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The American Journal of Tropical... Mar 2021Antimalarials, in particular artemisinin-based combination therapies (ACTs), are critical tools in reducing the global burden of malaria, which is concentrated in...
Antimalarials, in particular artemisinin-based combination therapies (ACTs), are critical tools in reducing the global burden of malaria, which is concentrated in sub-Saharan Africa. Performing and reporting antimalarial efficacy studies in a transparent and standardized fashion permit comparison of efficacy outcomes across countries and time periods. This systematic review summarizes study compliance with WHO laboratory and reporting guidance pertaining to antimalarial therapeutic efficacy studies and evaluates how well studies from sub-Saharan Africa adhered to these guidelines. We included all published studies (January 2020 or before) performed in sub-Saharan Africa where ACT efficacy for treatment of uncomplicated Plasmodium falciparum infection was reported. The primary outcome was a composite indicator for study methodology consistent with WHO guidelines for statistical analysis of corrected efficacy, defined as an article presenting a Kaplan-Meier survival analysis of corrected efficacy or reporting a per-protocol analysis where new infections were excluded from the numerator and denominator. Of 581 articles screened, we identified 279 for the review. Molecular correction was used in 83% (232/279) to distinguish new infections from recrudescences in subjects experiencing recurrent parasitemia. Only 45% (99/221) of articles with therapeutic efficacy as a primary outcome and performing molecular correction reported corrected efficacy outcomes calculated in a way consistent with WHO recommendations. These results indicate a widespread lack of compliance with WHO-recommended methods of analysis, which may result in biases in how antimalarial effectiveness is being measured and reported from sub-Saharan Africa.
Topics: Africa South of the Sahara; Analysis of Variance; Antimalarials; Artemisinins; Data Interpretation, Statistical; Drug Resistance; Guideline Adherence; Guidelines as Topic; Humans; Kaplan-Meier Estimate; Malaria, Falciparum; Plasmodium falciparum; Recurrence; Treatment Outcome
PubMed: 33724925
DOI: 10.4269/ajtmh.20-1481 -
Canadian Journal of Kidney Health and... 2021Chronic pain is a common and distressing symptom reported by patients with chronic kidney disease (CKD). Clinical practice and research in this area do not appear to be...
BACKGROUND
Chronic pain is a common and distressing symptom reported by patients with chronic kidney disease (CKD). Clinical practice and research in this area do not appear to be advancing sufficiently to address the issue of chronic pain management in patients with CKD.
OBJECTIVES
To determine the prevalence and severity of chronic pain in patients with CKD.
DESIGN
Systematic review and meta-analysis.
SETTING
Interventional and observational studies presenting data from 2000 or later. Exclusion criteria included acute kidney injury or studies that limited the study population to a specific cause, symptom, and/or comorbidity.
PATIENTS
Adults with glomerular filtration rate (GFR) category 3 to 5 CKD including dialysis patients and those managed conservatively without dialysis.
MEASUREMENTS
Data extracted included title, first author, design, country, year of data collection, publication year, mean age, stage of CKD, prevalence of pain, and severity of pain.
METHODS
Databases searched included MEDLINE, CINAHL, EMBASE, and Cochrane Library, last searched on February 3, 2020. Two reviewers independently screened all titles and abstracts, assessed potentially relevant articles, and extracted data. We estimated pooled prevalence of overall chronic pain, musculoskeletal pain, bone/joint pain, muscle pain/soreness, and neuropathic pain and the statistic was computed to measure heterogeneity. Random effects models were used to account for variations in study design and sample populations and a double arcsine transformation was used in the model calculations to account for potential overweighting of studies reporting either very high or very low prevalence measurements. Pain severity scores were calibrated to a score out of 10, to compare across studies. Weighted mean severity scores and 95% confidence intervals were reported.
RESULTS
Sixty-eight studies representing 16 558 patients from 26 countries were included. The mean prevalence of chronic pain in hemodialysis patients was 60.5%, and the mean prevalence of moderate or severe pain was 43.6%. Although limited, pain prevalence data for peritoneal dialysis patients (35.9%), those managed conservatively without dialysis (59.8%), those following withdrawal of dialysis (39.2%), and patients with earlier GFR category of CKD (61.2%) suggest similarly high prevalence rates.
LIMITATIONS
Studies lacked a consistent approach to defining the chronicity and nature of pain. There was also variability in the measures used to determine pain severity, limiting the ability to compare findings across populations. Furthermore, most studies reported mean severity scores for the entire cohort, rather than reporting the prevalence (numerator and denominator) for each of the pain severity categories (mild, moderate, and severe). Mean severity scores for a population do not allow for "responder analyses" nor allow for an understanding of clinically relevant pain.
CONCLUSIONS
Chronic pain is common and often severe across diverse CKD populations providing a strong imperative to establish chronic pain management as a clinical and research priority. Future research needs to move toward a better understanding of the determinants of chronic pain and to evaluating the effectiveness of pain management strategies with particular attention to the patient outcomes such as overall symptom burden, physical function, and quality of life. The current variability in the outcome measures used to assess pain limits the ability to pool data or make comparisons among studies, which will hinder future evaluations of the efficacy and effectiveness of treatments. Recommendations for measuring and reporting pain in future CKD studies are provided.
TRIAL REGISTRATION
PROSPERO Registration number CRD42020166965.
PubMed: 33680484
DOI: 10.1177/2054358121993995 -
The Lancet. Global Health Apr 2021Increasing access to hepatitis C virus (HCV) care and treatment will require simplified service delivery models. We aimed to evaluate the effects of decentralisation and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increasing access to hepatitis C virus (HCV) care and treatment will require simplified service delivery models. We aimed to evaluate the effects of decentralisation and integration of testing, care, and treatment with harm-reduction and other services, and task-shifting to non-specialists on outcomes across the HCV care continuum.
METHODS
For this systematic review and meta-analysis, we searched PubMed, Embase, WHO Global Index Medicus, and conference abstracts for studies published between Jan 1, 2008, and Feb 20, 2018, that evaluated uptake of HCV testing, linkage to care, treatment, cure assessment, and sustained virological response at 12 weeks (SVR12) in people who inject drugs, people in prisons, people living with HIV, and the general population. Randomised controlled trials, non-randomised studies, and observational studies were eligible for inclusion. Studies with a sample size of ten or less for the largest denominator were excluded. Studies were categorised according to the level of decentralisation: full (testing and treatment at same site), partial (testing at decentralised site and referral elsewhere for treatment), or none. Task-shifting was categorised as treatment by specialists or non-specialists. Data on outcomes across the HCV care continuum (linkage to care, treatment uptake, and SVR12) were pooled using random-effects meta-analysis.
FINDINGS
Our search identified 8050 reports, of which 132 met the eligibility criteria, and an additional ten reports were identified from reference citations and grey literature. Therefore, the final synthesis included 142 studies from 34 countries (20 [14%] studies from low-income and middle-income countries) and a total of 489 996 patients (239 446 [49%] from low-income and middle-income countries). Rates of linkage to care were higher with full decentralisation compared with partial or no decentralisation among people who inject drugs (full 72% [95% CI 57-85] vs partial 53% [38-67] vs none 47% [11-84]) and among people in prisons (full 94% [79-100] vs partial 50% [29-71]), although the CIs overlap for people who inject drugs. Similarly, treatment uptake was higher with full decentralisation compared with partial or no decentralisation (people who inject drugs: full 73% [65-80] vs partial 66% [55-77] vs none 35% [23-48]; people in prisons: full 72% [48-91] vs partial 39% [17-63]), although CIs overlap for full versus partial decentralisation. The results in the general population studies were more heterogeneous. SVR12 rates were high (≥90%) across different levels of decentralisation in all populations. Task-shifting of care and treatment to a non-specialist was associated with similar SVR12 rates to treatment delivered by specialists. There was a severe or critical risk of bias for 46% of studies, and heterogeneity across studies tended to be very high (I>90%).
INTERPRETATION
Decentralisation and integration of HCV care to harm-reduction sites or primary care showed some evidence of improved access to testing, linkage to care, and treatment, and task-shifting of care and treatment to non-specialists was associated with similarly high cure rates to care delivered by specialists, across a range of populations and settings. These findings provide support for the adoption of decentralisation and task-shifting to non-specialists in national HCV programmes.
FUNDING
Unitaid.
Topics: Antiviral Agents; Delivery of Health Care, Integrated; Health Services Accessibility; Hepacivirus; Hepatitis C; Humans; Models, Organizational; National Health Programs; Observational Studies as Topic; Patient Acceptance of Health Care; Randomized Controlled Trials as Topic; Sustained Virologic Response
PubMed: 33639097
DOI: 10.1016/S2214-109X(20)30505-2 -
Critical Care Medicine Apr 2021Cost utility analyses compare the costs and health outcome of interventions, with a denominator of quality-adjusted life year, a generic health utility measure combining...
OBJECTIVES
Cost utility analyses compare the costs and health outcome of interventions, with a denominator of quality-adjusted life year, a generic health utility measure combining both quality and quantity of life. Cost utility analyses are difficult to compare when methods are not standardized. It is unclear how cost utility analyses are measured/reported in critical care and what methodologic challenges cost utility analyses pose in this setting. This may lead to differences precluding cost utility analyses comparisons. Therefore, we performed a systematic review of cost utility analyses conducted in critical care. Our objectives were to understand: 1) methodologic characteristics, 2) how health-related quality-of-life was measured/reported, and 3) what costs were reported/measured.
DESIGN
Systematic review.
DATA SOURCES
We systematically searched for cost utility analyses in critical care in MEDLINE, Embase, American College of Physicians Journal Club, CENTRAL, Evidence-Based Medicine Reviews' selected subset of archived versions of UK National Health Service Economic Evaluation Database, Database of Abstracts of Reviews of Effects, and American Economic Association electronic databases from inception to April 30, 2020.
SETTING
Adult ICUs.
PATIENTS
Adult critically ill patients.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Of 8,926 citations, 80 cost utility analyse studies were eligible. The time horizon most commonly reported was lifetime (59%). For health utility reporting, health-related quality-of-life was infrequently measured (29% reported), with only 5% of studies reporting baseline health-related quality-of-life. Indirect utility measures (generic, preference-based health utility measurement tools) were reported in 85% of studies (majority Euro-quality-of-life-5 Domains, 52%). Methods of estimating health-related quality-of-life were seldom used when the patient was incapacitated: imputation (19%), assigning fixed utilities for incapacitation (19%), and surrogates reporting on behalf of incapacitated patients (5%). For cost utility reporting transparency, separate incremental costs and quality-adjusted life years were both reported in only 76% of studies. Disaggregated quality-adjusted life years (reporting separate health utility and life years) were described in only 34% of studies.
CONCLUSIONS
We identified deficiencies which warrant recommendations (standardized measurement/reporting of resource use/unit costs/health-related quality-of-life/methodological preferences) for improved design, conduct, and reporting of future cost utility analyses in critical care.
Topics: Cost-Benefit Analysis; Critical Care; Humans; Intensive Care Units; Quality of Life; Quality-Adjusted Life Years
PubMed: 33591013
DOI: 10.1097/CCM.0000000000004851 -
Transplantation Oct 2021Hemodynamic instability (HDI) during liver transplantation (LT) can be difficult to manage and increases postoperative morbidity and mortality. In addition to surgical...
Hemodynamic instability (HDI) during liver transplantation (LT) can be difficult to manage and increases postoperative morbidity and mortality. In addition to surgical causes of HDI, patient- and graft-related factors are also important. Nitric oxide-mediated vasodilatation is a common denominator associated with end-stage liver disease related to HDI. Despite intense investigation, optimal management strategies remain elusive. In this consensus article, experts from the International Liver Transplantation Society, the Liver Intensive Care Group of Europe, and the Society for the Advancement of Transplant Anesthesia performed a rigorous review of the most current literature regarding the epidemiology, causes, and management of HDI during LT. Special attention has been paid to unique LT-associated conditions including the causes and management of vasoplegic syndrome, cardiomyopathies, LT-related arrhythmias, right and left ventricular dysfunction, and the specifics of medical and fluid management in end-stage liver disease as well as problems specifically related to portal circulation. When possible, management recommendations are made.
Topics: Consensus; Fluid Therapy; Hemodynamics; Humans; Intraoperative Complications; Kidney Failure, Chronic; Liver Transplantation; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 33534523
DOI: 10.1097/TP.0000000000003642 -
JAMA Psychiatry May 2021Task sharing-or training of nonspecialist providers with no formal training in counseling-is an effective strategy to improve access to evidence-based counseling... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Task sharing-or training of nonspecialist providers with no formal training in counseling-is an effective strategy to improve access to evidence-based counseling interventions and has the potential to address the burden of perinatal depression and anxiety.
OBJECTIVES
To identify the relevant implementation processes (who, what, where, and how) and to assess the effectiveness of counseling interventions delivered by nonspecialist providers for perinatal depression and anxiety in high-income countries.
DATA SOURCES
CINAHL, Ovid MEDLINE, Ovid MEDLINE In-Process, PsycINFO, Web of Science, Cochrane Central Register of Controlled Trials, and Embase through December 31, 2019. Relevant systematic reviews were also considered.
STUDY SELECTION
Randomized clinical trials of counseling interventions that assessed depression or anxiety after intervention, delivered by a nonspecialist provider for adults, and that targeted perinatal populations in a high-income country were included. Self-help interventions that did not include a provider component were excluded.
DATA EXTRACTION AND SYNTHESIS
Four researchers independently reviewed abstracts and full-text articles, and 2 independently rated the quality of included studies. Random-effects meta-analysis was used to estimate the benefits of the interventions. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed.
MAIN OUTCOMES AND MEASURES
For implementation processes, the frequencies represented by a total or percentage were estimated, where the denominator is the total number of eligible trials, unless otherwise indicated. For effectiveness, primary and secondary outcome data of depression, anxiety, or both symptoms were used, with separate analyses for prevention and treatment, stratified by depression or anxiety. Subgroup analyses compared outcome types (anxiety vs depression) and study objectives (treatment vs prevention).
RESULTS
In total, 46 trials (18 321 participants) were included in the systematic review; 44 trials (18 101 participants) were included in the meta-analysis. Interventions were implemented across 11 countries, with the majority in Australia, UK, and US. Two-thirds (65%) of counseling interventions were provided by nurses and midwives, lasted a mean of 11.2 weeks (95% CI, 6.4-16.0 weeks), and most were delivered face to face (31 [67.4%]). Only 2 interventions were delivered online. A dearth of information related to important implementation processes, such as supervision, fidelity, and participant sociodemographic characteristics, was observed in many articles. Compared with controls, counseling interventions were associated with lower depressive symptoms (standardized mean difference [SMD], 0.24 [95% CI, 0.14-0.34]; 43 trials; I2 = 81%) and anxiety scores (SMD, 0.30 [95% CI, 0.11-0.50]; 11 trials; I2 = 80%). Treatment interventions were reported to be effective for both depressive symptoms (SMD, 0.38 [95% CI, 0.17-0.59]; 15 trials; I2 = 69%) and anxiety symptoms (SMD, 0.34 [95% CI, 0.09-0.58]; 6 trials; I2 = 71%). However, heterogeneity was high among the trials included in this analysis.
CONCLUSIONS AND RELEVANCE
This study found evidence in high-income countries indicating that nonspecialist providers may be effective in delivering counseling interventions. Additional studies are needed to assess digital interventions and ensure the reporting of implementation processes to inform the optimal delivery and scale-up of these services.
Topics: Anxiety; Counseling; Depression; Developed Countries; Female; Humans; Outcome and Process Assessment, Health Care; Perinatal Care; Pregnancy; Pregnancy Complications; Psychosocial Intervention
PubMed: 33533904
DOI: 10.1001/jamapsychiatry.2020.4556 -
Frontiers in Cell and Developmental... 2020Ovarian insufficiency is identified as a perplexing entity in the long list of pathologies impairing fertility dynamics. The three distinct classifications of ovarian...
Reporting on the Role of miRNAs and Affected Pathways on the Molecular Backbone of Ovarian Insufficiency: A Systematic Review and Critical Analysis Mapping of Future Research.
Ovarian insufficiency is identified as a perplexing entity in the long list of pathologies impairing fertility dynamics. The three distinct classifications of ovarian insufficiency are poor ovarian response, premature ovarian insufficiency/failure, and advanced maternal age, sharing the common denominator of deteriorated ovarian reserve. Despite efforts to define clear lines among the three, the vast heterogeneity and overlap of clinical characteristics renders their diagnosis and management challenging. Lack of a consensus has prompted an empirically based management coupled by uncertainty from the clinicians' perspective. Profiling of patients in the era of precision medicine seems to be the way forward, while the necessity for a novel approach is underlined. Implicating miRNAs in the quest for patient profiling is promising in light of their fundamental role in cellular and gene expression regulation. To this end, the current study sets out to explore and compare the three pathophysiologies-from a molecular point of view-in order to enable profiling of patients in the context of fertilization treatment and enrich the data required to practice individualized medicine. Following a systematic investigation of literature, data referring to miRNAs were collected for each patient category based on five included studies. miRNA-target pairs were retrieved from the DIANA-TarBase repository and microT-CDS. Gene and miRNA annotations were derived from Ensembl and miRbase. A subsequent gene-set enrichment analysis of miRNA targets was performed for each category separately. A literature review on the most crucial of the detected pathways was performed to reveal their relevance to fertility deterioration. Results supported that all three pathophysiologies share a common ground regarding the affected pathways, naturally attributed to the common denominator of ovarian insufficiency. As evidenced, miRNAs could be employed to explore the fine lines and diverse nature of pathophysiology since they constitute invaluable biomarkers. Interestingly, it is the differentiation through miRNAs and not through the molecular affected pathways that corresponds to the three distinctive categories. Alarming discrepancies among publications were revealed, pertaining to employment of empirical and arbitrary criteria in categorizing the patients. Following bioinformatic analysis, the final step of the current study consisted of a critical analysis of the molecular data sourced, providing a clear and unique insight into the physiological mechanisms involved. It is our intention to contribute to mapping future research dedicated to ovarian insufficiency and to help researchers navigate the overwhelming information published in molecular studies.
PubMed: 33511114
DOI: 10.3389/fcell.2020.590106 -
Pulmonary Circulation 2021This systematic review of literature and online reports critically appraised incidence and prevalence estimates of pulmonary arterial hypertension and chronic...
Epidemiology of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: identification of the most accurate estimates from a systematic literature review.
This systematic review of literature and online reports critically appraised incidence and prevalence estimates of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension to identify the most accurate estimates. Medline® and Embase® databases were searched for articles published between 1 January 2003 and 31 August 2020. Studies were grouped according to whether they were registries (population-based estimates), clinical databases (hospital-based estimates) or claims/administrative databases. Registries were classified into systematic and non-systematic registries, according to whether every national centre participated. Of 7309 publications identified, 5414 were screened after removal of duplicates and 33 were included. Inclusion was based on study type, availability of a clear numerator (diagnosed population) and a population- or hospital-based denominator, or all primary data required to calculate estimates. Only the most recent publication from a database was included. Most studies were based on European data and very few included children. In adults, the range of estimates per million was approximately 20-fold for pulmonary arterial hypertension incidence (1.5-32) and prevalence (12.4-268) and of similar magnitude for chronic thromboembolic pulmonary hypertension incidence (0.9-39) and prevalence (14.5-144). Recent (≤5 years) national systematic registry data from centralised healthcare systems provided the following ranges in adult estimates per million: approximately 5.8 for pulmonary arterial hypertension incidence, 47.6-54.7 for pulmonary arterial hypertension prevalence, 3.1-6.0 for chronic thromboembolic pulmonary hypertension incidence and 25.8-38.4 for chronic thromboembolic pulmonary hypertension prevalence. These estimates were considered the most reliable and consistent for the scientific community to plan for resource allocation and improve detection rates.
PubMed: 33456755
DOI: 10.1177/2045894020977300 -
The Physician and Sportsmedicine Feb 2022To compare concussion incidence in male and female soccer players due to the specific concussion-causing activity. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare concussion incidence in male and female soccer players due to the specific concussion-causing activity.
METHODS/DATA SOURCES
PubMed, EMBASE, and Cochrane Library were searched for studies published between January 2000 and February 2020. Search terms included 'sex,' 'gender,' 'sex differences,' 'brain injury,' 'sports,' 'athletes,' 'incidence,' 'epidemiology,' 'symptoms,' and 'injury rate.' Studies that contained data on concussion incidence in soccer and featured comparisons by sex and soccer activity were included. Studies that were not written in English, contained data on non-sports-related concussions, or were conference abstracts were excluded.
RESULTS
Six studies were included in this meta-analysis, each of which contributed the number of concussions in males and females for a specific soccer activity. Concussion incidence rates were calculated using athlete-exposures as the denominator and a rate ratio was measured by dividing the concussion rate among female soccer players by the rate among male soccer players. Female soccer players were shown to have a greater rate of concussions from heading [1.65 (95% CI: 1.35, 2.03, p < 0.001)] and goalkeeping [1.63 (95% CI: 1.22, 2.17, p = 0.001)]. There were 3 studies comparing sex differences for general play. While the pooled rate ratio was statistically significant [1.51 (95% CI: 1.12, 2.04), p = 0.007], this result was largely driven by 1 study.
CONCLUSION
Concussion incidence rates were significantly higher in female soccer players compared to male players while heading. There is also some evidence to suggest that the incidence is higher for female goalkeepers. Soccer coaches and health care providers need to recognize this sex difference when coaching or treating players.
Topics: Athletic Injuries; Brain Concussion; Female; Humans; Incidence; Male; Sex Characteristics; Soccer
PubMed: 33357128
DOI: 10.1080/00913847.2020.1868955 -
Anesthesiology Research and Practice 2020Postoperative Cognitive Dysfunction (POCD) is characterized by a deterioration in cognitive performance after surgery and is increasingly addressed in research studies.... (Review)
Review
Postoperative Cognitive Dysfunction (POCD) is characterized by a deterioration in cognitive performance after surgery and is increasingly addressed in research studies. However, a uniform definition of POCD seems to be lacking, which is a major threat to clinical research in this area. We performed a focused systematic review to determine the current degree of heterogeneity in how POCD is defined across studies and to identify those diagnostic criteria that are used most commonly. The search identified 173 records, of which 30 were included. Neurocognitive testing was most commonly performed shortly before surgery and at 7 days postoperatively. A variety of neurocognitive tests were used to test a range of cognitive domains, including complex attention, language, executive functioning, perceptual-motor function, and learning and memory. The tests that were used most commonly were the Mini-Mental State Examination, the digit span test, the trail making test part A, and the digit symbol substitution test, but consensus on which test result would be considered "positive" for POCD was sparse. The results of this systematic review suggest the lack of a consistent approach towards defining POCD. However, commonalities were identified which may serve as a common denominator for deriving consensus-based diagnostic guidelines for POCD.
PubMed: 33281900
DOI: 10.1155/2020/7384394