Relative Odds Ratio Research Articles

Sex differences in reporting of statin-associated diabetes mellitus to the US Food and Drug Administration

Abstract Background Statins have been reported to precipitate diabetes mellitus (DM) in some patients. Limited evidence suggests that this occurs in women more frequently than men, but direct comparisons of rates of reporting of statin-associated DM between men and women are lacking. Purpose To determine whether there are sex-specific differences in post-marketing reporting of statin-associated DM. Methods We conducted a retrospective pharmacovigilance analysis of spontaneously reported adverse drug events (ADEs) submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System between January 1997 and September 2023. A Proportional Reporting Ratio (PRR) was used to identify the rate of reported statin-associated DM ADEs relative to the rate of DM ADEs reported with all other medications. We compared signals of disproportionate reporting (SDRs) between men and women using a modified relative odds ratio (ROR). Results During the study period, there were two-fold as many reports of statin-associated DM in women than in men (14,793 versus 7,307, respectively), despite the fact there were only 7% more non-DM statin ADEs reported in women compared to men (512,134 versus 480,849, respectively). Compared to the background rate of reporting for all ADEs (0.6%), statin-induced DM was disproportionally reported for all subjects in aggregate (2.1%, PRR=3.7) as well as for men only (1.5%, PRR=2.4) and for women only (2.9%, PRR=5.3). Significant PRRs for DM were observed with each statin and for all statins collectively (Figure 1). Statins were reported as the primary- or secondary-suspected cause of DM in women with considerably greater frequency than in men (58% versus 29%, respectively). Rates of reporting of statin-associated DM were higher in women than in men for all statins, with the greatest difference being observed with atorvastatin (ROR 3.0), and the lowest difference being observed with rosuvastatin (ROR 1.2) (Figure 1). Conclusions Post-marketing ADE surveillance data suggest a markedly higher rate of incident DM associated with statins than with other medications and a higher rate of reporting of statin-associated DM in women than in men. Future studies should consider sex-moderated mechanisms of statin-associated DM.Figure 1

Filovirus outbreak responses and occupational health effects of chlorine spraying in healthcare workers: a systematic review and meta-analysis of alternative disinfectants and application methods.

In the context of filovirus outbreaks, chlorine spraying has been the standard for infection prevention and control. Due to potential occupational health risks, public health institutions now recommend wiping, which is labor-intensive and may increase the risk of heat stress for healthcare workers wearing personal protective equipment. This systematic review and meta-analysis quantified the health effects of occupational exposure to chlorine-based products compared to other disinfectants, and the effects of spraying compared to general disinfection tasks (GDTs) like wiping and mopping, in healthcare settings. MEDLINE, Scopus, and ScienceDirect were searched for studies addressing the association between exposure to disinfectants applied by different application methods and occupational diseases in healthcare settings. Risk of bias was assessed by two independent reviewers using a validated tool. Two reviewers independently screened and performed data extraction and synthesis. A third reviewer resolved disagreements. Meta-analyses were conducted using fixed- and random-effects models based on the Higgins I2 statistic. 30 studies investigating chlorine-based products (7,123 participants), glutaraldehyde (6,256 participants), peracetic acid, acetic acid and hydrogen peroxide (4,728 participants), quaternary ammonium compounds (QACs) (9,270 participants), use of spray (4,568 participants) and GDTs (3,480 participants) were included. Most had a cross-sectional design and high risk of bias. Meta-analysis indicates a significant association between respiratory conditions and exposure to chlorine-based products (OR 1.71, 95%CI 1.41-2.08), glutaraldehyde (OR 1.44, 95%CI 1.14-1.81), QACs (OR 1.30, 95%CI 1.06-1.60), use of spray (OR 2.25, 95%CI 1.61-3.14) and GDTs (OR 2.20, 95%CI 1.66-2.90). The relative odds ratio (ROR) of respiratory conditions for chlorine-based products compared to QACs was 0.76 (95%CI 0.62-0.94). The ROR for the use of spray compared to GDTs was 0.98 (95%CI 0.74-1.29). Strengths include evaluating respiratory health risks of disinfectants, applying a validated tool, using both fixed- and random-effects models, and comparing pooled effect sizes. Limitations include high risk of bias for the majority of included articles, varying confounder adjustments, underreported non-respiratory outcomes, and unspecified disinfectants and PPE use for spray and GDTs articles. Chlorine-based disinfectants significantly increase respiratory risk compared to QACs. Sprays and general disinfection tasks present similar risks. Our findings advocate for using less hazardous products like QACs, rather than banning sprays in filovirus outbreak responses to enhance disinfection safety. CRD42023479363.

The association between mammographic density and breast cancer risk in Chinese women: a systematic review and meta-analysis

PurposeBreast density has consistently been shown to be an independent risk factor for breast cancer in Western populations; however, few studies have evaluated this topic in Chinese women and there is not yet a unified view. This study investigated the association between mammographic density (MD) and breast cancer risk in Chinese women.MethodsThe PubMed, Cochrane Library, Embase, and Wanfang databases were systematically searched in June 2023 to include all studies on the association between MD and breast cancer risk in Chinese women. A total of 13,977 breast cancer cases from 14 studies were chosen, including 10 case-control/cross-sectional studies, and 4 case-only studies. For case-control/cross-sectional studies, the odds ratios (ORs) of MD were combined using random effects models, and for case-only studies, relative odds ratios (RORs) were combinations of premenopausal versus postmenopausal breast cancer cases.ResultsWomen with BI-RADS density category II-IV in case-control/cross-sectional studies had a 0.93-fold (95% confidence interval [CI] 0.55, 1.57), 1.08-fold (95% CI 0.40, 2.94), and 1.24-fold (95% CI 0.42, 3.69) higher risk compared to women with the lowest density category. Combined RORs for premenopausal versus postmenopausal women in case-only studies were 3.84 (95% CI 2.92, 5.05), 22.65 (95% CI 7.21, 71.13), and 42.06 (95% CI 4.22, 419.52), respectively, for BI-RADS density category II-IV versus I.ConclusionsFor Chinese women, breast cancer risk is weakly associated with MD; however, breast cancer risk is more strongly correlated with mammographic density in premenopausal women than postmenopausal women. Further research on the factors influencing MD in premenopausal women may provide meaningful insights into breast cancer prevention in China.

Data Mining for ICD-10 Admission Diagnoses Preceding Tuberculosis within 1 Year among Non-HIV and Non-Diabetes Patients

Delayed diagnosis of tuberculosis (TB) increases mortality and extends the duration of disease transmission. This study aimed to identify significant ICD-10 admission diagnoses preceding TB. All hospital electronic medical records from fiscal year 2015 to 2020 in the Songkhla Province, Thailand were retrieved. After excluding diabetes and HIV patients, a case-control analysis was performed. Exposures of interest were ICD-10 diagnoses on admissions 1–12 months prior to the visit during which TB was detected. Incident cases of respiratory tuberculosis (A15.0–A16.9) that had been admitted with at least one such exposure were chosen. For every case, controls were retrieved from weekly concurrent OPD patients who had the same 10-year interval of age, sex, and preceding admission and discharge week as the case. The 10 most common comorbidities during hospitalization preceding TB with their relative odds ratios (RORs) and 95% confidence intervals were identified. These included five significant exposures related to lower respiratory infection without adequate TB investigation. Significant RORs ranged from 3.10 (unspecified pneumonia) to 34.69 (hemoptysis). Full TB investigation was not performed due to problems with health insurance. In conclusion, the physicians should be informed about this pitfall, and the insurance system should be revised accordingly.

Association between body mass index, waist circumference, and age at natural menopause: a population-based cohort study in Chinese women

ABSTRACT The purpose of the study was to investigate whether premenopausal body mass index (BMI) and waist circumference (WC) influence age at menopause. A total of 2116 women aged 35–64 years from two communities of the CMCS Beijing cohort were recruited in 1992 and followed up to 2018. Of 1439 premenopausal women at baseline, 6 women data were missing. Finally, 1433 women were included for analysis. Overweight was defined as BMI 24–27.99 kg/m2. Central obesity was defined as WC ≥80 cm. Age at menopause was categorized as <45 years, 45–49 years, 50–51 years (reference), and >51 years. Multinomial logistic regression models were used to estimate relative odds ratios (RORs) and 95% confidence intervals (CIs). Compared to women with normal weight and normal WC, overweight women with normal WC had higher risk of menopause at >51 years (ROR 1.64, 95% CI 1.10–2.45; P = .01); and overweight women with central obesity had higher risk of menopause at not only >51 years (ROR 1.82, 95% CI 1.13–2.93; P = .01) but also <45 years (ROR 3.13, 95% CI 1.20–8.43; P = .02) and 45–49 years (ROR 2.76, 95% CI 1.71–4.46; P < .001). When overweight women combine with central obesity, the risk of early menopause will increase in some of them.

Anti-cancer drugs associated with sudden death and ventricular arrhythmias: a cardio-oncology pharmacovigilance analysis

Abstract Background Experimental data have shown that some anticancer drugs can affect cardiac repolarization and induce life-threatening cardiac arrhythmias. Objective To identify anti-cancer drugs associated with the occurrence of sudden death (SD) and ventricular arrhythmias using the World Health Organization individual case safety report (ICSR) database, Vigibase. Methods The system organ class MEDRA was used to identify cases as ICSR with the terms sudden death, sudden cardiac death, cardiac arrest, ventricular fibrillation, ventricular tachycardia, ventricular arrhythmia and torsades de pointes (named as SD events) from Nov 1967 to Nov 2019. We used the ATC code L01 which regroups 219 antineoplastic agents. A disproportionality analysis was performed to estimate of relative Odds Ratio (ROR). Signals were considered significant when the lower boundary of the 99.97% confidence interval (ROR0.25) was ≥1. Results Among the 2,170,203 adverse events associated with anticancer drugs, 11,979 (0.55%) concerned SD events. A total of 49 molecules were significantly associated with SD events, among which 4 were withdrawn from market. These molecules were mainly anti-metabolites (20.0%), chemicals such as arsenic (17.8%,), anthracyclins (8.9%) and alkaloids (8.9%). When agents were grouped according to their mode of actions, the highest risks were observed for platinum-based drugs (n=1628 cases, ROR0.25=1.2) and anthracyclins (n=1323 cases, ROR0.25=1.3). While the risk for SD or severe arrhythmias was reported in the drug label for 29 agents (64.4%), we found that this risk was not identified or mentioned for 16 agents (35.5%). Conclusions We identified 49 anticancer drugs that are significantly associated with SD events overreporting. Appropriate monitoring and preventive measures should be considered for patients receiving these drugs. Funding Acknowledgement Type of funding source: None

The risk of sudden cardiac death or ventricular arrhythmias on Immune checkpoint Inhibitors

Abstract Background Immune checkpoint inhibitors (ICI) have significantly improved the prognosis of many advanced cancers, and may be given in non-metastatic cancer in the near future. ICI have recently been reported to induce fulminant cardiotoxic effects such as myocarditis, responsible for ∼50% mortality rates. Objective To estimate the risk of sudden death (SD) and ventricular arrhythmias in patients receiving ICI using the World Health Organization individual case safety report (ICSR) database, Vigibase (WHO international pharmacovigilance database). Methods The system organ class MEDRA was used to identify cases as ICSR with the terms sudden death, sudden cardiac death, cardiac arrest, ventricular fibrillation, ventricular tachycardia, ventricular arrhythmia and torsades de pointes (named as SD events) from Nov 1967 to Nov 2019. We used the ATC code L01 which regroups 219 antineoplastic agents including ICI avelumab (anti-PDL1), ipilimumab (anti CTLA4), nivolumab (anti-PD1) and pembrolizumab (anti-PD1). A disproportionality analysis was performed to estimate of relative Odds Ratio (ROR). Signals were considered significant when the lower boundary of the 99.97% confidence interval (ROR0.25) was ≥1. Results We found that avelumab was significantly associated with SD events (ROR0.25=1.7). This overreporting was not observed for other ICIs. Avelumab was associated with 12 cases of cardiac arrest (n=11) or sudden death (n=1), which were reported since 2017 as the drug became available. There were however no signals regarding other terms including ventricular arrhythmias. Conclusions In spite of the potential severity of ICI-myocarditis, ICI do not appear as associated with the occurrence of sudden death or life-threatening arrhythmias, with the exception of avelumab (anti-PDL1), one of the latest developed ICI, indicated in metastatic Merkel cell carcinoma and advanced renal cell carcinoma. Further attention is warranted to confirm this signal that may vary among ICI therapies. Funding Acknowledgement Type of funding source: None

Adverse Events Associated With Botox as Reported in a Food and Drug Administration Database.

Botulinum toxin treatment is the most frequently performed noninvasive cosmetic procedure performed in the USA. Because of its widespread use, an analysis of the adverse event (AE) profile of Botox injections is needed. The FDA Adverse Event Report System was queried using an online web-based tool to determine the top 15 adverse events reported for four Botox brand names: Botox/Botox Cosmetic, Dysport, and Xeomin. The proportional reporting ratios (PRR) and relative odds ratios (ROR) were determined. A literature review was performed for eight AEs of clinical significance: eyelid/eyebrow ptosis, asthenia, muscular weakness, facial paresis, dysphagia, botulism, and death. Botox/Botox Cosmetic had 38367 AEs. Dysport had 3582 AEs. Xeomin had 1405 AEs. All drugs with reported cases of eyelid and eyebrow ptosis had significant PRR and ROR values. The PRR and ROR values for asthenia were not significant in any of the drugs and only reached significance for Dysport for muscular weakness and dysphagia. Both Botox/Botox Cosmetic and Dysport had elevated PRRs and RORs for facial paresis and botulism. While all drugs had at least one reported case of death related to Botox injection use, none of the PRR or ROR values were significant. Known AEs for Botox injection use include eyelid/brow ptosis and muscular weakness. Feared but rare complications of Botox injection use include dysphagia, botulism, and possibly death, owing to systemic spread of the toxin. This is the first study to analyze the AE data reported to the FDA on Botox injection use. III.

Effect of Mobile Device-Assisted N-of-1 Trial Participation on Analgesic Prescribing for Chronic Pain: Randomized Controlled Trial.

Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for chronic musculoskeletal pain, despite limited evidence of effectiveness and well-documented adverse effects. We assessed the effects of participating in a structured, personalized self-experiment ("N-of-1 trial") on analgesic prescribing in patients with chronic musculoskeletal pain. We randomized 215 patients with chronic pain to participate in an N-of-1 trial facilitated by a mobile health app or to receive usual care. Medical records of participating patients were reviewed at enrollment and 6months later to assess analgesic prescribing. We established thresholds of ≥ 50, ≥ 20, and > 0 morphine milligram equivalents (MMEs) per day to capture patients taking relatively high doses only, patients taking low-moderate as well as relatively high doses, and patients taking any dose of opioids, respectively. There was no significant difference between the N-of-1 and control groups in the percentage of patients prescribed any opioids (relative odds ratio (ROR) = 1.05; 95% confidence interval [CI] = 0.61 to 1.80, p = 0.87). There was a clinically substantial but statistically not significant reduction of the percentage of patients receiving ≥ 20 MME (ROR = 0.58; 95% CI = 0.33 to 1.04, p = 0.07) and also in the percentage receiving ≥ 50 MME (ROR = 0.50; 95% CI = 0.19 to 1.34, p = 0.17). There was a significant reduction in the proportion of patients in the N-of-1 group prescribed NSAIDs compared with control (relative odds ratio = 0.53; 95% CI = 0.29 to 0.96, p = 0.04), with no concomitant increase in average pain intensity. There was no significant change in use of adjunctive medications (acetaminophen, gabapentenoids, or topicals). These exploratory results suggest that participation in N-of-1 trials may reduce long-term use of NSAIDs; there is also a weak signal for an effect on use of opioids. Additional research is needed to confirm these results and elucidate possible mechanisms. ClinicalTrials.gov Identifier: NCT02116621.

A Meta-Epidemiological Appraisal of the Effects of Interdisciplinary Multimodal Pain Therapy Dosing for Chronic Low Back Pain.

Using a meta-analysis, meta-regression, and a meta-epidemiological approach, we conducted a systematic review to examine the influence of interdisciplinary multimodal pain therapy (IMPT) dosage on pain, disability, return to work, quality of life, depression, and anxiety in published randomised controlled trials (RCTs) in patients with non-specific chronic low back pain (CLBP). We considered all RCTs of IMPT from a Cochrane review and searched PubMed for additional RCTs through 30 September 2018. A subgroup random-effects meta-analysis by length, contact, and intensity of treatment was performed followed by a meta-regression analysis. Using random and fixed-effect models and a summary relative odds ratio (ROR), we compared the effect sizes (ES) from short-length, non-daily contact, and low-intensity RCTs with long-length, daily contact, and high-intensity RCTs. Heterogeneity was quantified with the I2 metric. A total of 47 RCTs were selected. Subgroup meta-analysis showed that there were larger ES for pain and disability in RCTs with long-length, non-daily contact, and low intensity of treatment. Larger ES were also observed for quality of life in RCTs with short-length, non-daily contact, and low intensity treatment. However, these findings were not confirmed by the meta-regression analysis. Likewise, the summary RORs were not significant, indicating that the length, contact, and intensity of treatment did not have an overall effect on the investigated outcomes. For the outcomes investigated here, IMPT dosage is not generally associated with better ES, and an optimal dosage was not determined.

Self-selection in a population-based cohort study: impact on health service use and survival for bowel and lung cancer assessed using data linkage

BackgroundIn contrast to aetiological associations, there is little empirical evidence for generalising health service use associations from cohort studies. We compared the health service use of cohort study participants diagnosed with bowel or lung cancer to the source population of people diagnosed with these cancers in New South Wales (NSW), Australia to assess the representativeness of health service use of the cohort study participants.MethodsPopulation-based cancer registry data for NSW residents aged ≥45 years at diagnosis of bowel or lung cancer were linked to the 45 and Up Study, a NSW population-based cohort study (N~ 267,000). We measured hospitalisation, emergency department (ED) attendance and all-cause survival, and risk factor associations with these outcomes using administrative data for cohort study participants and the source population. We assessed bias in prevalence and risk factor associations using ratios of relative frequency (RRF) and relative odds ratios (ROR), respectively.ResultsPeople from major cities, non-English speaking countries and with comorbidites were under-represented among cohort study participants diagnosed with bowel (n = 1837) or lung (n = 969) cancer by 20–50%. Cohort study participants had similar hospitalisation and ED attendance compared with the source population. One-year survival after major surgical resection was similar, but cohort study participants had up to 25% higher post-diagnosis survival (lung cancer 3-year survival: RRF = 1.24, 95% confidence interval 1.12,1.37). Except for area-based socioeconomic position, risk factors associations with health service use measures and survival appeared relatively unbiased.ConclusionsAbsolute measures of health service use and risk factor associations in a non-representative sample showed little evidence of bias. Non-comparability of risk factor measures of cohort study participants and non-participants, such as area-based socioeconomic position, may bias estimates of risk factor associations. Primary and outpatient care outcomes may be more vulnerable to bias.

The Hispanic Paradox: Socioeconomic Factors and Race/Ethnicity in Breastfeeding Outcomes.

Breastfeeding has multiple benefits for both mother and infant. Previous studies have shown that Hispanic/Latina women have higher rates of breastfeeding and better health outcomes than non-Hispanic black (NHB) women of similar socioeconomic status. Our primary objective was to explore the association of race/ethnicity with breastfeeding rates and the impact of socioeconomic factors on initiation and continuation of breastfeeding. We performed a hypothesis-generating secondary analysis of a prospective cohort study of perinatal mental health in a diverse sample of 213 mothers. Twenty-eight participants self-identified as non-Hispanic white, 43 as NHB, and 142 as Hispanic/Latina. We examined bivariate relationships and performed logistic regression analysis for a series of maternal, infant, and psychosocial factors to examine their individual effect on the breastfeeding and race/ethnicity relationship odds ratio (OR). Hispanic/Latina women were more likely to initiate exclusive breastfeeding at delivery compared with NHB women (OR 2.4, 95% confidence interval: 1.2-4.9, p = 0.01). Adjustment for maternal, infant, and psychosocial factors measured did not statistically significantly attenuate the OR for initiation of breastfeeding between NHB and Hispanic/Latina women. Women with a history of sexual abuse were also more likely to initiate exclusive breastfeeding (67%) compared with women without a sexual abuse history (54%, p < 0.05). In this low socioeconomic status cohort study, Hispanic/Latina women had higher proportions of any amount of breastfeeding compared with their NHB counterparts. This difference was not attenuated by any of the maternal, infant, or psychosocial factors examined, although our secondary analysis of this prospective cohort was limited by the available covariates in the parent study.

Use of primary care data to predict those most vulnerable to cold weather: a case-crossover analysis.

BackgroundThe National Institute for Health and Care Excellence (NICE) recommends that GPs use routinely available data to identify patients most at risk of death and ill health from living in cold homes.AimTo investigate whether sociodemographic characteristics, clinical factors, and house energy efficiency characteristics could predict cold-related mortality.Design and settingA case-crossover analysis was conducted on 34 777 patients aged ≥65 years from the Clinical Practice Research Datalink who died between April 2012 and March 2014. The average temperature of date of death and 3 days previously were calculated from Met Office data. The average 3-day temperature for the 28th day before/after date of death were calculated, and comparisons were made between these temperatures and those experienced around the date of death.MethodConditional logistic regression was applied to estimate the odds ratio (OR) of death associated with temperature and interactions between temperature and sociodemographic characteristics, clinical factors, and house energy efficiency characteristics, expressed as relative odds ratios (RORs).ResultsLower 3-day temperature was associated with higher risk of death (OR 1.011 per 1°C fall; 95% CI = 1.007 to 1.015; P<0.001). No modifying effects were observed for sociodemographic characteristics, clinical factors, and house energy efficiency characteristics. Analysis of winter deaths for causes typically associated with excess winter mortality (N = 7710) showed some evidence of a weaker effect of lower 3-day temperature for females (ROR 0.980 per 1°C, 95% CI = 0.959 to 1.002, P = 0.082), and a stronger effect for patients living in northern England (ROR 1.040 per 1°C, 95% CI = 1.013 to 1.066, P = 0.002).ConclusionIt is unlikely that GPs can identify older patients at highest risk of cold-related death using routinely available data, and NICE may need to refine its guidance.

A Bias in the Evaluation of Bias Comparing Randomized Trials with Nonexperimental Studies.

In a recent BMJ article, the authors conducted a meta-analysis to compare estimated treatment effects from randomized trials with those derived from observational studies based on routinely collected data (RCD). They calculated a pooled relative odds ratio (ROR) of 1.31 (95% confidence interval [CI]: 1.03-1.65) and concluded that RCD studies systematically over-estimated protective effects. However, their meta-analysis inverted results for some clinical questions to force all estimates from RCD to be below 1. We evaluated the statistical properties of this pooled ROR, and found that the selective inversion rule employed in the original meta-analysis can positively bias the estimate of the ROR. We then repeated the random effects meta-analysis using a different inversion rule and found an estimated ROR of 0.98 (0.78-1.23), indicating the ROR is highly dependent on the direction of comparisons. As an alternative to the ROR, we calculated the observed proportion of clinical questions where the RCD and trial CIs overlap, as well as the expected proportion assuming no systematic difference between the studies. Out of 16 clinical questions, 50% CIs overlapped for 8 (50%; 25 to 75%) compared with an expected overlap of 60% assuming no systematic difference between RCD studies and trials. Thus, there was little evidence of a systematic difference in effect estimates between RCD and RCTs. Estimates of pooled RORs across distinct clinical questions are generally not interpretable and may be misleading.

The Association of Surgical Margins and Local Recurrence in Women with Ductal Carcinoma In Situ Treated with Breast-Conserving Therapy: A Meta-Analysis.

There is no consensus on adequate negative margins in breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). We systematically reviewed the evidence on margins in BCS for DCIS. A study-level meta-analysis of local recurrence (LR), microscopic margin status and threshold distance for negative margins. LR proportion was modeled using random-effects logistic meta-regression (frequentist) and network meta-analysis (Bayesian) that allows for multiple margin distances per study, adjusting for follow-up time. Based on 20 studies (LR: 865 of 7883), odds of LR were associated with margin status [logistic: odds ratio (OR) 0.53 for negative vs. positive/close (p<0.001); network: OR 0.45 for negative vs. positive]. In logistic meta-regression, relative to >0 or 1mm, ORs for 2mm (0.51), 3 or 5mm (0.42) and 10mm (0.60) showed comparable significant reductions in the odds of LR. In the network analysis, ORs relative to positive margins for 2 (0.32), 3 (0.30) and 10mm (0.32) showed similar reductions in the odds of LR that were greater than for >0 or 1mm (0.45). There was weak evidence of lower odds at 2mm compared with >0 or 1mm [relative OR (ROR) 0.72, 95% credible interval (CrI) 0.47-1.08], and no evidence of a difference between 2 and 10mm (ROR 0.99, 95% CrI 0.61-1.64). Adjustment for covariates, and analyses based only on studies using whole-breast radiotherapy, did not change the findings. Negative margins in BCS for DCIS reduce the odds of LR; however, minimum margin distances above 2mm are not significantly associated with further reduced odds of LR in women receiving radiation.

Comparative rates of harms in randomized trials from more developed versus less developed countries may be different

ObjectivesWe set up to evaluate the relative risk of harms in trials performed in less developed vs. more developed countries. Study Design and SettingMeta-epidemiologic evaluation using the Cochrane Database of Systematic Reviews. We considered meta-analyses with at least one randomized clinical trial (RCT) in a less developed country and one RCT in a more developed country. We targeted severe adverse events (AEs), discontinuations due to AEs, any AE, organ system–specific AEs, individual AEs, and all discontinuations due to any reason. We estimated the relative odds ratio (ROR) of harms between more and less developed countries for each topic and the summary ROR (sROR) across topics under each category of harms. ResultsWe identified 42 systematic reviews (128 meta-analyses, 521 independent RCTs). Summary sRORs did not differ significantly from 1.00 for any harm category. Nominally significant RORs were found in only 6/128 meta-analyses. However, in 27% (35/128) of meta-analyses the ROR point estimates indicated relative differences between country settings >2-fold. Considering also ROR 95% confidence intervals, in 92% (118/128) of meta-analyses one could not exclude a 2-fold difference in both directions. ConclusionsWe identified limited comparative evidence on harms in trials from these two country settings. Substantial differences in the risk point estimates were common; the potential for modest differences could rarely be excluded with confidence.

A systematic appraisal of allegiance effect in randomized controlled trials of psychotherapy.

BackgroundExperimenter’s allegiance (EA) refers to a personal confidence of the superiority of a specific psychotherapy treatment. This factor has been linked with larger treatment effects in favor of the preferred treatment. However, various studies have displayed contradictory results between EA and the pattern of treatment effects.AimsUsing a systematic approach followed by meta-analysis, we aimed to evaluate the impact of an allegiance effect on the results of psychotherapeutic studies.MethodWe considered the meta-analyses of randomized controlled trials (RCTs) of different types of psychotherapies in the Cochrane Database of Systematic Reviews. Eligible articles included meta-analyses of RCTs with at least one study showing evidence of EA (i.e., allegiant study). Effect sizes in allegiant RCTs were compared with non-allegiant using random and fixed models and a summary relative odds ratio (ROR) were calculated. Heterogeneity was quantified with the I2 metric.ResultsA total of 30 meta-analyses including 240 RCTs were analyzed. The summary ROR was 1.31 [(95 % confidence interval (CI: 1.03–1.66) P = 0.30, I2 = 53 %] indicating larger effects when allegiance exists. The impact of allegiance did not differ significantly (P > 0.05) when we compared psychiatric versus medical outcomes. Allegiance effect was significant for all forms of psychotherapy except for cognitive behavioral therapy. Moreover, the impact of allegiance was significant only when the treatment integrity of delivered psychotherapy was not assessed. Allegiance effect was even stronger where the experimenter was also both the developer of the preferred treatment and supervised or trained the therapists. No significant differences were found between allegiant and non-allegiant studies in terms of overall quality of studies.ConclusionsExperimenter’s allegiance influences the effect sizes of psychotherapy RCTs and can be considered non-financial conflict of interest introducing a form of optimism bias, especially since blinding is problematic in this kind of research. A clear reporting of EA in every single study should be given an opportunity to investigators of minimizing its overestimation effects.Electronic supplementary materialThe online version of this article (doi:10.1186/s12991-015-0063-1) contains supplementary material, which is available to authorized users.

1810 – An empirical assessment of psychotherapy allegiance in randomised controlled trials

Introduction An allegiance to a school of psychotherapy may distort the findings of treatment effectiveness in randomized clinical trials (RCT). Objectives To assess the influence of allegiance in treatment effectiveness. Aim Using a systematic approach across various psychotherapy studies we aim to identify if allegiance introduces systematic bias in the observed effects. Methods We considered meta-analyses of RCT of different types of psychotherapies in the Cochrane Database. Eligible articles included were those that had only RCTs and at least 1 study with allegiance of the experimenter. For each metaanalysis we calculated the relative odds ratio (ROR) of the allegiance studies vs. no allegiance odds ratios per meta-analysis and the summary ROR across all meta-analyses by using random effects models. Heterogeneity is quantified with the I 2 metric. Results A total of 30 meta-analyses including 240 RCTs were analyzed. Effect sizes of experimental intervention with psychotherapy allegiance (PA) has more favorable effect than experimental intervention without PA (sROR=1.31, 95% confidence interval (CI) 1.03-1.66, I 2 =53%). Subgroup analyses showed that this inflation is strongly type of psychotherapydependent (Cognitive Behavioral Therapy: sROR=1.07, 95% CI: 0.85-1.34, I 2 =19%; Supportive or counseling therapy: sROR=1.44, 95% CI: 1.01-2.05, I 2 =0%; and others: sROR=2.34, 95% CI: 1.03-1.66, I 2 =79%). Allegiance effect was also stronger where the therapeutic experimenter had both developed the therapy and supervised the therapist implemented the intervention (sROR=2.39 95% CI=1.15 - 4.99 I 2 =65). Conclusion PA can introduce systematic bias on effect sizes of various psychotherapy intervention trials in a similar way that conflict of interest does.

The association of frailty with serum 25-hydroxyvitamin D and parathyroid hormone levels in older European men.

the link between the vitamin D endocrine axis and frailty remains undefined, with few studies examining the joint effect of vitamin D and parathyroid hormone (PTH) levels. Our objective was to determine the association of frailty with serum 25-hydroxyvitamin D (25(OH)D) and PTH. cross-sectional analysis within the European Male Ageing Study (EMAS). a total of 1,504 community-dwelling men aged 60-79 years. frailty was classified using a frailty phenotype (FP) and frailty index (FI). The association of frailty with 25(OH)D and PTH was examined using multinomial logistic regression; individual FP criteria with 25(OH)D and PTH using binary logistic regression. Results were expressed as relative odds ratios (ROR) and 95% confidence intervals (CIs) for multinomial; odds ratios (OR) and 95% CIs for binary models. using the FP, 5.0% of subjects were classified as frail and 36.6% as prefrail. Lower levels of 25(OH)D were associated with being prefrail (per 1 SD decrease: ROR = 1.45; 95% CI: 1.26-1.67) and frail (ROR = 1.89; 95% CI: 1.30-2.76), after adjusting for age, centre and health and lifestyle confounders (robust group = base category). Higher levels of PTH were associated with being frail after adjustment for confounders (per 1 SD increase: ROR = 1.24; 95% CI: 1.01-1.52). Comparable results were found using the FI. Among the five FP criteria only sarcopenia was not associated with 25(OH)D levels, while only weakness was associated with PTH. lower 25(OH)D and higher PTH levels were positively associated with frailty in older men. Prospective data would enable the temporal nature of this relationship to be explored further.

Disparities in Fetal Death and First Day Death: The Influence of Risk Factors in 2 Time Periods

We examined how changes in risk factors over time influence fetal, first day, and combined fetal-first day mortality and subsequent racial/ethnic disparities. We selected deliveries to US resident non-Hispanic White and Black mothers from the linked live birth-infant death cohort and fetal deaths files (1995-1996; 2001-2002) and calculated changes over time of mortality rates, odds, and relative odds ratios (RORs) overall and among mothers with modifiable risk factors (smoking, diabetes, or hypertensive disorders). Adjusted odds ratios (AORs) for fetal mortality overall (AOR=0.99; 95% confidence interval [CI]=0.96, 1.01) and among Blacks (AOR=0.98; 95% CI=0.93, 1.03) indicated no change over time. Among women with modifiable risk factors, the RORs indicated no change in disparities. The ROR was not significant for fetal mortality (ROR=0.96; 95% CI=0.83, 1.01) among smokers, but there was evidence of some decline. There was evidence of increase in RORs in fetal death among mothers with diabetes and hypertensive disorders, but differences were not significant. Disparities in fetal, first day, and combined fetal-first day mortality have persisted and reflect discrepancies in care provision or other factors more challenging to measure.