Project description:AimsAntihypertensive drugs have been implicated in coronavirus disease 2019 (COVID-19) susceptibility and severity, but estimated associations may be susceptible to bias. We aimed to evaluate antihypertensive medications and COVID-19 diagnosis and mortality, accounting for healthcare-seeking behaviour.MethodsA population-based case-control study was conducted including 16 866 COVID-19 cases and 70 137 matched controls from the UK Clinical Practice Research Datalink. We evaluated all-cause mortality among COVID-19 cases. Exposures were angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (B), calcium-channel blockers (C), thiazide diuretics (D) and other antihypertensive drugs (O). Analyses were adjusted for covariates and consultation frequency.ResultsACEIs were associated with lower odds of COVID-19 diagnosis (adjusted odds ratio [AOR] 0.82, 95% confidence interval [CI] 0.77-0.88) as were ARBs (AOR 0.87, 95% CI 0.80-0.95) with little attenuation from adjustment for consultation frequency. C and D were also associated with lower odds of COVID-19 diagnosis. Increased odds of COVID-19 for B (AOR 1.19, 95% CI 1.12-1.26) were attenuated after adjustment for consultation frequency (AOR 1.01, 95% CI 0.95-1.08). Patients treated with ACEIs or ARBs had similar odds of mortality (AOR 1.00, 95% CI 0.83-1.20) to patients treated with classes B, C, D or O or patients receiving no antihypertensive therapy (AOR 0.99, 95% CI 0.83-1.18).ConclusionsThere was no evidence that antihypertensive therapy is associated with increased risk of COVID-19 diagnosis or mortality; most classes of antihypertensive therapy showed negative associations with COVID-19 diagnosis.
Project description:BACKGROUND:Whether chronic inflammation increases prostate cancer risk remains unclear. This study investigated whether chronic inflammatory diseases (CID) or anti-inflammatory medication use (AIM) were associated with prostate cancer risk. METHODS:Fifty-five thousand nine hundred thirty-seven cases (all prostate cancer, 2007-2012) and 279,618 age-matched controls were selected from the Prostate Cancer Database Sweden. CIDs and AIMs was determined from national patient and drug registers. Associations were investigated using conditional logistic regression, including for disease/drug subtypes and exposure length/dose. RESULTS:Men with a history of any CID had slightly increased risk of any prostate cancer diagnosis (OR: 1.08; 95%CI: 1.04-1.12) but not 'unfavourable' (high-risk or advanced) prostate cancer. Generally, risk of prostate cancer was highest for shorter exposure times. However, a positive association was observed for asthma >?5?years before prostate cancer diagnosis (OR: 1.21; 95%CI: 1.05-1.40). Risk of prostate cancer was increased with prior use of any AIMs (OR: 1.26; 95%CI: 1.24-1.29). A positive trend with increasing cumulative dose was only observed for inhaled glucocorticoids (p?<?0.011). CONCLUSION:Detection bias most likely explains the elevated risk of prostate cancer with prior history of CIDs or use of AIMs, given the higher risk immediately after first CID event and lack of dose response. However, findings for length of time with asthma and dose of inhaled glucocorticoids suggest that asthma may increase risk of prostate cancer through other pathways.
Project description:OBJECTIVES:The study aims to compare the risk of chronic kidney diseases (CKDs) between patients with schizophrenia using first and second-generation antipsychotics. SETTING:Datasets of 2000-2013 National Health Insurance in Taiwan were used. PARTICIPANTS:The National Health Insurance reimbursement claims data have been transferred to and managed by the National Health Research Institute in Taiwan since 1996. We used the Psychiatric Inpatient Medical Claims database, a subset of the National Health Insurance Research Database, comprising a cohort of patients hospitalised for psychiatric disorders between 2000 and 2013 (n=2 67 807). The database included patients with at least one psychiatric inpatient record and one discharge diagnosis of mental disorders coded by the International Classification of Diseases, Ninth Revision (ICD-9) codes 290-319. The age of patients at first admission was restricted to 18-65 years. PRIMARY OUTCOME:CKD (ICD-9 code 582, 583, 585, 586, 588) requiring hospitalisation or three outpatient visits. The diagnosis of CKD follows the criteria of 'Kidney Disease: Improving Global Outcomes' in Taiwan. CKD is defined as a kidney damage as albumin-to-creatinine ratio >30 mg/g in two of three spot urine specimens or glomerular filtration rate <60 mL/min/1.73 m2 for 3 months or more. RESULTS:We found that the risks for CKD were higher for those who used second-generation antipsychotics (SGAs) longer cumulatively than those who did not. Using non-users, patients did not have any SGA records, as reference group, the risks for CKD comparing those using SGAs for 90 to 180 days with non-users and those using SGAs for more than 1000 days were 1.42 (1.06-1.91) and 1.30 (1.13-1.51), respectively. CONCLUSIONS:The current study suggests the relationship between using SGAs and risk of CKD.
Project description:Coronavirus disease 2019 (COVID-19) is a severe disease caused by a new variant of beta-coronavirus that first appeared in China. Human genetic factors, including polymorphisms, serve pivotal roles in the high transmission of SARS-CoV-2 and the stubbornly progressing sickness seen in a small but significant percentage of infected people; however, but these factors remain ill-defined. A total of 288 COVID-19 patients and 288 controls were genotyped for TMPRSS2 polymorphisms using both restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) and amplification refractory mutation system (ARMS)-PCR techniques. Different genotypes of TMPRSS2 polymorphisms were compared in terms of disease susceptibility and mortality. The statistical analysis showed that minor alleles of all studied variants statistically increased the risk of COVID-19, except for the rs75603675 C > A variant. The T allele of rs12329760 conferred an increased risk of COVID-19. Moreover, the AG/AC/TT/AG combination of genotypes significantly enhanced the risk of COVID-19 in our population. Different haplotypes of rs17854725/rs75603675/rs12329760/rs4303795 polymorphisms, including GACA, GACG, GATG, GATA, AATA, ACCG, ACTG, ACTA, GCCA, and GCTG, were found to be associated with increased risk of the disease (odds ratio > 1). Regarding the clinical and paraclinical characteristics, a statistically significant difference was found between non-severe and severe forms except for gender, platelet, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and underlying diseases. In addition, case genotypes of TMPRSS2 rs17854725 A > G, rs12329760 C > T, and rs4303795 A > G were significantly different regarding severe and non-severe forms of the disease (P-value < 0.001). Specifically, death was more frequent in carriers of the AG genotype of rs17854725 A > G (P-value = 0.022). Patients who carry the minor alleles of the four studied TMPRSS2 variants were rather vulnerable to COVID-19 infection. Our findings indicated that rs17854725 A > G (AA vs. AG and AA vs. GG), rs12329760 C > T (CC vs. CT and CC vs. TT), and rs4303795 A > G (AA vs. AG) genotypes of TMPRSS2 variations are associated with a more invasive disorder pattern. More studies on larger populations are needed to confirm our results.
Project description:BackgroundOver 5,488,000 cases of coronavirus disease-19 (COVID-19) have been reported since December 2019. We aim to explore risk factors associated with mortality in COVID-19 patients and assess the use of D-dimer as a biomarker for disease severity and clinical outcome.MethodsWe retrospectively analyzed the clinical, laboratory, and radiological characteristics of 248 consecutive cases of COVID-19 in Renmin Hospital of Wuhan University, Wuhan, China from January 28 to March 08, 2020. Univariable and multivariable logistic regression methods were used to explore risk factors associated with in-hospital mortality. Correlations of D-dimer upon admission with disease severity and in-hospital mortality were analyzed. Receiver operating characteristic curve was used to determine the optimal cutoff level for D-dimer that discriminated those survivors versus non-survivors during hospitalization.ResultsMultivariable regression that showed D-dimer > 2.0 mg/L at admission was the only variable associated with increased odds of mortality [OR 10.17 (95% CI 1.10-94.38), P = 0.041]. D-dimer elevation (≥ 0.50 mg/L) was seen in 74.6% (185/248) of the patients. Pulmonary embolism and deep vein thrombosis were ruled out in patients with high probability of thrombosis. D-dimer levels significantly increased with increasing severity of COVID-19 as determined by clinical staging (Kendall's tau-b = 0.374, P = 0.000) and chest CT staging (Kendall's tau-b = 0.378, P = 0.000). In-hospital mortality rate was 6.9%. Median D-dimer level in non-survivors (n = 17) was significantly higher than in survivors (n = 231) [6.21 (3.79-16.01) mg/L versus 1.02 (0.47-2.66) mg/L, P = 0.000]. D-dimer level of > 2.14 mg/L predicted in-hospital mortality with a sensitivity of 88.2% and specificity of 71.3% (AUC 0.85; 95% CI = 0.77-0.92).ConclusionsD-dimer is commonly elevated in patients with COVID-19. D-dimer levels correlate with disease severity and are a reliable prognostic marker for in-hospital mortality in patients admitted for COVID-19.
Project description:BackgroundWe aimed to quantify the association between chronic musculoskeletal pain and all-cause mortality, and to investigate the extent to which this association is mediated by physical activity, smoking status, alcohol consumption, and opioid use.MethodsFor this population-based cohort study, we used data from UK Biobank, UK between baseline visit (2006-2010) to 18th December 2020. We assessed the associations between chronic musculoskeletal pain and all-cause mortality using a Cox proportional hazards model. We performed causal mediation analyses to examine the proportion of the association between chronic musculoskeletal pain and all-cause mortality.FindingsOf the 384,367 included participants, a total of 187,269 participants reported chronic musculoskeletal pain. Higher number of pain sites was associated with increased risk of all-cause mortality compared to having no pain (e.g., four sites vs no site of pain, Hazard Ratio [HR] 1.46, 95% Confidence Interval [CI] 1.35 to 1.57). The multiple mediator analyses showed that the mediating proportions of all four mediators ranged from 53.4% to 122.6%: among participants with two or more pain sites, the effect estimate reduced substantially, for example, HR reduced from 1.25 (95% CI: 1.21 to 1.30; two pain sites) to 1.07 (95% CI: 1.01 to 1.11; two pain sites).InterpretationWe found that higher number of pain sites was associated with increased risk of all-cause mortality compared to having no pain, and at least half of the association of chronic musculoskeletal pain with increased all-cause mortality may be accounted for by four mediators.FundingTwins Research Australia.
Project description:Purpose: Patients with osteoporosis are at an increased risk of cardiovascular disease (CVD). Several antiosteoporosis medications have been demonstrated with the benefit of preventing osteoporosis. Our aim is to assess the CVD risks associated with antiosteoporosis medications using the National Health Insurance Research Database in Taiwan between 2000 and 2016. Methods: Among 41,102 patients of 40+ years old with newly diagnosed osteoporosis, 69.1% (N = 28,387) of patients were included in the user cohort of antiosteoporosis medicines, of whom 13, 472 developed CVD by the end of 2016, while 14,915 did not. Using the nested case-control analysis in the user cohort (88.0% women and 77.4% elderly), we applied conditional logistic regression to estimate odds ratios (ORs) of eight types of CVD for the users of denosumab, bisphosphonate, teriparatide, and hormone replacement therapy (HRT). Results: The adjusted ORs of overall CVDs were 0.13 (95% CI: 0.12-0.15) for denosumab users, 0.52 (95% CI: 0.45-0.61) for teriparatide users, and 0.80 (95% CI: 0.76-0.85) for bisphosphonate users. The HRT users were at higher odds of coronary artery and peripheral artery diseases, heart failure, pulmonary embolism, and deep vein thrombosis. Conclusion: Denosumab, teriparatide, and bisphosphonate may have more protective effects against CVD than hormone therapy. Physicians may take subsequent cardiovascular risks into account when choosing an adequate antiosteoporosis medication for patients with osteoporosis.
Project description:BACKGROUND:Chronic pain is highly prevalent in the working population. People tend to attempt self-initiated treatments to manage their pain. The self-efficacy of behavioural change is a suitable model for guiding the development of an electronic pain management programme (ePain). The aim in this study is to develop ePain and to evaluate its effectiveness at improving pain self-efficacy, reducing pain intensity and negative emotions, and increasing quality of life. METHODS:This study will be a randomized controlled trial. ePain will take the form of a 6-week online pain management programme. Participants will be aged 15 years or above, have chronic pain, and be employed. They must complete the baseline questionnaire and will be randomized into intervention and control groups. They will receive notifications to encourage their participation in ePain and complete the evaluation questionnaires. They will complete the process evaluation at week 3, the post assessment at week 6, and the follow-up assessment at week 12. The study will focus on pain self-efficacy; pain situations; negative emotions including levels of depression, anxiety, and stress; and quality of life. The participants' opinions of ePain will be collected as feedback. Data will be analysed on an intention-to-treat basis and generalized estimating equations will be used to investigate the time-averaged difference and differences at each follow-up time. DISCUSSION:The study will provide information about the pain situations of online users in the working population. The participants will benefit from improvements in pain self-efficacy, pain situations, emotional status, and quality of life. The study will illustrate whether online learning is an effective intervention for improving the pain self-efficacy of the working population. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03718702. Registered on 23 October 2018.
Project description:Until coronavirus disease 2019 (COVID-19) drugs specifically developed to treat COVID-19 become more widely accessible, it is crucial to identify whether existing medications have a protective effect against severe disease. Toward this objective, we conducted a large population study in Clalit Health Services (CHS), the largest healthcare provider in Israel, insuring over 4.7 million members. Two case-control matched cohorts were assembled to assess which medications, acquired in the last month, decreased the risk of COVID-19 hospitalization. Case patients were adults aged 18 to 95 hospitalized for COVID-19. In the first cohort, five control patients, from the general population, were matched to each case (n=6202); in the second cohort, two non-hospitalized SARS-CoV-2 positive control patients were matched to each case (n=6919). The outcome measures for a medication were: odds ratio (OR) for hospitalization, 95% confidence interval (CI), and the p-value, using Fisher's exact test. False discovery rate was used to adjust for multiple testing. Medications associated with most significantly reduced odds for COVID-19 hospitalization include: ubiquinone (OR=0.185, 95% CI [0.058 to 0.458], p<0.001), ezetimibe (OR=0.488, 95% CI [0.377 to 0.622], p<0.001), rosuvastatin (OR=0.673, 95% CI [0.596 to 0.758], p<0.001), flecainide (OR=0.301, 95% CI [0.118 to 0.641], p<0.001), and vitamin D (OR=0.869, 95% CI [0.792 to 0.954], p<0.003). Remarkably, acquisition of artificial tears, eye care wipes, and several ophthalmological products were also associated with decreased risk for hospitalization. Ubiquinone, ezetimibe, and rosuvastatin, all related to the cholesterol synthesis pathway were associated with reduced hospitalization risk. These findings point to a promising protective effect which should be further investigated in controlled, prospective studies. This research was supported in part by the Intramural Research Program of the National Institutes of Health, NCI.
Project description:IntroductionCigarette smoking is associated with development of significant comorbidities. Patients with underlying comorbidities have been found to have worse outcomes associated with Coronavirus Disease 2019 (Covid-19). This study evaluated 30-day mortality in Covid-19 positive patients based on smoking status.MethodsThis retrospective study of veterans nationwide examined Covid-19 positive inpatients between March 2020 and January 2021. Bivariate analysis compared patients based on smoking history. Propensity score matching adjusted for age, gender, race, ethnicity, Charlson comorbidity index (0-5 and 6-19) and dexamethasone use was performed. A multivariable logistic regression with backwards elimination and Cox Proportional Hazards Ratio was utilized to determine odds of 30-day mortality.ResultsThe study cohort consisted of 25,958 unique Covid-19 positive inpatients. There was a total of 2,995 current smokers, 12,169 former smokers, and 8,392 non-smokers. Death was experienced by 13.5% (n = 3503) of the cohort within 30 days. Former smokers (OR 1.15; 95% CI, 1.05-1.27) (HR 1.13; 95% CI, 1.03-1.23) had higher risk of 30-day mortality compared with non-smokers. Former smokers had a higher risk of death compared to current smokers (HR 1.16 95% CI 1.02-1.33). The odds of death for current vs. non-smokers did not significantly differ.ConclusionCompared to veteran non-smokers with Covid-19, former, but not current smokers with Covid-19 had a significantly higher risk of 30-day mortality.