Gabapentinoids and Risk for Severe Exacerbation in Chronic Obstructive Pulmonary Disease : A Population-Based Cohort Study.

BACKGROUND: North American and European health agencies recently warned of severe breathing problems associated with gabapentinoids, including in patients with chronic obstructive pulmonary disease (COPD), although supporting evidence is limited. OBJECTIVE: To assess whether gabapentinoid use is associated with severe exacerbation in patients with COPD. DESIGN: Time-conditional propensity score-matched, new-user cohort study. SETTING: Health insurance databases from the Régie de l'assurance maladie du Québec in Canada. PATIENTS: Within a base cohort of patients with COPD between 1994 and 2015, patients initiating gabapentinoid therapy with an indication (epilepsy, neuropathic pain, or other chronic pain) were matched 1:1 with nonusers on COPD duration, indication for gabapentinoids, age, sex, calendar year, and time-conditional propensity score. MEASUREMENTS: The primary outcome was severe COPD exacerbation requiring hospitalization. Hazard ratios (HRs) associated with gabapentinoid use were estimated in subcohorts according to gabapentinoid indication and in the overall cohort. RESULTS: The cohort included 356 gabapentinoid users with epilepsy, 9411 with neuropathic pain, and 3737 with other chronic pain, matched 1:1 to nonusers. Compared with nonuse, gabapentinoid use was associated with increased risk for severe COPD exacerbation across the indications of epilepsy (HR, 1.58 [95% CI, 1.08 to 2.30]), neuropathic pain (HR, 1.35 [CI, 1.24 to 1.48]), and other chronic pain (HR, 1.49 [CI, 1.27 to 1.73]) and overall (HR, 1.39 [CI, 1.29 to 1.50]). LIMITATION: Residual confounding, including from lack of smoking information. CONCLUSION: In patients with COPD, gabapentinoid use was associated with increased risk for severe exacerbation. This study supports the warnings from regulatory agencies and highlights the importance of considering this potential risk when prescribing gabapentin and pregabalin to patients with COPD. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research and Canadian Lung Association.

Association between access to primary care and unplanned emergency department return visits among patients 75 years and older.

OBJECTIVE: To identify factors associated with unplanned return visits to the emergency department (ED) among the population aged 75 years and older. Moreover, it aims to determine the association between patients' access to primary care and unplanned return visits. DESIGN: Data were collected from structured interviews, administrative databases, and medical charts at the index visits, and follow-up telephone calls were made at 3 months. SETTING: Emergency departments of the 3 tertiary care hospitals in Montréal, Que. PARTICIPANTS: Community-dwelling patients aged 75 years and older. MAIN OUTCOME MEASURES: Zero-inflated negative binomial regression analysis was conducted of unplanned return visits within 3 months. Rate ratios (RRs) and odds ratios (ORs) with 95% CIs are presented. RESULTS: During the study period, 4577 patients were identified, 2303 were recruited, and 1998 were retained for the analysis. Among the analysis sample, 33% were 85 and older, 34% lived alone, and 91% had a family physician. Before their ED visits, 16% of patients attempted to contact their family physicians. More than half of the patients reported having difficulty seeing their physicians for urgent problems, more than 40% had difficulty speaking with their family physicians by telephone, and more than one-third had difficulty booking appointments for new health problems. Within 3 months, 562 patients (28%) had made 894 return visits. Factors associated with a lower return visit rate included age 85 years and older (RR=0.80; 95% CI 0.67 to 0.96), less severe triage score (RR=0.83; 95% CI 0.74 to 0.92), and hospitalization at the index visit (RR=0.76; 95% CI 0.64 to 0.90). Factors that resulted in a higher return visit rate were difficulty booking appointments for new problems with their family physicians (RR=1.19; 95% CI 1.01 to 1.41), having had ED visits within the previous 6 months (RR=1.47; 95% CI 1.28 to 1.68), and higher Charlson comorbidity index scores (RR=1.06; 95% CI 1.01 to 1.11). Having had ED visits within the previous 6 months (OR=2.11; 95% CI 1.27 to 3.49), having a higher Charlson comorbidity index score (OR=1.41; 95% CI 1.19 to 1.68), and having received community care services (OR=3.00; 95% CI 0.95 to 9.53) also increased the odds of return visits. CONCLUSION: Although most people 75 years and older have a family physician, problems still exist in terms of timely access. Unplanned return visits to the ED are associated with having more comorbidities, having had previous ED visits, having already received community services, and having difficulty booking appointments with family physicians for new problems.

Treatment with isoniazid or rifampin for latent tuberculosis infection: population-based study of hepatotoxicity, completion and costs.

Clinical trials suggest less hepatotoxicity and better adherence with 4 months rifampin (4R) versus 9 months isoniazid (9H) for treating latent tuberculosis infection (LTBI). Our objectives were to compare frequencies of severe hepatic adverse events and treatment completion, and direct health system costs of LTBI regimens 4R and 9H, in the general population of the province of Quebec, Canada, using provincial health administrative data.Our retrospective cohort included all patients starting rifampin or isoniazid regimens between 2003 and 2007. We estimated hepatotoxicity from hospitalisation records, treatment completion from community pharmacy records and direct costs from billing records and fee schedules. We compared rifampin to isoniazid using logistic (hepatotoxicity), log-binomial (completion), and gamma (costs) regression, with adjustment for age, co-morbidities and other confounders.10 559 individuals started LTBI treatment (9684 isoniazid; 875 rifampin). Rifampin patients were older with more baseline co-morbidities. Severe hepatotoxicity risk was higher with isoniazid (n=15) than rifampin (n=1), adjusted OR=2.3 (95% CI: 0.3-16.1); there were two liver transplants and one death with isoniazid and none with rifampin. Overall, patients without co-morbidities had lower hepatotoxicity risk (0.1% versus 1.0%). 4R completion (53.5%) was higher than 9H (36.9%), adjusted RR=1.5 (95% CI: 1.3-1.7). Mean costs per patient were lower for rifampin than isoniazid: adjusted cost ratio=0.7 (95% CI: 0.5-0.9).Risk of severe hepatotoxicity and direct costs were lower, and completion was higher, for 4R than 9H, after adjustment for age and co-morbidities. Severe hepatotoxicity resulted in death or liver transplant in three patients receiving 9H, compared with no patients receiving 4R.

Predictors of hospitalization of tuberculosis patients in Montreal, Canada: a retrospective cohort study.

BACKGROUND: Hospitalization is the most costly health system component of tuberculosis (TB) control programs. Our objectives were to identify how frequently patients are hospitalized, and the factors associated with hospitalizations and length-of-stay (LOS) of TB patients in a large Canadian city. METHODS: We extracted data from the Montreal TB Resource database, a retrospective cohort of all active TB cases reported to the Montreal Public Health Department between January 1996 and May 2007. Data included patient demographics, clinical characteristics, and dates of treatment and hospitalization. Predictors of hospitalization and LOS were estimated using logistic regression and Cox proportional hazards regression, respectively. RESULTS: There were 1852 active TB patients. Of these, 51% were hospitalized initially during the period of diagnosis and/or treatment initiation (median LOS 17.5 days), and 9.0% hospitalized later during treatment (median LOS 13 days). In adjusted models, patients were more likely to be hospitalized initially if they were children, had co-morbidities, smear-positive symptomatic pulmonary TB, cavitary or miliary TB, and multi- or poly-TB drug resistance. Factors predictive of longer initial LOS included having HIV, renal disease, symptomatic pulmonary smear-positive TB, multi- or poly-TB drug resistance, and being in a teaching hospital. CONCLUSIONS: We found a high hospitalization rate during diagnosis and treatment of patients with TB. Diagnostic delay due to low index of suspicion may result in patients presenting with more severe disease at the time of diagnosis. Earlier identification and treatment, through interventions to increase TB awareness and more targeted prevention programs, might reduce costly TB-related hospital use.

Predictors of residential stability among homeless young adults: a cohort study.

BACKGROUND: Homelessness episodes have been shown to be associated with serious health outcomes among youth. This study was undertaken to estimate the probability of reaching residential stability over time and to identify predictors of residential stability among homeless young adults aged 18 to 25 years. METHODS: A prospective cohort study was carried out in Montréal, Canada, between April 5(th) 2006 and January 21(th) 2009. Interviews conducted every three months included questions on life conditions and social and mental health factors that are known to influence residential trajectories. Residential status was determined, starting on the first day after recruitment; each follow-up day was classified as a homeless day or a housed day. A period of 90 days was used to define residential stability; therefore the main study outcome was the occurrence of the first consecutive 90 housed days during the follow-up period. Kaplan-Meier and Cox proportional-hazards regression analyses were conducted. RESULTS: Of the 359 participants, 284 reached 90 days of residential stability over the study period, representing an annual probability of 80.5 %. In multivariate analysis, youth who had a high school degree, had a formal sector activity, and those who had sought psychological help were more likely to reach residential stability. Being a man, injecting substances, and having an informal sector activity were associated with a decreased probability to reach residential stability. CONCLUSION: Exposure to factors related to opportunities that promote social integration increases the chance of reaching residential stability. On the other hand, factors related to high level of street entrenchment seem to interfere with stabilization. Maximum efforts should be made to prevent chronic homelessness among youth, targeting not only individual impairments but also hinging on services adapted to foster social connections among the youth.

Hospital stay on acute care units for non-acute reasons: Effects of patient pre-hospitalization and admission factors.

This study identifies patient risk factors present prior to an acute hospitalization that are associated with occupying acute care beds for non-acute reasons on the 30th day of a hospitalization. Data from 952 adult patients were obtained, among which 333 (35%) were evaluated as non-acute on their 30th day. Inability to move in and out of the bed, cognitive impairment, receiving home or community healthcare services prior to hospitalization, unavailable family resources, a secondary diagnosis within the mental and behavioural category, and age ≥75 years were found to increase the risk of occupying acute care beds for non-acute reasons, while patients with a feeding tube were less likely to be non-acute at day 30.

Lymphoma risk in systemic lupus: effects of disease activity versus treatment.

OBJECTIVE: To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). METHODS: We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses. RESULTS: We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls. CONCLUSIONS: In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.

Residential trajectories of street youth-the Montréal Cohort Study.

Little is known about the course of homelessness among youth between the ages of 18 and 25 despite the many characteristics distinguishing them from adolescents and from older street-involved populations. We examined the residential trajectories of homeless young adults in Montréal over a 21-month period and identified determinants of various trajectory profiles. The 365 study participants (79 % men, mean age 21.9 years) were followed for an average of 515 days (range 81-630 days). We assessed housing status with a questionnaire based on the residential follow-back calendar designed by the New Hampshire Dartmouth Research Center. Using latent growth analysis to examine achievement of residential stability over time, we observed three different trajectories: group 1 presented a low probability of housing throughout the entire study period; group 2 showed a high probability of early and stable housing; group 3 displayed a fluctuating pattern. Protective correlates of residential stability included high school education, birth in Canada, and presence of mental health problems. Drug abuse or dependence was associated with a decreased probability of housing.

Concomitant Use of Selective Serotonin Reuptake Inhibitors With Oral Anticoagulants and Risk of Major Bleeding.

Importance: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants associated with a small increased risk of major bleeding. However, the risk of bleeding associated with the concomitant use of SSRIs and oral anticoagulants (OACs) has not been well characterized. Objectives: To assess whether concomitant use of SSRIs with OACs is associated with an increased risk of major bleeding compared with OAC use alone, describe how the risk varies with duration of use, and identify key clinical characteristics modifying this risk. Design, Setting, and Participants: A population-based, nested case-control study was conducted among patients with atrial fibrillation initiating OACs between January 2, 1998, and March 29, 2021. Patients were from approximately 2000 general practices in the UK contributing to the Clinical Practice Research Datalink. With the use of risk-set sampling, for each case of major bleeding during follow-up, up to 30 controls were selected from risk sets defined by the case and matched on age, sex, cohort entry date, and follow-up duration. Exposures: Concomitant use of SSRIs and OACs (direct OACs and vitamin K antagonists [VKAs]) compared with OAC use alone. Main Outcomes and Measures: The main outcome was incidence rate ratios (IRRs) of hospitalization for bleeding or death due to bleeding. Results: There were 42 190 patients with major bleeding (mean [SD] age, 74.2 [9.3] years; 59.8% men) matched to 1 156 641 controls (mean [SD] age, 74.2 [9.3] years; 59.8% men). Concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OACs alone (IRR, 1.33; 95% CI, 1.24-1.42). The risk peaked during the initial months of treatment (first 30 days of use: IRR, 1.74; 95% CI, 1.37-2.22) and persisted for up to 6 months. The risk did not vary with age, sex, history of bleeding, chronic kidney disease, and potency of SSRIs. An association was present both with concomitant use of SSRIs and direct OACs compared with direct OAC use alone (IRR, 1.25; 95% CI, 1.12-1.40) and concomitant use of SSRIs and VKAs compared with VKA use alone (IRR, 1.36; 95% CI, 1.25-1.47). Conclusions and Relevance: This study suggests that among patients with atrial fibrillation, concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OAC use alone, requiring close monitoring and management of risk factors for bleeding, particularly in the first few months of use.

Cancer risk in systemic lupus: an updated international multi-centre cohort study.

OBJECTIVE: To update estimates of cancer risk in SLE relative to the general population. METHODS: A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. RESULTS: Across 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person-years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin's lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61-0.88), endometrial (SIR 0.44, 95% CI 0.23-0.77), and possibly ovarian cancers (0.64, 95% CI 0.34-1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23). CONCLUSION: These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL, and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing.

Information on myocardial ischemia and arrhythmias added by prehospital electrocardiograms.

BACKGROUND: The prehospital electrocardiogram (ECG) allows earlier identification of acute ST-segment elevation myocardial infarction (STEMI). Its utility for detection of other acute cardiac events, as well as for transient ST-segment abnormalities no longer present when the first hospital ECG is performed, is not well characterized. OBJECTIVE: We sought to examine whether the prehospital ECG adds supplemental information to the first ECG obtained in hospital, by comparing data on possible cardiac ischemia and arrhythmias provided by the two ECGs, in ambulance patients later diagnosed as having cardiac disorders, including STEMI. METHODS: Ambulance personnel acquired 12-lead ECGs for patients suspected of having an acute ischemic event, prior to transport to hospital. The first emergency department 12-lead ECG was provided by medical records at the receiving hospital, and the principal hospital diagnosis for the event was extracted from chart data. Two cardiologists, blinded to the hospital diagnosis, provided their consensus interpretation of 1,209 pairs of ECGs, noting the presence or absence of specific abnormalities on each tracing. RESULTS: Among the 82 patients who had an eventual hospital diagnosis of STEMI, the study cardiologists identified 71 with ST-segment elevations on the ECGs they examined. The vast majority of these (97%) were observed on both ECGs, but the prehospital ECG showed ST-segment elevation for two additional patients (3%). No additional instances were seen only on the hospital ECG. Among the 116 patients with a hospital diagnosis of non-ST-segment elevation myocardial infarction (NSTEMI), the cardiologists identified 36 with ST-segment depressions: 28 (78%) of these were present on both ECGs, seven (19%) only on the prehospital ECG, and one (3%) only on the hospital ECG. Among the 567 patients with any cardiac hospital diagnosis, the cardiologists identified 87 with arrhythmias: 73 (84%) on both ECGs, 12 (14%) only on the prehospital ECG, and two (2%) only on the hospital ECG. CONCLUSIONS: Beyond identifying ST-segment elevation earlier, prehospital ECGs detect important transient abnormalities, information not otherwise available from the first emergency department ECG. These data can expedite diagnosis and clinical management decisions among patients suspected of having an acute cardiac event. The prehospital ECG should be fully integrated into emergency medicine practice.

Oral Anticoagulants and the Risk of Dementia in Patients With Nonvalvular Atrial Fibrillation: A Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Nonvalvular atrial fibrillation (NVAF) is associated with an increased risk of dementia. Oral anticoagulants (OACs) are essential for stroke prevention in NVAF, and studies have shown a possible protective effect on dementia. However, findings have been inconsistent and hampered by methodological limitations. Thus, we assessed whether the use of OACs is associated with a decreased incidence of dementia in patients with NVAF. In addition, we explored the impact of the cumulative duration of OAC use on the incidence of dementia. METHODS: Using the UK Clinical Practice Research Datalink, we formed a cohort of all patients aged 50 years or older with an incident diagnosis of NVAF between 1988 and 2017 and no prior OAC use, with a follow-up until 2019. Patients were considered unexposed until 6 months after their first OAC prescription for latency considerations and exposed thereafter until the end of follow-up. We used time-dependent Cox regression models to estimate hazard ratios (HRs), adjusted for 54 covariates, with 95% CIs for dementia associated with OAC use, compared with nonuse. We also assessed whether the risk varied with the cumulative duration of OAC use, compared with nonuse, by comparing prespecified exposure categories defined in a time-varying manner and by modeling the HR using a restricted cubic spline. RESULTS: The cohort included 142,227 patients with NVAF, with 8,023 cases of dementia over 662,667 person-years of follow-up (incidence rate 12.1, 95% CI 11.9-12.4 per 1,000 person-years). OAC use was associated with a decreased risk of dementia (HR 0.88, 95% CI 0.84-0.92) compared with nonuse. A restricted cubic spline also indicated a decreased risk of dementia, reaching a low at approximately 1.5 years of cumulative OAC use and stabilizing thereafter. Moreover, OAC use decreased the risk in patients aged 75 years and older (HR 0.84, 95% CI 0.80-0.89), but not in younger patients (HR 0.99, 95% CI 0.90-1.10). DISCUSSION: In patients with incident NVAF, OACs were associated with a decreased risk of dementia, particularly in elderly individuals. This warrants consideration when weighing the risks and benefits of anticoagulation in this population. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with NVAF, OAC use (vs nonuse) is associated with a decreased risk of dementia.

Neuropilin-1 is upregulated in hepatocellular carcinoma and contributes to tumour growth and vascular remodelling.

BACKGROUND & AIMS: Neuropilin-1 (NRP1) is a transmembrane co-receptor for semaphorins and heparin-binding pro-angiogenic cytokines, principally members of the vascular endothelial growth factor family. Recent studies revealed an important role of NRP1 in angiogenesis and malignant progression of many cancers. The role of NRP1 in the development of hepatocellular carcinoma (HCC) is not completely understood. METHODS: We used human tissue microarrays and a mouse transgenic model of HCC to establish the spatio-temporal patterns of NRP1 expression in HCC. To evaluate the therapeutic potential of targeting NRP1 in HCC, we treated HCC mice with peptide N, an NRP1 binding recombinant protein and competitive inhibitor of the VEGF-A(165)/NRP1 interaction. RESULTS: We demonstrate that NRP1 is expressed in hepatic endothelial cells of both human healthy biopsies and in HCC samples, but not in normal hepatocytes. We found that increased NRP1 expression in human tumour hepatocytes is significantly associated with primary HCC. Using RT-PCR, Western blot and immunofluorescence analysis we show that NRP1 expression in the liver of transgenic HCC mice is increased with disease progression, in both vascular and tumour compartments. Blocking NRP1 function with peptide N leads to the inhibition of vascular remodelling and tumour liver growth in HCC mice. CONCLUSIONS: Our results indicate a specific role of NRP1 in HCC growth and vascular remodelling and highlight the possibility of therapeutically targeting NRP1 for the treatment of HCC.

Is there a role for rifampicin, ofloxacin and minocycline (ROM) therapy in the treatment of leprosy? Systematic review and meta-analysis.

BACKGROUND: A combination of rifampicin, ofloxacin and minocycline (ROM) is one of the newer recommendations for treatment of leprosy. We performed a systematic review and a meta-analysis of studies that had evaluated the efficacy of ROM therapy in treatment of paucibacillary and multibacillary leprosy patients. METHODS: Studies were identified by searching the PubMed, Embase, LILACS and Cochrane databases. Data were abstracted from all relevant studies, and fixed effects models were used to calculate the summary estimate of effect in paucibacillary and multibacillary leprosy patients. RESULTS: Six studies comparing ROM therapy to multidrug therapy and eight studies that evaluated the effect of ROM therapy alone (no comparison group) were included in the review and meta-analysis. The combined estimate for single dose ROM vs. multidrug therapy in paucibacillary leprosy patients suggested that ROM was less effective than multidrug therapy in these patients [relative risk: 0.91, 95% confidence intervals (CI): 0.86-0.97]. However, the combined estimate for multiple doses of ROM vs. multidrug therapy in multibacillary leprosy patients suggested that ROM was as effective as multidrug therapy in reducing bacillary indices in these patients (proportion change: -4%, 95% CI -31% to 23%). No major side effects were reported in either the ROM or the multidrug treatment groups. CONCLUSIONS: Single-dose ROM therapy was less effective than multidrug therapy in paucibacillary patients. However, there are insufficient data to come to a valid conclusion on the efficacy of multidose ROM therapy in multibacillary leprosy, and additional studies with ROM therapy in multibacillary leprosy are needed. Furthermore, multiple doses may be considered as another alternative even for paucibacillary patients, and randomised controlled trials of this therapy may be useful to understand its contribution in the treatment and control of leprosy.

Residential trajectory and HIV high-risk behaviors among Montréal street youth--a reciprocal relationship.

Evidence has linked residential instability and engagement in high-risk behaviors. This paper longitudinally examines the relationship between changes in residential stability and changes in HIV risk behaviors among Montréal street youth (SY). Between April 2006 and May 2007, 419 SY (18-25 years old) were recruited in a cohort study. SY (using Montréal street youth agencies services) were eligible if they had had at least one 24-hour episode of homelessness in the previous 30 days. Baseline and follow-up interviews, carried out every 3 months, included completion of a questionnaire (based on Life History Calendar Technique) assessing daily sleeping arrangements since the last interview, and monthly sexual and drug use behaviors. Using mixed-effects logistic regression method, we examined the association between various risk behaviors and residential stability, reached when a youth resided in any of the following settings for a whole month: own place; friends'/partner's/parent's place; any types of housing service (excluding emergency shelters). Analyses were carried out controlling for gender, age, education level, lifetime duration of homelessness, childhood sexual trauma, and lifetime mental health disorders. As of January 2009, 360 SY (79% boys) had completed at least one follow-up interview, representing 4,889 months of follow-up. Residential stability was significantly associated with the following: sex exchange (adjusted odd ratio [AOR], 0.25; 95% confidence interval [CI], 0.14-0.37), drug injection (AOR, 0.55; CI, 0.33-0.76), daily alcohol consumption (AOR, 0.58; CI, 0.42-0.74), polydrug consumption (AOR, 0.61; CI, 0.50-0.73), polydrug consumption excluding marijuana (AOR, 0.55; CI, 0.45-0.65), and multiple sex partners (≥3 partners; AOR, 0.57; CI, 0.40-0.74). Our results suggest a reciprocal relationship between residential instability and HIV risk behaviors. This calls for more integrated services combining both individual and structural-level interventions to improve the health of street youth.

Thiazolidinediones and the risk of incident congestive heart failure among patients with type 2 diabetes mellitus.

BACKGROUND: Clinical trials suggest that thiazolidinediones (TZDs) may increase the risk of congestive heart failure (CHF). However, their effect on the risk of incident CHF in unselected populations has not been thoroughly investigated. METHODS: Using data from the UK's General Practice Research Database, we conducted a case-control study within a population-based cohort of patients with type 2 diabetes. Cases were identified by a clinical diagnosis of incident CHF and were then classified as possible or probable cases using prescription data. A 90-day drug exposure window was used in the primary analysis, which compared patients prescribed TZDs with those with no prescriptions for anti-diabetic medications. RESULTS: We identified 3405 incident cases (2632 probable and 773 possible) of CHF and 32,042 corresponding controls. TZDs were prescribed in 6.4% of cases and 6.3% of controls. Prescription of TZDs was associated with an increased rate of possible or probable CHF (adjusted rate ratio (RR) = 1.24, 95% CI = 1.01, 1.54 and adjusted RR = 1.24, 95% CI = 0.98, 1.58, respectively). Similar results were obtained when using a 180-day exposure window (RR = 1.38, 95% CI = 1.11, 1.72 and RR = 1.44, 95% CI = 1.12, 1.84, respectively). CONCLUSIONS: Given the totality of the evidence from this and previous studies, the probability of an increased risk for CHF with these agents remains high. However, any increase in CHF risk associated with TZDs may be lower than previously reported.

Increased risk of miscarriage among women experiencing physical or sexual intimate partner violence during pregnancy in Guatemala City, Guatemala: cross-sectional study.

BACKGROUND: Violence against women by their male intimate partners (IPV) during pregnancy may lead to negative pregnancy outcomes. We examined the role of IPV as a potential risk factor for miscarriage in Guatemala. Our objectives were: (1) To describe the magnitude and pattern of verbal, physical and sexual violence by male intimate partners in the last 12 months (IPV) in a sample of pregnant Guatemalans; (2) To evaluate the influence of physical or sexual IPV on miscarriage as a pregnancy outcome. METHODS: All pregnant women reporting to the maternity of a major tertiary care public hospital in Guatemala City from June 1st to September 30th, 2006 were invited to participate in this cross-sectional study. The admitting physician assessed occurrence of miscarriage, defined as involuntary pregnancy loss up to and including 28 weeks gestation. Data on IPV, social and demographic characteristics, risk behaviours, and medical history were collected by interviewer-administered questionnaire. Laboratory testing was performed for HIV and syphilis. The relationship between IPV and miscarriage was assessed through multivariable logistic regression. RESULTS: IPV affected 18% of the 1897 pregnant Guatemalan women aged 15-47 in this sample. Verbal IPV was most common (16%), followed by physical (10%) and sexual (3%) victimisation. Different forms of IPV were often co-prevalent. Miscarriage was experienced by 10% of the sample (n = 190). After adjustment for potentially confounding factors, physical or sexual victimisation by a male intimate partner in the last 12 months was significantly associated with miscarriage (ORadj 1.1 to 2.8). Results were robust under a range of analytic assumptions. CONCLUSIONS: Physical and sexual IPV is associated with miscarriage in this Guatemalan facility-based sample. Results cohere well with findings from population-based surveys. IPV should be recognised as a potential cause of miscarriage. Reproductive health services should be used to screen for spousal violence and link to assistance.

Association between antibiotic use and risk of prostate cancer.

The association between antibiotics and risk of cancer has been addressed in different studies, most of which were addressing breast cancer. The objective of this study was to assess the association between antibiotics use and risk of prostate cancer. We carried out a population-based case-control study using data from Saskatchewan Health administrative databases (Canada) between the years 1981 and 2000. Cases identified by the Saskatchewan Cancer Agency were matched to 4 controls, using incidence density sampling. The effect of dosage and timing of antibiotic use, over a minimum of 15 years before diagnosis, on prostate cancer risk was assessed. Number of prescriptions and number of tablets were used as exposure definitions. Moreover, the effect of different classes of antibiotics on prostate cancer was also studied. A total of 4,052 prostate cancer cases and 16,208 matched controls were included in this study. Antibiotics exposure (number of prescriptions) during the period of 1-15 years in the past was significantly associated with an increased risk of prostate cancer; RR = 1.69, 2.61, 2.71, and 2.83 for the 4 quartiles, respectively, p-trend = 0.0001. When number of units was taken as the exposure definition, similar results were found. We did not find any effect of the timing or class of antibiotic exposure on prostate cancer risk. We found a dose-dependent association between antibiotics exposure up to 15 years in the past and risk of prostate cancer. However, the lack of temporal trends and the absence of class specific effects suggest a noncausal relationship.

Screening for glaucoma in high-risk populations using optical coherence tomography.

OBJECTIVE: To estimate the diagnostic accuracy of Stratus optical coherence tomography (OCT) for glaucoma screening in high-risk populations. DESIGN: Cross-sectional evaluation of a diagnostic test for screening. PARTICIPANTS: Three hundred thirty-three community-based volunteer participants with risk factors for glaucoma. METHODS: The optic nerve and peripapillary retinal nerve fiber layer (RNFL) of participants' eyes were scanned using the Stratus OCT. Based on an ophthalmologic examination and frequency doubling perimetry, eyes were classified into 4 categories: normal, possible glaucoma, probable glaucoma, and definitive glaucoma. MAIN OUTCOME MEASURES: The sensitivities, specificities, positive and negative likelihood ratios of the RNFL, optic disc parameters, and their combinations were calculated. RESULTS: The right eyes were retained for analyses. After excluding eyes with missing data or with poor quality scans, the data of 210 right eyes were analyzed. Six eyes had definitive glaucoma. Combining the best performing optic nerve head parameters (cup diameter or cup/disc vertical ratio or cup/disc area ratio) and RNFL parameters (superior average or inferior average or overall average) using AND-logic resulted in a sensitivity of 67% (95% confidence interval [CI], 24%-94%), specificity of 96% (95% CI, 92%-98%), a positive likelihood ratio of 17.08 (95% CI, 7.06-41.4), and a negative likelihood ratio of 0.35 (95% CI, 0.11-1.08). CONCLUSIONS: When adequate quality scans may be obtained, the Stratus has moderate sensitivity and high specificity for definitive glaucoma. Specificity is increased when parameters from both the optic nerve head and RNFL scans are combined.