Paul A. Bain

Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies

BACKGROUND Concerns have been raised about the risk of fractures with acid-suppressive medications, such as proton pump inhibitors and histamine(2)-receptor antagonists. METHODS This meta-analysis evaluated the association between proton pump inhibitor or histamine(2)-receptor antagonist use and fractures. We performed a systematic search of published literature (1970 to October 10, 2010) in MEDLINE, EMBASE, and other sources. Ten publications reporting 11 studies were considered eligible for analysis. RESULTS All studies were observational case-control or cohort studies and primarily evaluated older adults. The summary effect estimate for risk of hip fracture increased modestly among individuals taking proton pump inhibitors (relative risk [RR] 1.30, 95% confidence interval [CI], 1.19-1.43). There also was an increase in spine (RR 1.56, 95% CI, 1.31-1.85) and any-site fractures (RR 1.16, 95% CI, 1.04-1.30) among proton pump inhibitor users. These findings were similar in both men and women and after stratification by duration of use. In contrast, histamine(2)-receptor antagonist use was not significantly associated with increased risk of hip fracture (RR 1.12, 95% CI, 0.97-1.30). CONCLUSION In this meta-analysis of observational studies, proton pump inhibitors modestly increased the risk of hip, spine, and any-site fractures, whereas histamine(2)-receptor antagonists were not associated with fracture risk. The possibility of residual confounding cannot be excluded. Further skeletal evaluation should be considered for patients who are taking proton pump inhibitors and also at risk for osteoporotic fracture.

Knowledge and Awareness of HPV Vaccine and Acceptability to Vaccinate in Sub-Saharan Africa: A Systematic Review

Objectives We assessed the knowledge and awareness of cervical cancer, HPV and HPV vaccine, and willingness and acceptability to vaccinate in sub-Saharan African (SSA) countries. We further identified countries that fulfill the two GAVI Alliance eligibility criteria to support nationwide HPV vaccination. Methods We conducted a systematic review of peer-reviewed studies on the knowledge and awareness of cervical cancer, HPV and HPV vaccine, and willingness and acceptability to vaccinate. Trends in Diphtheria-tetanus-pertussis (DTP3) vaccine coverage in SSA countries from 1990–2011 were extracted from the World Health Organization database. Findings The review revealed high levels of willingness and acceptability of HPV vaccine but low levels of knowledge and awareness of cervical cancer, HPV or HPV vaccine. We identified only six countries to have met the two GAVI Alliance requirements for supporting introduction of HPV vaccine: 1) the ability to deliver multi-dose vaccines for no less than 50% of the target vaccination cohort in an average size district, and 2) achieving over 70% coverage of DTP3 vaccine nationally. From 2008 through 2011 all SSA countries, with the exception of Mauritania and Nigeria, have reached or maintained DTP3 coverage at 70% or above. Conclusion There is an urgent need for more education to inform the public about HPV, HPV vaccine, and cervical cancer, particularly to key demographics, (adolescents, parents and healthcare professionals), to leverage high levels of willingness and acceptability of HPV vaccine towards successful implementation of HPV vaccination programs. There is unpreparedness in most SSA countries to roll out national HPV vaccination as per the GAVI Alliance eligibility criteria for supporting introduction of the vaccine. In countries that have met 70% DTP3 coverage, pilot programs need to be rolled out to identify the best practice and strategies for delivering HPV vaccines to adolescents and also to qualify for GAVI Alliance support.

Perceptibility and acceptability thresholds for colour differences in dentistry

INTRODUCTION Data on acceptability (AT) and perceptibility thresholds (PT) for colour differences vary in dental literature. There is consensus that the determination of ΔE* is appropriate to define AT and PT, however there is no consensus regarding the values that should be used. The aim of this clinical review was to provide a systematic approach to the topic of colour science of high clinical relevance to dental research. MATERIALS AND METHODS MEDLINE/PubMed, WoS and EBSCO databases were searched up to January 7, 2013; the outcome was restricted to English, and to clinical studies were spectrophotometers were used for measurement. RESULTS Forty-eight studies were eligible and met the inclusion criteria. Of the 48 studies there appeared to be a trend in their source references: 44% referred to the same study for the PT (ΔE*=1); and 35% referred to the same article for the AT (ΔE*=3.7). CONCLUSIONS More than half the studies defined PT as ΔE*=1, and one third of the studies referred to ΔE*=3.7 as the threshold at which 50% of observers accepted the colour difference. Most clinical studies refer to the same few in vitro literature that have attempted to determine PT and AT from decades ago.

Sleep-Disordered Breathing and Gestational Diabetes Mellitus: A meta-analysis of 9,795 participants enrolled in epidemiological observational studies

OBJECTIVE Recently, sleep-disordered breathing (SDB) has been reported to be associated with the development of gestational diabetes mellitus (GDM). Accordingly, as this is emergent area of research that has significant clinical relevance, the objective of this meta-analysis is to examine the relationship between SDB with GDM. RESEARCH DESIGN AND METHODS We searched several electronic databases for all of the studies published before January 2013 and reviewed references of published articles. Meta-analytic procedures were used to estimate the unadjusted and BMI-adjusted odds ratios (ORs) using a random effects model. Significant values, weighted effect sizes, and 95% CIs were calculated, and tests of homogeneity of variance were performed. RESULTS Results from nine independent studies with a total of 9,795 pregnant women showed that SDB was significantly associated with an increased risk of GDM. Women with SDB had a more than threefold increased risk of GDM, with a pooled BMI-adjusted OR 3.06 (95% CI 1.89–4.96). CONCLUSIONS These findings demonstrate a significant association between SDB and GDM that is evident even after considered confounding by obesity. This meta-analysis indicates a need to evaluate the role of early recognition and treatment of SDB early during pregnancy.

Systematic review of short- (5-10 years) and long-term (10 years or more) survival and success of full-arch fixed dental hybrid prostheses and supporting implants.

OBJECTIVES The aim of this systematic review was to investigate the short-term (5-10 year mean follow-up) and long-term (10 year or more) survival and success of fixed full arch dental hybrid prosthesis and supporting dental implants. METHODS Studies reporting interventions with full-arch fixed dental hybrid prostheses were identified by searching PubMed/Medline (NCBI), Web of Science (Thomson Reuters), the Cochrane Register of Controlled Clinical Trials (EBSCO), and Dentistry and Oral Sciences Source (DOSS; EBSCO) from the earliest available dates through July 17, 2013. Through a series of review process by two examiners, potentially qualifying studies were identified and assessed with respect to the inclusion criteria. RESULTS A total of 18 studies were included for the quality assessment and the systematic review. Within the limitation of available studies, high short-term survival rates of full arch fixed dental hybrid prostheses (93.3-100%) and supporting implants (87.89-100%) were found. However, the availability of studies investigating long-term outcomes seemed scarce. Furthermore, the included studies were subjected to potential sources of bias (i.e. publication, reporting, attrition bias). CONCLUSIONS Despite seemingly high short-term survival, long-term survival of implant supported full arch fixed dental hybrid prosthesis could not be determined due to limited availability of true long-term studies. Although it may be a valuable option for a patient with a completely edentulous ridge(s), the strategic removal of teeth with satisfactory prognosis for the sake of delivering an implant supported full-arch dental hybrid prosthesis should be avoided.

Prevalence of human papillomavirus genotypes among African women with normal cervical cytology and neoplasia: a systematic review and meta-analysis.

Background Several meta-analyses confirmed the five most prevalent human papillomavirus (HPV) strains in women with and without cervical neoplastic diseases are HPV16, 18, 31, 52, and 58. HPV16/18 are the predominant oncogenic genotypes, causing approximately 70% of global cervical cancer cases. The vast majority of the women studied in previous analyses were from Europe, North America, Asia, and most recently Latin America and the Caribbean. Despite the high burden of cervical cancer morbidity and mortality in Africa, a robust meta-analysis of HPV genotype prevalence and distribution in African women is lacking. Methods and Findings We systematically searched 14 major databases from inception to August 2013 without language restriction, following the Meta-Analysis of Observational Studies in Epidemiology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Seventy-one studies from 23 African countries were identified after screening 1162 citations and data abstracted and study quality appraised from 195 articles. HPV type-specific prevalence and distribution was estimated from 17,273 cases of women with normal cervical cytology; 1019 women with atypical squamous cells of undetermined significance (ASCUS); 1444 women with low-grade squamous intraepithelial lesion (LSIL); 1571 women with high-grade squamous intraepithelial lesion (HSIL); and 4,067 cases of invasive cervical carcinoma (ICC). Overall prevalence of HPV16/18 were 4.4% and 2.8% of women with normal cytology, 12.0% and 4.4% with ASCUS, 14.5% and 10.0% with LSIL, 31.2% and 13.9% with HSIL, and 49.7% and 18.0% with ICC, respectively. Study limitations include the lack of adequate data from Middle and Northern African regions, and variations in the HPV type-specific sensitivity of different genotyping protocols. Conclusions To our knowledge, this study is the most comprehensive assessment of the overall prevalence and distribution of HPV genotypes in African women with and without different cervical neoplasias. We have established that HPV16/18 account for 67.7% of ICC cases among African women. Based on our findings, we highly recommend the administration of existing prophylactic vaccines to younger women not infected with HPV16/18 and an increase in HPV screening efforts for high-risk genotypes to prevent cervical cancer. Review registration: International Prospective Register of Systematic Reviews CRD42013006558.

A systematic review of randomized controlled trials of interventions designed to decrease child abuse in high-risk families.

Child abuse is a global problem, and parents with histories of childhood abuse are at increased risk of abusing their offspring. The objective of this systematic review is to provide a clear overview of the existing literature of randomized controlled trials evaluating the effectiveness of interventions to prevent child abuse. PubMed, PsychINFO, Web of Science, Sociological Abstracts, and CINAHL were systematically searched and expanded by hand search. This review includes all randomized controlled trials (RCTs) of interventions designed to prevent abuse among mothers identified as high-risk. Of the eight studies identified, only three found statistically significant reductions in abuse by any measure, and only two found reductions in incidents reported to child protective services. While much has been written about child abuse in high-risk families, few RCTs have been performed. Only home visitation has a significant evidence base for reducing child abuse, and the findings vary considerably. Also, data from low- and middle-income countries are limited.

Moderation of antidepressant and placebo outcomes by baseline severity in late-life depression: A systematic review and meta-analysis.

BACKGROUND Baseline severity is a crucial moderator of trial outcomes in adult depression, with the advantage of antidepressants over placebo increasing as severity increases. However, this relationship has not been examined in late-life depression. METHODS PubMed, Embase, Web of Science, PsycINFO, and Cochrane were searched for studies published through September 2014. Randomized, acute phase, and double-blind studies comparing an antidepressant group with a placebo group in depressed elderly patients were included. RESULTS Nineteen studies met all inclusion criteria. Within-group effect sizes revealed significant improvement in antidepressant groups (g=1.35, p<.000), as well as in placebo groups (g=.96, p<.000). Change in depressive symptoms assessed by Hamilton Depression Rating Scale (HDRS) was moderated by baseline severity in antidepressant groups (Z=2.67, p=.008) and placebo groups (Z=4.46, p<.000). However, this would be expected as a result of regression toward the mean, and mean differences between groups did not increase (r=.19, p=.469) as a function of baseline severity. LIMITATIONS Limited to published data and information was only analyzed at the level of treatment groups. CONCLUSION Baseline severity was not associated with an antidepressant-placebo difference and placebo responses are large in the treatment of depressed elderly people. We propose a stepwise approach, i.e., to initially offer elderly depressed patients psychosocial interventions and only consider antidepressants if patients do not respond.

A Systematic Review and Meta-analysis of Migraine and Suicidal Ideation

Background: Previous studies have demonstrated an association between migraine and major depressive disorder. However, relatively little is known about the relationship between suicidal ideation, with or without concurrent depression, and migraine. Objective: We conducted a systematic literature review to synthesize the available research focused on investigating the association of migraine with suicidal ideation. Methods: Relevant research papers were identified through searches of major electronic databases including PubMed, Embase (Elsevier), Web of Science (Thomson Reuters), PsycINFO (EBSCO), and Google Scholar. We performed a meta-analysis to estimate the pooled unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between migraine and suicidal ideation extracted from each study. Results: A total of 148,977 participants in 6 studies were included in this analysis. Overall, findings from available studies documented elevated odds of suicidal ideation among individuals with migraines. In unadjusted models, the odds of suicidal ideation was 2.49-fold higher among individuals with migraine (OR, 2.49; 95% CI, 2.34-2.65) compared with those without migraine. In multivariate-adjusted models, the pooled adjusted OR of suicidal ideation was 1.31 (OR, 1.31; 95% CI, 1.10-1.55). Conclusions: A meta-analysis of available studies suggests a modest positive association between migraine and suicidal ideation. Further studies allowing for a more comprehensive investigation of the association between migraine and the full range of suicidal behaviors are warranted. A larger and more robust evidence-base may be useful to inform the clinical screening and diagnoses of comorbid conditions in migraineurs.

Assessing Strength of Evidence of Appropriate Use Criteria for Diagnostic Imaging Examinations

OBJECTIVE For health information technology tools to fully inform evidence-based decisions, recommendations must be reliably assessed for quality and strength of evidence. We aimed to create an annotation framework for grading recommendations regarding appropriate use of diagnostic imaging examinations. METHODS The annotation framework was created by an expert panel (clinicians in three medical specialties, medical librarians, and biomedical scientists) who developed a process for achieving consensus in assessing recommendations, and evaluated by measuring agreement in grading the strength of evidence for 120 empirically selected recommendations using the Oxford Levels of Evidence. RESULTS Eighty-two percent of recommendations were assigned to Level 5 (expert opinion). Inter-annotator agreement was 0.70 on initial grading (κ = 0.35, 95% CI, 0.23-0.48). After systematic discussion utilizing the annotation framework, agreement increased significantly to 0.97 (κ = 0.88, 95% CI, 0.77-0.99). CONCLUSIONS A novel annotation framework was effective for grading the strength of evidence supporting appropriate use criteria for diagnostic imaging exams.