Hospital infections and health-related quality of life after cardiac surgery: a multicenter survey.

BACKGROUND: Recent research suggested that hospital infections are a predictive marker for physical non-recovery one year after cardiothoracic surgery. The purpose of this study was to explore whether this risk factor is etiologic. Additional, the influence of a potential effect modifying factor, diabetes mellitus, was investigated. METHODS: In this multicenter study, patients underwent elective or urgent cardiothoracic surgery between 01-01-2015 and 31-12-2019, and completed pre- and one year post-operative Short Form Health Survey 36/12 quality of life questionnaires. A binary logistic regression model, in which the inverse of the propensity score for infection risk was included as a weight variable, was used. Second, this analysis was stratified for diabetes mellitus status. RESULTS: 8577 patients were included. After weighing for the propensity score, the standardized mean differences of all variables decreased and indicated sufficient balance between the infection and non-infection groups. Hospital infections were found to be a risk factor for non-recovery after cardiothoracic surgery in the original and imputed dataset before weighting. However, after propensity score weighing, hospital infections did not remain significantly associated with recovery (OR for recovery = 0.79; 95% CI [0.60-1.03]; p = 0.077). No significant interaction between diabetes mellitus and hospital infections on recovery was found (p = 0.845). CONCLUSIONS: This study could not convincingly establish hospital infections as an etiologic risk factor for non-improvement of physical recovery in patients who underwent cardiothoracic surgery. In addition, there was no differential effect of hospital infections on non-improvement of physical recovery for patients with and without diabetes mellitus. Trial registration International Clinical Trials Registry Platform ID NL9818; date of registration, 22-10-2021 ( https://trialsearch.who.int/ ).

Prevalence of chronic kidney disease in the Netherlands and its cardiovascular and renal complications.

BACKGROUND: Knowledge on prevalence, comorbidities and consequences of chronic kidney disease (CKD) is mandatory to estimate the potential of cardiovascular risk management on a population level. We studied the prevalence of CKD with or without type 2 diabetes mellitus (T2D) and/or heart failure and its cardiorenal complications in The Netherlands. METHODS: A descriptive cross-sectional and longitudinal cohort study was performed, using data from the Dutch PHARMO Data Network. Prevalence of CKD at a single time point was determined by a recorded diagnosis or by ≥ 2 estimated glomerular filtration rate (eGFR) measurements and urine albumin/creatinine ratio (UACR) that define CKD. A representative group of adults with CKD was included in a longitudinal analysis to study cardiorenal complications. Those were followed until first complication, end of study or death, whichever occurred first. RESULTS: The prevalence of CKD was 8.9% in a representative population of 2,187,962 adult Dutch individuals. The average age of persons with CKD was 72 years, 57% were female, 19.9% had T2D, 7.7% heart failure, and 3.0% both T2D and heart failure. In the longitudinal analysis, cerebrovascular events (11/1,000 person-years), hospitalizations for heart failure (10/1,000 person-years), myocardial infarction (5.5/1,000 person-years), and hospitalization for CKD (6.2/1,000 person-years) were the most common first cardiorenal complications. People with CKD with T2D and/or heart failure generally had higher rates of cardiovascular or renal complications or mortality than people with CKD without these comorbidities. CONCLUSION: The prevalence of CKD in The Netherlands is 8.9%. People with T2D or heart failure, or both, in addition to CKD, had numerically higher mortality and cardiorenal complication rates than people without these comorbidities. Optimizing up-to-date cardiovascular risk management in these high-risk individuals may provide health benefits.

[Prevalence and drug treatment of people with type 2 diabetes mellitus and a very high risk of cardiovascular disease]. / Diabetes type 2 én een hoog risico op hart- en vaatziekten.

OBJECTIVE: Dutch diabetes guidelines have been updated to incorporate specific therapies with cardiovascular and kidney outcomes benefit in type 2 diabetes patients (T2D) at very high risk for cardiorenal complications. This is part of a comprehensive approach to reduce the risk of diabetes-related complications, including management of glycemia, blood pressure, and lipids. The current study examines the prevalence of T2D at very high cardiorenal risk and the deployment of evidence-based approaches to lower this risk. DESIGN: Cross-sectional, observational study. METHOD: A representative population) with T2D in primary care (N= 64,224) was selected from the PHARMO Data Network. A very high risk of CVD was defined as: 1) established CVD, 2) CKD with (very) high cardiovascular risk and 3) heart failure. Drug treatment was determined according to prescriptions in 2019. RESULTS: 25,901 subjects with T2D had a very high risk of CVD (mean age 73.3 years; 42% female). Established CVD, CKD with (very) high cardiovascular risk, and heart failure were observed in 82%, 26% and 22% of patients, respectively. Low-dose salicylates, lipid-lowering and blood pressure-lowering medication were used by 39%, 70% and 69%, respectively. Glucose-lowering medication use included metformin (53%), sulfonylurea-derivatives (24%), and insulin (19%). 2% of the population used a SGLT2 inhibitor or GLP1-receptor agonist. CONCLUSION: 40% of people with DM2 have a very high risk of CVD. Although our findings reflect the recommendations of the previous treatment guideline for DM2, they also show that the new guideline has significant implications for the treatment of a large proportion of people with DM2.

Conservative versus Liberal Oxygenation Targets in Intensive Care Unit Patients (ICONIC): A Randomized Clinical Trial.

Rationale: Supplemental oxygen is widely administered to ICU patients, but appropriate oxygenation targets remain unclear. Objectives: This study aimed to determine whether a low-oxygenation strategy would lower 28-day mortality compared with a high-oxygenation strategy. Methods: This randomized multicenter trial included mechanically ventilated ICU patients with an expected ventilation duration of at least 24 hours. Patients were randomized 1:1 to a low-oxygenation (PaO2, 55-80 mm Hg; or oxygen saturation as measured by pulse oximetry, 91-94%) or high-oxygenation (PaO2, 110-150 mm Hg; or oxygen saturation as measured by pulse oximetry, 96-100%) target until ICU discharge or 28 days after randomization, whichever came first. The primary outcome was 28-day mortality. The study was stopped prematurely because of the COVID-19 pandemic when 664 of the planned 1,512 patients were included. Measurements and Main Results: Between November 2018 and November 2021, a total of 664 patients were included in the trial: 335 in the low-oxygenation group and 329 in the high-oxygenation group. The median achieved PaO2 was 75 mm Hg (interquartile range, 70-84) and 115 mm Hg (interquartile range, 100-129) in the low- and high-oxygenation groups, respectively. At Day 28, 129 (38.5%) and 114 (34.7%) patients had died in the low- and high-oxygenation groups, respectively (risk ratio, 1.11; 95% confidence interval, 0.9-1.4; P = 0.30). At least one serious adverse event was reported in 12 (3.6%) and 17 (5.2%) patients in the low- and high-oxygenation groups, respectively. Conclusions: Among mechanically ventilated ICU patients with an expected mechanical ventilation duration of at least 24 hours, using a low-oxygenation strategy did not result in a reduction of 28-day mortality compared with a high-oxygenation strategy. Clinical trial registered with the National Trial Register and the International Clinical Trials Registry Platform (NTR7376).

Incidence of Lyme Borreliosis in the Dutch General Practice Population: A Large-Scale Population-Based Cohort Study Across the Netherlands Between 2015 and 2019.

Background: There is a need for updated incidence rates (IRs) of Lyme borreliosis (LB) in Europe, including the Netherlands. We estimated LB IRs stratified by geographic area, year, age, sex, immunocompromised status, and socioeconomic status (SES). Methods: All subjects registered in the PHARMO General Practitioner (GP) Database without prior diagnosis of LB or disseminated LB and having ≥1 year of continuous database enrolment were included. IRs and corresponding confidence intervals (CIs) of GP-recorded LB, erythema migrans (EM), and disseminated LB were estimated during the period 2015‒2019. Results: We identified 14,794 events (suspected, probable, or confirmed) with a diagnostic code for LB that included 8219 with a recorded clinical manifestation: 7985 (97%) with EM and 234 (3%) with disseminated LB. National annual LB IRs were relatively consistent, ranging from 111 (95% CI 106‒115) in 2019 to 131 (95% CI 126‒136) in 2018 per 100,000 person-years. Incidence of LB showed a bimodal age distribution, with peak IRs observed among subjects aged 5‒14 and 60‒69 years in men and women. Higher LB incidence was found in subjects who were residents of the provinces of Drenthe and Overijssel, immunocompromised, or of lower SES. Similar patterns were observed for EM and disseminated LB. Conclusions: Our findings confirm that LB incidence remains substantial throughout the Netherlands with no indication of decline in the past 5 years. Foci in two provinces and among vulnerable populations suggest potential initial target groups for preventive strategies such as vaccination.

Evaluating the real-life effect of MP-AzeFlu on asthma outcomes in patients with allergic rhinitis and asthma in UK primary care.

BACKGROUND: MP-AzeFlu (Dymista®; spray of azelastine/fluticasone propionate) is the most effective allergic rhinitis (AR) treatment available. Its effect on asthma outcomes in patients with AR and asthma is unknown. METHODS: This pre-post historical cohort study, using the Optimum Patient Care Research Database, included patients aged ≥12 years, from UK general practice with active asthma (defined as a recorded diagnosis, with ≥1 prescription for reliever or controller inhaler) in the year before or at the initiation date. The primary study outcome was change in number of acute respiratory events (i.e. exacerbation or antibiotic course for a respiratory event) between baseline and outcome years. The effect size of MP-AzeFlu was quantified as the difference in % of patients that improved and worsened. RESULTS: Of the 1,188 patients with AR and asthma included, many had a record of irreversible obstruction (67%), and uncontrolled asthma (70.4%), despite high mean daily doses of reliever/controller therapy and acute oral corticosteroid use, in the year pre-MP-AzeFlu initiation. MP-AzeFlu initiation was associated with fewer acute respiratory events (effect size (e) = 5.8%, p = 0.0129) and a reduction in daily use of short-acting ß2-agonists, with fewer patients requiring >2 SABA puffs/week (e = 7.7% p < 0.0001). More patients had well-controlled asthma 1-year post-MP-AzeFlu initiation (e = 4.1%; p = 0.0037), despite a reduction in inhaled corticosteroids (e = 4.8%; p = 0.0078). CONCLUSIONS: This study provides the first direct evidence of the beneficial effect of MP-AzeFlu on asthma outcomes in co-morbid patients in primary care in the United Kingdom. TRIAL REGISTRATION: EUPAS30940. Registered August 13, 2019.

Determinants of non-recovery in physical health-related quality of life one year after cardiac surgery: a prospective single Centre observational study.

BACKGROUND: Recent studies show that substantial percentage of patients experienced worsening of health related quality of life (HRQoL) 1 year after cardiac surgery. The aim of this study is to identify risk factors that interfere with improvement of HRQoL. METHODS: From December 2015 till July 2017 a prospective single centre observational study was carried out in 1920 patients participated who underwent non-salvage cardiac surgery. All patients were requested to complete a Short Form 36 (SF-36) questionnaire before and 1 year after surgery. Primary aim of the study was to identify risk factors for non-recovery in the physical domain of the SF-36 in all cardiac surgery patients. Secondary aim was to identify identical risk factors in patients with isolated coronary artery bypass grafting. RESULTS: After cardiac surgery, the questionnaires for physical and mental health were completed by respectively 803 and 807 patients. Median age was 69[62-75] years, and 77% was male. In comparison to the preoperative status, 176 patients (21.9%) did not display an improvement in the SF-36 physical domain score 1 year after cardiac surgery. In a multivariate analysis independent risk factors for non-recovery in the SF-36 physical domain were baseline SF36 physical domain score (OR 0.954[0.942-0.965], P < 0.001), diabetes (OR 0.437 [0.265-0.720], P 0.001), female sex (OR 0.492 [0.307-0.789], P 0.003), post-operative infection (OR 0.240 [0.109-0.525], P < 0.001) and PCI within 1 year (OR 0.113 [0.036-0.349], P < 0.001) For isolated CABG, 23.2% of patients did not display an improvement in the physical domain score and risk factors appeared to be identical. CONCLUSIONS: Twenty two percent of all cardiac surgery patients did not show an improvement in the physical domain score of the HRQoL between the preoperative period and 1 year after surgery. Independent risk factors for non-recovery after cardiac surgery were baseline SF-36 physical domain score, diabetes, female sex, any postoperative infection and the need for PCI in the first year. Further research is needed to tailor the patient selection procedure prior to surgery and potentially modify risk factors in the perioperative process. TRIAL REGISTRATION: Due to type of study not applicable. https://www.ccmo.nl/metcs/erkende-metcs/regionale-toetsingscommissie-patientgebonden-onderzoek .

Distribution, Temporal Stability and Appropriateness of Therapy of Patients With COPD in the UK in Relation to GOLD 2019.

BACKGROUND: The 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report made recommendations for the assessment, initial and subsequent treatment chronic obstructive pulmonary disease (COPD) based on biomarkers, including blood eosinophil counts. METHODS: We evaluated the distribution of UK COPD patients initiating maintenance therapy and established patients by GOLD group, the prevalence of comorbidities and appropriateness of therapy using electronic patient records from the Optimum Patient Care Research Database (OPCRD). Changes in effective GOLD group, therapy and exacerbation rates over the next 2 years were analysed. FINDINGS: 11,409 established COPD patients and 699 starting therapy were studied. 44·3%, 25·7%, 13·8% & 16·2% of established COPD patients and 45·2%, 28·5%, 15·7% & 10·6% initiating therapy were in GOLD groups A, B, C & D respectively.The overall proportion in each GOLD group was similar after 2 years but there was substantial movement of patients between groups. Diabetes and cardiovascular disease were the most common comorbidities in all groups in both cohorts.LAMA monotherapy was the commonest initial therapy in all GOLD groups. In both cohorts there was over-treatment with escalation, de-escalation or switching in nearly 50% during follow-up.In both cohorts, exacerbation rates were highest in group D and appeared higher in over-treated patients. INTERPRETATION: Most patients are not at risk of exacerbations and co-morbidities are common. Many patients change effective GOLD group and therapy over time. Prescribing is not in accordance with guideline recommendations and many patients still appear over treated.

Animal exposure over the life-course and risk of multiple sclerosis: A case-control study within two cohorts of US women.

BACKGROUND: Whether animal exposure and specifically the timing of such exposure alters multiple sclerosis (MS) risk is unclear. We examined whether animal exposure was associated with MS risk, and whether risk differed by the participants' age. METHODS: We conducted a case-control study within the Nurses' Health Study ((NHS)/NHSII cohorts). Overall, 151 women with MS and 235 controls, matched by age and study cohort, completed an animal exposure history questionnaire. Animal exposure pre-MS onset was assessed as 'any' exposure, then by the participants age, and animal family. Conditional logistic regression was used to estimate relative MS risks, adjusted (adj.RR) for potential confounders. RESULTS: 'Any' animal exposure was reported by 136 (90.1%) MS cases compared to 200 (85.1%) matched controls, with dog exposure being the most common [120 (79.5%) cases vs. 170 (72.3%) controls]. There was no association between 'any' animal exposure and MS risk (adj.RR:1.52;95%CI:0.76-3.04). However, both 'any' animal and specifically dog exposure at ages 10-14 years were associated with an increased MS risk (adj.RR:1.67;95%CI:1.05-2.66 and 1.76;95%CI:1.12-2.78, respectively). CONCLUSION: Animal exposure, and specifically dog exposure, in early adolescence was associated with an increased risk of MS. Further work is needed to confirm this finding.

Pattern of risks of rheumatoid arthritis among patients using statins: A cohort study with the clinical practice research datalink.

We examined the association between statin use and the risk of rheumatoid arthritis (RA), with special focus on describing the patterns of risks of RA during statin exposure in a large population-based cohort in the United Kingdom. In the Clinical Practice Research Datalink, patients aged ≥40 years with at least one prescription of statins (1995-2009) were selected, and matched by age (+/-5 years), sex, practice and date of first prescription of statins to non-users. The follow-up period of statin use was divided into periods of current, recent and past exposure, with patients moving between these three exposure categories over time. Time-dependent Cox models were used to derive hazard ratios (HRs) of RA, adjusted for disease history and previous drug use. The study population included 1,023,240 patients, of whom 511,620 were statin users. No associations were found between RA and current (HRadj,1.06;99%CI:0.88-1.27) or past statin users (HRadj,1.18;99%CI:0.88-1.57). However, in patients who currently used statins, hazard rates were increased shortly after the first prescription of statins and then gradually decreased to baseline level. The risk of developing RA was increased in recent statin users, as compared to non-users (HRadj,1.39;99%CI:1.01-1.90). The risk of RA is substantially increased in the first year after the start of statins and then diminishes to baseline level. These findings may suggest that statins might accelerate disease onset in patients susceptible to develop RA, but in other patients, statins are probably safe and well tolerated, even after prolonged use. Alternatively, we cannot rule out that confounding by cardiovascular risk factors and ascertainment bias may have influenced the findings.

Pattern of risks of systemic lupus erythematosus among statin users: a population-based cohort study.

OBJECTIVES: To examine the association between the use of statins and the risk of systemic lupus erythematosus (SLE) with focus on describing the patterns of risks over time. SETTING: A population-based cohort study using the UK Clinical Practice Research Datalink. PARTICIPANTS: All patients aged 40 years or older who had at least one prescription of statins during the period 1995-2009 were selected and matched by age, sex, practice and date of first prescription to non-users. The follow-up period of statin users was divided into periods of current, recent and past exposure, with patients moving among these three exposure categories over time. Current statin users were also stratified into ≤1 year or >1 year of use. MAIN OUTCOME MEASURES: Time-dependent Cox models were used to calculate HRs of SLE, adjusted for disease history and previous drug exposure. RESULTS: We included 1 039 694 patients, of whom 519 847 were statin users. Current statin users did not have an increased risk of developing SLE among patients aged ≥40 years (HRadjusted 0.75, 95% CI 0.53 to 1.07). Current statin users who continued the therapy for >1 year had a 38% lower risk of developing SLE (HRadjusted 0.62, 95% CI 0.42 to 0.93). When more specific definitions for SLE were used, this latter finding, however, was not observed. CONCLUSIONS: Our findings showed no effect of statins on the risk of developing SLE among patients aged ≥40 years. Further research is needed to study the long-term effects of statins on SLE.

Evaluating the safety of ß-interferons in MS: A series of nested case-control studies.

OBJECTIVE: To examine the association between interferon-ß (IFN-ß) and potential adverse events using population-based health administrative data in British Columbia, Canada. METHODS: Patients with relapsing-remitting multiple sclerosis (RRMS) who were registered at a British Columbia Multiple Sclerosis Clinic (1995-2004) were eligible for inclusion and were followed up until death, absence from British Columbia, exposure to a non-IFN-ß disease-modifying drug, or December 31, 2008. Incidence rates were estimated for each potential adverse event (selected a priori and defined with ICD-9/10 diagnosis codes from physician and hospital claims). A nested case-control study was conducted to assess the odds of previous IFN-ß exposure for each potential adverse event with at least 30 cases. Cases were matched by age (±5 years), sex, and year of cohort entry, with up to 20 randomly selected (by incidence density sampling) controls. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated with conditional logistic regression adjusted for age at cohort entry. RESULTS: Of the 2,485 eligible patients, 77.9% were women, and 1,031 were treated with IFN-ß during follow-up. From the incidence analyses, 27 of the 47 potential adverse events had at least 30 cases. Patients with incident stroke (ORadj 1.83, 95% CI 1.16-2.89), migraine (ORadj 1.55, 95% CI 1.18-2.04), depression (ORadj 1.33, 95% CI 1.13-1.56), and hematologic abnormalities (ORadj 1.32, 95% CI 1.01-1.72) were more likely to have previous exposure to IFN-ß than controls. CONCLUSIONS: Among patients with RRMS, IFN-ß was associated with a 1.8- and 1.6-fold increase in the risk of stroke and migraine and 1.3-fold increases in depression and hematologic abnormalities.

Association between the use of selective serotonin reuptake inhibitors and multiple sclerosis disability progression.

BACKGROUND: Benefits of selective serotonin reuptake inhibitors (SSRIs) in modifying the multiple sclerosis (MS) disease course have been suggested, but their ability to delay disability progression remains unknown. We examined the association between SSRI exposure and MS disability progression. METHODS: A nested case-control study was conducted using the British Columbia (Canada) Multiple Sclerosis clinical data linked to health administrative data. The primary outcome was a sustained score of 6 (requires a cane to walk) on the Expanded Disability Status Scale (EDSS), and the secondary outcome was the onset of secondary progressive MS (SPMS, an advanced stage of MS). The cases were those who reached a study outcome and were matched with up to four randomly selected controls by sex, age, EDSS and calendar year at study entry using incidence density sampling. The associations between disability worsening and SSRI exposure were assessed with conditional logistic regression models, adjusted for confounders. RESULTS: A total of 3920 patients were included in the main analyses, of which 272 reached sustained EDSS 6 and 187 reached SPMS. SSRI exposure was significantly different between patients who reached sustained EDSS 6 and controls [adjusted odds ratio (adjOR):1.44; 95% confidence interval (CI):1.03-2.01]. However, SSRI exposure was not significantly different between those who reached SPMS and their controls (adjOR:1.35; 95%CI:0.89-2.04). CONCLUSION: We found no evidence to suggest that SSRI exposure was associated with a delay in MS disability accumulation or progression. Copyright © 2016 John Wiley & Sons, Ltd.

Statin use and markers of immunity in the Doetinchem cohort study.

It has been suggested that statins can both stimulate and suppress the immune system, and thereby, may influence autoimmune diseases. Therefore, we studied effects of statins on innate and adaptive immunity, and self-tolerance by measuring serological levels of C-reactive protein (CRP), neopterin, immunoglobulin E (IgE) antibodies and the presence of autoantibodies (antinuclear antibodies (ANA) and IgM rheumatoid factor (RF)) in the general population. We conducted a nested case-control study within the population-based Doetinchem cohort. Data from health questionnaires, serological measurements and information on medication from linkage to pharmacy-dispensing records were available. We selected 332 statin users (cases) and 331 non-users (controls), matched by age, sex, date of serum collection, history of cardiovascular diseases, diabetes mellitus type II and stroke. Multivariate regression analyses were performed to estimate effect of statins on the immune system. The median level of CRP in statin users (1.28 mg/L, interquartile range (IQR): 0.59-2.79) was lower than in non-users (1.62 mg/L, IQR: 0.79-3.35), which after adjustment was estimated to be a 28% lower level. We observed an inverse association between duration of statin use and CRP levels. Elevated levels of IgE (>100 IU/mL) were more prevalent in statin users compared to non-users. A trend towards increased levels of IgE antibodies in statin users was observed, whereas no associations were found between statin use and levels of neopterin or the presence of autoantibodies. In this general population sub-sample, we observed an anti-inflammatory effect of statin use and a trend towards an increase of IgE levels, an surrogate marker for Th (helper) 2 responses without a decrease in neopterin levels, a surrogate marker for Th1 response and/or self-tolerance. We postulate that the observed decreased inflammatory response during statin therapy may be important but is insufficient to induce loss of self-tolerance.

Suboptimal prescribing of proton-pump inhibitors in low-dose aspirin users: a cohort study in primary care.

OBJECTIVE: Determine the adherence to recommendations of concomitant proton-pump inhibitor (PPI) treatment in regular low-dose of aspirin (LDASA) users, taking factors associated with the probability of receiving a PPI into account. DESIGN: Cohort study. SETTING: Data were obtained from 120 Dutch primary care centres participating in the Netherlands Information Network of Primary Care (LINH). PARTICIPANTS: Patients 18 years and older who were regularly prescribed LDASA (30-325 mg) in 2008-2010 were included. MAIN OUTCOME MEASURES: Regular medication use was defined as receiving each consecutive prescription within 6 months after the previous one. Based on national guidelines, we categorised LDASA users into low and high gastrointestinal (GI) risk. A multilevel multivariable logistic regression analysis was applied to identify patient characteristics that influenced on the probability of regular PPI prescriptions. RESULTS: We identified 12 343 patients who started LDASA treatment, of whom 3213 (26%) were at increased risk of GI complications. In this group, concomitant regular use of PPI was 46%, 36% did not receive PPI prescriptions and 18% obtained prescriptions irregularly (p<0.0001). The chance to obtain regularly PPI prescriptions versus no PPI was significantly influenced by, among others, previous GI complications (OR 13.9 (95% CI 11.8 to 16.4)), use of non-steroidal anti-inflammatory drugs (OR 5.2 (4.3 to 6.3)), glucocorticosteroids (6.1 (4.6 to 8.0)), selective serotonin reuptake inhibitors (9.1 (6.7 to 12.2)), drugs for functional GI disorders (2.4 (1.9 to 3.0)) and increased age. CONCLUSIONS: Primary care physicians do not fully adhere to the current recommendations to prescribe PPIs regularly to LDASA users with an increased GI risk. More than 50% of the patients with an increased GI risk are not treated sufficiently with a concomitant PPI, increasing the risk of GI side effects. This finding underlines the necessity to consider merging recommendations into one common, standard and frequently used recommendation by primary care physicians.

Statin-associated polymyalgia rheumatica. An analysis using WHO global individual case safety database: a case/non-case approach.

OBJECTIVE: To assess whether there is an association between statin use and the occurrence of polymyalgia rheumatic (PMR) in the spontaneous reporting database of the World Health Organisation (WHO). METHODS: We conducted a case/non-case study based on individual case safety reports (ICSR) in the WHO global ICSR database (VigiBase). Case reports containing the adverse event term polymyalgia rheumatica (WHOART or MedDRA Preferred Term) were defined as cases. Non-cases were all case reports containing other adverse event terms. Each case was matched to five non-cases by age, gender, and time of reporting. Case reports regarding a statin as suspected or concomitant drug were identified using the Anatomical Therapeutic Chemical (ATC) classification. Multivariate logistic regression was used to calculate reporting odds ratios (RORs) with 95% confidence intervals (CI). RESULTS: We identified 327 reports of PMR as cases and 1635 reports of other ADRs as non-cases. Among cases, statins were more frequently reported as suspected agent (29.4%) compared to non-cases (2.9%). After adjustment for several covariates, statins were significantly associated with reports of PMR (ROR 14.21; 95% CI 9.89-20.85). CONCLUSION: The results of this study lends support to previous anecdotal case reports in the literature suggesting that the use of a statin may be associated with the occurrence of PMR. Further studies are needed to study the strength of the association in more detail and to elucidate the underlying mechanism.