A population-based case–control study: proton pump inhibition and risk of hip fracture by use of bisphosphonate

Background

Studies on the risk of osteoporotic fractures related to the use of proton pump inhibitors (PPIs) have been inconsistent. One recent cohort study reported that there was an interaction between PPIs and bisphosphonates (BPs). Thus we performed a case–control study aimed at evaluating the risk of hip fractures related to PPIs and exploring the interaction between PPIs and BPs.

Methods

A case–control study was performed using the Korean Health Insurance Review and Assessment Service database from 2005 January to 2006 June. The cases were all incident hip fractures identified from July 2005 to June 2006, and up to four controls were matched to each case by age, gender, and osteoporosis. Conditional logistic regression was used to calculate the adjusted odds ratio (aOR) and its 95 % confidence intervals.

Results

A total of 24,710 cases were identified and 98,642 controls were matched to the cases. The aOR and its 95 % CI of hip fractures related to the use of PPIs was 1.34 (95 % CI 1.24–1.44). When the study participants were stratified according to BP use, the aOR was 1.30 (95 % CI 1.19–1.42) in BP non-users, which was significantly different from the 1.71 (95 % CI 1.31–2.23) of BP users. Only BP users showed a decreasing tendency toward fracture risk as exposure to PPI became less recent, and a trend of increasing risk with increasing cumulative doses.

Conclusions

Our results suggest that the mechanism for increased risk of hip fracture by PPIs may arise mainly from interaction of BP and PPIs.     

The association between the use of non-steroidal anti-inflammatory drugs and atrial fibrillation: A nationwide case–control study

Background

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The goal of the present study was to investigate whether exposure to non-steroidal anti-inflammatory drugs (NSAIDs) was a risk factor for AF, and to discern which patients were at the highest risk for AF due to NSAID use.

Methods

A total of 7280 patients with newly diagnosed AF from 2000 to 2009 were identified from the National Health Insurance Research Database. On the same date of enrollment, 10 patients without AF, who were matched for age, sex, and underlying disease for each study patient, were selected to be the control group. The relationship between NSAID exposure before enrollment and AF risk was analyzed.

Results

The NSAID use was associated with an increased AF risk, especially for new users (odds ratio [OR] = 1.651). Among new users, subgroup analysis revealed that patients with heart failure were at the highest risk for AF (OR = 1.920). For patients who were only exposed to selective cyclooxygenase 2 (COX2) inhibitors, no significant associations were found between AF and selective COX2 inhibitor use, except for patients with chronic kidney or pulmonary disease (OR = 1.656 and 1.707, respectively).

Conclusions

New NSAID use may predispose patients to AF, and the risk is almost doubled in heart failure patients. Use of selective COX2 inhibitors was not significantly related to AF occurrence, except in patients with chronic kidney or pulmonary disease.     

Medical history and risk of lymphoma: results of a European case–control study (EPILYMPH)

Introduction  Lymphomas are a heterogeneous group of immune-cell malignancies. Immunology-related conditions are among the few factors for which consistent evidence exists relating them to lymphoma risk. Materials and methods   We used the data from the European case–control study Epilymph on 2,362 lymphoma cases and 2,458 controls to investigate associations between a medical history of infectious and non-infectious diseases with overall and subentity-specific lymphoma risk. Results   As key results, we observed an increased odds ratio (OR) for self-reported infections with hepatitis B virus (HBV, OR = 1.91, 95% CL = 1.24–2.94) and a null result for rheumatoid arthritis. Additionally, we found an increased OR for infectious mononucleosis (OR = 1.68, 95% CL = 1.14–2.48), an inverse association to frequency of sickness in childhood (OR = 0.68, 95% CL = 0.55–0.84), and—as casual finding—an increased OR with acetaminophen intake (OR = 2.29, 95% CL = 1.49–3.51). Conclusion   Our results are consistent with the current knowledge about the association with mononucleosis as indicator of Epstein–Barr-virus infection, suggest serological study of the association to HBV infection and do not support the view of a positive association between rheumatoid arthritis and lymphoma risk.     

Thyroid cancer in patients with acromegaly: a case–control study

Several studies have associated acromegaly with an increased risk of benign and malignant tumors. While simple and multinodular goiters are common findings in acromegaly, the prevalence of thyroid cancer is uncertain. The objective of this study was to estimate the prevalence of thyroid cancer in a series of acromegalic patients from three hospitals in northeast of Brazil. The methodology used included morphological, cytological and histological thyroid analysis of acromegalic patients and volunteers over 18 years, matched for age and sex and with nodule (s) ≥1 cm. The subjects of this study were 124 acromegalic patients, including 76 females (61.3%) and 48 men (38.7%), with a mean age 45.1 years. Results of the study showed that thyroid ultrasonography was normal in 31 cases (25%), 25 had diffuse goiter (20.1%), 67 had nodules (54%) and one agenesis of the right lobe (0.8%). Thirty-six patients underwent fine needle aspiration biopsy (FNAB) of their nodules and 9 cases of papillary cancer were found (7.2%). The control group consisted of 263 subjects, 156 females (59.3%) and 107 males (40.7%), mean age 44.7 years. In ultrasound assessment, 96 had nodules (36.5%). Of these, 13 were punctured and 2 cases of papillary carcinoma were found (0.7%). These results gave an odds ratio of 10.21 (p = 0.0011, 95% CI 2.17 to 48.01). These findings demonstrate an increased prevalence of thyroid cancer, statistically significant when compared to our control group. Thus, it is suggested that acromegalic patients should be routinely submitted to thyroid ultrasound evaluation, followed by FNAB of nodules when indicated.     

Antibiotic use and development of nonalcoholic fatty liver disease: A population-based case–control study

Background and Aims

Antibiotics affect the gut microbiome. Preclinical studies suggest a role of gut dysbiosis in the development of nonalcoholic fatty liver disease (NAFLD), but data from large cohorts with liver histology are lacking.

Methods

In this nationwide case–control study, Swedish adults with histologically confirmed early-stage NAFLD (total n = 2584; simple steatosis n = 1435; steatohepatitis (NASH) n = 383; non-cirrhotic fibrosis n = 766) diagnosed January 2007–April 2017 were included and matched to ≤5 population controls (n = 12 646) for age, sex, calendar year and county of residence. Data for cumulative antibiotic dispensations and defined daily doses were accrued until 1 year before the matching date. Using conditional logistic regression, multivariable-adjusted odds ratios (aORs) were calculated. In a secondary analysis, NAFLD patients were compared with their full siblings (n = 2837).

Results

Previous antibiotic use was seen in 1748 (68%) NAFLD patients versus 7001 (55%) controls, corresponding to 1.35-fold increased odds of NAFLD (95% CI = 1.21–1.51) in a dose-dependent manner (p_{for trend} < .001). Estimates were comparable for all histologic stages (p > .05). The highest risk of NAFLD was observed after treatment with fluoroquinolones (aOR 1.38; 95% CI = 1.17–1.59). Associations remained robust when patients were compared with their full siblings (aOR 1.29; 95% CI = 1.08–1.55). Antibiotic treatment was only linked to NAFLD in patients without metabolic syndrome (aOR 1.63; 95% CI = 1.35–1.91) but not in those with metabolic syndrome (aOR 1.09; 95% CI = 0.88–1.30).

Conclusions

Antibiotic use may be a risk factor for incident NAFLD, especially in individuals without the metabolic syndrome. The risk was highest for fluoroquinolones and remained robust in sibling comparisons with whom individuals share genetic and early environmental susceptibilities.     

Bladder cancer with pioglitazone: A case–control study

BackgroundVaried reports suggest a contentious relationship of bladder malignancy with pioglitazone in patients with type 2 diabetes.AimTo study an association (prevalence and predictors) of bladder malignancy with pioglitazone therapy in Asian-Indian type 2 diabetes patients.MethodIn this observational multicenter study, type 2 diabetic patients attending out-patient diabetes-clinic were evaluated. A detailed history of anti-diabetic medication, dose, duration, pioglitazone usage, time since initiation of pioglitazone, physical examination, biochemical tests and details pertaining to prevalent neuropathy, retinopathy and nephropathy were recorded. Details of bladder cancer or any malignancy (if present), time since diagnosis, risk factors for bladder cancer and histopathology records were noted. The study cohort was divided into two groups-pioglitazone ever users (Group A) and never users (Group B).ResultsA total of 8000 patients were screened out of which 1560 were excluded. Among 6440 included patients, 1056 (16.3%) patients were in group A and 5384 (83.6%) group B. Patients on pioglitazone were older (59.1 vs 57.7 years, p < 0.001), had longer duration of diabetes (12.7 vs 10.6 years, p < 0.001) with poor glycemic control (HbA1c 8.5 vs 8.3%, p < 0.01). A total of 74 patients had prevalent bladder cancer [16 (1.5%) in Group A and 58 in Group B (1.0%)]. Prevalent bladder cancer was not significantly greater in ever-users (odds ratio OR = 1.29, 95% confidence interval CI, 0.83–2.00) compared to never-users (odds ratio OR = 0.94, 95% confidence interval CI, 0.834–1.061) of pioglitazone (p = 0.207). However, history of hematuria in pioglitazone-users; while older age (>58 year), history of smoking and hematuria in the whole cohort were significant associated with bladder cancer. In the entire study cohort, 254 patients; 3.5% of males (128 out of 3575) and 4.6% of females (126 out of 2713) developed any malignancy. Age was significantly associated with prevalent malignancy in people with diabetes (odds ratio OR 1.036, 95% confidence interval CI: 1.022–1.051, p = 0.00) on multivariate forward regression.ConclusionPioglitazone use in Asian-Indians is not associated with an increased bladder cancer risk. However, pioglitazone should be restricted in individuals with history of hematuria. Age more than 58 years is a significant risk factor for development of any malignancy, particularly bladder cancer.     

MDR1 gene C3435T polymorphism and cancer risk: a meta-analysis of 34 case–control studies

Background

P-glycoprotein, the product of the MDR1 gene, is a transmembrane active efflux pump for a variety of environmental toxins and xenobiotics. Epidemiological studies have evaluated the association between MDR1 C3435T polymorphism and cancer susceptibility. However, published data are still inconclusive.

Methods

To derive a more precise assessment of this relevance, we performed a meta-analysis, up to September 2010, of 5,196 cases with different cancer types and 6,827 controls from 34 published case–control studies. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for MDR1 C3435T polymorphism and cancer were estimated using fixed- and random-effects models when appropriate.

Results

The overall results suggested that the variant was associated with a moderately increased cancer risk in all comparison models tested (OR?=?1.26, 95% CI: 1.06–1.50 for TT vs. CC; OR?=?1.19, 95% CI: 1.04–1.37 for CT vs. CC; OR?=?1.15, 95% CI: 1.01–1.32 for recessive model; OR?=?1.21, 95% CI: 1.06–1.38 for domain model, and OR?=?1.14, 95% CI: 1.04–1.26 for allele contrast). In the subgroup analysis by cancer types, significant associations were found in breast cancer (OR?=?1.66, 95% CI: 1.24–2.21 for TT vs. CC; OR?=?1.44, 95% CI: 1.14–1.82 for recessive model; OR?=?1.41, 95% CI: 1.10–1.81 for domain model; and OR?=?1.31, 95% CI: 1.13–1.52 for allele contrast) and renal cancer (OR?=?1.99, 95% CI: 1.37–2.90 for TT vs. CC; OR?=?1.74, 95% CI: 1.25–2.42 for domain model; OR?=?1.43, 95% CI: 1.09–1.88 for recessive model; and OR?=?1.40, 95% CI: 1.17–1.68 for allele contrast). However, no significant associations were found in colorectal cancer, gastric cancer, and acute lymphoblastic leukemia for all genetic models. In the ethnicity subgroup analysis, a significant association with cancer among Caucasians was found under the dominant model, homozygote comparison, CT versus CC comparison, and allele comparison.

Conclusions

In summary, this meta-analysis suggests that the MDR1 C3435T polymorphism is associated with cancer susceptibility, increasing the risk of breast and renal cancer.     

Non-steroidal anti-inflammatory drugs and risk of cerebrovascular events in patients with osteoarthritis: a nested case–control study

Recent studies show that the risk of cardiovascular adverse events for certain traditional non-steroidal anti-inflammatory drugs (NSAIDs) is similar to that of rofecoxib. While these results are focused on ischemic cardiomyopathy, there is little evidence concerning the risk of ischemic stroke/transient ischemic attack and hemorrhagic stroke. Additionally, there is no information on nimesulide and ketoprofen, the most frequently prescribed NSAIDs in Italy, along with diclofenac. This study aims to determine whether the use of NSAIDs is associated with an increased risk of cerebrovascular events in Italy. We performed a case–control analysis nested in a cohort of patients with osteoarthritis between 2002 and 2011 who were newly treated with NSAIDs. The patients were followed until December 31, 2012. Conditional logistic regression was used to estimate odds ratios (ORs) with 95 % confidence intervals (95 % CI) of cerebrovascular events (index date) associated with current (until 30 days before the index date), recent (31–365 days) and past (>365 days) use of NSAIDs. Within a cohort of 29,722 patients, 1566 cases (1546 matched with controls) were identified (incidence rate = 11.0/1000 person–years). The overall rate of cerebrovascular event was not elevated with current NSAIDs overall when compared with past use. Among individual NSAIDs, diclofenac and ketoprofen were the molecules significantly associated with an increased rate of cerebrovascular events (OR = 1.53; 95 % CI 1.04–2.24; OR = 1.62; 95 % CI 1.02–2.58, respectively). The most frequent event was hemorrhagic stroke following the use of ketoprofen (OR = 2.09; 95 % CI 1.05–4.15). Diclofenac and ketoprofen seemed to increase the risk of cerebrovascular events. These findings might influence the choice of NSAIDs according to patient characteristics.     

Perception of risk and impact of the COVID-19 pandemic on patients with rheumatic diseases: a case–control study

Clinical Rheumatology - Risk perception of the COVID-19 pandemic may affect chronic disease outcomes among patients with rheumatic diseases (RD). To describe and compare the perception of risk and...