Use Of Clinical Guidelines Research Articles

The latest evidence and clinical guidelines for use of meal replacements in very-low-calorie diets or low-calorie diets for the treatment of obesity.

Obesity is a complex chronic disease with increasing prevalence across the globe. Medical nutrition therapy (MNT) is an important component of obesity treatment, and low-calorie diets (LCDs) and very-low-calorie diets (VLCDs) are part of the MNT toolbox. This narrative review focuses on the latest evidence and clinical guidelines regarding the use and impact of meal replacements (MRs) as part of LCDs/VLCDs for the treatment of obesity and some associated complications. MRs can be used in conjunction with food as partial diet replacement (PDR) or can be used exclusively to serve as the sole source of dietary energy (total diet replacement [TDR]). Use of MR may be associated with better control of cravings and hunger typically observed during reduced calorie intake through effects of ketosis or stimuli narrowing, although the exact mechanisms for these effects remain unclear. Several clinical guidelines have endorsed the use of MRs as a part of MNT for obesity, primarily based on evidence that shows an average weight reduction of ~10 kg or more with TDR over at least 12 months in large, randomized controlled trials. When compared to usual care controls, these effects are 6-8 kg greater, and when compared to food-based diets, the effects are nearly twice the effect of a food-based diet. MR-based diets have been found to be safe and associated with improvements in quality of life. These diets are also effective for improving key cardiometabolic health outcomes, including dysglycaemia, blood pressure, lipids, and metabolic associated fatty liver. The effectiveness, safety, and associated health improvement makes MRs use a valuable strategy for several higher risk clinical scenarios where weight reduction is indicated.

Why do clinical guidelines for probiotics differ?

Clinical guidelines are recommendations for healthcare providers regarding patients with specific conditions. These guidelines should be based on practice experience and the best available research evidence. However, guidelines developed by various health organisations worldwide often do not agree with each other. This is also true for the current guidelines for the clinical use of probiotics. This article aims to provide examples of conflicting clinical guidelines for probiotics, define reasons for this phenomenon, describe standard tools for improving their quality, and suggest ways to enhance the development and assessment of suitable clinical guidelines for the appropriate clinical use of probiotics in specific conditions.

Progress and Discussion of Perioperative Targeted Therapy in Patients with EGFR-mutated Resectable Non-small Cell Lung Cancer

Lung cancer is still the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer, accounting for about 80%. Approximately 30% of all patients with NSCLC have resectable early and middle stage disease at the time of diagnosis. Recently, the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have made a major breakthrough in the adjuvant targeted therapy of EGFR-mutated resectable NSCLC, and are recommended by the guidelines for clinical use. In this review, we summarize the clinical research progress of perioperative adjuvant targeted therapy for EGFR-mutated resectable NSCLC, and discuss the key issues in the clinical researches. .

The science of micronutrients in clinical practice – Report on the ESPEN symposium

The European Society for Clinical Nutrition and Metabolism published its first clinical guidelines for use of micronutrients (MNs) in 2022. A two-day web symposium was organized in November 2022 discussing how to apply the guidelines in clinical practice. The present paper reports the main findings of this symposium. Current evidence was discussed, the first day being devoted to clarifying the biology underlying the guidelines, especially regarding the definition of deficiency, the impact of inflammation, and the roles in antioxidant defences and immunity. The second day focused on clinical situations with high prevalence of MN depletion and deficiency. The importance of the determination of MN status in patients at risk and diagnosis of deficiencies is still insufficiently perceived, considering the essential role of MNs in immune and antioxidant defences. Epidemiological data show that deficiencies of several MNs (iron, iodine, vitamin D) are a global problem that affects human health and well-being including immune responses such as to vaccination. Clinical conditions frequently associated with MN deficiencies were discussed including cancer, obesity with impact of bariatric surgery, diseases of the gastrointestinal tract, critical illness, and aging. In all these conditions, MN deficiency is associated with worsening of outcomes. The recurrent problem of shortage of MN products, but also lack of individual MN-products is a worldwide problem. Despite important progress in epidemiology and clinical nutrition, numerous gaps in practice persist. MN depletion and deficiency are frequently insufficiently searched for in clinical conditions, leading to inadequate treatment. The symposium concluded that more research and continued education are required to improve patient outcome.

Artificial intelligence-based image analysis in clinical testing: lessons from cervical cancer screening.

Novel screening and diagnostic tests based on artificial intelligence (AI) image recognition algorithms are proliferating. Some initial reports claim outstanding accuracy followed by disappointing lack of confirmation, including our own early work on cervical screening. This is a presentation of lessons learned, organized as a conceptual step-by-step approach to bridge the gap between the creation of an AI algorithm and clinical efficacy. The first fundamental principle is specifying rigorously what the algorithm is designed to identify and what the test is intended to measure (eg, screening, diagnostic, or prognostic). Second, designing the AI algorithm to minimize the most clinically important errors. For example, many equivocal cervical images cannot yet be labeled because the borderline between cases and controls is blurred. To avoid a misclassified case-control dichotomy, we have isolated the equivocal cases and formally included an intermediate, indeterminate class (severity order of classes: case>indeterminate>control). The third principle is evaluating AI algorithms like any other test, using clinical epidemiologic criteria. Repeatability of the algorithm at the borderline, for indeterminate images, has proven extremely informative. Distinguishing between internal and external validation is also essential. Linking the AI algorithm results to clinical risk estimation is the fourth principle. Absolute risk (not relative) is the critical metric for translating a test result into clinical use. Finally, generating risk-based guidelines for clinical use that match local resources and priorities is the last principle in our approach. We are particularly interested in applications to lower-resource settings to address health disparities. We note that similar principles apply to other domains of AI-based image analysis for medical diagnostic testing.

186 Rethinking Emergency Department Clinical Guidelines for Use at the Bedside

Study Objective: Despite the benefits of clinical guidelines as evidence-based workflows that improve care, emergency departments (EDs) often have low and variable rates of clinical guideline utilization. At our institution - an urban, safety net, academic-affiliated Level I trauma center - fewer than one user per week accessed clinical guidelines on our ED’s legacy cloud-based system between October 2019-October 2020. Our team’s objective was to utilize a design-thinking approach to improve clinical guideline design and accessibility, with the goal that this intervention would ultimately increase clinical guideline utilization in the ED.

Venous Thromboembolic Events are Exceedingly Rare in Spinal Fusion for Adolescent Idiopathic Scoliosis.

Review of health care record database and determination of population statistics. The purpose of this study was to quantify the incidence of clinically significant venous thromboembolic (VTE) events in patients undergoing spinal fusion surgery for adolescent idiopathic scoliosis (AIS) and to identify risk factors for VTE. VTE is a serious complication that can cause disability and even death following surgery. Incidence of VTE following AIS surgery has not been well studied; the use of a national database allows the assessment of rare, yet important complications. The PearlDiver Database was used to identify AIS patients who underwent primary instrumented spinal fusion between 2010 and 2020. Patient records were cross-referenced for documented VTEs within 30 and 90 postoperative days. Patients with nonidiopathic scoliosis were excluded. Logistic regression was used to evaluate risk factors for correlation with VTE events. Thirty-eight of 11,775 (0.323%) patients undergoing surgery for AIS developed a VTE complication within 90 postoperative days. Hypercoagulability [odds ratio (OR)=13.50, P <0.0001], spinal fusion involving 13+ vertebral levels (OR=2.61, P <0.0001), obesity (OR=1.30, P <0.005), and older (15-18 y) compared with younger adolescence (10-14 y) (OR=2.12, P <0.0001) were associated with VTE. Seven of 38 (18.4%) patients with a diagnosed thrombophilia experienced VTE. The incidence of clinically significant VTEs in pediatric patients following spinal fusion surgery for AIS is low with an incidence of 0.323%. Postoperative chemoprophylaxis in the general pediatric population is not indicated. Patients with obesity, those undergoing spinal fusion of 13 or more vertebrae, and adolescents 15-18 years old were found to have higher but still small risk of VTE following surgery. Further prospective studies are needed to validate the risk profile of patients with hypercoagulability and establish clinical guidelines for use of postoperative chemoprophylaxis in this cohort. Level III.

Correlation of Ki67 working group prognostic risk categories with oncotype DX recurrence score (RS) in early breast cancer (EBC).

553 Background: The 21-gene RS (Oncotype DX) provides prognostic information for distant recurrence risk and is predictive of adjuvant chemotherapy benefit in hormone receptor (HR)-positive, HER-2 negative EBC. Ki67 protein expression is a proliferation marker that is determined by immunohistochemistry (IHC). The International Ki67 Working Group (IKWG) has provided guidelines for clinical use of Ki67 for prognostic classification (PMID: 33369635). The objectives of this study were to determine the correlation between IHC-measured Ki67 with the 21-gene RS, and evaluate their association with other anatomic and biologic tumor features. Methods: We performed a retrospective chart review of women with HR-positive, HER-2 negative EBC with 0-3 positive lymph nodes who had both Ki67 (via IHC using MIB-1 antibody on surgical specimen at our institutional pathology CLIA laboratory) and 21-gene RS between 2013 to 2021. Patients were categorized into Ki67 low (≤ 5%), intermediate (6-29%), and high (≥30%) based on IKWG recommendations. Overall and risk stratified agreement between Ki67 and RS were assessed using the proportion of agreement and Kappa statistic. Linear regression was used to test for associations between tumor features of ER%, PR%, and tumor size and log transformed Ki67 and RS. A t-test was used to compare average log transformed Ki67 and RS by tumor differentiation and nodal status. Results: We identified 461 patients with HR-positive BC of whom 26.7% were ≤ 50 years at diagnosis, 30% pre-menopausal and 10% node-positive. Overall, 29% (n = 137) of patients had low Ki67, 49% (n = 227) intermediate, and 21% (n = 97) high Ki67. 18% (n = 85) had RS 0-10, 67% (n = 311) had RS 11-25 and 14% (n = 65) had RS ≥ 26. There was no significant agreement (kappa &lt; 0) between Ki67 and RS (Kappa = -0.0035, p = 0.5406) in the overall population and fair agreement (kappa 0.21-0.40) between high Ki67 and RS (Kappa = 0.2510, p &lt; 0.0001). Higher ER% was significantly associated with lower RS (p &lt; 0.0001) and lower Ki67 (p = 0.0042). High tumor grade was associated with higher RS and higher Ki67 (p &lt; 0.0001). Higher PR% was associated with lower RS (p &gt; 0.0001) but not lower Ki67. Positive nodal status and larger tumor size were associated with higher Ki67 (p = 0.0081, p &lt; 0.0001) but not RS. Among the 49% of patients with intermediate Ki67 of 6-29%, the distribution of low, intermediate, and high RS was 24%, 65%, and 11%, respectively. Conclusions: In this group of patients selected to have a 21-gene RS, there was no correlation between Ki67 and RS in the overall population, and fair agreement between high Ki67 and high RS. Among the approximately one-half with an intermediate Ki67 of 6-29%, 89% would be spared chemotherapy based on a low-intermediate RS. In patients with high Ki67, 68% might be spared chemotherapy based on the RS. In the low Ki67 group, 6% had a high RS. Ki67 has limited utility in identifying patients with high or low RS.

Examining the Risk of Potentially Preventable Hospitalization in Adults With Congenital and Acquired Disabilities

Physical distancing and restriction of movements as measures to prevent the spread of Covid-19 required people to change their work, home and social lives. Loneliness and social isolation have emerged as key public health issues during the pandemic. Traditionally when considering loneliness the focus is often on individual factors rather than within the context of structural and environmental dimensions. This paper will utilise data from the Coping with Loneliness, Isolation and Covid-19 global online survey which had over 20, 000 global responses from people aged 18+ in 2020. Analysis will use the lens of ‘place’ and the 5-item UCLA scale and 6-item Lubben social network scale to understand the social and demographic characteristics and structural and environmental factors associated with those experiencing loneliness and/or social isolation in rural and urban areas both before and during the pandemic. The paper will conclude with key messages from a public health perspective.

Examining the Risk of Potentially Preventable Hospitalization in Adults with Congenital and Acquired Disabilities

<h3>Research Objectives</h3> Adults with congenital (cerebral palsy/spina bifida (CP/SB)) or acquired disabilities (spinal cord injury (SCI) or multiple sclerosis (MS)) are more likely than those without disability to develop medical complications. Little is known about potentially preventable hospitalizations (PPH) among adults with disabilities. PPHs are preventable if a patient had timely access to care. Our objective was to estimate PPH risk for each of the aforementioned disabilities. <h3>Design</h3> Logistic regression models with repeated measures were subsequently applied, adjusting for age, sex, race/ethnicity, health indicators, U.S. census divisions, and socioeconomic variables. Odd ratios (OR) were compared over 4-years of follow up. <h3>Setting</h3> We used private payer claims data from 2007-2017 to identify adults (18+) with diagnoses of CP/SB (n=10,617), SCI (n=5,173), and MS (n=6,198). Adults without these disabilities were included as controls.We propensity score matched individuals for age and sex. Logistic regression models with repeated measures were subsequently applied, adjusting for age, sex, race/ethnicity, health indicators, U.S. census divisions, and socioeconomic variables. <h3>Participants</h3> Adults (18+) with diagnoses of CP/SB (n=10,617), SCI (n=5,173), and MS (n=6,198). <h3>Interventions</h3> Use of preventative services and their interactions with our exposure variable (specific disability type). <h3>Main Outcome Measures</h3> Risk and cost of potentially preventable hospitalization. <h3>Results</h3> Adults with CP/SB, SCI, and MS had higher odds of any PPH compared with adults without disability [CP/SB: (OR=4.10; 95% CI: 2.31-7.31); SCI: (OR=1.67; 95% CI: 1.21-2.32); and MS: (OR=1.48; 95% CI: 1.00-2.25)]. Use of preventative services reduced the PPH risk. For example, wellness visit reduced the odds of PPH by almost half [CP/SB: (OR=0.52; 95% CI: 0.41-0.67); SCI: (OR=0.57; 95% CI: 0.45-0.71); and MS: (OR=0.53; 95% CI: 0.40-0.66)]. <h3>Conclusions</h3> Adults with disabilities are at greater odds of PPH compared to adults without disabilities. Clinical guidelines for use of preventative care for adults living with disabilities need to be accordingly updated. <h3>Author(s) Disclosures</h3> There is no conflict of interest to disclose.

Прецизионная диагностика люпус-нефрита: возможности и роль биомаркеров

Наиболее частым осложнением у пациентов с системной красной волчанкой является волчаночный нефрит — люпус-нефрит (ЛН), состояние, которое может привести к терминальной стадии заболевания почек. В последние годы было предложено множество биомаркеров сыворотки крови и мочи, генетические исследования для ранней диагностики ЛН, однако ни один из них не вошел в рекомендации для клинического использования. Большинство исследований, проведенных в этом направлении, были одноцентровыми со значительной вариабельностью в когортах, анализах и хранении образцов, что привело к неубедительным результатам. На сегодняшний день нет единого биомаркера, достаточного и валидного для диагностики ЛН, выявления обострения патологического процесса и определения реакции на терапию и прогноз. Более вероятный сценарий будущей диагностики — комплексный подход с определением панели биомаркеров мочи, сыворотки крови, почечной ткани и генетических биомаркеров. В обзоре обобщены данные относительно традиционных и новых сывороточных, мочевых и генетических биомаркеров, обсуждены целесообразность их использования в клинической практике и возможности имплементации для более точной диагностики ЛН. Каждая панель биомаркеров обеспечит уникальное понимание различных клинических вопросов развития и прогрессирования болезни. Так, генетическая панель может определить вероятность развития у пациента с системной красной волчанкой нефрита и какие именно воспалительные пути будут вовлечены в реализацию развития ЛН. Панель биомаркеров мочи может помочь различить воспаление и фиброз, устраняя необходимость повторных биопсий. Панель биомаркеров сыворотки может идентифицировать нефритогенные аутоантитела, которые увеличивают количество обострений, обусловливают их тяжесть и ухудшают ответ на лечение. Более систематический и целенаправленный подход к исследованию биомаркеров позволит прецизионной диагностике стать реальностью для пациентов с ЛН.

Can Clinicians Use Dimensional Information to Make a Categorical Diagnosis of Paraphilic Disorders? An ICD-11 Field Study

BackgroundThe diagnosis of paraphilic disorder is a complicated clinical judgment based on the integration of information from multiple dimensions to arrive at a categorical (present/absent) conclusion. The recent update of the guidelines for paraphilic disorders in ICD-11 presents an opportunity to investigate how mental health professionals use the diagnostic guidelines to arrive at a diagnosis which thereby can optimize the guidelines for clinical use. AimThis study examined clinicians’ ability to use the ICD-11 diagnostic guidelines for paraphilic disorders which contain multiple dimensions that must be simultaneously assessed to arrive at a diagnosis. MethodsThe study investigated the ability of 1,263 international clinicians to identify the dimensions of paraphilic disorder in the context of written case vignettes that varied on a single dimension only. OutcomesParticipants provided diagnoses for the case vignettes along with dimensional ratings of the degree of presence of five dimensions of paraphilic disorder (arousal, consent, action, distress, and risk). ResultsAcross a series of analyses, clinicians demonstrated a clear ability to recognize and appropriately integrate the dimensions of paraphilic disorders; however, there was some evidence that clinicians may over-diagnose non-pathological cases. Clinical TranslationClinicians would likely benefit from targeted training on the ICD-11 definition of paraphilic disorder and should be cautious of over-diagnosing. Strengths and LimitationsThis study represents a large international sample of health professionals and is the first to examine clinicians’ ability to apply the ICD-11 diagnostic guidelines for paraphilic disorders. Important limitations include not generalizing to all clinicians and acknowledging that results may be different in direct clinical interactions vs written case vignettes. ConclusionThese results indicate that clinicians appear capable of interpreting and implementing the diagnostic guidelines for paraphilic disorders in ICD-11. Keeley JW, Briken P, Evans SC, et al. Can Clinicians Use Dimensional Information to Make a Categorical Diagnosis of Paraphilic Disorders? An ICD-11 Field Study. J Sex Med 2021;18:1592–1606.

Global Oral Health Policies and Guidelines: Using Silver Diamine Fluoride for Caries Control.

Silver diamine fluoride (SDF) was developed in Japan in the 1960s. It is a clear solution containing silver and fluoride ions. Because of its anti-bacterial and remineralizing effect, silver diamine fluoride has been used in managing dental caries for decades worldwide. This paper aims to summarize and discuss the global policies, guidelines, and relevant information on utilizing SDF for caries management. SDF can be used for treating dental caries in most countries. However, it is not permitted to be used in mainland China. Several manufacturers, mainly in Australia, Brazil, India, Japan, and the United States, produce SDF at different concentrations that are commercially available around the world. The prices differ between contents and brands. Different government organizations and dental associations have developed guidelines for clinical use of SDF. Dental professionals can refer to the specific guidelines in their own countries or territories. Training for using SDF is part of undergraduate and/or postgraduate curriculums in almost all countries. However, real utilization of SDF of dentists, especially in the private sector, remains unclear in most places because little research has been conducted. There are at least two ongoing regional-wide large-scale oral health programs, using SDF as one of the components to manage dental caries in young children (one in Hong Kong and one in Mongolia). Because SDF treatment does not require caries removal, and it is simple, non-invasive, and inexpensive, SDF is a valuable strategy for caries management in young children, elderly people, and patients with special needs. In addition, to reduce the risk of bacteria or virus transmission in dental settings, using SDF as a non-aerosol producing procedure should be emphasized under the COVID-19 outbreak.

Potential Impact of DPYD Variation on Fluoropyrimidine Drug Response in sub-Saharan African Populations.

Cancer is a critical health burden in Africa, and mortality rates are rising rapidly. Treatments are expensive and often cause adverse drug reactions (ADRs). Fluoropyrimidine treatments can lead to severe toxicity events which have been linked to variants within the dihydropyrimidine dehydrogenase (DPYD) gene. There are clinical guidelines to improve safety outcomes of treatment, but these are primarily based on variants assessed in non-African populations. Whole genome sequencing data from the 1000 Genomes Project and the African Genome Variation Project were mined to assess variation in DPYD in eight sub-Saharan African populations. Variant functional annotation was performed with a series of bioinformatics tools to assess potential likelihood of deleterious impact. There were 29 DPYD coding variants identified in the datasets assessed, of which 25 are rare, and some of which are known to be deleterious. One African-specific variant (rs115232898-C), is common in sub-Saharan Africans (1–4%) and known to reduce the function of the dihydropyrimidine dehydrogenase enzyme (DPD), having been linked to cases of severe toxicity. This variant, once validated in clinical trials, should be considered for inclusion in clinical guidelines for use in sub-Saharan African populations. The rs2297595-C variant is less well-characterized in terms of effect, but shows significant allele frequency differences between sub-Saharan African populations (0.5–11.5%; p = 1.5 × 10−4), and is more common in East African populations. This study highlights the relevance of African-data informed guidelines for fluorouracil drug safety in sub-Saharan Africans, and the need for region-specific data to ensure that Africans may benefit optimally from a precision medicine approach.

Systematic Appraisal of Dementia Clinical Guidelines for Use in Occupational Therapy

Systematic Appraisal of Dementia Clinical Guidelines for Use in Occupational Therapy

Prolonged (post-thaw) shelf life of -80°C frozen AB apheresis plasma.

ABSTRACTBACKGROUNDEarly plasma transfusion is important in the treatment of patients with major hemorrhage. Prolonged shelf life of AB type frozen −80°C and cold‐stored (4°C) deep frozen plasma (DFP) will improve strategic stock management, minimize need for resupply, and make pre‐hospital implementation more feasible.METHODS AND MATERIALSPlasma products type AB of different age and origin (−30°C Fresh Frozen [(FFP], −80°C DFP [short (±1 year) and long (±7 year)] stored) were thawed (Day 0), stored at 4°C, and sampled on Days 7 and 14. Additionally, samples of plasma containing blood products (Octaplas LG®, whole blood and platelets) were compared for coagulation factor activity, phospholipid clotting time (PPL), and kaolin TEG during 4°C or 22°C storage.RESULTSCoagulation profiles of FFP, short‐ and long‐stored −80°C DFP were not significantly different after thaw. Cold storage did not affect fibrinogen, Protein C, and Antithrombin III activities whereas factor V, VII, VIII, and Protein S decreased in all blood products. After 14 days DFP still meets the guidelines for clinical use, except for Protein S (0.4 IU/mL). With exception of Octaplas LG®, phospholipid activity and TEG coagulation were similar between plasma containing blood components during storage.CONCLUSIONAB DFP quality was unaffected by almost 7 years of frozen storage. Quality of thawed 14‐day stored AB DFP met, with exception of Protein S, all minimal guidelines which implies that its quality is sufficient for use in the (pre)‐hospital (military) environment for treatment of major hemorrhage.

Deciphering the Morphology of Motor Evoked Potentials.

Motor Evoked Potentials (MEPs) are used to monitor disability progression in multiple sclerosis (MS). Their morphology plays an important role in this process. Currently, however, there is no clear definition of what constitutes a normal or abnormal morphology. To address this, five experts independently labeled the morphology (normal or abnormal) of the same set of 1,000 MEPs. The intra- and inter-rater agreement between the experts indicates they agree on the concept of morphology, but differ in their choice of threshold between normal and abnormal morphology. We subsequently performed an automated extraction of 5,943 time series features from the MEPs to identify a valid proxy for morphology, based on the provided labels. To do this, we compared the cross-validation performances of one-dimensional logistic regression models fitted to each of the features individually. We find that the approximate entropy (ApEn) feature can accurately reproduce the majority-vote labels. The performance of this feature is evaluated on an independent test set by comparing to the majority vote of the neurologists, obtaining an AUC score of 0.92. The model slightly outperforms the average neurologist at reproducing the neurologists consensus-vote labels. We can conclude that MEP morphology can be consistently defined by pooling the interpretations from multiple neurologists and that ApEn is a valid continuous score for this. Having an objective and reproducible MEP morphological abnormality score will allow researchers to include this feature in their models, without manual annotation becoming a bottleneck. This is crucial for large-scale, multi-center datasets. An exploratory analysis on a large single-center dataset shows that ApEn is potentially clinically useful. Introducing an automated, objective, and reproducible definition of morphology could help overcome some of the barriers that are currently obstructing broad adoption of evoked potentials in daily care and patient follow-up, such as standardization of measurements between different centers, and formulating guidelines for clinical use.

Effects of Ketamine Anesthesia on Efficacy, Tolerability, Seizure Response, and Neurocognitive Outcomes in Electroconvulsive Therapy: A Comprehensive Meta-analysis of Double-Blind Randomized Controlled Trials.

Electroconvulsive therapy (ECT) remains the most effective treatment for major depressive disorder. Ketamine is an anesthetic gaining attention for its rapid antidepressant effect. Numerous randomized controlled trials have investigated the effect of ketamine anesthesia in ECT on various clinical outcomes. Previous systematic reviews have not found benefit for overall depression response, although some have found evidence of benefit early in the ECT course. Clear quantitative conclusions have not been established regarding other outcomes, particularly while only using data from high-quality studies. We aimed to examine all data from double-blind randomized controlled trials comparing ketamine to other anesthetics via meta-analysis, to make recommendations regarding ECT practice and future research. Data were extracted for depressive symptoms, seizure duration and electrical dose, neuropsychological performance, and adverse effects. Effect sizes were calculated using Hedge's g and odds ratios. Eighteen studies (n = 915) were included in the meta-analysis. Ketamine was not found to enhance improvement of depressive symptoms, either early in ECT course or at end of study. Ketamine had a large effect on increasing seizure duration both overall (Hedge's g = 0.71, P = 0.038) and in the subgroup receiving ketamine in combination with another anesthetic (Hedge's g = 0.78, P < 0.01), and on decreasing electrical dose (Hedge's g = 1.98, P = 0.039). There was no significant effect of ketamine on any individual neuropsychological domain. Ketamine was not associated with increased adverse effects, except for hypertension in patients receiving ketamine monotherapy. Significant heterogeneity was present for many outcomes, and sensitivity analyses suggested a relation to methodological variation in most cases. This study supports the finding that ketamine does not enhance ECT's antidepressant effect, including on early improvement, but provides substantial evidence for enhancing seizure duration and reducing electrical dose. No significant benefit was found on neurocognitive outcomes, but analysis was limited by small sample sizes and high heterogeneity. Ketamine is generally safe in ECT, particularly as a coanesthetic. Our findings provide meta-analytic support to the recommendations in ECT clinical guidelines for use of coadjuvant ketamine in ECT where seizures are suboptimal. Further studies targeting neurocognitive outcomes are encouraged.

Can pathology diagnostic services for cancer be stratified and serve global health?

Before initiating cancer therapy, a diagnostic tumor tissue sample evaluated within a pathology laboratory by a pathologist is essential to confirm the malignancy type and provide key prognostic factors that direct the treatment offered. Pathology evaluation includes multiple expensive reagents, complex equipment, and both laboratory and pathologist technical skills. By using breast cancer as an example, at a minimum, key tumor prognostic information required before the initiation of treatment includes subtype, tumor grade, tumor size, lymph node status when possible, and biomarker expression determined by immunohistochemistry for estrogen receptor. The additional determination of biomarker expression of progesterone receptor and human epidermal growth factor receptor (HER2) is the standard of care in high-resource settings, but assays may not be affordable in low-income and middle-income countries. With positive tests, patients are eligible for either tamoxifen (for estrogen receptor-positive/progesterone receptor-positive cancers) or monoclonal antibody therapy (for HER2-positive cancers). For settings in which endocrine therapy and/or HER2-targeted therapy is unavailable, biomarker studies have no utility, and high-resource setting standards for pathology evaluation and reporting are unachievable. Resource-stratified pathology evaluation guidelines in cancer diagnosis have not been developed, in contrast to excellent comprehensive, resource-stratified clinical guidelines for use in low-income and middle-income countries, and these are long overdue. The challenges of pathology evaluation in the context of global health are being met by innovative solutions, which may change the face of pathology practice.

Challenges of Valproate Treatment During Pregnancy: Pros and Cons

Valproic acid and its salt, sodium valproate, are an effective treatment for epilepsy, the most common chronic neurologic disorder worldwide. Teratogenic associations reported after embryofetal exposure has limited the recommendations of valproate use in women of childbearing age, after careful evaluation of the benefits and risks of this medication. The mechanisms of valproate damage during pregnancy are complex and incompletely clarified up to date. Maternal and fetal impact of valproate is a critical issue, standing at the base of the new consensus on practical guidelines for clinical use of antiepileptic treatment in fertile women.