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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 -
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 -
Journal of the American Medical... Jan 2021To conduct a systematic review and meta-analysis to assess: 1) changes in medication error rates and associated patient harm following electronic medication system (EMS)... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a systematic review and meta-analysis to assess: 1) changes in medication error rates and associated patient harm following electronic medication system (EMS) implementation; and 2) evidence of system-related medication errors facilitated by the use of an EMS.
MATERIALS AND METHODS
We searched Medline, Scopus, Embase, and CINAHL for studies published between January 2005 and March 2019, comparing medication errors rates with or without assessments of related harm (actual or potential) before and after EMS implementation. EMS was defined as a computer-based system enabling the prescribing, supply, and/or administration of medicines. Study quality was assessed.
RESULTS
There was substantial heterogeneity in outcomes of the 18 included studies. Only 2 were strong quality. Meta-analysis of 5 studies reporting change in actual harm post-EMS showed no reduced risk (RR: 1.22, 95% CI: 0.18-8.38, P = .8) and meta-analysis of 3 studies reporting change in administration errors found a significant reduction in error rates (RR: 0.77, 95% CI: 0.72-0.83, P = .004). Of 10 studies of prescribing error rates, 9 reported a reduction but variable denominators precluded meta-analysis. Twelve studies provided specific examples of system-related medication errors; 5 quantified their occurrence.
DISCUSSION AND CONCLUSION
Despite the wide-scale adoption of EMS in hospitals around the world, the quality of evidence about their effectiveness in medication error and associated harm reduction is variable. Some confidence can be placed in the ability of systems to reduce prescribing error rates. However, much is still unknown about mechanisms which may be most effective in improving medication safety and design features which facilitate new error risks.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Inpatients; Length of Stay; Medical Order Entry Systems; Medication Errors; Medication Systems, Hospital
PubMed: 33164058
DOI: 10.1093/jamia/ocaa230 -
BMC Medicine Oct 2020Novel biological and precision therapies and their associated predictive biomarker tests offer opportunities for increased tumor response, reduced adverse effects, and... (Meta-Analysis)
Meta-Analysis
Are there socio-economic inequalities in utilization of predictive biomarker tests and biological and precision therapies for cancer? A systematic review and meta-analysis.
BACKGROUND
Novel biological and precision therapies and their associated predictive biomarker tests offer opportunities for increased tumor response, reduced adverse effects, and improved survival. This systematic review determined if there are socio-economic inequalities in utilization of predictive biomarker tests and/or biological and precision cancer therapies.
METHODS
MEDLINE, Embase, Scopus, CINAHL, Web of Science, PubMed, and PsycINFO were searched for peer-reviewed studies, published in English between January 1998 and December 2019. Observational studies reporting utilization data for predictive biomarker tests and/or cancer biological and precision therapies by a measure of socio-economic status (SES) were eligible. Data was extracted from eligible studies. A modified ISPOR checklist for retrospective database studies was used to assess study quality. Meta-analyses were undertaken using a random-effects model, with sub-group analyses by cancer site and drug class. Unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed for each study. Pooled utilization ORs for low versus high socio-economic groups were calculated for test and therapy receipt.
RESULTS
Among 10,722 citations screened, 62 papers (58 studies; 8 test utilization studies, 37 therapy utilization studies, 3 studies on testing and therapy, 10 studies without denominator populations or which only reported mean socio-economic status) met the inclusion criteria. Studies reported on 7 cancers, 5 predictive biomarkers tests, and 11 biological and precision therapies. Thirty-eight studies (including 1,036,125 patients) were eligible for inclusion in meta-analyses. Low socio-economic status was associated with modestly lower predictive biomarker test utilization (OR 0.86, 95% CI 0.71-1.05; 10 studies) and significantly lower biological and precision therapy utilization (OR 0.83, 95% CI 0.75-0.91; 30 studies). Associations with therapy utilization were stronger in lung cancer (OR 0.71, 95% CI 0.51-1.00; 6 studies), than breast cancer (OR 0.93, 95% CI 0.78-1.10; 8 studies). The mean study quality score was 6.9/10.
CONCLUSIONS
These novel results indicate that there are socio-economic inequalities in predictive biomarker tests and biological and precision therapy utilization. This requires further investigation to prevent differences in outcomes due to inequalities in treatment with biological and precision therapies.
Topics: Biomarkers, Tumor; Female; Humans; Immunotherapy; Male; Neoplasms; Precision Medicine; Retrospective Studies; Socioeconomic Factors
PubMed: 33092592
DOI: 10.1186/s12916-020-01753-0 -
Pneumonia (Nathan Qld.) 2020The etiology of community-acquired pneumonia (CAP) has evolved since the beginning of the antibiotic era. Recent guidelines encourage immediate empiric antibiotic... (Review)
Review
BACKGROUND
The etiology of community-acquired pneumonia (CAP) has evolved since the beginning of the antibiotic era. Recent guidelines encourage immediate empiric antibiotic treatment once a diagnosis of CAP is made. Concerns about treatment recommendations, on the one hand, and antibiotic stewardship, on the other, motivated this review of the medical literature on the etiology of CAP.
METHODS
We conducted a systematic review of English-language literature on the etiology of CAP using methods defined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed using a combination of the keywords 'pneumonia', 'CAP', 'etiology', 'microbiology', 'bacteriology', and 'pathogen'. We examined articles on antibiotics that were develop to treat pneumonia. We reviewed all 'related articles' as well as studies referenced by those that came up in the search. After we excluded articles that did not give sufficient microbiological data or failed to meet other predetermined criteria, 146 studies remained. Data were stratified into diagnostic categories according to the microbiologic studies that were done; results are presented as the percentage in each category of all cases in which an etiology was established.
RESULTS
remains the most common cause of CAP although declining in incidence; this decline has been greater in the US than elsewhere. is the second most common cause of CAP, followed by and Gram negative bacilli. The incidence of all bacteria as causes of CAP has declined because, with routine use of PCR for viruses, the denominator, cases with an established etiology, has increased. Viruses were reported on average in about 10% of cases, but recent PCR-based studies identified a respiratory virus in about 30% of cases of CAP, with substantial rates of viral/bacterial coinfection.
CONCLUSION
The results of this study justify current guidelines for initial empiric treatment of CAP. With pneumococcus and continuing to predominate, efforts at antibiotic stewardship might be enhanced by greater attention to the routine use of sputum Gram stain and culture. Because viral/bacterial coinfection is relatively common, the identification of a virus by PCR does not, by itself, allow for discontinuation of the antibiotic therapy.
PubMed: 33024653
DOI: 10.1186/s41479-020-00074-3 -
Journal of Clinical Epidemiology Jan 2021To investigate if Cochrane reviews that assess screening interventions address their major harms.
OBJECTIVE
To investigate if Cochrane reviews that assess screening interventions address their major harms.
STUDY DESIGN AND SETTING
A systematic search for Cochrane reviews that assess screening interventions was performed. Two authors independently screened abstracts, assessed full-texts, and extracted data from included reviews. For each review, two authors judged whether each predefined harm was relevant. When the harm was judged as of questionable relevance, the review was excluded from the denominator in our calculations.
RESULTS
Forty-seven reviews were included. Overdiagnosis was addressed in 6 of 39 (15%), overtreatment in 7 of 43 (16%), and psychosocial consequences in 30 of 47 (64%) of reviews where this was judged relevant. When data on harms were included, they were generally not treated with the same methodological rigor as the benefits, with no assessment of the risk of bias or certainty of the evidence. About half of the Abstracts, Plain Language Summaries, and Summary of Findings tables did not include any harms.
CONCLUSION
The underreporting of harms of screening in Cochrane reviews likely reflects primary research and is problematic. We call for broad collaboration to develop reporting guidelines and core outcome sets for studies of screening interventions.
Topics: Bias; Humans; Mass Screening; Medical Overuse; Psychology; Research Report; Risk Assessment
PubMed: 33010402
DOI: 10.1016/j.jclinepi.2020.09.030 -
BMC Medicine Aug 2020An effective vaccine against Bordetella pertussis was introduced into the Expanded Programme on Immunisation (EPI) by WHO in 1974, leading to a substantial global... (Meta-Analysis)
Meta-Analysis
The burden of laboratory-confirmed pertussis in low- and middle-income countries since the inception of the Expanded Programme on Immunisation (EPI) in 1974: a systematic review and meta-analysis.
BACKGROUND
An effective vaccine against Bordetella pertussis was introduced into the Expanded Programme on Immunisation (EPI) by WHO in 1974, leading to a substantial global reduction in pertussis morbidity and mortality. In low- and middle-income countries (LMICs), however, the epidemiology of pertussis remains largely unknown. This impacts negatively on pertussis control strategies in these countries. This study aimed to systematically and comprehensively review published literature on the burden of laboratory-confirmed pertussis in LMICs over the 45 years of EPI.
METHODS
Electronic databases were searched for relevant literature (1974 to December 2018) using common and MeSH terms for pertussis. Studies using PCR, culture or paired serology to confirm Bordetella pertussis and parapertussis in symptomatic individuals were included if they had clearly defined numerators and denominators to determine prevalence and mortality rates.
RESULTS
Eighty-two studies (49,167 participants) made the inclusion criteria. All six WHO regions were represented with most of the studies published after 2010 and involving mainly upper middle-income countries (n = 63; 77%). PCR was the main diagnostic test after the year 2000. The overall median point prevalence of PCR-confirmed Bordetella pertussis was 11% (interquartile range (IQR), 5-27%), while culture-confirmed was 3% (IQR 1-9%) and paired serology a median of 17% (IQR 3-23%) over the period. On average, culture underestimated prevalence by 85% (RR = 0.15, 95% CI, 0.10-0.22) compared to PCR in the same studies. Risk of pertussis increased with HIV exposure [RR, 1.4 (95% CI, 1.0-2.0)] and infection [RR, 2.4 (95% CI, 1.1-5.1)]. HIV infection and exposure were also related to higher pertussis incidences, higher rates of hospitalisation and pertussis-related deaths. Pertussis mortality and case fatality rates were 0.8% (95% CI, 0.4-1.4%) and 6.5% (95% CI, 4.0-9.5%), respectively. Most deaths occurred in infants less than 6 months of age.
CONCLUSIONS
Despite the widespread use of pertussis vaccines, the prevalence of pertussis remains high in LMIC over the last three decades. There is a need to increase access to PCR-based diagnostic confirmation in order to improve surveillance. Disease control measures in LMICs must take into account the persistent significant infant mortality and increased disease burden associated with HIV infection and exposure.
Topics: Bordetella pertussis; Developing Countries; Female; History, 20th Century; Humans; Immunization Programs; Male; Whooping Cough
PubMed: 32854714
DOI: 10.1186/s12916-020-01699-3 -
Bulletin of the World Health... Aug 2020To calculate prevalence estimates and evaluate the quality of studies reporting lacking histidine-rich proteins 2 and 3, to inform an international response plan.
OBJECTIVE
To calculate prevalence estimates and evaluate the quality of studies reporting lacking histidine-rich proteins 2 and 3, to inform an international response plan.
METHODS
We searched five online databases, without language restriction, for articles reporting original data on -infected patients with deletions of the and/or genes (). We calculated prevalence estimates of deletions and mapped the data by country. The denominator was all -positive samples testing positive by microscopy and confirmed positive by species-specific polymerase chain reaction testing (PCR). If microscopy was not performed, we used the number of samples based on a different diagnostic method or PCR alone. We scored studies for risk of bias and the quality of laboratory methods using a standardized scoring system.
FINDINGS
A total of 38 articles reporting 55 studies from 32 countries and one territory worldwide were included in the review. We found considerable heterogeneity in the populations studied, methods used and estimated prevalence of parasites with deletions. The derived prevalence of deletions ranged from 0% to 100%, including focal areas in South America and Africa. Only three studies (5%) fulfilled all seven criteria for study quality.
CONCLUSION
The lack of representative surveys or consistency in study design impairs evaluations of the risk of false-negative results in malaria diagnosis due to deletions. Accurate mapping and strengthened monitoring of the prevalence of deletions is needed, along with harmonized methods that facilitate comparisons across studies.
Topics: Antigens, Protozoan; Humans; Malaria, Falciparum; Plasmodium falciparum; Polymerase Chain Reaction; Prevalence; Proteins; Protozoan Proteins
PubMed: 32773901
DOI: 10.2471/BLT.20.250621 -
Clinical Genitourinary Cancer Oct 2020We performed a systematic review and meta-analysis on the response rates of patients with treatment-refractory urothelial carcinoma treated with programmed cell death 1... (Meta-Analysis)
Meta-Analysis Review
We performed a systematic review and meta-analysis on the response rates of patients with treatment-refractory urothelial carcinoma treated with programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors. We reviewed the literature for prospective studies evaluating PD-1/PD-L1 inhibitors in refractory urothelial carcinoma patients, which formed the basis for US Food and Drug Administration approval of 5 different antagonistic antibodies targeting PD-1 or PD-L1 (atezolizumab, durvalumab, avelumab, nivolumab, and pembrolizumab). We considered studies examining PD-1/PD-L1-treated patients, which we identified using the following key terms in the Pubmed, Scopus, Web of Science, ClinicalTrial.gov, and Cochrane Library databases. Eligible studies had ≥ 20 patients each and reported response rates, duration of response, and overall survival (OS). We performed fixed and random-effects meta-analyses to model the point estimates for objective response rate and complete response. The median progression-free survival (PFS) and OS for studies reporting these statistics were evaluated. We found 10 eligible studies that met our inclusion criteria, providing extractable numerators and denominators for response rates, PFS, and OS for 1934 patients with metastatic urothelial carcinoma. The objective response rate was 18% (95% confidence interval, 15-22) for second-line or later therapies. The random-effects estimate for complete response was 4% (95% confidence interval, 3-5), including all disease locations and all PD-1 and PD-L1 inhibitors. Median OS and PFS were < 13 months and 3 months, respectively, across all studies, irrespective of PD-L1 expression. We found that the estimated response rates of agents included in this meta-analysis seem to be more favorable than other salvage therapies.
Topics: B7-H1 Antigen; Carcinoma, Transitional Cell; Humans; Immune Checkpoint Inhibitors; Neoplasm Recurrence, Local; Programmed Cell Death 1 Receptor; Prospective Studies; Urinary Bladder Neoplasms
PubMed: 32146152
DOI: 10.1016/j.clgc.2020.01.004