Summary
A large Canadian cohort was studied over 10 years to see if proton pump inhibitor (PPI) use increased the risk of sustaining a fragility fracture. We found an increased risk of fracture in ...individuals who used PPIs. The risk remained after controlling for other known fracture risk factors.
Introduction
Multiple retrospective studies have linked proton pump inhibitor use with increased risk of fragility fracture. We prospectively studied the association between PPI use and fracture in a large cohort over a 10-year period while controlling for known fracture risk factors.
Methods
We studied 9,423 participants in the Canadian Multicenter Osteoporosis Study. The cohort was formed in 1995–1997 and followed for 10 years with monitoring for incident nontraumatic fracture and PPI use. Cox regression analyses were used to assess the association between PPI use and incident fracture risk.
Results
PPI use, coded as a time-dependent variable, was associated with a shorter time to first nontraumatic fracture, hazard ratio (HR) = 1.75 (95 % confidence interval (CI) 1.41–2.17,
p
< 0.001). After controlling for multiple risk factors, including femoral neck bone density, the association remained significant, HR = 1.40 (95 % CI 1.11–1.77,
p
= 0.004). Similar results were obtained after controlling for bisphosphonate use, using PPI “ever” use, or when the outcome was restricted to hip fracture.
Conclusions
In this large prospective population-based cohort study, we found an association between PPI use and increased risk of fragility fracture. Although the increased risk found was modest, this finding is important, given the high prevalence of PPI use and the excess morbidity and mortality associated with osteoporosis-related fractures.
The use of proton pump inhibitors has been associated with an increased risk of hip fracture. We sought to further explore the relation between duration of exposure to proton pump inhibitors and ...osteoporosis-related fractures.
We used administrative claims data to identify patients with a fracture of the hip, vertebra or wrist between April 1996 and March 2004. Cases were each matched with 3 controls based on age, sex and comorbidities. We calculated adjusted odds ratios (OR) for the risk of hip fracture and all osteoporosis-related fractures for durations of proton pump inhibitor exposure ranging from 1 or more years to more than 7 years.
We matched 15 792 cases of osteoporosis-related fractures with 47 289 controls. We did not detect a significant association between the overall risk of an osteoportic fracture and the use of proton pump inhibitors for durations of 6 years or less. However, exposure of 7 or more years was associated with increased risk of an osteoporosis-related fracture (adjusted OR 1.92, 95% confidence interval CI 1.16-3.18, p = 0.011). We also found an increased risk of hip fracture after 5 or more years of exposure (adjusted OR 1.62, 95% CI 1.02-2.58, p = 0.04), with even higher risk after 7 or more years exposure (adjusted OR 4.55, 95% CI 1.68-12.29, p = 0.002).
Use of proton pump inhibitors for 7 or more years is associated with a significantly increased risk of an osteoporosis-related fracture. There is an increased risk of hip fracture after 5 or more years exposure. Further study is required to determine the clinical importance of this finding and to determine the value of osteoprotective medications for patients with long-term use of proton pump inhibitors.
Summary
Background
Proton pump inhibitor (PPI) use is associated with an increased risk of Clostridium difficile infection (CDI), though the mechanism is unclear. PPI induced alterations to the gut ...microbiome may facilitate the emergence of CDI, though the effects of PPIs on gut microbiota are not well characterised. Correction added on 10 March 2016, after first online publication: microflora has been changed to microbiota throughout the article.
Aim
To compare the faecal microbiomes of long‐term PPI users to those with no history of PPI use.
Methods
We used a population‐based database to identify individuals with ≥5 years of continuous PPI use along with non‐PPI using controls. Stool samples were subjected to microbiological analysis, with hierarchical clustering at genus level, along with alpha and beta diversity measures comparing the two groups. Metadata was accounted for using quantile regression to eliminate potential confounding variables in taxonomic abundance comparisons.
Results
Sixty‐one subjects (32 PPI, 29 controls) were analysed. While no significant differences in alpha diversity were found between the PPI users and controls, a moderate shift of the PPI users away from the non‐PPI user cluster in the beta diversity was observed. After controlling for pertinent confounders, we discovered a decrease in Bacteroidetes and an increase in Firmicutes at the phylum level. We also performed species classifications and found Holdemania filiformis and Pseudoflavonifractor capillosus to be increased and decreased in the PPI cohort, respectively.
Conclusions
Long‐term PPIs use has an effect on the gut microbiome. The alteration in the ratio of Firmicutes to Bacteroidetes may pre‐dispose to the development of CDI.
Linked Content
This article is linked to Torvinen‐Kiiskinen et al papers. To view these articles visit https://doi.org/10.1111/apt.14589 and https://doi.org/10.1111/apt.14666.
Abstract
Introduction
A new clinician-administered inflammatory bowel disease (IBD) Disability Index (IBDDI) was recently developed and validated among a population in France. We aimed to validate ...the IBDDI in a North American setting and adapt for use as a self-report tool.
Methods
Persons 18-65 years old from the population-based University of Manitoba IBD Research Registry were mailed a self-administered survey. This survey included the IBDDI and several scales that should correlate with a disability measure- the World Health Organization (WHO) Disability Assessment Scale (WHODAS) 2.0, Work and Social Adjustment Scale (WSAS), the Inflammatory Bowel Disease Questionnaire (IBDQ), and the K6-Kessler Emotional Distress Scale. We used Pearson correlation coefficients to assess construct validity, Cronbach's alpha to assess internal consistency, and Factor analysis to assess which of the IBDDI items likely belonged to a single IBD-related disability factor.
Results
In response to the survey request,1143 (46% of those contacted) participated (61% female, mean age 51, 52% with Crohn's disease). On an index scale from 0-100, 14% had a score ≥50 (extreme disability, 18% of those with Crohn's disease; 10% of those with ulcerative colitis). There were strong correlations between IBDDI and WSAS (0.76), WHODAS (0.76), K6 (0.73), and an inverse correlation with IBDQ (-0.86). The Cronbach's alpha was high (0.88). All but 2 items (number of liquid stools in the past week and arthritis/arthralgia) of the 14 identified for IBDDI loaded highly onto a single factor (factor loading > 0.40).
Conclusions
The findings support the validity of this new self-report version of the IBDDI as a sound measure of disability in IBD.
Summary
Background
Predictors of complicated Crohn's disease (CD), defined as stricturing or penetrating behaviour, and surgery have largely been derived from referral centre populations.
Aim
To ...investigate whether serological markers, susceptibility genes or psychological characteristics are associated with complicated CD or surgery in a population‐based cohort.
Methods
One hundred and eighty‐two members of the Manitoba IBD Cohort with CD phenotyped using the Montreal classification underwent genetic and serological analysis at enrolment and after 5 years. One hundred and twenty‐seven had paired sera at baseline and 5 years later and their data were used to predict outcomes at a median of 9.3 years. Serological analysis consisted of a seven antibody panel, and DNA was tested for CD‐associated NOD2 variants (rs2066845,rs2076756,rs2066847), ATG16L1 (rs3828309, rs2241880) and IL23R (rs11465804). Psychological characteristics were assessed using semi‐structured interviews and validated survey measures.
Results
Sixty‐five per cent had complicated CD and 42% underwent surgery. Multivariate analysis indicated that only ASCA IgG‐positive serology was predictive of stricturing/penetrating behaviour (OR = 3.01; 95% CI: 1.28–7.09; P = 0.01) and ileal CD (OR = 2.2; 95% CI: 1.07–4.54, P = 0.03). Complicated CD behaviour was strongly associated with surgery (OR = 5.6; 95% CI: 2.43–12.91; P < 0.0001), whereas in multivariate analysis, only ASCA IgG was associated (OR = 2.66; 95% CI, 1.40–5.06, P = 0.003). ASCA titre results were similar at baseline and follow‐up. Psychological characteristics were not significantly associated with disease behaviour, serological profile or genotype.
Conclusions
ASCA IgG at baseline was significantly associated with stricturing/penetrating disease at 9–10 years from diagnosis. Stricturing/penetrating disease was significantly associated with surgery. In a model including serology, the genotypes assessed did not significantly associate with complicated disease or surgery.
Summary
Background
It is believed that women with inflammatory bowel disease (IBD) have heightened symptoms around their menses. However, there is little information regarding normative changes and ...which symptoms emerge in relation to menses.
Aim
To determine the relationship between gastrointestinal and other symptoms and menses in a population‐based cohort of women with IBD vs. healthy women.
Methods
Women enrolled in the University of Manitoba IBD Research Registry who were between 18 and 65 years were mailed a survey. A control group of adult women were recruited through out‐patient gynaecology clinics. Participants were asked to consider their menstrual periods in the recent several months and report on symptoms 1–5 days prior to and during the days of their menses.
Results
There were 151 premenopausal women with Crohn's disease (CD), 87 with ulcerative colitis (UC) and 156 premenopausal controls. Mean age of menses onset was similar in all three cohorts and the percentage in each group with regular menstrual periods was similar. Premenstrually, abdominal pain was less commonly reported in UC (36.8%) than CD (51%, P = 0.034) and controls (57.6%, P = 0.002). Premenstrually, and during menses diarrhoea was more commonly reported in CD (47.7% and 59.6% respectively) than UC (26.4% P = 0.001 and 42.5%, P = 0.01 respectively) and controls (24.4%, P < 0.0001 and 28.2%, P < 0.0001 respectively). Premenstrually, women with CD (46%) vs. UC (26%) were more likely to report worsening of their IBD symptoms (P = 0.0007), but there was no difference between CD (47%) and UC (39%) for reporting worsening during menses (P = 0.24).
Conclusions
Compared to healthy women, women with IBD had similar symptom experiences premenstrually, except that those with CD were more likely to have increased diarrhoea premenstrually. During menses, women with CD or UC were more likely to experience diarrhoea than healthy controls.
Summary
Background When faced with the same set of facts, healthcare providers often make different diagnoses, employ different tests and prescribe disparate therapies.
Aim To perform a national ...survey to measure process of care and variations in decision‐making in Crohn’s disease, and the compared results between experts and community providers.
Methods We constructed a survey with five vignettes to elicit provider beliefs regarding the appropriateness of diagnostic tests and therapies in Crohn’s disease. We measured agreement between community gastroenterologists and Crohn’s disease experts, and measured variation within each group using the RAND Disagreement Index (DI), which is a validated measure of provider variation.
Results We received 186 responses (42% response rate). Experts and community providers generally agreed on diagnostic testing decisions in Crohn’s disease. However, there was a significant disagreement between groups for several decisions (use of 5‐aminosalicylate in particular), and there was evidence of ‘extreme variation’ (defined as DI > 1.0) within groups across a range of decisions.
Conclusions Although experts and community providers are in general consensus about diagnostic decision‐making in Crohn’s disease, extreme variation exists both between and within groups for key therapeutic decisions in Crohn’s disease. We must understand and decrease this variation prior to future efforts of creating explicit quality indicators in Crohn’s disease.
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