Nested Case Control Analysis Research Articles

Paracetamol, Ibuprofen, and Recurrent Major Cardiovascular and Major Bleeding Events in 19 120 Patients With Recent Ischemic Stroke.

The presumed safety of paracetamol in high-cardiovascular risk patients has been questioned. We determined whether paracetamol or ibuprofen use is associated with major cardiovascular events (MACE) or major bleeding in 19 120 patients with recent ischemic stroke or transient ischemic attack of mainly atherothrombotic origin included in the Prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) trial. We performed 2 nested case-control analysis (2153 cases with MACE during trial follow-up and 4306 controls matched on Essen stroke risk score; 809 cases with major bleeding matched with 1616 controls) and a separate time-varying analysis. 12.3% were prescribed paracetamol and 2.5% ibuprofen. Median duration of treatment was 14 (interquartile range 5-145) days for paracetamol and 9 (5-30) days for ibuprofen. Paracetamol, but not ibuprofen, was associated with increased risk of MACE (odds ratio 1.21, 95% confidence interval [CI] 1.04-1.42) or a major bleeding (odds ratio 1.60, 95% CI 1.26-2.03), with no impact of daily dose and duration of paracetamol treatment. Time-varying analysis found an increased risk of MACE with both paracetamol (hazard ratio 1.22, 95% CI 1.05-1.43) and ibuprofen (hazard ratio 1.47, 95% CI 1.06-2.03) and of major bleeding with paracetamol (hazard ratio 1.95, 95% CI 1.45-2.62). There was a weak and inconsistent signal for association between paracetamol or ibuprofen and MACE or major bleeding, which may be related to either a genuine but modest effect of these drugs or to residual confounding. http://www.isrctn.com. Unique identifier: ISRCTN66157730.

Proton pump inhibitors and gastroenteritis.

An association between proton pump inhibitor (PPI) therapy and bacterial gastroenteritis has been suggested as well as contradicted. The aim of this study was to examine the association between the use of PPIs and occurrence of bacterial gastroenteritis in the prospective Rotterdam Study. The Rotterdam Study is a population-based cohort study among 14,926 subjects aged 45 years and older with up to 24 years of follow-up. Analyses were performed with a generalized estimating equations method in participants who handed-in a diagnostic stool sample. Furthermore, a nested case–control analysis was performed using the total cohort as a reference group. A bacterial microorganism was isolated in 125 samples, whereas 1174 samples were culture negative. In the generalized estimating equations analysis, we found that participants with a bacterial gastroenteritis were more likely than controls to be current users of PPIs (adjusted OR 1.94; 95 % CI 1.15–3.25). Different sensitivity analyses did not change this result. A considerably higher effect was observed (adjusted OR 6.14; 95 % CI 3.81–9.91), using the total cohort as a reference in a nested case–control analysis. Current PPI therapy is associated with an increased risk of bacterial gastroenteritis. However, by reducing the risk of selection and information bias in our study design, we demonstrated that the effect is lower than previously assumed.

Antidepressants in association with reducing risk of oral cancer occurrence: a nationwide population-based cohort and nested case-control studies.

ObjectivesSeveral studies suggested that antidepressant use may increase or decrease the risk of cancer occurrence, depending on specific cancer types. The possible carcinogenic effect of antidepressants has received substantial attention; however, evidence remains inconclusive. Here we investigated associations between the use of antidepressants and occurrences of oral cancer (OC).MethodsTwo million samples were randomly collected from the National Health Insurance Research Database in Taiwan, which covers 98% of the total population (23 million). All patients from2000 to 2009 were followed up. We identified 5103 patients newly diagnosed with OC after antidepressants use in addition to 20,412 non-OC matched subjects and 95,452 unmatched non-OC subjects.ResultsIn nested case control analysis, factors associating with OC, including age [OR = 1.02; 95% confidence interval (CI) = 1.01–1.03) and male (OR = 5.30; 95% CI = 4.92–5.70) were independently associated with increased risk of OC. Based on the functions of antidepressants, antidepressants treatment medications were further classified to investigate risk of OC. Selective serotonin reuptake inhibitors (OR = 0.61; 95% CI = 0.53–0.70) and tricyclic antidepressants (OR = 0.57; 95% CI = 0.52–0.63) were associated with reduced risk of OC. The risk of developing OC among subjects taking antidepressants was less than 26% [hazard ratio (HR) =0.74; 95% CI = 0.68–0.81] in prospective cohort study. The effect of a cumulative duration and dose was a significantly reduced risk of OC.ConclusionsThe association between antidepressant use and decreasing OC risk were demonstrated by both prospective and nested case–control studies.

Incidence and risk factors for severe renal impairment after first diagnosis of heart failure: A cohort and nested case–control study in UK general practice

ObjectiveWe aimed to evaluate the incidence, time-course and risk factors for severe renal impairment (SRI) among incident heart failure (HF) patients. Methods and resultsPatients aged 1–89years from 2000 to 2005 with incident HF and without SRI or cancer (N=18,049) were identified from The Health Improvement Network (a primary care database representative of the UK population). Patients with a first ever record of SRI during follow-up were identified and eligible non-cases used as controls (N=5377; mean age 74years). Cohort and nested case–control analyses were conducted to identify risk factors for SRI. 2818 patients (15.6%, mean age 75years) in the HF cohort developed SRI over a mean of 2.84years with incidence highest in the first year following HF diagnosis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were as follows: diabetes (1.96, 1.80–2.14), hypertension (1.23, 1.14–1.33), peripheral artery disease (1.29, 1.15–1.45), ischemic cerebrovascular disease (1.14, 1.03–1.26), and anemia (1.19, 1.06–1.34). Several cardiovascular medications were associated with SRI in the case–control analysis, odds ratios (95% CIs): 5.07 (3.87–6.64) for all diuretics, 3.22 (2.83–3.66) for potassium-sparing diuretics, 2.40 (1.96–2.93) for thiazide and related diuretics and 3.27 (2.67–4.01) for loop-diuretics. ConclusionSRI is a frequent complication in patients with newly diagnosed HF. Comorbidities may contribute to its development and should be adequately treated. Robust clinical trial data on beneficial or possibly deleterious effects of diuretics, especially loop-diuretics and potassium-sparing diuretics, on SRI development in HF patients are warranted.

Risk of Seizures Associated with Antidepressant Use in Patients with Depressive Disorder: Follow-up Study with a Nested Case-Control Analysis Using the Clinical Practice Research Datalink.

Antidepressant use has been associated with an increased risk of seizures. Evidence on the association between antidepressant use at therapeutic doses and seizures mainly comes from clinical trials that were not designed to investigate this potential relationship. The objective of this study was to assess the risk of first-time seizures in association with exposure to antidepressants in patients with depressive disorders. We conducted a retrospective follow-up study with a nested case-control analysis between 1998 and 2012, using data from the UK-based Clinical Practice Research Datalink (CPRD). We estimated crude incidence rates with 95 % confidence intervals (CIs) of seizures in depressed patients who used selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), 'other antidepressants', no antidepressants, or who had used antidepressants in the past. To adjust for potential confounding, we estimated odds ratios of antidepressant drug use among cases with seizures and matched controls in a nested case-control analysis. Of 151,005 depressed patients, 619 had an incident seizure during follow-up. Incidence rates per 10,000 person-years were 12.44 (95 % CI 10.67-14.21) in SSRI users, 15.44 (95 % CI 8.99-21.89) in SNRI users, 8.33 (95 % CI 4.68-11.98) in TCA users, 9.33 (95 % CI 6.19-12.46) in non-users of antidepressants, and 5.05 (95 % CI 4.49-5.62) in past users of antidepressants. In the case-control analysis, relative risk estimates for seizures were increased in current users of SSRIs (adjusted odds ratio 1.98, 95 % CI 1.48-2.66) and SNRIs (adjusted odds ratio 1.99, 95 % CI 1.20-3.29), but not TCAs (adjusted odds ratio 0.99, 95 % CI 0.63-1.53), compared with non-users. Current use of SSRIs or SNRIs was associated with a twofold increased risk of first-time seizures compared with non-use, while current use of TCAs (mostly low dose) was not associated with seizures. Treatment initiation in SSRI and SNRI users was associated with a higher risk of seizures than longer-term treatment.

Sending Repeat Cultures: Is There a Role in the Management of Bacteremic Episodes? (SCRIBE Study)

Background: In the management of bacteremia, positive repeat blood cultures (persistent bacteremia) are associated with increased mortality. However, blood cultures are costly and it is likely unnecessary to repeat them for many patients. We assessed predictors of persistent bacteremia that should prompt repeat blood cultures. Methods: We conducted a retrospective cohort study of bacteremias at an academic hospital from April 2010 to June 2014. We examined variables associated with patients undergoing repeat blood cultures, and with repeat cultures being positive. A nested case control analysis was performed on a subset of patients with repeat cultures. Results: Among 1801 index bacteremias, repeat cultures were drawn for 701 patients (38.9 %), and 118 persistent bacteremias (6.6 %) were detected. Endovascular source (adjusted odds ratio [aOR], 7.66; 95 % confidence interval [CI], 2.30-25.48), epidural source (aOR, 26.99; 95 % CI, 1.91-391.08), and Staphylococcus aureus bacteremia (aOR, 4.49; 95 % CI, 1.88-10.73) were independently associated with persistent bacteremia. Escherichia coli (5.1 %, P=0.006), viridans group (1.7 %, P = 0.035) and β-hemolytic streptococci (0 %, P = 0.028) were associated with a lower likelihood of persistent bacteremia. Patients with persistent bacteremia were less likely to have achieved source control within 48 h of the index event (29.7 % vs 52.5 %, P < .001), but after variable reduction, source control was not retained in the final multivariable model. Conclusions: Patients with S. aureus bacteremia or endovascular infection are at risk of persistent bacteremia. Achieving source control within 48 h of the index bacteremia may help clear the infection. Repeat cultures after 48 h are low yield for most Gram-negative and streptococcal bacteremias.

Antipsychotic drug use and the risk of seizures: follow-up study with a nested case-control analysis.

To investigate the association between antipsychotic drug use and the development of first-time seizures in patients with schizophrenia, affective disorders, or dementia. We used data from the UK-based Clinical Practice Research Datalink database to conduct a follow-up study with a nested case-control analysis between 1998 and 2013. We identified patients with schizophrenia, affective disorders, or dementia, and estimated incidence rates of seizures among users of four antipsychotic drug subclasses, defined according to existing hypotheses on their seizure-inducing potential (1, olanzapine or quetiapine; 2, amisulpride, aripiprazole, risperidone, or sulpiride; 3, low-to-medium potency first-generation antipsychotic drugs [chlorpromazine, zuclopenthixol, flupenthixol, pericyazine, promazine, thioridazine]; 4, medium-to-high potency first-generation antipsychotic drugs [haloperidol, prochlorperazine, trifluoperazine]), and among those who did not use antipsychotic drugs. To adjust for confounding, we estimated odds ratios for seizures separately among patients with affective disorders or dementia, stratified by antipsychotic drug use and timing of use. In the total cohort of 60,121 patients (who had schizophrenia, affective disorders, or dementia), the incidence rate of seizures per 10,000 person-years was 32.6 (95% confidence interval [CI] 22.6-42.6) in users of olanzapine or quetiapine, 24.1 (95% CI 13.2-34.9) in users of amisulpride, aripiprazole, risperidone, or sulpiride, 49.4 (95% CI 27.7-71.0) in users of low-to-medium potency antipsychotic drugs, 59.1 (95% CI 40.1-78.2) in users of medium-to-high potency antipsychotic drugs, and 11.7 (95% CI 10.0-13.4) in non-users of antipsychotic drugs. Patients with dementia had significantly higher incidence rates of first-time seizures compared with patients with affective disorders, irrespective of antipsychotic drug use. In patients with affective disorders, current use of medium-to-high potency first-generation antipsychotic drugs was associated with an increased risk of seizures (adjusted odds ratio 2.51 [95% CI 1.51-4.18]) compared with non-use, while use of other antipsychotic drugs was not associated with seizures. In patients with dementia, current use of olanzapine or quetiapine (adjusted odds ratio 2.37 [95% CI 1.35-4.15]), low-to-medium potency first-generation antipsychotic drugs (adjusted odds ratio 3.08 [95% CI 1.34-7.08]), and medium-to-high potency first-generation antipsychotic drugs (adjusted odds ratio 2.24 [95% CI 1.05-4.81]) was associated with an increased risk of seizures compared with non-use, but current use of amisulpride, aripiprazole, risperidone, or sulpiride (adjusted odds ratio 0.92 [95% CI 0.48-1.75]) was not. Use of antipsychotic drugs in patients with schizophrenia could not be investigated because of small numbers. Current use of medium-to-high potency first-generation antipsychotic drugs was associated with a 2.5-fold increased risk of seizures compared with non-use of antipsychotic drugs in patients with affective disorders. In these patients, current use of all other antipsychotic drug subclasses was not associated with seizures. In patients with dementia, current and past use of all antipsychotic drug subclasses, except amisulpride, aripiprazole, risperidone, or sulpiride, was associated with an increased risk of seizures.

Plasma matrix metalloproteinase 2 levels and breast cancer risk

Matrix metalloproteinase 2 (MMP2) is an enzyme with important functions in breast cancer invasion and metastasis. However, it is unclear whether circulating MMP2 levels may predict breast cancer risk. We conducted a prospective nested case–control analysis in the Nurses’ Health Study among 1136 cases who were diagnosed with invasive breast cancer between 1992 and 2004 and 1136 matched controls. All participants provided blood samples in 1989–1990, and a subset (170 cases, 170 controls) contributed an additional sample in 2000–2002. Pre-diagnostic plasma MMP2 levels were measured via immunoassay, and conditional logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for breast cancer risk factors. No association was observed between plasma MMP2 levels and risk of total invasive breast cancer (top vs. bottom quartile, OR=1.0; 95% CI: 0.7, 1.2; p-trend=0.89). Findings did not vary significantly by time since blood draw, body mass index, postmenopausal hormone use, or menopausal status at either blood draw or breast cancer diagnosis. MMP2 was associated with a greater risk of nodal metastases at diagnosis (top vs. bottom quartile, OR=1.5; 95% CI: 1.0, 2.2; p-heterogeneity, any vs. no lymph nodes=0.002), but no significant associations were observed with other tumor characteristics or with recurrent or fatal cancers. Plasma MMP2 levels do not appear to be predictive of total invasive breast cancer risk, although associations with aggressive disease warrant further study.

Soft tissue sarcoma, non-Hodgkin's lymphoma and chronic lymphocytic leukaemia in workers exposed to phenoxy herbicides: extended follow-up of a UK cohort

ObjectivesTo provide further information on the possible carcinogenicity of phenoxy herbicides, and in particular their relationship to soft tissue sarcoma (STS), non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL).MethodsWe extended...

Autism spectrum disorder and particulate matter air pollution before, during, and after pregnancy: a nested case-control analysis within the Nurses' Health Study II Cohort.

BackgroundAutism spectrum disorder (ASD) is a developmental disorder with increasing prevalence worldwide, yet has unclear etiology.ObjectiveWe explored the association between maternal exposure to particulate matter (PM) air pollution and odds of ASD in her child.MethodsWe conducted a nested case–control study of participants in the Nurses’ Health Study II (NHS II), a prospective cohort of 116,430 U.S. female nurses recruited in 1989, followed by biennial mailed questionnaires. Subjects were NHS II participants’ children born 1990–2002 with ASD (n = 245), and children without ASD (n = 1,522) randomly selected using frequency matching for birth years. Diagnosis of ASD was based on maternal report, which was validated against the Autism Diagnostic Interview-Revised in a subset. Monthly averages of PM with diameters ≤ 2.5 μm (PM2.5) and 2.5–10 μm (PM10–2.5) were predicted from a spatiotemporal model for the continental United States and linked to residential addresses.ResultsPM2.5 exposure during pregnancy was associated with increased odds of ASD, with an adjusted odds ratio (OR) for ASD per interquartile range (IQR) higher PM2.5 (4.42 μg/m3) of 1.57 (95% CI: 1.22, 2.03) among women with the same address before and after pregnancy (160 cases, 986 controls). Associations with PM2.5 exposure 9 months before or after the pregnancy were weaker in independent models and null when all three time periods were included, whereas the association with the 9 months of pregnancy remained (OR = 1.63; 95% CI: 1.08, 2.47). The association between ASD and PM2.5 was stronger for exposure during the third trimester (OR = 1.42 per IQR increase in PM2.5; 95% CI: 1.09, 1.86) than during the first two trimesters (ORs = 1.06 and 1.00) when mutually adjusted. There was little association between PM10–2.5 and ASD.ConclusionsHigher maternal exposure to PM2.5 during pregnancy, particularly the third trimester, was associated with greater odds of a child having ASD.CitationRaz R, Roberts AL, Lyall K, Hart JE, Just AC, Laden F, Weisskopf MG. 2015. Autism spectrum disorder and particulate matter air pollution before, during, and after pregnancy: a nested case–control analysis within the Nurses’ Health Study II cohort. Environ Health Perspect 123:264–270; http://dx.doi.org/10.1289/ehp.1408133

Risk of uncomplicated peptic ulcer disease in a cohort of new users of low-dose acetylsalicylic acid for secondary prevention of cardiovascular events.

BackgroundThe aim of this study was to analyse the risk of uncomplicated peptic ulcer disease (PUD) in a cohort of new users of low-dose acetylsalicylic acid (ASA) for secondary prevention of cardiovascular events in a UK primary care setting.MethodsNew users of low-dose ASA for secondary prevention of cardiovascular events, aged 50-84 years in 2000-2007, were identified from The Health Improvement Network. Among those 38,975 individuals, 309 patients were considered to be incident cases of uncomplicated PUD. Incidence of uncomplicated PUD was calculated and a nested case–control analysis adjusted for potential confounding factors was performed to calculate the odds ratios (ORs) for the association of potential risk factors with uncomplicated PUD.ResultsThe crude incidence of uncomplicated PUD was 1.41 per 1000 person-years (95% confidence interval [CI], 1.26-1.58). Individuals with a history of PUD were more likely to develop uncomplicated PUD than those without such a history (hazard ratio [HR], 2.22, 95% CI, 1.60-3.09). In nested case–control analyses, the risk of uncomplicated PUD was associated with current use of non-steroidal anti-inflammatory drugs, oral steroids or acid suppressants. Other risk factors for developing uncomplicated PUD included smoking, stress, depression, anaemia and social deprivation.ConclusionOur results indicate that several risk factors significantly increase the risk of development of uncomplicated PUD in new users of low-dose ASA. Therefore, physicians should monitor ASA users for gastrointestinal symptoms and signs of ulcer, particularly if they have additional risk factors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-014-0205-y) contains supplementary material, which is available to authorized users.

Does comedy kill? A retrospective, longitudinal cohort, nested case–control study of humour and longevity in 53 British comedians

ObjectivesThis work aims to test the hypothesis that the funniest comedians are most at risk of a premature death and reduced longevity compared to their relatively less funny counterparts. MethodsA retrospective longitudinal cohort study with a nested case–control analysis of longevity of 53 male British comedians born between 1900 and 1954 was conducted. All comedians were given a subjective score from 1 (relatively funny) to 10 (hilariously funny) by the study investigators. The survival profile of all comedians was then examined adjusting for decade of birth, whether they worked in a comedy team and their comedy score. A nested case–control analysis examined the longevity of those comedians working in teams according to their pre-specified status within the team (straight/less funny versus funny team member). ResultsOn an adjusted basis, there was no correlation between the decade of birth (HR 0.94, 95% 0.65 to 1.38 per incremental decade; p=0.763) and comedy team status (HR 1.13, 95% 0.51 to 2.48 versus independent comedian; p=0.761) with longevity. However, an increasingly funny comedy score was associated with increased mortality (HR 1.24, 95% CI 1.06 to 1.44 per unit funny score; p=0.006). Of the 23 comedians adjudged to be very funny (score 8–10), 18 (78%) had died versus 12 (40%) of the rest; mean age at death 63.3±12.2 versus 72.3±14.7 (p=0.079). Within comedy teams, those identified as the funnier member(s) of the partnership were, on an adjusted basis, more than three times more likely to die prematurely when compared to their more serious comedy partners (HR 3.52, 95% CI 1.22, 10.1; p=0.020). ConclusionsThese data suggest that elite comedians are at increased risk of premature death compared to their less funny counterparts. Mental health issues and personality characteristics that help shape their comedic talent and success may well explain their reduced longevity and raises serious issues for identifying and mitigating their risk of a premature death.

Risk of cancer in workers exposed to styrene at eight British companies making glass-reinforced plastics

ObjectivesTo provide further information on the risks of lymphohaematopoietic (LH) and other cancers associated with styrene.MethodsWe extended follow-up to December 2012 for 7970 workers at eight companies in England which...

Incidence and risk factors of HPV-related and HPV-unrelated Head and Neck Squamous Cell Carcinoma in HIV-infected individuals

To examine the risk and trends of HPV-related and HPV-unrelated Head and Neck Squamous Cell Carcinoma (HNSCC) in HIV-infected individuals and assess whether immunosuppression (measured through CD4 cell count) and other risk factors impact HNSCC risk. Incident HNSCCs at HPV-related and HPV-unrelated anatomic sites were detected in HIV-infected participants from pooled data from 17 prospective studies in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) between 1996 and 2009. HNSCC cases were validated using chart review or cancer registry matching. Risk factors for incident HPV-related and HPV-unrelated HNSCC were explored using mixed effects Poisson regression in a full prospective analysis, and the effect of CD4 prior to cancer diagnosis was examined in a nested case control analysis. 66 HPV-related and 182 HPV-unrelated incident HNSCCs were detected among 82,375 HIV-infected participants. Standardized incidence ratios (SIRs) for both HPV-related (SIR=3.2, 95%CI=2.5-3.4) and HPV-unrelated (SIR=3.0, 95%CI=2.5-4.1) HNSCC were significantly elevated in HIV-infected individuals compared with the US general population. Between 1996 and 2009, the age-standardized HPV-related HNSCC incidence increased non-significantly from 6.8 to 11.4per 100,000 person-years (p-trend=0.31) while the age-standardized incidence of HPV-unrelated HNSCC decreased non-significantly from 41.9 to 29.3 per 100,000 person-years (p-trend=0.16). Lower CD4 cell count prior to cancer diagnosis was significantly associated with increased HPV-related and HPV-unrelated HNSCC risk. The standardized incidence of HPV-related and HPV-unrelated HNSCC are both elevated in HIV-infected individuals. Immunosuppression may have a role in the development of both HPV-related and HPV-unrelated HNSCC.

The use of metformin in patients with prostate cancer and the risk of death.

Given the conflicting results from observational studies, we assessed whether the use of metformin after a prostate cancer diagnosis is associated with a decreased risk of cancer-specific and all-cause mortality. This study was conducted linking four databases from the United Kingdom. A cohort of men newly diagnosed with nonmetastatic prostate cancer with a history of treated type II diabetes, between April 1, 1998 and December 31, 2009, was followed until October 1, 2012. Nested case-control analyses were performed for cancer-specific mortality and all-cause mortality, in which exposure was defined as use of metformin during the time to risk-set. Conditional logistic regression was used to estimate adjusted rate ratios (RR) of each outcome with 95% confidence intervals (CI). The cohort consisted of 935 men with prostate cancer and a history of type II diabetes. After a mean follow-up of 3.7 years, 258 deaths occurred, including 112 from prostate cancer. Overall, the post-diagnostic use of metformin was not associated with a decreased risk of cancer-specific mortality (RR, 1.09; 95% CI, 0.51-2.33). In a secondary analysis, a cumulative duration ≥938 days was associated with an increased risk (RR, 3.20; 95% CI, 1.00-10.24). The post-diagnostic use of metformin was not associated with all-cause mortality (RR, 0.79; 95% CI, 0.50-1.23). The use of metformin after a prostate cancer diagnosis was not associated with an overall decreased risk of cancer-specific and all-cause mortality. The results of this study do not support a role for metformin in the prevention of prostate cancer outcomes.

Plasma magnesium and risk of ischemic stroke among women.

Lower plasma magnesium levels may be associated with higher blood pressure and endothelial dysfunction, but sparse prospective data are available for stroke. Among 32,826 participants in the Nurses' Health Study who provided blood samples in 1989 to 1990, incident ischemic strokes were identified and confirmed by medical records through 2006. We conducted a nested case-control analysis of 459 cases, matched 1:1 to controls on age, race/ethnicity, smoking status, date of blood draw, fasting status, menopausal status, and hormone use. We used conditional logistic regression models to estimate the multivariable adjusted association of plasma magnesium and the risk of ischemic stroke and ischemic stroke subtypes. Median magnesium levels did not differ between ischemic stroke cases and controls (median, 0.86 mmol/L for both; P=0.14). Conditional on matching factors, women in the lowest magnesium quintile had a relative risk of 1.34 (95% confidence interval, 0.86-2.10; P trend=0.13) for total ischemic stroke compared with women in the highest quintile. Additional adjustment for risk factors and confounders did not substantially alter the risk estimates for total ischemic stroke. Women with magnesium levels<0.82 mmol/L had significantly greater risk of total ischemic stroke (multivariable relative risk, 1.57; 95% confidence interval, 1.09-2.27; P=0.01) and thrombotic stroke (multivariable relative risk, 1.66; 95% confidence interval, 1.03-2.65; P=0.03) compared with women with magnesium levels≥0.82 mmol/L. No significant effect modification was observed by age, body mass index, hypertension, or diabetes mellitus. Lower plasma magnesium levels may contribute to higher risk of ischemic stroke among women.

Cardiac glycosides use and the risk of lung cancer: a nested case-control study.

BackgroundTwo studies have reported statistically significant associations between the use of cardiac glycosides (CGs) and an increased risk of lung cancer. However, these studies had a number of methodological limitations. Thus, the objective of this study was to assess this association in a large population-based cohort of patients.MethodsWe used the United Kingdom Clinical Practice Research Datalink (CPRD) to identify a cohort of patients, at least 40 years of age, newly-diagnosed with heart failure, or supra-ventricular arrhythmia. A nested case–control analysis was conducted where each incident case of lung cancer identified during follow-up was randomly matched with up to 10 controls. Exposure to CGs was assessed in terms of ever use, cumulative duration of use and cumulative dose. Rate ratios (RRs) with 95% confidence intervals (CIs) were estimated using conditional logistic regression after adjusting for potential confounders.ResultsA total of 129,002 patients were included, and followed for a mean (SD) of 4.7 (3.8) years. During follow-up, 1237 patients were newly-diagnosed with lung cancer. Overall, ever use of CGs was not associated with an increased risk of lung cancer when compared to never use (RR = 1.09, 95% CI: 0.94-1.26). In addition, no dose–response relationship was observed in terms of cumulative duration of use and cumulative dose with all RRs around the null value across quartile categories.ConclusionThe results of this large population-based study indicate that the use of CGs is not associated with an increased risk of lung cancer.

Serum 25-hydroxyvitamin D concentrations and risk of prostate cancer: results from the Prostate Cancer Prevention Trial.

Epidemiologic studies have reported inconsistent associations of vitamin D and prostate cancer risk; however, few have adequately controlled for detection bias related to prostate-specific antigen (PSA) screening, and the results of many studies may be affected by occult prostate cancers among controls. Data for this nested case-control analysis (n = 1,695 cases/1,682 controls) are from the Prostate Cancer Prevention Trial. Baseline serum was analyzed for 25-hydroxyvitamin D [25(OH)D]. The presence or absence of cancer was subsequently determined by prostate biopsy. Polytomous logistic regression models were used to estimate associations of 25(OH)D with risk of total, Gleason 2-6, Gleason 7, and Gleason 8-10 prostate cancer. Results are presented for placebo and finasteride arms separately and combined. There were no associations of serum 25(OH)D with total prostate cancer risk. For Gleason 2-6 cancers, results were inconsistent across treatment arms with a suggestion of increased risk in the placebo arm only; however, there was no dose-response relationship. For Gleason 8-10 prostate cancers, 25(OH)D concentrations were associated with a linear decrease in risk among combined treatment arms [quartile 4 vs. 1: OR, 0.55; 95% confidence interval (CI), 0.32-0.94; P(trend) = 0.04]. These findings were somewhat stronger among men ≥65 versus 55-64 years at baseline (quartile 4 vs. 1: OR, 0.40; 95% CI, 0.18-0.88 vs. OR, 0.73; 95% CI, 0.35-1.52, respectively; P(interaction) = 0.52). Higher serum 25(OH)D may modestly increase risk of Gleason 2-6 disease and more substantially reduce risk of Gleason 8-10 prostate cancer. Vitamin D may have different effects for different stages of prostate cancers.

Connecting combat-related mild traumatic brain injury with posttraumatic stress disorder symptoms through brain imaging

Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) may share common symptom and neuropsychological profiles in military service members (SMs) following deployment; while a connection between the two conditions is plausible, the relationship between them has been difficult to discern. The intent of this report is to enhance our understanding of the relationship between findings on structural and functional brain imaging and symptoms of PTSD. Within a cohort of SMs who did not meet criteria for PTSD but were willing to complete a comprehensive assessment within 2 months of their return from combat deployment, we conducted a nested case–control analysis comparing those with combat-related mTBI to age/gender-matched controls with diffusion tensor imaging, resting state functional magnetic resonance imaging and a range of psychological measures. We report degraded white matter integrity in those with a history of combat mTBI, and a positive correlation between the white matter microstructure and default mode network (DMN) connectivity. Higher clinician-administered and self-reported subthreshold PTSD symptoms were reported in those with combat mTBI. Our findings offer a potential mechanism through which mTBI may alter brain function, and in turn, contribute to PTSD symptoms.

Systemic Cytokine Levels Show Limited Correlation With Risk of HIV-1 Acquisition

It has been hypothesized that immune activation and inflammation may increase HIV-1 susceptibility, and that cytokines may be useful biomarkers for risk. Within a prospective cohort, we conducted a nested case-control analysis of plasma cytokine levels among women who acquired HIV-1 <3 months after sampling, compared with 3 different control groups. We observed associations between lower interleukin (IL)-6 and IL-10 and higher IL-7 levels with HIV-1 acquisition, however, these associations were inconsistent when comparing with different control groups. Inconsistent results within our study and among previous studies suggest that reproducible findings are needed before cytokines are useful biomarkers for HIV-1 susceptibility.