnesia.

It has been shown that depressive symptoms can produce significant impairment of retrograde memory.[68],[69] It has also been demonstrated that sine-wave ECT produces significantly more impairment of retrograde memory as compared to brief-pulse ECT.[70] However, from the 1990s onward, sine-wave ECT has been completely replaced by brief-pulse ECT, and it is unclear as to the implications of cognitive impairment from the sine-wave era in contemporary ECT practice.Another area of concern are reports of subjective memory impairment following ECT. One of the pioneers of research into subjective memory impairment were Squire and Chace who published a series of studies in the 1970s demonstrating the adverse effect of bilateral ECT on subjective assessment of memory.[62],[63],[64],[65] However, most of the studies conducted post 1980 – from when sine-wave ECT was replaced by brief-pulse ECT report a general improvement in subjective memory assessments following ECT.[71] In addition, most of the recent studies have failed to find a significant association between measures of subjective and objective memory.[63],[66],[70],[72],[73],[74] It has also been shown that subjective memory impairment is strongly associated with the severity of depressive symptoms.[75] In light of these facts, the validity and value of measures of subjective memory impairment as a marker of cognitive impairment and brain damage following ECT have been questioned. However, concerns regarding subjective memory impairment and catastrophic retrograde amnesia continue to persist, with significant dissonance between the findings of different research groups and patient self-reports in various media.[57]Some studies reported the possibility of ECT being associated with the development of subsequent dementia.[76],[77] However, a recent large, well-controlled prospective Danish study found that the use of ECT was not associated with elevated incidence of dementia.[78] Conclusion Our titular question is whether ECT leads to brain damage, where damage indicates destruction or degeneration of nerves or nerve tracts in the brain, which leads to loss of function. This issue was last addressed by Devanand et al. In 1994 since which time our understanding of ECT has grown substantially, helped particularly by the advent of modern-day neuroimaging techniques which we have reviewed in detail.

And, what these studies reveal is rather than damaging the brain, ECT has a neuromodulatory effect on the brain. The various lines of evidence – structural neuroimaging studies, functional neuroimaging studies, neurochemical and metabolic studies, and serum BDNF studies all point toward this. These neuromodulatory changes have been localized to the hippocampus, amygdala, and certain other parts of the limbic system. How exactly these changes mediate the improvement of depressive symptoms is a question that remains unanswered. However, there is little by way of evidence from neuroimaging studies which indicates that ECT causes destruction or degeneration of neurons.

Though cognitive impairment studies do show that there is objective impairment of certain functions – particularly memory immediately after ECT, these impairments are transient with full recovery within a span of 2 weeks. Perhaps, the single-most important unaddressed concern is retrograde amnesia, which has been shown to persist for up to 2 months post ECT. In this regard, the recent neurometabolic studies have offered a tentative mechanism of action of ECT, producing a transient inflammation in the limbic cortex, which, in turn, drives neurogenesis, thereby exerting a neuromodulatory effect. This hypothesis would explain both the cognitive adverse effects of ECT – due to the transient inflammation – and the long-term improvement in mood – neurogenesis in the hippocampus. Although unproven at present, such a hypothesis would imply that cognitive impairment is tied in with the mechanism of action of ECT and not an indicator of damage to the brain produced by ECT.The review of literature suggests that ECT does cause at least structural and functional changes in the brain, and these are in all probability related to the effects of the ECT.

However, these cannot be construed as brain damage as is usually understood. Due to the relative scarcity of data that directly examines the question of whether ECT causes brain damage, it is not possible to conclusively answer this question. However, in light of enduring ECT survivor accounts, there is a need to design studies that specifically answer this question.Financial support and sponsorshipNil.Conflicts of interestThere are no conflicts of interest. References 1.Payne NA, Prudic J. Electroconvulsive therapy.

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31.Wade BS, Joshi SH, Njau S, Leaver AM, Vasavada M, Woods RP, et al. Effect of electroconvulsive therapy on striatal morphometry in major depressive disorder. Neuropsychopharmacology 2016;41:2481-91. 32.Wolf RC, Nolte HM, Hirjak D, Hofer S, Seidl U, Depping MS, et al. Structural network changes in patients with major depression and schizophrenia treated with electroconvulsive therapy.

Eur Neuropsychopharmacol 2016;26:1465-74. 33.Ende G, Braus DF, Walter S, Weber-Fahr W, Henn FA. The hippocampus in patients treated with electroconvulsive therapy. A proton magnetic resonance spectroscopic imaging study. Arch Gen Psychiatry 2000;57:937-43.

34.Michael N, Erfurth A, Ohrmann P, Arolt V, Heindel W, Pfleiderer B. Metabolic changes within the left dorsolateral prefrontal cortex occurring with electroconvulsive therapy in patients with treatment resistant unipolar depression. Psychol Med 2003;33:1277-84. 35.Michael N, Erfurth A, Ohrmann P, Arolt V, Heindel W, Pfleiderer B. Neurotrophic effects of electroconvulsive therapy.

A proton magnetic resonance study of the left amygdalar region in patients with treatment-resistant depression. Neuropsychopharmacology 2003;28:720-5. 36.Pfleiderer B, Michael N, Erfurth A, Ohrmann P, Hohmann U, Wolgast M, et al. Effective electroconvulsive therapy reverses glutamate/glutamine deficit in the left anterior cingulum of unipolar depressed patients. Psychiatry Res 2003;122:185-92.

37.Merkl A, Schubert F, Quante A, Luborzewski A, Brakemeier EL, Grimm S, et al. Abnormal cingulate and prefrontal cortical neurochemistry in major depression after electroconvulsive therapy. Biol Psychiatry 2011;69:772-9. 38.Jorgensen A, Magnusson P, Hanson LG, Kirkegaard T, Benveniste H, Lee H, et al. Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression.

Acta Psychiatr Scand 2016;133:154-64. 39.Njau S, Joshi SH, Espinoza R, Leaver AM, Vasavada M, Marquina A, et al. Neurochemical correlates of rapid treatment response to electroconvulsive therapy in patients with major depression. J Psychiatry Neurosci 2017;42:6-16. 40.Cano M, Martínez-Zalacaín I, Bernabéu-Sanz Á, Contreras-Rodríguez O, Hernández-Ribas R, Via E, et al.

Brain volumetric and metabolic correlates of electroconvulsive therapy for treatment-resistant depression. A longitudinal neuroimaging study. Transl Psychiatry 2017;7:e1023. 41.Figiel GS, Krishnan KR, Doraiswamy PM. Subcortical structural changes in ECT-induced delirium.

J Geriatr Psychiatry Neurol 1990;3:172-6. 42.Rotheneichner P, Lange S, O'Sullivan A, Marschallinger J, Zaunmair P, Geretsegger C, et al. Hippocampal neurogenesis and antidepressive therapy. Shocking relations. Neural Plast 2014;2014:723915.

43.Singh A, Kar SK. How electroconvulsive therapy works?. Understanding the neurobiological mechanisms. Clin Psychopharmacol Neurosci 2017;15:210-21. 44.Gbyl K, Videbech P.

Electroconvulsive therapy increases brain volume in major depression. A systematic review and meta-analysis. Acta Psychiatr Scand 2018;138:180-95. 45.Oltedal L, Narr KL, Abbott C, Anand A, Argyelan M, Bartsch H, et al. Volume of the human hippocampus and clinical response following electroconvulsive therapy.

Biol Psychiatry 2018;84:574-81. 46.Breggin PR. Brain-Disabling Treatments in Psychiatry. Drugs, Electroshock, and the Role of the FDA. New York.

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Principles and recent advances. J Magn Reson Imaging 2013;37:1301-25. 48.Simmons ML, Frondoza CG, Coyle JT. Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 1991;45:37-45.

49.Obergriesser T, Ende G, Braus DF, Henn FA. Long-term follow-up of magnetic resonance-detectable choline signal changes in the hippocampus of patients treated with electroconvulsive therapy. J Clin Psychiatry 2003;64:775-80. 50.Bramham CR, Messaoudi E. BDNF function in adult synaptic plasticity.

The synaptic consolidation hypothesis. Prog Neurobiol 2005;76:99-125. 51.Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry 2006;59:1116-27.

52.Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Molteni R, Nielsen MG, Placentino A, et al. Serum and plasma BDNF levels in major depression. A replication study and meta-analyses. World J Biol Psychiatry 2010;11:763-73. 53.Brunoni AR, Lopes M, Fregni F.

A systematic review and meta-analysis of clinical studies on major depression and BDNF levels. Implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol 2008;11:1169-80. 54.Rocha RB, Dondossola ER, Grande AJ, Colonetti T, Ceretta LB, Passos IC, et al. Increased BDNF levels after electroconvulsive therapy in patients with major depressive disorder.

A meta-analysis study. J Psychiatr Res 2016;83:47-53. 55.UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders. A systematic review and meta-analysis.

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58.Tulving E, Madigan SA. Memory and verbal learning. Annu Rev Psychol 1970;21:437-84. 59.Rose D, Fleischmann P, Wykes T, Leese M, Bindman J. Patients' perspectives on electroconvulsive therapy.

Systematic review. BMJ 2003;326:1363. 60.Semkovska M, McLoughlin DM. Measuring retrograde autobiographical amnesia following electroconvulsive therapy. Historical perspective and current issues.

J ECT 2013;29:127-33. 61.Fraser LM, O'Carroll RE, Ebmeier KP. The effect of electroconvulsive therapy on autobiographical memory. A systematic review. J ECT 2008;24:10-7.

62.Squire LR, Chace PM. Memory functions six to nine months after electroconvulsive therapy. Arch Gen Psychiatry 1975;32:1557-64. 63.Squire LR, Slater PC. Electroconvulsive therapy and complaints of memory dysfunction.

A prospective three-year follow-up study. Br J Psychiatry 1983;142:1-8. 64.Squire LR, Slater PC, Miller PL. Retrograde amnesia and bilateral electroconvulsive therapy. Long-term follow-up.

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66.Calev A, Nigal D, Shapira B, Tubi N, Chazan S, Ben-Yehuda Y, et al. Early and long-term effects of electroconvulsive therapy and depression on memory and other cognitive functions. J Nerv Ment Dis 1991;179:526-33. 67.Sackeim HA, Prudic J, Devanand DP, Nobler MS, Lisanby SH, Peyser S, et al. A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities.

Arch Gen Psychiatry 2000;57:425-34. 68.Abrams R. Does brief-pulse ECT cause persistent or permanent memory impairment?. J ECT 2002;18:71-3. 69.Peretti CS, Danion JM, Grangé D, Mobarek N.

Bilateral ECT and autobiographical memory of subjective experiences related to melancholia. A pilot study. J Affect Disord 1996;41:9-15. 70.Weiner RD, Rogers HJ, Davidson JR, Squire LR. Effects of stimulus parameters on cognitive side effects.

Ann N Y Acad Sci 1986;462:315-25. 71.Prudic J, Peyser S, Sackeim HA. Subjective memory complaints. A review of patient self-assessment of memory after electroconvulsive therapy. J ECT 2000;16:121-32.

72.Sackeim HA, Prudic J, Devanand DP, Kiersky JE, Fitzsimons L, Moody BJ, et al. Effects of stimulus intensity and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. N Engl J Med 1993;328:839-46. 73.Frith CD, Stevens M, Johnstone EC, Deakin JF, Lawler P, Crow TJ. Effects of ECT and depression on various aspects of memory.

Br J Psychiatry 1983;142:610-7. 74.Ng C, Schweitzer I, Alexopoulos P, Celi E, Wong L, Tuckwell V, et al. Efficacy and cognitive effects of right unilateral electroconvulsive therapy. J ECT 2000;16:370-9. 75.Coleman EA, Sackeim HA, Prudic J, Devanand DP, McElhiney MC, Moody BJ.

Subjective memory complaints prior to and following electroconvulsive therapy. Biol Psychiatry 1996;39:346-56. 76.Berggren Š, Gustafson L, Höglund P, Johanson A. A long-term longitudinal follow-up of depressed patients treated with ECT with special focus on development of dementia. J Affect Disord 2016;200:15-24.

77.Brodaty H, Hickie I, Mason C, Prenter L. A prospective follow-up study of ECT outcome in older depressed patients. J Affect Disord 2000;60:101-11. 78.Osler M, Rozing MP, Christensen GT, Andersen PK, Jørgensen MB. Electroconvulsive therapy and risk of dementia in patients with affective disorders.

A cohort study. Lancet Psychiatry 2018;5:348-56. Correspondence Address:Dr. Shubh Mohan SinghDepartment of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh IndiaSource of Support. None, Conflict of Interest.

NoneDOI. 10.4103/psychiatry.IndianJPsychiatry_239_19 Tables [Table 1], [Table 2].

How to cite buy lasix usa this article:Singh How to get cipro in the us O P. Aftermath of celebrity suicide – Media coverage and role of psychiatrists. Indian J Psychiatry 2020;62:337-8Celebrity suicide is one of the buy lasix usa highly publicized events in our country.

Indians got a glimpse of this following an unfortunate incident where a popular Hindi film actor died of suicide. As expected, the media went into a buy lasix usa frenzy as newspapers, news channels, and social media were full of stories providing minute details of the suicidal act. Some even going as far as highlighting the color of the cloth used in the suicide as well as showing the lifeless body of the actor.

All kinds of personal details were dug up, and speculations and hypotheses became the order of the day in the next few days that followed. In the process, reputations of many people associated with the actor were besmirched and their private and personal details were freely and blatantly broadcast and discussed on electronic, print, buy lasix usa and social media. We understand that media houses have their own need and duty to report and sensationalize news for increasing their visibility (aka TRP), but such reporting has huge impacts on the mental health of the vulnerable population.The impact of this was soon realized when many incidents of copycat suicide were reported from all over the country within a few days of the incident.

Psychiatrists suddenly started getting distress calls from their patients in despair buy lasix usa with increased suicidal ideation. This has become a major area of concern for the psychiatry community.The Indian Psychiatric Society has been consistently trying to engage with media to promote ethical reporting of suicide. Section 24 (1) of Mental Health Care Act, 2017, forbids publication of photograph of mentally ill person without his consent.[1] The Press Council of buy lasix usa India has adopted the guidelines of World Health Organization report on Preventing Suicide.

A resource for media professionals, which came out with an advisory to be followed by media in reporting cases of suicide. It includes points forbidding them from putting stories in prominent positions and unduly repeating them, explicitly describing the method used, providing details about the site/location, using sensational headlines, or using photographs and video footage of the incident.[2] Unfortunately, the advisory seems to have little effect in the aftermath of celebrity suicides. Channels were full of speculations about the person's mental condition and illness and also his buy lasix usa relationships and finances.

Many fictional accounts of his symptoms and illness were touted, which is not only against the ethics but is also contrary to MHCA, 2017.[1]It went to the extent that the name of his psychiatrist was mentioned and quotes were attributed to him without taking any account from him. The Indian Psychiatric Society has buy lasix usa written to the Press Council of India underlining this concern and asking for measures to ensure ethics in reporting suicide.While there is a need for engagement with media to make them aware of the grave impact of negative suicide reporting on the lives of many vulnerable persons, there is even a more urgent need for training of psychiatrists regarding the proper way of interaction with media. This has been amply brought out in the aftermath of this incident.

Many psychiatrists and mental health professionals were called by buy lasix usa media houses to comment on the episode. Many psychiatrists were quoted, or “misquoted,” or “quoted out of context,” commenting on the life of a person whom they had never examined and had no “professional authority” to do so. There were even stories with byline of a psychiatrist where the content provided was not only unscientific but also way beyond the expertise of a psychiatrist.

These types of viewpoints perpetuate stigma, myths, and “misleading concepts” about psychiatry and are detrimental to the image of psychiatry buy lasix usa in addition to doing harm and injustice to our patients. Hence, the need to formulate a guideline for interaction of psychiatrists with the media is imperative.In the infamous Goldwater episode, 12,356 psychiatrists were asked to cast opinion about the fitness of Barry Goldwater for presidential candidature. Out of 2417 respondents, 1189 psychiatrists reported him to be mentally unfit while none had actually examined him.[3] This led to the formulation of “The Goldwater Rule” by the American Psychiatric Association in 1973,[4] but we have witnessed the same phenomenon at the time of presidential candidature of Donald Trump.Psychiatrists should be encouraged to interact with media to provide scientific information about mental illnesses and reduction of stigma, but “statements to the media” can be a double-edged sword, and we should know about the rules of engagements and boundaries of buy lasix usa interactions.

Methods and principles of interaction with media should form a part of our training curriculum. Many professional societies have guidelines and resource books for interacting buy lasix usa with media, and psychiatrists should familiarize themselves with these documents. The Press Council guideline is likely to prompt reporters to seek psychiatrists for their expert opinion.

It is useful for them to have a template ready with suicide rates, emphasizing multicausality of suicide, role of mental disorders, as well as help available.[5]It is about time that the Indian Psychiatric Society formulated its own guidelines laying down the broad principles and boundaries governing the interaction of Indian psychiatrists with the media. Till then, it is desirable to be guided by the following broad principles:It should be assumed that no statement goes “off the record” as the media person is most likely recording the interview, and we should also record any such conversation from our endIt should be clarified in which capacity comments are being made – professional, personal, or as a representative of an organizationOne should not comment on buy lasix usa any person whom he has not examinedPsychiatrists should take any such opportunity to educate the public about mental health issuesThe comments should be justified and limited by the boundaries of scientific knowledge available at the moment. References Correspondence Address:Dr.

O P SinghAA 304, Ashabari Apartments, O/31, Baishnabghata, Patuli Township, Kolkata - 700 094, buy lasix usa West Bengal IndiaSource of Support. None, Conflict of Interest. NoneDOI.

10.4103/psychiatry.IndianJPsychiatry_816_20Abstract Electroconvulsive therapy (ECT) is an effective modality of treatment for a variety of psychiatric disorders. However, it has always been accused of being a coercive, unethical, and dangerous modality of treatment. The dangerousness of ECT has been mainly attributed to its claimed ability to cause brain damage.

This narrative review aims to provide an update of the evidence with regard to whether the practice of ECT is associated with damage to the brain. An accepted definition of brain damage remains elusive. There are also ethical and technical problems in designing studies that look at this question specifically.

Thus, even though there are newer technological tools and innovations, any review attempting to answer this question would have to take recourse to indirect methods. These include structural, functional, and metabolic neuroimaging. Body fluid biochemical marker studies.

And follow-up studies of cognitive impairment and incidence of dementia in people who have received ECT among others. The review of literature and present evidence suggests that ECT has a demonstrable impact on the structure and function of the brain. However, there is a lack of evidence at present to suggest that ECT causes brain damage.Keywords.

Adverse effect, brain damage, electroconvulsive therapyHow to cite this article:Jolly AJ, Singh SM. Does electroconvulsive therapy cause brain damage. An update.

Indian J Psychiatry 2020;62:339-53 Introduction Electroconvulsive therapy (ECT) as a modality of treatment for psychiatric disorders has existed at least since 1938.[1] ECT is an effective modality of treatment for various psychiatric disorders. However, from the very beginning, the practice of ECT has also faced resistance from various groups who claim that it is coercive and harmful.[2] While the ethical aspects of the practice of ECT have been dealt with elsewhere, the question of harmfulness or brain damage consequent upon the passage of electric current needs to be examined afresh in light of technological advances and new knowledge.[3]The question whether ECT causes brain damage was reviewed in a holistic fashion by Devanand et al. In the mid-1990s.[4],[5] The authors had attempted to answer this question by reviewing the effect of ECT on the brain in various areas – cognitive side effects, structural neuroimaging studies, neuropathologic studies of patients who had received ECT, autopsy studies of epileptic patients, and finally animal ECS studies.

The authors had concluded that ECT does not produce brain damage.This narrative review aims to update the evidence with regard to whether ECT causes brain damage by reviewing relevant literature from 1994 to the present time. Framing the Question The Oxford Dictionary defines damage as physical harm that impairs the value, usefulness, or normal function of something.[6] Among medical dictionaries, the Peter Collins Dictionary defines damage as harm done to things (noun) or to harm something (verb).[7] Brain damage is defined by the British Medical Association Medical Dictionary as degeneration or death of nerve cells and tracts within the brain that may be localized to a particular area of the brain or diffuse.[8] Going by such a definition, brain damage in the context of ECT should refer to death or degeneration of brain tissue, which results in the impairment of functioning of the brain. The importance of precisely defining brain damage shall become evident subsequently in this review.There are now many more tools available to investigate the structure and function of brain in health and illness.

However, there are obvious ethical issues in designing human studies that are designed to answer this specific question. Therefore, one must necessarily take recourse to indirect evidences available through studies that have been designed to answer other research questions. These studies have employed the following methods:Structural neuroimaging studiesFunctional neuroimaging studiesMetabolic neuroimaging studiesBody fluid biochemical marker studiesCognitive impairment studies.While the early studies tended to focus more on establishing the safety of ECT and finding out whether ECT causes gross microscopic brain damage, the later studies especially since the advent of advanced neuroimaging techniques have been focusing more on a mechanistic understanding of ECT.

Hence, the primary objective of the later neuroimaging studies has been to look for structural and functional brain changes which might explain how ECT acts rather than evidence of gross structural damage per se. However, put together, all these studies would enable us to answer our titular question to some satisfaction. [Table 1] and [Table 2] provide an overview of the evidence base in this area.

Structural and Functional Neuroimaging Studies Devanand et al. Reviewed 16 structural neuroimaging studies on the effect of ECT on the brain.[4] Of these, two were pneumoencephalography studies, nine were computed tomography (CT) scan studies, and five were magnetic resonance imaging (MRI) studies. However, most of these studies were retrospective in design, with neuroimaging being done in patients who had received ECT in the past.

In the absence of baseline neuroimaging, it would be very difficult to attribute any structural brain changes to ECT. In addition, pneumoencephalography, CT scan, and even early 0.3 T MRI provided images with much lower spatial resolution than what is available today. The authors concluded that there was no evidence to show that ECT caused any structural damage to the brain.[4] Since then, at least twenty more MRI-based structural neuroimaging studies have studied the effect of ECT on the brain.

The earliest MRI studies in the early 1990s focused on detecting structural damage following ECT. All of these studies were prospective in design, with the first MRI scan done at baseline and a second MRI scan performed post ECT.[9],[11],[12],[13],[41] While most of the studies imaged the patient once around 24 h after receiving ECT, some studies performed multiple post ECT neuroimaging in the first 24 h after ECT to better capture the acute changes. A single study by Coffey et al.

Followed up the patients for a duration of 6 months and repeated neuroimaging again at 6 months in order to capture any long-term changes following ECT.[10]The most important conclusion which emerged from this early series of studies was that there was no evidence of cortical atrophy, change in ventricle size, or increase in white matter hyperintensities.[4] The next major conclusion was that there appeared to be an increase in the T1 and T2 relaxation time immediately following ECT, which returned to normal within 24 h. This supported the theory that immediately following ECT, there appears to be a temporary breakdown of the blood–brain barrier, leading to water influx into the brain tissue.[11] The last significant observation by Coffey et al. In 1991 was that there was no significant temporal changes in the total volumes of the frontal lobes, temporal lobes, or amygdala–hippocampal complex.[10] This was, however, something which would later be refuted by high-resolution MRI studies.

Nonetheless, one inescapable conclusion of these early studies was that there was no evidence of any gross structural brain changes following administration of ECT. Much later in 2007, Szabo et al. Used diffusion-weighted MRI to image patients in the immediate post ECT period and failed to observe any obvious brain tissue changes following ECT.[17]The next major breakthrough came in 2010 when Nordanskog et al.

Demonstrated that there was a significant increase in the volume of the hippocampus bilaterally following a course of ECT in a cohort of patients with depressive illness.[18] This contradicted the earlier observations by Coffey et al. That there was no volume increase in any part of the brain following ECT.[10] This was quite an exciting finding and was followed by several similar studies. However, the perspective of these studies was quite different from the early studies.

In contrast to the early studies looking for the evidence of ECT-related brain damage, the newer studies were focused more on elucidating the mechanism of action of ECT. Further on in 2014, Nordanskog et al. In a follow-up study showed that though there was a significant increase in the volume of the hippocampus 1 week after a course of ECT, the hippocampal volume returned to the baseline after 6 months.[19] Two other studies in 2013 showed that in addition to the hippocampus, the amygdala also showed significant volume increase following ECT.[20],[21] A series of structural neuroimaging studies after that have expanded on these findings and as of now, gray matter volume increase following ECT has been demonstrated in the hippocampus, amygdala, anterior temporal pole, subgenual cortex,[21] right caudate nucleus, and the whole of the medial temporal lobe (MTL) consisting of the hippocampus, amygdala, insula, and the posterosuperior temporal cortex,[24] para hippocampi, right subgenual anterior cingulate gyrus, and right anterior cingulate gyrus,[25] left cerebellar area VIIa crus I,[29] putamen, caudate nucleus, and nucleus acumbens [31] and clusters of increased cortical thickness involving the temporal pole, middle and superior temporal cortex, insula, and inferior temporal cortex.[27] However, the most consistently reported and replicated finding has been the bilateral increase in the volume of the hippocampus and amygdala.

In light of these findings, it has been tentatively suggested that ECT acts by inducing neuronal regeneration in the hippocampus – amygdala complex.[42],[43] However, there are certain inconsistencies to this hypothesis. Till date, only one study – Nordanskog et al., 2014 – has followed study patients for a long term – 6 months in their case. And significantly, the authors found out that after increasing immediately following ECT, the hippocampal volume returns back to baseline by 6 months.[19] This, however, was not associated with the relapse of depressive symptoms.

Another area of significant confusion has been the correlation of hippocampal volume increase with improvement of depressive symptoms. Though almost all studies demonstrate a significant increase in hippocampal volume following ECT, a majority of studies failed to demonstrate a correlation between symptom improvement and hippocampal volume increase.[19],[20],[22],[24],[28] However, a significant minority of volumetric studies have demonstrated correlation between increase in hippocampal and/or amygdala volume and improvement of symptoms.[21],[25],[30]Another set of studies have used diffusion tensor imaging, functional MRI (fMRI), anatomical connectome, and structural network analysis to study the effect of ECT on the brain. The first of these studies by Abbott et al.

In 2014 demonstrated that on fMRI, the connectivity between right and left hippocampus was significantly reduced in patients with severe depression. It was also shown that the connectivity was normalized following ECT, and symptom improvement was correlated with an increase in connectivity.[22] In a first of its kind DTI study, Lyden et al. In 2014 demonstrated that fractional anisotropy which is a measure of white matter tract or fiber density is increased post ECT in patients with severe depression in the anterior cingulum, forceps minor, and the dorsal aspect of the left superior longitudinal fasciculus.

The authors suggested that ECT acts to normalize major depressive disorder-related abnormalities in the structural connectivity of the dorsal fronto-limbic pathways.[23] Another DTI study in 2015 constructed large-scale anatomical networks of the human brain – connectomes, based on white matter fiber tractography. The authors found significant reorganization in the anatomical connections involving the limbic structure, temporal lobe, and frontal lobe. It was also found that connection changes between amygdala and para hippocampus correlated with reduction in depressive symptoms.[26] In 2016, Wolf et al.

Used a source-based morphometry approach to study the structural networks in patients with depression and schizophrenia and the effect of ECT on the same. It was found that the medial prefrontal cortex/anterior cingulate cortex (ACC/MPFC) network, MTL network, bilateral thalamus, and left cerebellar regions/precuneus exhibited significant difference between healthy controls and the patient population. It was also demonstrated that administration of ECT leads to significant increase in the network strength of the ACC/MPFC network and the MTL network though the increase in network strength and symptom amelioration were not correlated.[32]Building on these studies, a recently published meta-analysis has attempted a quantitative synthesis of brain volume changes – focusing on hippocampal volume increase following ECT in patients with major depressive disorder and bipolar disorder.

The authors initially selected 32 original articles from which six articles met the criteria for quantitative synthesis. The results showed significant increase in the volume of the right and left hippocampus following ECT. For the rest of the brain regions, the heterogeneity in protocols and imaging techniques did not permit a quantitative analysis, and the authors have resorted to a narrative review similar to the present one with similar conclusions.[44] Focusing exclusively on hippocampal volume change in ECT, Oltedal et al.

In 2018 conducted a mega-analysis of 281 patients with major depressive disorder treated with ECT enrolled at ten different global sites of the Global ECT-MRI Research Collaboration.[45] Similar to previous studies, there was a significant increase in hippocampal volume bilaterally with a dose–response relationship with the number of ECTs administered. Furthermore, bilateral (B/L) ECT was associated with an equal increase in volume in both right and left hippocampus, whereas right unilateral ECT was associated with greater volume increase in the right hippocampus. Finally, contrary to expectation, clinical improvement was found to be negatively correlated with hippocampal volume.Thus, a review of the current evidence amply demonstrates that from looking for ECT-related brain damage – and finding none, we have now moved ahead to looking for a mechanistic understanding of the effect of ECT.

In this regard, it has been found that ECT does induce structural changes in the brain – a fact which has been seized upon by some to claim that ECT causes brain damage.[46] Such statements should, however, be weighed against the definition of damage as understood by the scientific medical community and patient population. Neuroanatomical changes associated with effective ECT can be better described as ECT-induced brain neuroplasticity or ECT-induced brain neuromodulation rather than ECT-induced brain damage. Metabolic Neuroimaging Studies.

Magnetic Resonance Spectroscopic Imaging Magnetic resonance spectroscopic imaging (MRSI) uses a phase-encoding procedure to map the spatial distribution of magnetic resonance (MR) signals of different molecules. The crucial difference, however, is that while MRI maps the MR signals of water molecules, MRSI maps the MR signals generated by different metabolites – such as N-acetyl aspartate (NAA) and choline-containing compounds. However, the concentration of these metabolites is at least 10,000 times lower than water molecules and hence the signal strength generated would also be correspondingly lower.

However, MRSI offers us the unique advantage of studying in vivo the change in the concentration of brain metabolites, which has been of great significance in fields such as psychiatry, neurology, and basic neuroscience research.[47]MRSI studies on ECT in patients with depression have focused largely on four metabolites in the human brain – NAA, choline-containing compounds (Cho) which include majorly cell membrane compounds such as glycerophosphocholine, phosphocholine and a miniscule contribution from acetylcholine, creatinine (Cr) and glutamine and glutamate together (Glx). NAA is located exclusively in the neurons, and is suggested to be a marker of neuronal viability and functionality.[48] Choline-containing compounds (Cho) mainly include the membrane compounds, and an increase in Cho would be suggestive of increased membrane turnover. Cr serves as a marker of cellular energy metabolism, and its levels are usually expected to remain stable.

The regions which have been most widely studied in MRSI studies include the bilateral hippocampus and amygdala, dorsolateral prefrontal cortex (DLPFC), and ACC.Till date, five MRSI studies have measured NAA concentration in the hippocampus before and after ECT. Of these, three studies showed that there is no significant change in the NAA concentration in the hippocampus following ECT.[33],[38],[49] On the other hand, two recent studies have demonstrated a statistically significant reduction in NAA concentration in the hippocampus following ECT.[39],[40] The implications of these results are of significant interest to us in answering our titular question. A normal level of NAA following ECT could signify that there is no significant neuronal death or damage following ECT, while a reduction would signal the opposite.

However, a direct comparison between these studies is complicated chiefly due to the different ECT protocols, which has been used in these studies. It must, however, be acknowledged that the three older studies used 1.5 T MRI, whereas the two newer studies used a higher 3 T MRI which offers betters signal-to-noise ratio and hence lesser risk of errors in the measurement of metabolite concentrations. The authors of a study by Njau et al.[39] argue that a change in NAA levels might reflect reversible changes in neural metabolism rather than a permanent change in the number or density of neurons and also that reduced NAA might point to a change in the ratio of mature to immature neurons, which, in fact, might reflect enhanced adult neurogenesis.

Thus, the authors warn that to conclude whether a reduction in NAA concentration is beneficial or harmful would take a simultaneous measurement of cognitive functioning, which was lacking in their study. In 2017, Cano et al. Also demonstrated a significant reduction in NAA/Cr ratio in the hippocampus post ECT.

More significantly, the authors also showed a significant increase in Glx levels in the hippocampus following ECT, which was also associated with an increase in hippocampal volume.[40] To explain these three findings, the authors proposed that ECT produces a neuroinflammatory response in the hippocampus – likely mediated by Glx, which has been known to cause inflammation at higher concentrations, thereby accounting for the increase in hippocampal volume with a reduction in NAA concentration. The cause for the volume increase remains unclear – with the authors speculating that it might be due to neuronal swelling or due to angiogenesis. However, the same study and multiple other past studies [21],[25],[30] have demonstrated that hippocampal volume increase was correlated with clinical improvement following ECT.

Thus, we are led to the hypothesis that the same mechanism which drives clinical improvement with ECT is also responsible for the cognitive impairment following ECT. Whether this is a purely neuroinflammatory response or a neuroplastic response or a neuroinflammatory response leading to some form of neuroplasticity is a critical question, which remains to be answered.[40]Studies which have analyzed NAA concentration change in other brain areas have also produced conflicting results. The ACC is another area which has been studied in some detail utilizing the MRSI technique.

In 2003, Pfleiderer et al. Demonstrated that there was no significant change in the NAA and Cho levels in the ACC following ECT. This would seem to suggest that there was no neurogenesis or membrane turnover in the ACC post ECT.[36] However, this finding was contested by Merkl et al.

In 2011, who demonstrated that NAA levels were significantly reduced in the left ACC in patients with depression and that these levels were significantly elevated following ECT.[37] This again is contested by Njau et al. Who showed that NAA levels are significantly reduced following ECT in the left dorsal ACC.[39] A direct comparison of these three studies is complicated by the different ECT and imaging parameters used and hence, no firm conclusion can be made on this point at this stage. In addition to this, one study had demonstrated increased NAA levels in the amygdala following administration of ECT,[34] with a trend level increase in Cho levels, which again is suggestive of neurogenesis and/or neuroplasticity.

A review of studies on the DLPFC reveals a similarly confusing picture with one study, each showing no change, reduction, and elevation of concentration of NAA following ECT.[35],[37],[39] Here, again, a direct comparison of the three studies is made difficult by the heterogeneous imaging and ECT protocols followed by them.A total of five studies have analyzed the concentration of choline-containing compounds (Cho) in patients undergoing ECT. Conceptually, an increase in Cho signals is indicative of increased membrane turnover, which is postulated to be associated with synaptogenesis, neurogenesis, and maturation of neurons.[31] Of these, two studies measured Cho concentration in the B/L hippocampus, with contrasting results. Ende et al.

In 2000 demonstrated a significant elevation in Cho levels in B/L hippocampus after ECT, while Jorgensen et al. In 2015 failed to replicate the same finding.[33],[38] Cho levels have also been studied in the amygdala, ACC, and the DLPFC. However, none of these studies showed a significant increase or decrease in Cho levels before and after ECT in the respective brain regions studied.

In addition, no significant difference was seen in the pre-ECT Cho levels of patients compared to healthy controls.[34],[36],[37]In review, we must admit that MRSI studies are still at a preliminary stage with significant heterogeneity in ECT protocols, patient population, and regions of the brain studied. At this stage, it is difficult to draw any firm conclusions except to acknowledge the fact that the more recent studies – Njau et al., 2017, Cano, 2017, and Jorgensen et al., 2015 – have shown decrease in NAA concentration and no increase in Cho levels [38],[39],[40] – as opposed to the earlier studies by Ende et al.[33] The view offered by the more recent studies is one of a neuroinflammatory models of action of ECT, probably driving neuroplasticity in the hippocampus. This would offer a mechanistic understanding of both clinical response and the phenomenon of cognitive impairment associated with ECT.

However, this conclusion is based on conjecture, and more work needs to be done in this area. Body Fluid Biochemical Marker Studies Another line of evidence for analyzing the effect of ECT on the human brain is the study of concentration of neurotrophins in the plasma or serum. Neurotrophins are small protein molecules which mediate neuronal survival and development.

The most prominent among these is brain-derived neurotrophic factor (BDNF) which plays an important role in neuronal survival, plasticity, and migration.[50] A neurotrophic theory of mood disorders was suggested which hypothesized that depressive disorders are associated with a decreased expression of BDNF in the limbic structures, resulting in the atrophy of these structures.[51] It was also postulated that antidepressant treatment has a neurotrophic effect which reverses the neuronal cell loss, thereby producing a therapeutic effect. It has been well established that BDNF is decreased in mood disorders.[52] It has also been shown that clinical improvement of depression is associated with increase in BDNF levels.[53] Thus, serum BDNF levels have been tentatively proposed as a biomarker for treatment response in depression. Recent meta-analytic evidence has shown that ECT is associated with significant increase in serum BDNF levels in patients with major depressive disorder.[54] Considering that BDNF is a potent stimulator of neurogenesis, the elevation of serum BDNF levels following ECT lends further credence to the theory that ECT leads to neurogenesis in the hippocampus and other limbic structures, which, in turn, mediates the therapeutic action of ECT.

Cognitive Impairment Studies Cognitive impairment has always been the single-most important side effect associated with ECT.[55] Concerns regarding long-term cognitive impairment surfaced soon after the introduction of ECT and since then has grown to become one of the most controversial aspects of ECT.[56] Anti-ECT groups have frequently pointed out to cognitive impairment following ECT as evidence of ECT causing brain damage.[56] A meta-analysis by Semkovska and McLoughlin in 2010 is one of the most detailed studies which had attempted to settle this long-standing debate.[57] The authors reviewed 84 studies (2981 participants), which had used a combined total of 22 standardized neuropsychological tests assessing various cognitive functions before and after ECT in patients diagnosed with major depressive disorder. The different cognitive domains reviewed included processing speed, attention/working memory, verbal episodic memory, visual episodic memory, spatial problem-solving, executive functioning, and intellectual ability. The authors concluded that administration of ECT for depression is associated with significant cognitive impairment in the first few days after ECT administration.

However, it was also seen that impairment in cognitive functioning resolved within a span of 2 weeks and thereafter, a majority of cognitive domains even showed mild improvement compared to the baseline performance. It was also demonstrated that not a single cognitive domain showed persistence of impairment beyond 15 days after ECT.Memory impairment following ECT can be analyzed broadly under two conceptual schemes – one that classifies memory impairment as objective memory impairment and subjective memory impairment and the other that classifies it as impairment in anterograde memory versus impairment in retrograde memory. Objective memory can be roughly defined as the ability to retrieve stored information and can be measured by various standardized neuropsychological tests.

Subjective memory or meta-memory, on the other hand, refers to the ability to make judgments about one's ability to retrieve stored information.[58] As described previously, it has been conclusively demonstrated that anterograde memory impairment does not persist beyond 2 weeks after ECT.[57] However, one of the major limitations of this meta-analysis was the lack of evidence on retrograde amnesia following ECT. This is particularly unfortunate considering that it is memory impairment – particularly retrograde amnesia which has received the most attention.[59] In addition, reports of catastrophic retrograde amnesia have been repeatedly held up as sensational evidence of the lasting brain damage produced by ECT.[59] Admittedly, studies on retrograde amnesia are fewer and less conclusive than on anterograde amnesia.[60],[61] At present, the results are conflicting, with some studies finding some impairment in retrograde memory – particularly autobiographical retrograde memory up to 6 months after ECT.[62],[63],[64],[65] However, more recent studies have failed to support this finding.[66],[67] While they do demonstrate an impairment in retrograde memory immediately after ECT, it was seen that this deficit returned to pre-ECT levels within a span of 1–2 months and improved beyond baseline performance at 6 months post ECT.[66] Adding to the confusion are numerous factors which confound the assessment of retrograde amnesia. It has been shown that depressive symptoms can produce significant impairment of retrograde memory.[68],[69] It has also been demonstrated that sine-wave ECT produces significantly more impairment of retrograde memory as compared to brief-pulse ECT.[70] However, from the 1990s onward, sine-wave ECT has been completely replaced by brief-pulse ECT, and it is unclear as to the implications of cognitive impairment from the sine-wave era in contemporary ECT practice.Another area of concern are reports of subjective memory impairment following ECT.

One of the pioneers of research into subjective memory impairment were Squire and Chace who published a series of studies in the 1970s demonstrating the adverse effect of bilateral ECT on subjective assessment of memory.[62],[63],[64],[65] However, most of the studies conducted post 1980 – from when sine-wave ECT was replaced by brief-pulse ECT report a general improvement in subjective memory assessments following ECT.[71] In addition, most of the recent studies have failed to find a significant association between measures of subjective and objective memory.[63],[66],[70],[72],[73],[74] It has also been shown that subjective memory impairment is strongly associated with the severity of depressive symptoms.[75] In light of these facts, the validity and value of measures of subjective memory impairment as a marker of cognitive impairment and brain damage following ECT have been questioned. However, concerns regarding subjective memory impairment and catastrophic retrograde amnesia continue to persist, with significant dissonance between the findings of different research groups and patient self-reports in various media.[57]Some studies reported the possibility of ECT being associated with the development of subsequent dementia.[76],[77] However, a recent large, well-controlled prospective Danish study found that the use of ECT was not associated with elevated incidence of dementia.[78] Conclusion Our titular question is whether ECT leads to brain damage, where damage indicates destruction or degeneration of nerves or nerve tracts in the brain, which leads to loss of function. This issue was last addressed by Devanand et al.

In 1994 since which time our understanding of ECT has grown substantially, helped particularly by the advent of modern-day neuroimaging techniques which we have reviewed in detail. And, what these studies reveal is rather than damaging the brain, ECT has a neuromodulatory effect on the brain. The various lines of evidence – structural neuroimaging studies, functional neuroimaging studies, neurochemical and metabolic studies, and serum BDNF studies all point toward this.

These neuromodulatory changes have been localized to the hippocampus, amygdala, and certain other parts of the limbic system. How exactly these changes mediate the improvement of depressive symptoms is a question that remains unanswered. However, there is little by way of evidence from neuroimaging studies which indicates that ECT causes destruction or degeneration of neurons.

Though cognitive impairment studies do show that there is objective impairment of certain functions – particularly memory immediately after ECT, these impairments are transient with full recovery within a span of 2 weeks. Perhaps, the single-most important unaddressed concern is retrograde amnesia, which has been shown to persist for up to 2 months post ECT. In this regard, the recent neurometabolic studies have offered a tentative mechanism of action of ECT, producing a transient inflammation in the limbic cortex, which, in turn, drives neurogenesis, thereby exerting a neuromodulatory effect.

This hypothesis would explain both the cognitive adverse effects of ECT – due to the transient inflammation – and the long-term improvement in mood – neurogenesis in the hippocampus. Although unproven at present, such a hypothesis would imply that cognitive impairment is tied in with the mechanism of action of ECT and not an indicator of damage to the brain produced by ECT.The review of literature suggests that ECT does cause at least structural and functional changes in the brain, and these are in all probability related to the effects of the ECT. However, these cannot be construed as brain damage as is usually understood.

Due to the relative scarcity of data that directly examines the question of whether ECT causes brain damage, it is not possible to conclusively answer this question. However, in light of enduring ECT survivor accounts, there is a need to design studies that specifically answer this question.Financial support and sponsorshipNil.Conflicts of interestThere are no conflicts of interest. References 1.Payne NA, Prudic J.

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Correspondence Address:Dr. Shubh Mohan SinghDepartment of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh IndiaSource of Support. None, Conflict of Interest.

NoneDOI. 10.4103/psychiatry.IndianJPsychiatry_239_19 Tables [Table 1], [Table 2].

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The guidance documents lasix 40mg are for. Incident reporting for medical devices foreign risk notification for medical devices summary reports and issue-related analyses of safety and effectiveness for medical devices guide to new authorities on the amendments to include power to require assessments and power to require tests and studiesNote. To inform us of notifiable actions under foreign risk lasix 40mg notification requirements for medical devices, industry will be using an electronic form. We will make this form available on Canada.ca in the coming months. You can lasix 40mg find information on what’s required in the form in the Guidance Document for Foreign Risk Notification for Medical Devices.Contact usIf you have questions about this notice, please contact:Medical Devices DirectorateHealth Products and Food Branch11 Holland Avenue, Tower AAddress Locator 3002AE-mail.

Hc.meddevices-instrumentsmed.sc@canada.caTelephone. 613-957-4786Facsimile. 613-957-6345Teletypewriter. 1-800-465-7735 (Service Canada)Therapeutic Goods Administration (TGA) Australia Austrian Agency for Health and Food Safety (AGES) Austria Federal Agency for Medicines and Health Products (FAMHP) Belgium National Health Surveillance Agency (ANVISA) Brazil Bulgarian Drug Agency Bulgaria National Medical Products Administration China Agency for Medicinal Products and Medical Devices of Croatia (HALMED) Croatia Cyprus Medical Devices Competent Authority Cyprus State Institute for Drug Control Czechia Danish Medicines Agency Denmark Health Board, Medical Devices Department Estonia Finnish Medicines Agency (FIMEA) Finland National Agency for the Safety of Medicine and Health Products (ANSM) France Federal Institute for Drugs and Medical Devices (BfArM) Germany National Organization for Medicines (EOF) Greece National Institute of Pharmacy and Nutrition (OGYEI) Hungary Health Products Regulatory Authority (HPRA) Ireland Medical Devices and Active Implantable Medical Devices, Ministry of Health Italy Pharmaceuticals and Medical Devices Agency (PMDA) and the Ministry of Health, Labour and Welfare (MHLW) Japan Ministry of Health of the Republic of Latvia- Health Inspectorate Latvia State Health Care Accreditation Agency (VASPVT) Lithuania State Health Care Agency, Ministry of Health Luxembourg Malta Competition and Consumer Affairs Authority (MCCAA) Malta Federal Commission for Protection Against Sanitary Risk (COFEPRIS) Mexico Healthcare and Youth Care Inspectorate (IGZ) Netherlands Medicines and Medical Devices Safety Authority (MEDSAFE) New Zealand Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Poland National Authority of Medicines and Health Products (INFARMED) Portugal National Agency for Medicines and Medical Devices (NAMMDR) Romania Russian Ministry of Health Russia Health Sciences Authority (HSA) Singapore State Institute for Drug Control (SIDC) Slovak Republic Agency for Medicinal Products and Medical Devices of the Republic (JAZMP) Slovenia Ministry of Food and Drug Safety South Korea Spanish Agency for Medicines and Health Products (AEMPS) Spain Medical Products Agency (MPA) Sweden Swiss Agency for Therapeutic Products (Swissmedic) Switzerland Medicines and Healthcare Products Regulatory Agency (MHRA) United Kingdom United States Food and Drug Administration (US FDA) United States of America.

On this page buy lasix usa Changes to the regulationsHealth Canada is making regulatory changes to the Medical Devices Regulations to strengthen the lifecycle approach to the regulation of medical devices by increasing post-market surveillance authorities. With these amendments, we have implemented certain powers included in Vanessa’s Law and additional measures to improve post-market surveillance of medical devices. Together these will help to reduce the risk of medical devices and improve their safety, quality and effectiveness.The post-market surveillance regulations amending the buy lasix usa Medical Devices Regulations will improve our ability to identify, assess and manage new risks for medical devices used in Canada.Consultations and publicationIn the spring of 2018, Health Canada published a notice on our intent to strengthen the post-market surveillance and risk management of medical devices in Canada. We consulted with manufacturers and importers of medical devices on the proposed regulatory changes and related guidance documents.The proposed regulations were published in Canada Gazette, Part I, on June 15, 2019. Stakeholders had 70 days within which buy lasix usa to comment.

We also made available guidance documents for comment.In June 2020, Health Canada advised that this regulatory initiative had been delayed due to the hypertension medications lasix. However, it has now been published.Coming into forceThe post-market surveillance regulations amending the Medical Devices Regulations were published in the Canada Gazette, Part II (CGII) on December buy lasix usa 23, 2020. The various provisions under the regulations are coming into force as follows. Amending Regulations Coming into Force Date Note Summary Reports (Medical Device Regulations) First anniversary after publication in CGII December 23, 2021 Relates to Summary Report provisions under sections 61.4, 61.5 and 61.6 Other amendments to the Medical Devices Regulations Six months after publication in CGII June 23, 2021 Excludes sections related to Summary Report provisions under sections 61.4, 61.5 and 61.6 Guidance documentsWe have prepared and updated 4 guidance buy lasix usa documents. We’ll be releasing and publishing these guidance documents in the weeks following publication of the amending regulations in Canada Gazette, Part II.

The guidance buy lasix usa documents are for. Incident reporting for medical devices foreign risk notification for medical devices summary reports and issue-related analyses of safety and effectiveness for medical devices guide to new authorities on the amendments to include power to require assessments and power to require tests and studiesNote. To inform us of notifiable actions under foreign risk notification requirements buy lasix usa for medical devices, industry will be using an electronic form. We will make this form available on Canada.ca in the coming months. You can find information on what’s required in the form in the Guidance Document for Foreign Risk Notification for Medical Devices.Contact usIf you have questions about this notice, please contact:Medical Devices DirectorateHealth Products and Food Branch11 Holland Avenue, Tower buy lasix usa AAddress Locator 3002AE-mail.

Hc.meddevices-instrumentsmed.sc@canada.caTelephone. 613-957-4786Facsimile. 613-957-6345Teletypewriter. 1-800-465-7735 (Service Canada)Therapeutic Goods Administration (TGA) Australia Austrian Agency for Health and Food Safety (AGES) Austria Federal Agency for Medicines and Health Products (FAMHP) Belgium National Health Surveillance Agency (ANVISA) Brazil Bulgarian Drug Agency Bulgaria National Medical Products Administration China Agency for Medicinal Products and Medical Devices of Croatia (HALMED) Croatia Cyprus Medical Devices Competent Authority Cyprus State Institute for Drug Control Czechia Danish Medicines Agency Denmark Health Board, Medical Devices Department Estonia Finnish Medicines Agency (FIMEA) Finland National Agency for the Safety of Medicine and Health Products (ANSM) France Federal Institute for Drugs and Medical Devices (BfArM) Germany National Organization for Medicines (EOF) Greece National Institute of Pharmacy and Nutrition (OGYEI) Hungary Health Products Regulatory Authority (HPRA) Ireland Medical Devices and Active Implantable Medical Devices, Ministry of Health Italy Pharmaceuticals and Medical Devices Agency (PMDA) and the Ministry of Health, Labour and Welfare (MHLW) Japan Ministry of Health of the Republic of Latvia- Health Inspectorate Latvia State Health Care Accreditation Agency (VASPVT) Lithuania State Health Care Agency, Ministry of Health Luxembourg Malta Competition and Consumer Affairs Authority (MCCAA) Malta Federal Commission for Protection Against Sanitary Risk (COFEPRIS) Mexico Healthcare and Youth Care Inspectorate (IGZ) Netherlands Medicines and Medical Devices Safety Authority (MEDSAFE) New Zealand Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Poland National Authority of Medicines and Health Products (INFARMED) Portugal National Agency for Medicines and Medical Devices (NAMMDR) Romania Russian Ministry of Health Russia Health Sciences Authority (HSA) Singapore State Institute for Drug Control (SIDC) Slovak Republic Agency for Medicinal Products and Medical Devices of the Republic (JAZMP) Slovenia Ministry of Food and Drug Safety South Korea Spanish Agency for Medicines and Health Products (AEMPS) Spain Medical Products Agency (MPA) Sweden Swiss Agency for Therapeutic Products (Swissmedic) Switzerland Medicines and Healthcare Products Regulatory Agency (MHRA) United Kingdom United States Food and Drug Administration (US FDA) United States of America.

Lasix 80mg twice a day

Protecting the safety lasix 80mg twice a day and health of essential workers who support America’s food security—including the meat, poultry, and pork processing industries—is a top priority for the Occupational Safety and Health Administration (OSHA).OSHA and the Centers for Disease Control and Prevention issued additional guidance to reduce the risk of exposure to the hypertension and keep workers safe and healthy in the meatpacking and meat processing industries —including those blog involved in beef, pork, and poultry operations. This new guidance provides specific recommendations for employers to meet their obligations to protect workers in these facilities, where people normally work closely together and share workspaces and equipment. Here are lasix 80mg twice a day eight ways to help minimize meat processing workers’ exposure to the hypertension. Screen workers before they enter the workplace.

If a worker becomes sick, send them home and disinfect their workstation and any tools they used. Move workstations farther apart lasix 80mg twice a day. Install partitions between workstations using strip curtains, plexiglass, or similar materials. To limit spread lasix 80mg twice a day between groups, assign the same workers to the same shifts with the same coworkers.

Prevent workers from using other workers’ equipment. Allow workers to wear face coverings when entering, inside, and exiting the facility. Encourage workers to report any safety and health concerns lasix 80mg twice a day to their supervisors.OSHA is committed to ensuring that workers and employers in essential industries have clear guidance to keep workers safe and healthy from the hypertension—including guidance for essential workers in construction, manufacturing, package delivery, and retail. Workers and employers who have questions or concerns about workplace safety can contact OSHA online or by phone at 1-800-321-6742 (OSHA).

You can find additional resources and learn more about OSHA’s response lasix 80mg twice a day to the hypertension at www.osha.gov/hypertension. Loren Sweatt is the Principal Deputy Assistant Secretary for the U.S. Department of Labor’s Occupation Safety and Health Administration Editor’s Note. It is important to note that information and guidance about lasix 80mg twice a day hypertension medications continually evolve as conditions change.

Workers and employers are encouraged to regularly refer to the resources below for updates:September is National Preparedness Month, and now is a good time to prepare for a natural disaster or emergency in the workplace.The Occupational Safety and Health Administration (OSHA) reminds workers and employers to make a plan, so you know where to go and what to do to stay safe in an emergency. Here are a few things you can do to prepare. Develop a plan and understand how to lasix 80mg twice a day put it into action. Employers should develop emergency plans and ensure workers know how to execute them.

Plans should describe lasix 80mg twice a day shelter locations, policies to ensure all personnel are accounted for, procedures for addressing hazardous materials in the workplace, and maps that designate specific evacuation routes and exits. OSHA’s Evacuation Plans and Procedures eTool is a helpful resource to use. Build an emergency kit. Put together an emergency kit with the supplies and personal lasix 80mg twice a day protective equipment you might need during an emergency.

Include items like safety glasses or face shields for eye protection, cell phones with chargers, flashlights, and first aid kits. Shelter in lasix 80mg twice a day place. Follow local emergency official announcements related to sheltering in place. In certain situations, you may need to take immediate shelter whether you are working from home, at the job site, or in between.

If you see large amounts of debris in the air, or if local authorities say the air is badly contaminated, you may lasix 80mg twice a day want to “shelter in place.” Evacuate. Be aware if local emergency officials call for a mandatory evacuation of your area. Employers should examine how to safely shut down a facility if an evacuation is warranted. Don’t wait until too lasix 80mg twice a day late.

Due to hypertension medications, the Centers for Disease Control and Prevention recommends that if you need to seek public shelter to bring at least two cloth face coverings for each person and hand sanitizer. Know what may impact your area and how you lasix 80mg twice a day should respond. Stay aware of weather forecasts and warnings, and follow instructions issued by your local officials. Check the websites of your local National Weather Service and emergency management office.

Employers should consider how an emergency might impact workers sheltering in place at a lasix 80mg twice a day job site versus workers attempting to evacuate to safety. If local authorities or the on-site coordinators tell you to evacuate or seek medical treatment, do so immediately.OSHA provides resources on workplace preparedness and response for a variety of hazards. For more information on protecting workers from emergency events, lasix 80mg twice a day visit OSHA’s Emergency Preparedness and Response page. In addition to these resources, seek guidance from your local fire department, police department, and emergency management agency.

For additional information and resources on how to better prepare for emergencies, visit Ready.gov, the National Oceanic and Atmospheric Administration and the Centers for Disease Control and Prevention. Loren Sweatt is the Principal Deputy Assistant Secretary lasix 80mg twice a day for the U.S. Department of Labor’s Occupational Safety and Health Administration. Follow OSHA on Twitter at @OSHA_DOL..

Protecting the safety and health of essential workers who support America’s food security—including the meat, poultry, and pork processing industries—is a top priority for the Occupational Safety and Health Administration (OSHA).OSHA buy lasix usa buy lasix online uk and the Centers for Disease Control and Prevention issued additional guidance to reduce the risk of exposure to the hypertension and keep workers safe and healthy in the meatpacking and meat processing industries —including those involved in beef, pork, and poultry operations. This new guidance provides specific recommendations for employers to meet their obligations to protect workers in these facilities, where people normally work closely together and share workspaces and equipment. Here are eight ways to help minimize meat processing workers’ buy lasix usa exposure to the hypertension.

Screen workers before they enter the workplace. If a worker becomes sick, send them home and disinfect their workstation and any tools they used. Move workstations buy lasix usa farther apart.

Install partitions between workstations using strip curtains, plexiglass, or similar materials. To limit spread between groups, assign the same workers to the same shifts with the buy lasix usa same coworkers. Prevent workers from using other workers’ equipment.

Allow workers to wear face coverings when entering, inside, and exiting the facility. Encourage workers to report any safety and health concerns to their supervisors.OSHA is committed to ensuring that workers and buy lasix usa employers in essential industries have clear guidance to keep workers safe and healthy from the hypertension—including guidance for essential workers in construction, manufacturing, package delivery, and retail. Workers and employers who have questions or concerns about workplace safety can contact OSHA online or by phone at 1-800-321-6742 (OSHA).

You can find additional resources and learn more about buy lasix usa OSHA’s response to the hypertension at www.osha.gov/hypertension. Loren Sweatt is the Principal Deputy Assistant Secretary for the U.S. Department of Labor’s Occupation Safety and Health Administration Editor’s Note.

It is important to note that information and guidance about hypertension medications continually evolve as conditions change buy lasix usa. Workers and employers are encouraged to regularly refer to the resources below for updates:September is National Preparedness Month, and now is a good time to prepare for a natural disaster or emergency in the workplace.The Occupational Safety and Health Administration (OSHA) reminds workers and employers to make a plan, so you know where to go and what to do to stay safe in an emergency. Here are a few things you can do to prepare.

Develop a buy lasix usa plan and understand how to put it into action. Employers should develop emergency plans and ensure workers know how to execute them. Plans should describe shelter locations, policies to ensure all personnel are accounted for, procedures for addressing hazardous materials buy lasix usa in the workplace, and maps that designate specific evacuation routes and exits.

OSHA’s Evacuation Plans and Procedures eTool is a helpful resource to use. Build an emergency kit. Put together an emergency kit with the supplies and personal protective equipment buy lasix usa you might need during an emergency.

Include items like safety glasses or face shields for eye protection, cell phones with chargers, flashlights, and first aid kits. Shelter in place buy lasix usa. Follow local emergency official announcements related to sheltering in place.

In certain situations, you may need to take immediate shelter whether you are working from home, at the job site, or in between. If you see large amounts of debris in the air, or buy lasix usa if local authorities say the air is badly contaminated, you may want to “shelter in place.” Evacuate. Be aware if local emergency officials call for a mandatory evacuation of your area.

Employers should examine how to safely shut down a facility if an evacuation is warranted. Don’t wait buy lasix usa until too late. Due to hypertension medications, the Centers for Disease Control and Prevention recommends that if you need to seek public shelter to bring at least two cloth face coverings for each person and hand sanitizer.

Know what buy lasix usa may impact your area and how you should respond. Stay aware of weather forecasts and warnings, and follow instructions issued by your local officials. Check the websites of your local National Weather Service and emergency management office.

Employers should consider how an emergency might impact workers sheltering in place at a job site versus workers attempting buy lasix usa to evacuate to safety. If local authorities or the on-site coordinators tell you to evacuate or seek medical treatment, do so immediately.OSHA provides resources on workplace preparedness and response for a variety of hazards. For more information on protecting workers from emergency events, buy lasix usa visit OSHA’s Emergency Preparedness and Response page.

In addition to these resources, seek guidance from your local fire department, police department, and emergency management agency. For additional information and resources on how to better prepare for emergencies, visit Ready.gov, the National Oceanic and Atmospheric Administration and the Centers for Disease Control and Prevention. Loren Sweatt is the Principal Deputy Assistant Secretary for the U.S buy lasix usa.

Department of Labor’s Occupational Safety and Health Administration. Follow OSHA on Twitter at @OSHA_DOL..

Lithium and lasix interaction

User Experience (UX) Design is the process of enhancing a persons experience with a given product, system or service. UX involves an in depth understanding of a users behaviors, attitudes, and emotions in order to create a successful design.
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Lithium and lasix interaction

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