Retracted publications in pharmacy systematic reviews.

OBJECTIVE: Systematic reviews and other evidence syntheses, the pinnacle of the evidence pyramid, embody comprehensiveness and rigor; however, retracted data are being incorporated into these publications. This study examines the use of retracted publications in the field of pharmacy, describes characteristics of retracted publications cited by systematic reviews, and discusses factors associated with citation likelihood. METHODS: Using data from Retraction Watch, we identified retracted publications in the pharmacy field. We identified all articles citing these retracted publications in Web of Science and Scopus and limited results to systematic reviews. We classified the retraction reason, determined whether the citation occurred before or after retraction, and analyzed factors associated with the likelihood of systematic reviews citing a retracted publication. RESULTS: Of 1,396 retracted publications, 283 were cited 1,096 times in systematic reviews. Most (65.0%) (712/1096) citations occurred before retraction. Citations were most often to items retracted due to data falsification or manipulation (39.2%), followed by items retracted due to ethical misconduct including plagiarism (30.4%), or concerns about or errors in data or methods (26.2%). Compared to those not cited in systematic reviews, cited items were significantly more likely to be retracted due to data falsification and manipulation, were published in high impact factor journals, and had longer delays between publication and retraction. CONCLUSIONS: Further analysis of systematic reviews citing retracted publications is needed to determine the impact of flawed data. Librarians understand the nuances involved and can advocate for greater transparency around the retraction process and increase awareness of challenges posed by retractions.

Incidence, risk factors, treatment, and consequences of antibody-mediated kidney transplant rejection: A systematic review.

BACKGROUND: Antibody-mediated rejection (AMR) is a leading cause of kidney allograft failure, but its incidence, risk factors, and outcomes are not well understood. METHODS: We searched Ovid MEDLINE, Cochrane, EMBASE, and Scopus from January 2000 to January 2020 to identify published cohorts of ≥500 incident adult or 75 pediatric kidney transplant recipients followed for ≥1 year post-transplant. RESULTS: At least two reviewers screened 5061 articles and abstracts; 28 met inclusion criteria. Incidence of acute AMR was 1.1%-21.5%; most studies reported 3%-12% incidence, usually within the first year post-transplant. Few studies reported chronic AMR incidence, from 7.5%-20.1% up to 10 years. Almost all patients with acute or chronic AMR received corticosteroids and intravenous immunoglobulin; most received plasmapheresis, and approximately half with rituximab. Most studies examining death-censored graft failure identified AMR as an independent risk factor. Few reported refractory AMR rates or outcomes, and none examined costs. Most studies were single-center and varied greatly in design. CONCLUSIONS: Cohort studies of kidney transplant recipients demonstrate that AMR is common and associated with increased risk of death-censored graft failure, but studies vary widely regarding populations, definitions, and reported incidence. Gaps remain in our understanding of refractory AMR, its costs, and resulting quality of life.

Health system interventions for adults with type 2 diabetes in low- and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: Effective health system interventions may help address the disproportionate burden of diabetes in low- and middle-income countries (LMICs). We assessed the impact of health system interventions to improve outcomes for adults with type 2 diabetes in LMICs. METHODS AND FINDINGS: We searched Ovid MEDLINE, Cochrane Library, EMBASE, African Index Medicus, LILACS, and Global Index Medicus from inception of each database through February 24, 2020. We included randomized controlled trials (RCTs) of health system interventions targeting adults with type 2 diabetes in LMICs. Eligible studies reported at least 1 of the following outcomes: glycemic change, mortality, quality of life, or cost-effectiveness. We conducted a meta-analysis for the glycemic outcome of hemoglobin A1c (HbA1c). GRADE and Cochrane Effective Practice and Organisation of Care methods were used to assess risk of bias for the glycemic outcome and to prepare a summary of findings table. Of the 12,921 references identified in searches, we included 39 studies in the narrative review of which 19 were cluster RCTs and 20 were individual RCTs. The greatest number of studies were conducted in the East Asia and Pacific region (n = 20) followed by South Asia (n = 7). There were 21,080 total participants enrolled across included studies and 10,060 total participants in the meta-analysis of HbA1c when accounting for the design effect of cluster RCTs. Non-glycemic outcomes of mortality, health-related quality of life, and cost-effectiveness had sparse data availability that precluded quantitative pooling. In the meta-analysis of HbA1c from 35 of the included studies, the mean difference was -0.46% (95% CI -0.60% to -0.31%, I2 87.8%, p < 0.001) overall, -0.37% (95% CI -0.64% to -0.10%, I2 60.0%, n = 7, p = 0.020) in multicomponent clinic-based interventions, -0.87% (-1.20% to -0.53%, I2 91.0%, n = 13, p < 0.001) in pharmacist task-sharing studies, and -0.27% (-0.50% to -0.04%, I2 64.1%, n = 7, p = 0.010) in trials of diabetes education or support alone. Other types of interventions had few included studies. Eight studies were at low risk of bias for the summary assessment of glycemic control, 15 studies were at unclear risk, and 16 studies were at high risk. The certainty of evidence for glycemic control by subgroup was moderate for multicomponent clinic-based interventions but was low or very low for other intervention types. Limitations include the lack of consensus definitions for health system interventions, differences in the quality of underlying studies, and sparse data availability for non-glycemic outcomes. CONCLUSIONS: In this meta-analysis, we found that health system interventions for type 2 diabetes may be effective in improving glycemic control in LMICs, but few studies are available from rural areas or low- or lower-middle-income countries. Multicomponent clinic-based interventions had the strongest evidence for glycemic benefit among intervention types. Further research is needed to assess non-glycemic outcomes and to study implementation in rural and low-income settings.

Abiraterone acetate in combination with androgen deprivation therapy compared to androgen deprivation therapy only for metastatic hormone-sensitive prostate cancer.

BACKGROUND: Systemic androgen deprivation therapy (ADT), also referred to as hormone therapy,àhas long been the primary treatment for metastatic prostate cancer. Additional agents have been reserved for the castrate-resistant disease stage when ADT start becoming less effective. Abiraterone is an agent with an established role in that disease stage, which has only recently been evaluated in the hormone-sensitive setting. OBJECTIVES: To assess the effects of early abiraterone acetate, in combination with systemic ADT, for newly diagnosed metastatic hormone-sensitive prostate cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, six other databases, two trials registries, grey literature, and conference proceedings, up to 15 May 2020. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included randomized trials, in which men diagnosed with hormone-sensitive prostate cancer were administered abiraterone acetate and prednisolone with ADT or ADTàalone. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data from the included studies. We performed statistical analyses using a random-effects model. We rated the quality of evidence according to the GRADE approach. MAIN RESULTS: The search identified two randomized controlled trials (RCT), with 2201 men, who were assigned to receive either abiraterone acetate 1000 mg once daily and low dose prednisone (5mg) in addition to ADT, or ADT alone. In the LATITUDE trial, the median age and range of men in the intervention group was 68 (38 to 89) years, and 67 (33 to 92) years in the control group. Nearly all of the men in thisàstudy (97.6%) had prostate cancer with a Gleason score of at least 8 (ISUP grade group 4). Primary outcomes The addition of abiraterone acetate to ADT reduces the probability of death from any cause compared to ADT alone (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.56 to 0.73; 2 RCTs, 2201 men; high certainty of evidence); this corresponds to 163 fewer deaths per 1000 men with hormone-sensitive metastaticàprostate cancerà(210 fewer to 115 fewer) at five years. Abiraterone acetate in addition to ADT probably results in little to no differenceàin quality of life compared to ADT alone, measured with the Functional Assessment of Cancer Therapy-prostate total score (FACT-P; range 0 to 156; higher values indicates better quality of life),àat 12 months (mean difference [MD] 2.90 points, 95% CI 0.11 to 5.60; 1 RCT, 838 men; moderate certainty of evidence). Secondary outcomes Abiraterone plus ADT increases the risk of grades III to V adverse events compared to ADT alone (risk ratio [RR] 1.34, 95% CI 1.22 to 1.47; 1 RCT, 1199 men; high certainty of evidence); this corresponds to 162 more grade III to Vàevents per 1000 men with hormone-sensitive metastaticàprostate cancerà(105 more to 224 more) at a median follow-up of 30àmonths. Abiraterone acetate in addition to ADT probably reduces the probability of death due to prostate cancer compared to ADT alone (HR 0.58, 95% CI 0.50 to 0.68; 2 RCTs, 2201 men; moderate certainty of evidence). This corresponds to 120 fewer death from prostate cancer per 1000 men with hormone-sensitive metastaticàprostate cancerà(95% CI 145 fewer to 90 fewer) afteràa median follow-up of 30 months. The addition of abiraterone acetate to ADT probably decreases the probability of disease progression compared to ADT alone (HR 0.35, 95%CI 0.26 to 0.49; 2 RCTs, 2097 men; moderate certainty of evidence). This corresponds to 369 fewer incidences of disease progression per 1000 men with hormone-sensitive metastaticàprostate cancerà(456 fewer to 256 fewer)àafter a median follow-up of 30 months. The addition of abiraterone acetate to ADT probably increases the risk of discontinuing treatment due to adverse events compared to ADT alone (RR 1.50, 95% CI 1.17 to 1.92; 1 RCT, 1199 men; moderate certainty of evidence). This corresponds to 51 more men (95% CI 17 more to 93 more) discontinuing treatment because of adverse events per 1000 men treated with abiraterone acetate and ADT compared to ADT alone afteràa median follow-up of 30 months. AUTHORS' CONCLUSIONS: The addition of abiraterone acetate to androgen deprivation therapy improves overall survival but probably not quality of life. Itàprobably also extends disease-specific survival, and delays disease progression compared to androgen deprivation therapy alone. However, the risk of grades III to V adverse events is increased, and probably, so is the risk of discontinuing treatment due to adverse events.

Identification of retracted publications and completeness of retraction notices in public health.

OBJECTIVES: Retraction is intended to be a mechanism to correct the published body of knowledge when necessary due to fraudulent, fatally flawed, or ethically unacceptable publications. However, the success of this mechanism requires that retracted publications be consistently identified as such and that retraction notices contain sufficient information to understand what is being retracted and why. Our study investigated how clearly and consistently retracted publications in public health are being presented to researchers. STUDY DESIGN AND SETTING: This is a cross-sectional study, using 441 retracted research publications in the field of public health. Records were retrieved for each of these publications from 11 resources, while retraction notices were retrieved from publisher websites and full-text aggregators. The identification of the retracted status of the publication was assessed using criteria from the Committee on Publication Ethics and the National Library of Medicine. The completeness of the associated retraction notices was assessed using criteria from Committee on Publication Ethics and Retraction Watch. RESULTS: Two thousand eight hundred forty-one records for retracted publications were retrieved, of which less than half indicated that the article had been retracted. Less than 5% of publications were identified as retracted through all resources through which they were available. Within single resources, if and how retracted publications were identified varied. Retraction notices were frequently incomplete, with no notices meeting all the criteria. CONCLUSIONS: The observed inconsistencies and incomplete notices pose a threat to the integrity of scientific publishing and highlight the need to better align with existing best practices to ensure more effective and transparent dissemination of information on retractions.

The relationship between methodological quality and the use of retracted publications in evidence syntheses.

BACKGROUND: Evidence syntheses cite retracted publications. However, citation is not necessarily endorsement, as authors may be criticizing or refuting its findings. We investigated the sentiment of these citations-whether they were critical or supportive-and associations with the methodological quality of the evidence synthesis, reason for the retraction, and time between publication and retraction. METHODS: Using a sample of 286 evidence syntheses containing 324 citations to retracted publications in the field of pharmacy, we used AMSTAR-2 to assess methodological quality. We used scite.ai and a human screener to determine citation sentiment. We conducted a Pearson's chi-square test to assess associations between citation sentiment, methodological quality, and reason for retraction, and one-way ANOVAs to investigate association between time, methodological quality, and citation sentiment. RESULTS: Almost 70% of the evidence syntheses in our sample were of critically low quality. We found that these critically low-quality evidence syntheses were more associated with positive statements while high-quality evidence syntheses were more associated with negative citation of retracted publications. In our sample of 324 citations, 20.4% of citations to retracted publications noted that the publication had been retracted. CONCLUSION: The association between high-quality evidence syntheses and recognition of a publication's retracted status may indicate that best practices are sufficient. However, the volume of critically low-quality evidence syntheses ultimately perpetuates the citation of retracted publications with no indication of their retracted status. Strengthening journal requirements around the quality of evidence syntheses may lessen the inappropriate citation of retracted publications.

Caregiver-Implemented Communication Interventions for Children Identified as Having Language Impairment 0 Through 48 Months of Age: A Scoping Review.

PURPOSE: Caregiver-implemented interventions are frequently used to support the early communication of young children with language impairment. Although there are numerous studies and meta-analyses supporting their use, there is a need to better understand the intervention approaches and identify potential gaps in the research base. With that premise, we conducted a scoping review to synthesize existing data with an end goal of informing future research directions. METHOD: We identified relevant studies by comprehensively searching four databases. After deduplication, we screened 5,703 studies. We required included studies (N = 59) to evaluate caregiver-implemented communication interventions and include at least one caregiver communication outcome measure. We extracted information related to the (a) study, child, and caregiver characteristics; (b) intervention components (e.g., strategies taught, delivery method and format, and dosage); and (c) caregiver and child outcome measures (e.g., type, quality, and level of evidence). RESULTS: We synthesized results by age group of the child participants. There were no studies with children in the prenatal through 11-month-old age range identified in our review that yielded a caregiver language outcome measure with promising or compelling evidence. For the 12- through 23-month group, there were seven studies, which included eight communication intervention groups; for the 24- through 35-month group, there were 21 studies, which included 26 intervention groups; and for the 36- through 48-month group, there were 21 studies, which included 23 intervention groups. Across studies and age groups, there was considerable variability in the reporting of study characteristics, intervention approaches, and outcome measures. CONCLUSION: Our scoping review highlights important research gaps and inconsistencies in study reporting that should be addressed in future investigations. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.20289195.

Strategies and settings of clinical pharmacogenetic implementation: a scoping review of pharmacogenetics programs.

Pharmacogenetic (PGx) literature has shown beneficial outcomes in safety, efficacy and cost when evidence-based gene-drug decision making is incorporated into clinical practice. PGx programs with successfully implemented clinical services have been published in a variety of settings including academic health centers and community practice. The primary objective was to systematically scope the literature to characterize the current trends, extent, range and nature of clinical PGx programs. Forty articles representing 19 clinical PGx programs were included in analysis. Most programs are in urban, academic institutions. Education, governance and workflow were commonly described while billing/reimbursement and consent were not. This review provides an overview of current PGx models that can be used as a reference for institutions beginning the implementation process.

Long-Term Outcomes after Early Neonatal Hyperglycemia in VLBW Infants: A Systematic Review.

INTRODUCTION: Long-term effects of early hyperglycemia in VLBW infants are poorly characterized. The objective of this study was to systematically review the effect of early hyperglycemia on growth, metabolic health, and neurodevelopment after neonatal intensive care unit discharge in VLBW infants. METHODS: The systematic review was conducted in accordance with the PRISMA guidelines. A study protocol was registered in PROSPERO (CRD42019123335). Data sources included Ovid MEDLINE, Embase, Cochrane Library, CINAHL, and Scopus. Selected studies included infants with a blood glucose concentration >150 mg/dL (8.3 mmol/L) during the first 28 days of life, a gestational age (GA) <32 weeks, and/or a birth weight <1,500 g and longitudinal data on growth, metabolic health, or neurodevelopment outcomes. The GRADE system was used to assess quality of evidence. RESULTS: Eight studies (n = 987 infants) reported long-term outcomes from 4-month corrected GA to 7 years old. Most studies compared long-term outcomes of preterm infants with and without hyperglycemia. Two studies addressed outcomes related to interventions following early hyperglycemia. Some studies found differences in growth, metabolic health, and neurodevelopment outcomes between VLBW preterm infants with hyperglycemia and without hyperglycemia, while other studies found no differences between groups. The overall graded quality of evidence was low. CONCLUSIONS: Well-designed randomized controlled and prospective studies are necessary to determine the effect of early hyperglycemia and its treatment on later metabolic and neurodevelopmental outcomes in VLBW infants. Authors propose a potential study design for standardizing the assessment of long-term metabolic and neurodevelopmental outcomes following early hyperglycemia in preterm infants.

CYP2D6 Genetic Polymorphisms and Risperidone Pharmacokinetics: A Systematic Review and Meta-analysis.

BACKGROUND: Risperidone is a second-generation antipsychotic drug metabolized to an active metabolite, 9-hydroxyrisperidone, primarily by cytochrome P450 (CYP) 2D6 and to a lesser extent by CYP3A4. The extent to which drug metabolism genetics impacts risperidone and 9-hydroxyrisperidone exposure has not been clarified. OBJECTIVE: A systematic review and meta-analysis evaluated the impact of genetically defined CYP2D6 function on risperidone pharmacokinetics applying a standardized genotype-phenotype translation system. METHODS: A comprehensive electronic database search identified studies reporting relationships between genetically determined CYP2D6 metabolism and risperidone pharmacokinetic properties. The exposure of risperidone or active moiety (risperidone + 9-hydroxyrisperidone) was measured by dose-adjusted steady-state serum or plasma concentration or area under the concentration-time curve as primary outcomes. Subjects were assigned to CYP2D6 poor metabolizer, intermediate metabolizer, normal metabolizer, or ultrarapid metabolizer groups using a standardized genotype-phenotype translation method. Effect sizes between groups were pooled and stratified by single or multiple dosing regimens. RESULTS: A total of 15 studies involving 2125 adult subjects were included in the meta-analysis. Following multiple-dose oral administration, compared with CYP2D6 normal metabolizers, the risperidone dose-adjusted steady-state serum/plasma concentration was 2.35-fold higher in intermediate metabolizers (95% confidence interval [CI] 1.77-3.13, p<0.0001) and 6.20-fold higher in poor metabolizers (95% CI 5.05-7.62, p<0.0001); the active moiety dose-adjusted steady-state concentration was 1.18-fold higher in intermediate metabolizers (95% CI 1.11-1.25, p<0.0001) and 1.44-fold higher in poor metabolizers (95% CI 1.23-1.69, p<0.0001). Higher area under the concentration-time curve of risperidone and active moiety was also found in single-dose studies. CONCLUSION: Genetically defined impaired CYP2D6 activity is associated with increased exposure of both risperidone and risperidone + 9-hydroxyrisperidone in adults receiving oral formulations. Additional studies are needed to quantify the clinical impact of these relationships.

Educational Curricula and Programs in Adolescent Medicine for Health Workers in Low- and Middle-Income Countries: A Scoping Review.

BACKGROUND: Adolescent medicine (AM) has been increasingly recognized as critically important to the health of individuals during their transition to adulthood. On a global scale, AM is often underprioritized and underfunded. In low- and middle-income countries (LMICs), education and AM training is developing, and AM physicians often are from general medicine backgrounds. OBJECTIVE: The objective of our scoping review was to identify existing training curricula and educational tools designed to teach AM skills to health care workers in LMICs. METHODS: We followed PRISMA guidelines for scoping reviews for article identification and inclusion. Online databases, including MEDLINE, Embase, CINAHL, and Scopus, were used to identify papers. We included studies that took place in a LMIC, were available in English, and described any of the following: published educational curricula in AM, education-based intervention for HCWs that focused on AM, or a training opportunity in AM located in a LMIC. RESULTS: Our review includes 14 publications: 5 published curricula and 9 articles describing educational interventions or training opportunities in AM in LMICs. Curricula were relatively consistent in the topics included, although they varied in implementation and teaching strategies. The scholarly articles described educational materials and identified a number of innovative strategies for training programs. CONCLUSIONS: Our review found existing high-quality AM curricula designed for LMICs. However, there is limited published data on their implementation and utilization. There is a continued need for funding and implementation of education in AM in resource-constrained settings.