HIV and risk of venous thromboembolism: a Danish nationwide population‐based cohort study

Objective

The association between HIV infection and the risk of venous thromboembolism (VTE) is controversial. We examined the risk of VTE in HIV‐infected individuals compared with the general population and estimated the impact of low CD4 cell count, highly active antiretroviral therapy (HAART) and injecting drug use (IDU).

Methods

We identified 4333 Danish HIV‐infected patients from the Danish HIV Cohort Study and a population‐based age‐ and gender‐matched comparison cohort of 43 330 individuals. VTE diagnoses were extracted from the Danish National Hospital Registry. Cumulative incidence curves were constructed for time to first VTE. Incidence rate ratios (IRRs) and impact of low CD4 cell count and HAART were estimated by Cox regression analyses. Analyses were stratified by IDU, adjusted for comorbidity and disaggregated by overall, provoked and unprovoked VTE.

Results

The 5‐year risk of VTE was 8.0% [95% confidence interval (CI) 5.78–10.74%] in IDU HIV‐infected patients, 1.5% (95% CI 1.14–1.95%) in non‐IDU HIV‐infected patients and 0.3% (95% CI 0.29–0.41%) in the population comparison cohort. In non‐IDU HIV‐infected patients, adjusted IRRs for unprovoked and provoked VTE were 3.42 (95% CI 2.58–4.54) and 5.51 (95% CI 3.29–9.23), respectively, compared with the population comparison cohort. In IDU HIV‐infected patients, the adjusted IRRs were 12.66 (95% CI 6.03–26.59) for unprovoked VTE and 9.38 (95% CI 1.61–54.50) for provoked VTE. Low CD4 cell count had a minor impact on these risk estimates, while HAART increased the overall risk (IRR 1.93; 95% CI 1.00–3.72).

Conclusion

HIV‐infected patients are at increased risk of VTE, especially in the IDU population. HAART and possibly low CD4 cell count further increase the risk.     

The world‐wide incidence of Kaposi's sarcoma in the HIV/AIDS era

Objectives

Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of endothelial origin typically occurring in the context of immunosuppression or immunodeficiency. Consequently, KS is one of the most common cancers in HIV‐infected individuals and frequently occurs among transplant recipients. Nevertheless, its incidence in different populations is not well understood.

Methods

We searched online databases for publications on KS incidence. A random‐effect meta‐analysis was performed to combine the KS incidences and incidence rate ratios (IRRs) for associated risk factors.

Results

Seventy‐six eligible studies representing 71 time periods were included. For HIV‐infected people, the overall KS incidence was 481.54 per 100 000 person‐years with a 95% confidential interval (CI) of 342.36–677.32 per 100 000 person‐years. HIV‐infected men who have sex with men (MSM) had the highest incidence of KS (1397.11 per 100 000 person‐years; 95% CI 870.55–2242.18 per 100 000 person‐years). The incidence of KS was significantly lower in female than in male individuals (IRR 3.09; 95% CI 1.70–5.62). People receiving highly active antiretroviral therapy (HAART) had a lower incidence compared with people who had never received HAART (IRR 6.57; 95% CI 1.91–24.69). The incidence of KS was 68.59 (95% CI 31.39–149.86) per 100 000 person‐years in transplant recipients, 52.94 (95% CI 39.90–70.20) per 100 000 person‐years in children with HIV infection, and 1.53 (95% CI 0.33–7.08) per 100 000 person‐years in the general population.

Conclusions

Globally, a relatively high incidence of KS was found among HIV‐seropositive people and, in particular, in HIV‐infected MSM. The introduction of HAART has largely prevented the development of KS, but it has not entirely removed the challenge of KS. In Africa, in particular, KS imposes a very heavy disease burden, which can mainly be attributed to the high prevalence of KS‐associated herpesvirus and poor access to HAART.

     

An Overview of Clinical Outcomes in Transvenous and Subcutaneous ICD Patients

Purpose of Review

Clear guidelines on when to select a subcutaneous ICD (S-ICD) over a transvenous ICD (TV-ICD) are lacking. This review will provide an overview of the most recent clinical data on S-ICD and TV-ICD therapy by pooling comparison studies in order to aid clinical decision making.

Recent Findings

Pooling of observational-matched studies demonstrated an incidence rate ratio (IRR) for device-related complication of 0.90 (95% CI 0.58–1.42) and IRR for lead-related complications of 0.15 (95% CI 0.06–0.39) in favor of S-ICD. The IRR for device infections was 2.00 (95% CI 0.95–4.22) in favor of TV-ICD. Both appropriate shocks (IRR 0.67 (95% CI 0.42–1.06)) and inappropriate shocks (IRR 1.17 (95% CI 0.77–1.79)) did not differ significantly between both groups.

Summary

With randomized data underway, the observational data demonstrate that the S-ICD is associated with reduced lead complications, but this has not yet resulted in a significant reduction in total number of complications compared to TV-ICDs. New technologies are expected to make the S-ICD a more attractive alternative.

     

Implementing the number needed to harm in clinical practice: risk of myocardial infarction in HIV‐1‐infected patients treated with abacavir

Objectives

The D:A:D study group reported a 1.9‐fold increased relative risk (RR) of myocardial infarction (MI) associated with current or recent use of abacavir. The number needed to harm (NNH) incorporates information about the underlying risk of MI and the increased RR of MI in patients taking abacavir.

Methods

NNH was calculated as the reciprocal of the difference between the underlying risks of MI with and without abacavir use. A parametric statistical model was used to calculate the underlying risk of MI over 5 years.

Results

The relationship between NNH and underlying risk of MI is reciprocal, resulting in wide variation in the NNH with small changes in underlying risk of MI. The smallest changes in NNH are in the medium‐ and high‐risk groups of MI. The NNH changes as risk components are modified; for example, for a patient who smokes and has a systolic blood pressure (sBP) of 160 mmHg and a 5‐year risk of MI of 1.3% the NNH is 85, but the NNH increases to 277 if the patient is a nonsmoker and to 370 if sBP is within the normal range (120 mmHg).

Conclusions

We have illustrated that the impact of abacavir use on risk of MI varies according to the underlying risk and it may be possible to increase considerably the NNH by decreasing the underlying risk of MI using standard of care interventions, such as smoking cessation or control of hypertension.     

The importance of the disease process and disease‐modifying antirheumatic drug treatment in the development of septic arthritis in patients with rheumatoid arthritis

Objective

To evaluate the effect of disease‐modifying antirheumatic drugs (DMARDs) on the likelihood of patients with rheumatoid arthritis (RA) developing septic arthritis (SA).

Methods

The United Kingdom General Practice Research Database (GPRD) was used to identify adults with RA, and age‐, sex‐, and practice‐matched control subjects. Subjects were studied between 1987 and 2002. The risk of developing SA (excluding infected joint replacements) for individuals with RA was calculated and the effect of DMARD use determined.

Results

A total of 136,977 subjects (34,250 patients with RA, 102,747 controls) were identified. SA was identified in 345 subjects, of which 321 (236 in patients with RA, 85 in controls) cases occurred during the study period. The incidence rate of SA was 12.9 times higher in subjects with RA than in those without (95% confidence interval [95% CI] 10.1–16.5, P < 0.001). The incident rate ratios (IRRs) for developing SA while receiving DMARDs compared with receiving no DMARDs were different for different medications. Penicillamine (adjusted IRR 2.51, 95% CI 1.29–4.89, P = 0.004), sulfasalazine (adjusted IRR 1.74, 95% CI 1.04–2.91, P = 0.03), and prednisolone (adjusted IRR 2.94, 95% CI 1.93–4.46, P < 0.001) were associated with an increased incidence of SA when compared with not receiving any DMARD. The use of other DMARDs including methotrexate showed no such effect.

Conclusion

Individuals with RA have an increased risk of developing SA. This increased risk can be attributed to both the disease process and the use of DMARDs.     

Mode of delivery in HIV‐infected pregnant women and prevention of mother‐to‐child transmission: changing practices in Western Europe

Objectives

The aim of the study was to examine temporal and geographical patterns of mode of delivery in the European Collaborative Study (ECS), identify factors associated with elective caesarean section (CS) delivery in the highly active antiretroviral therapy (HAART) era and explore associations between mode of delivery and mother‐to‐child transmission (MTCT).

Methods

The ECS is a cohort study in which HIV‐infected pregnant women are enrolled and their infants prospectively followed. Data on 5238 mother–child pairs (MCPs) enrolled in Western European ECS sites between 1985 and 2007 were analysed.

Results

The elective CS rate increased from 16% in 1985–1993 to 67% in 1999–2001, declining to 51% by 2005–2007. In 2002–2004, 10% of infants were delivered vaginally, increasing to 34% by 2005–2007. During the HAART era, women in Belgium, the United Kingdom and the Netherlands were less likely to deliver by elective CS than those in Italy and Spain [adjusted odds ratio (AOR) 0.07; 95% confidence interval (CI) 0.04–0.12]. The MTCT rate in 2005–2007 was 1%. Among MCPs with maternal HIV RNA<400 HIV‐1 RNA copies/mL (n=960), elective CS was associated with 80% decreased MTCT risk (AOR 0.20; 95% CI 0.05–0.65) adjusting for HAART and prematurity. Two infants born to 559 women with viral loads <50 copies/mL were infected, one of whom was delivered by elective CS (MTCT rate 0.4%; 95% CI 0.04–1.29).

Conclusions

Our findings suggest that elective CS prevents MTCT even at low maternal viral loads, but the study was insufficiently powered to enable a conclusion to be drawn as to whether this applies for viral loads <50 copies/mL. Diverging mode of delivery patterns in Europe reflect uncertainties regarding the risk–benefit balance of elective CS for women on successful HAART.

     

High incidence of potentially virus‐induced malignancies in systemic lupus erythematosus: A long‐term followup study in a Danish cohort

Objective

Patients with systemic lupus erythematosus (SLE) seem to experience an increased prevalence of oncogenic virus infections. The aim of the present study was to investigate whether SLE patients have an increased risk of virus‐associated malignancies, defined as malignancies potentially caused by virus infection.

Methods

A hospital‐based cohort of 576 SLE patients was linked to the Danish Cancer Registry. The cohort was followed up for malignancies from the date of SLE diagnosis, and standardized incidence ratios (SIRs) were calculated for various forms of cancer.

Results

The median duration of followup was 13.2 years. Compared to the general population, the patients experienced an increased overall risk of cancer (SIR 1.6 [95% confidence interval (95% CI)] 1.2–2.0). We observed an increased risk of virus‐associated cancers combined (SIR 2.9 [95% CI 2.0–4.1]). Among human papillomavirus (HPV)–associated malignant and premalignant conditions, high risk was found for anal cancer (SIR 26.9 [95% CI 8.7–83.4]), vaginal/vulvar cancer (SIR 9.1 [95% CI 2.3–36.5]), epithelial dysplasia/carcinoma in situ of the uterine cervix (SIR 1.8 [95% CI 1.2–2.7]), and nonmelanoma skin cancer (SIR 2.0 [95% CI 1.2–3.6]). Increased SIRs were also found for other potentially virus‐induced cancer types (liver cancer SIR 9.9 [95% CI 2.5–39.8], bladder cancer SIR 3.6 [95% CI 1.4–9.7], and non‐Hodgkin's lymphoma SIR 5.0 [95% CI 1.9–13.3]).

Conclusion

The patients in this SLE cohort experienced an increased risk of HPV‐associated tumors and other potentially virus‐induced cancers during long‐term followup. Our findings call for clinical alertness to oncogenic virus infections in SLE patients.

     

Association of widespread body pain with an increased risk of cancer and reduced cancer survival: A prospective,population‐based study

Objective

To determine whether reported widespread body pain is related to an increased incidence of cancer and/or reduced survival from cancer, since our previous population surveys have demonstrated a relationship between widespread body pain and a subsequent 2‐fold increase in mortality from cancer over an 8‐year period.

Methods

A total of 6,565 subjects in Northwest England participated in 2 health surveys during 1991–1992. The subjects were classified according to their reported pain status (no pain, regional pain, and widespread pain), and were subsequently followed up prospectively until December 31, 1999. During followup, information was collected on incidence of cancer and survival rates among those developing cancer. Associations between the original pain status and development of cancer and cancer survival were expressed as the incidence rate ratio (IRR) and mortality rate ratio (MRR), respectively. All analyses were adjusted for age, sex, and study location, the latter being a proxy measure of socioeconomic status.

Results

Among the study population, 6,331 had never been diagnosed with cancer at the time of participation in the survey. Of these subjects, 956 (15%) were classified as having widespread pain, 3,061 (48%) as having regional pain, and 2,314 (37%) as having no pain. There were a total of 395 first malignancies recorded during followup. In comparison with subjects reporting no pain, those with regional pain (IRR 1.19, 95% confidence interval [95% CI] 0.94–1.50) and widespread pain (IRR 1.61, 95% CI 1.21–2.13) experienced an excess incidence of cancer during the followup period. The increased incidence among subjects previously reporting widespread pain was related, most strongly, to breast cancer (IRR 3.67, 95% CI 1.39–9.68), but there were also cancers of the prostate (IRR 3.46, 95% CI 1.25–9.59), large bowel (IRR 2.35, 95% CI 0.96–5.77), and lung (IRR 2.04, 95% CI 0.96–4.34). Subjects reporting widespread pain who subsequently developed cancer, in comparison with those previously reporting no pain, had an increased risk of death (MRR 1.82, 95% CI 1.18–2.80). This decreased survival was highest among subjects with cancers of the breast and prostate, although the effects on site‐specific survival were nonsignificant.

Conclusion

This study has demonstrated that widespread pain reported in population surveys is associated with a substantial subsequent increased incidence of cancer and reduced cancer survival. At present there are no satisfactory biologic explanations for this observation, although several possible leads have been identified.

     

Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral‐naïve patients

Objectives

The aim of the study was to determine whether the incidence of first‐line treatment discontinuations and their causes changed according to the time of starting highly active antiretroviral therapy (HAART) in an Italian cohort.

Methods

We included in the study patients from the Italian COhort Naïve Antiretrovirals (ICoNA) who initiated HAART when naïve to antiretroviral therapy (ART). The endpoints were discontinuation within the first year of ≥1 drug in the first HAART regimen for any reason, intolerance/toxicity, poor adherence, immunovirological/clinical failure and simplification. We investigated whether the time of starting HAART (stratified as ‘early’, 1997–1999; ‘intermediate’, 2000–2002; ‘recent’, 2003–2007) was associated with the probability of reaching the endpoints by a survival analysis.

Results

Overall, the 1‐year probability of discontinuation of ≥1 drug in the first regimen was 36.1%. The main causes of discontinuation were intolerance/toxicity (696 of 1189 patients; 58.5%) and poor adherence (285 of 1189 patients; 24%). The hazards for all‐reason change were comparable according to calendar period [2000–2002, adjusted relative hazard (ARH) 0.82, 95% confidence interval (CI) 0.69–0.98; 2003–2007, ARH 0.94, 95% CI 0.76–1.16, vs. 1997–1999; global P‐value=0.08]. Patients who started HAART during the ‘recent’ period were less likely to change their initial regimen because of intolerance/toxicity (ARH 0.67, 95% CI 0.51–0.89 vs. ‘early’ period). Patients who started in the ‘intermediate’ and ‘recent’ periods had a higher risk of discontinuation because of simplification (ARH 15.26, 95% CI 3.21–72.45, and ARH 37.97, 95% CI 7.56–190.64, vs. ‘early’ period, respectively).

Conclusions

It seems important to evaluate reason‐specific trends in the incidence of discontinuation in order to better understand the determinants of changes over time. The incidence of discontinuation because of intolerance/toxicity has declined over time while simplification strategies have become more frequent in recent years. Intolerance/toxicity remains the major cause of drug discontinuation.     

Increased morbidity from ischemic heart disease in patients with Wegener's granulomatosis

Objective

Experimental studies indicate that patients with Wegener's granulomatosis (WG) experience accelerated atherosclerosis. The purpose of this study was to investigate whether the occurrence of overt ischemic heart disease (IHD) is increased in WG.

Methods

A total of 293 WG patients were included in the study. Information on all hospitalizations for IHD in Denmark from 1977 to 2006 was obtained from the Danish National Hospital Register. The WG patients were compared with the Danish background population with respect to rates of hospitalization for clinical manifestations of IHD after the date of vasculitis diagnosis by calculating standardized ratios of observed to expected (O:E) events.

Results

Sixty‐three first IHD events were registered in the WG group during the 2,482 patient‐years of followup, corresponding to a significantly increased O:E ratio for IHD of 1.9 (95% confidence interval [95% CI] 1.4–2.4). A significantly increased risk was found for acute myocardial infarction (MI) (O:E ratio 2.5 [95% CI 1.6–3.7]), but not for angina pectoris (O:E ratio 1.3 [95% CI 0.7–2.1]). In analyses stratified according to the time between the diagnosis of vasculitis and the cardiovascular event, increased O:E ratios were found for IHD and acute MI occurring <5.0 years after WG diagnosis (2.1 [95% CI 1.4–3.0] for IHD and 3.6 [95% CI 2.0–5.9] for acute MI) and for IHD occurring ≥10.0 years after WG diagnosis (2.2 [95% CI 1.3–3.4]). Significantly increased O:E ratios for IHD and acute MI were found in patients who were ≥50.0 years of age at the time of diagnosis of WG, in male patients, and in patients who received high cumulative doses of cyclophosphamide.

Conclusion

Compared with the background population, WG patients seem to experience an increased number of both early and late cardiovascular events due to IHD.

     

Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: A population‐based cohort study

Objective

To examine the risk of clinical coronary heart disease (CHD) in patients with rheumatoid arthritis (RA) compared with age‐ and sex‐matched non‐RA subjects, and to determine whether RA is a risk factor for CHD after accounting for traditional CHD risk factors.

Methods

We assembled a population‐based incidence cohort of 603 Rochester, Minnesota residents ages ≥18 years who first fulfilled the American College of Rheumatology (ACR) 1987 criteria for RA between January 1, 1955 and January 1, 1995, and 603 age‐ and sex‐matched non‐RA subjects. All subjects were followed up through their complete inpatient and outpatient medical records, beginning at age 18 years until death, migration, or January 1, 2001. Data were collected on CHD events and traditional CHD risk factors (diabetes mellitus, hypertension, dyslipidemia, body mass index, smoking) using established diagnostic criteria. CHD events included hospitalized myocardial infarction (MI), unrecognized MI, coronary revascularization procedures, angina pectoris, and sudden CHD deaths. Conditional logistic regression and Cox regression models were used to estimate the risk of CHD associated with RA, both prior to and following RA diagnosis, after adjusting for CHD risk factors.

Results

During the 2‐year period immediately prior to fulfillment of the ACR criteria, RA patients were significantly more likely to have been hospitalized for acute MI (odds ratio [OR] 3.17, 95% confidence interval [95% CI] 1.16–8.68) or to have experienced unrecognized MIs (OR 5.86, 95% CI 1.29–26.64), and less likely to have a history of angina pectoris (OR 0.58, 95% CI 0.34–0.99) compared with non‐RA subjects. After the RA incidence date, RA patients were twice as likely to experience unrecognized MIs (hazard ratio [HR] 2.13, 95% CI 1.13–4.03) and sudden deaths (HR 1.94, 95% CI 1.06–3.55) and less likely to undergo coronary artery bypass grafting (HR 0.36, 95% CI 0.16–0.80) compared with non‐RA subjects. Adjustment for the CHD risk factors did not substantially change the risk estimates.

Conclusion

Patients with RA have a significantly higher risk of CHD when compared with non‐RA subjects. RA patients are less likely to report symptoms of angina and more likely to experience unrecognized MI and sudden cardiac death. The risk of CHD in RA patients precedes the ACR criteria–based diagnosis of RA, and the risk cannot be explained by an increased incidence of traditional CHD risk factors in RA patients.

     

Antimalarial treatment may have a time‐dependent effect on lupus survival: Data from a multinational Latin American inception cohort

Objective

To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort.

Methods

Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser).

Results

Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6–98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P< 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6–11 months, 146 (12.8%) for 1–2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person‐months of followup) were 3.85 (95% confidence interval [95% CI] 1.41–8.37), 2.7 (95% CI 1.41–4.76), and 0.54 (95% CI 0.37–0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18–4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39–0.99).

Conclusion

Antimalarial drugs were shown to have a protective effect, possibly in a time‐dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus.

     

Simultaneous assessment of short‐term gastrointestinal benefits and cardiovascular risks of selective cyclooxygenase 2 inhibitors and nonselective nonsteroidal antiinflammatory drugs: An instrumental variable analysis

Objective

To simultaneously assess the short‐term reduction in risk of gastrointestinal (GI) complications and increase in risk of acute myocardial infarction (MI) by celecoxib compared with rofecoxib and several nonselective nonsteroidal antiinflammatory drugs (NSAIDs) using instrumental variable analysis.

Methods

A population of 49,711 Medicare beneficiaries ages 65 years and older who initiated nonselective NSAID or selective cyclooxygenase 2 inhibitor therapy between January 1, 1999, and December 31, 2002, was identified. The increase in risk of GI complications and MI within 180 days after initiation of NSAID (rofecoxib, diclofenac, ibuprofen, and naproxen compared with celecoxib) therapy was assessed using instrumental variable analysis.

Results

Compared with nonselective NSAIDs, celecoxib reduced the risk of GI complications by 1.4 per 100 users but increased the risk of MI by 0.3 per 100 users. Rofecoxib decreased GI complications by 1.1 per 100 users and increased the risk of MI by 0.3 per 100 users. Using celecoxib as the reference exposure showed an increase in the MI risk for rofecoxib (risk difference [RD] 1.40, 95% confidence interval [95% CI] −0.20, 3.01) and diclofenac (RD 6.07, 95% CI −0.02, 12.15). The RD for naproxen as well as its upper 95% CI was the lowest of all NSAIDs (RD −0.30, 95% CI −2.74, 2.14) and there was no significant difference in GI complication rates among all NSAIDs.

Conclusion

In this instrumental variable analysis, diclofenac and rofecoxib had the least favorable benefit–risk balance among NSAIDs in older adults.

     

Comparison of mid‐ to long‐term clinical outcomes between anatomical testing and usual care in patients with suspected coronary artery disease: A meta‐analysis of randomized trials

Background

Controversies remain regarding clinical outcomes following initial strategies of coronary computed tomography angiography (CCTA) vs usual care with functional testing in patients with suspected coronary artery disease (CAD).

Hypothesis

CCTA as initial diagnostic strategy results in better mid‐ to long‐term outcomes than usual care in patients with suspected CAD.

Methods

We searched PubMed, Embase, and Cochrane Library for randomized controlled trials comparing clinical outcomes during ≥6 months' follow‐up between initial anatomical testing by CCTA vs usual care with functional testing in patients with suspected CAD. Occurrence of all‐cause mortality, nonfatal myocardial infarction (MI), and major adverse cardiovascular events (MACE), and use of invasive coronary angiography and coronary revascularization, were compared between the 2 diagnostic strategies.

Results

Twelve trials were included (20 014 patients; mean follow‐up, 20.5 months). Patients undergoing CCTA as initial noninvasive testing had lower risk of nonfatal MI compared with those treated with usual care (risk ratio [RR]: 0.70, 95% confidence interval [CI]: 0.52‐0.94, P = 0.02). There was a tendency for reduced MACE following initial CCTA strategy, but not for risk of all‐cause mortality. Compared with functional testing, the CCTA strategy increased use of invasive coronary angiography (RR: 1.53, 95% CI: 1.12‐2.09, P = 0.007) and coronary revascularization (RR: 1.49, 95% CI: 1.11‐2.00, P = 0.007).

Conclusions

Anatomical testing with CCTA as the initial noninvasive diagnostic modality in patients with suspected CAD resulted in lower risk of nonfatal MI than usual care with functional testing, at the expense of more frequent use of invasive procedures.

     

Severe Cutaneous Reactions Requiring Hospitalization in Allopurinol Initiators: A Population‐Based Cohort Study

Objective

Rare but potentially life‐threatening cutaneous adverse reactions have been associated with allopurinol, but population‐based data on the incidence and mortality of such reactions are scarce.

Methods

We conducted a propensity score–matched cohort study to evaluate the incidence rate (IR) and in‐hospital mortality of hospitalization for severe cutaneous adverse reactions (SCARs) in allopurinol initiators compared to non–allopurinol users, using data from 5 large Medicaid programs. The primary outcome was identified by the principal discharge diagnosis code 695.1. A Cox proportional hazards model evaluated the relative risk of SCARs associated with the use of allopurinol and determined the relative risk of SCARs associated with allopurinol dose.

Results

During a followup period of 65,625 person‐years for allopurinol initiators, 45 were hospitalized with SCARs. The crude IR was 0.69 (95% confidence interval [95% CI] 0.50–0.92) per 1,000 person‐years. All 45 cases occurred within 365 days and 41 (91.1%) occurred within 180 days after initiating treatment with allopurinol. Twelve patients (26.7%) died during the hospitalization. The crude IR in non–allopurinol users was 0.04 (95% CI 0.02–0.08) per 1,000 person‐years. The risk of SCARs was increased in allopurinol initiators versus nonusers (hazard ratio [HR] 9.68, 95% CI 4.55–20.57). Among allopurinol initiators, the HR for high‐dosage (>300 mg/day) versus low‐dosage allopurinol was 1.30 (95% CI 0.31–5.36) after adjusting for age, comorbidities, and recent diuretic use.

Conclusion

Among allopurinol initiators, SCARs were found to be rare but often fatal, and occurred mostly in the first 180 days of treatment. The risk of SCARs was 10 times as high in allopurinol initiators as compared to allopurinol nonusers.     

Occupation and Risk of Developing Rheumatoid Arthritis: Results From a Population‐Based Case–Control Study

Objective

Environmental factors are of importance for the etiology of rheumatoid arthritis (RA), but much remains unknown concerning the contributions from distinct occupational hazards. We explored the association between occupation and the risk of anti–citrullinated protein antibody (ACPA)+ RA or ACPA? RA.

Methods

We analyzed 3,522 cases and 5,580 controls from the Swedish population–based Epidemiological Investigation of Rheumatoid Arthritis case–control study. A questionnaire was used to obtain information on work history and lifestyle factors. Blood samples were drawn for serologic analyses. Unconditional logistic regression was used to calculate the odds ratio (OR) of RA associated with the last occupation before study inclusion. Analyses were performed with adjustments for known environmental exposures and lifestyle factors, including pack‐years of cigarette smoking, alcohol use, body mass index, and education.

Results

Among men, bricklayers and concrete workers (OR 2.9, 95% confidence interval [95% CI] 1.4–5.7), material handling operators (OR 2.4, 95% CI 1.3–4.4), and electrical and electronics workers (OR 2.1, 95% CI 1.1–3.8) had an increased risk of ACPA+ RA. For ACPA? RA, bricklayers and concrete workers (OR 2.4, 95% CI 1.0–5.7) and electrical and electronics workers (OR 2.6, 95% CI 1.3–5.0) had an increased risk. Among women, assistant nurses and attendants had a moderately increased risk of ACPA+ RA (OR 1.3, 95% CI 1.1–1.6). No occupations were significantly associated with ACPA? RA among women.

Conclusion

Mainly occupations related to potential noxious airborne agents were associated with an increased risk of ACPA+ or ACPA? RA, after adjustments for previously known confounders.

     

Autoimmune diseases in women with Turner's Syndrome

Objective

In terms of number of X chromosomes, women with Turner's syndrome cytogenetically resemble men. An increased risk of autoimmune diseases has been observed among women with Turner's syndrome. This study was undertaken to investigate whether the autoimmune disease profile in women with Turner's syndrome is characterized by diseases with a female or male predominance.

Methods

Using the Danish Cytogenetic Central Register, the Danish National Patient Register, and the Danish Civil Registration System, we estimated relative risk of 46 different autoimmune diseases in a cohort of 798 Danish women with Turner's syndrome followed up for 12,461 person‐years between 1980 and 2004. Standardized incidence ratios (SIRs) of first hospitalization for autoimmune disease and 95% confidence intervals (95% CIs) were used as measures of relative risk.

Results

The overall risk of autoimmune disease among women with Turner's syndrome was twice that among Danish women in general (SIR 2.1 [95% CI 1.6–2.7]). For autoimmune diseases with a female predominance, the SIR among women with Turner's syndrome was 1.7 (95% CI 1.2–2.4), whereas the SIR for autoimmune diseases with a male predominance among these women was 3.9 (95% CI 2.5–5.8). Associations were strongest for Hashimoto thyroiditis (SIR 14.6 [95% CI 6.7–27.1]), a strongly female‐predominant condition, and type 1 diabetes mellitus (SIR 4.1 [95% CI 2.5–6.3]).

Conclusion

Women with Turner's syndrome are at excess risk of autoimmune diseases, notably autoimmune diseases characterized by male predominance.

     

Risk of high‐level viraemia in HIV‐infected patients on successful antiretroviral treatment for more than 6 months

Objectives

According to the Swiss Federal Commission for HIV/AIDS, HIV‐infected patients on successful antiretroviral treatment have a negligible risk of transmitting HIV sexually. We estimated the risk that patients considered to have an undetectable viral load (VL) are actually viraemic.

Methods

A Danish, population‐based nationwide cohort study of HIV‐infected patients with VL <51 HIV‐1 RNA copies/mL for more than 6 months was carried out for the study period 2000–2008. The observation time was calculated from 6 months after the first VL <51 copies/mL to the last measurement of VL or the first VL >50 copies/mL. The time at risk of transmitting HIV sexually was calculated as 50% of the time from the last VL <51 copies/mL to the subsequent VL if it was >1000 copies/mL. The outcome was the time at risk of transmitting HIV sexually divided by the observation time.

Results

We identified 2680 study subjects contributing 9347.7 years of observation time and 56.4 years of risk of transmitting HIV (VL>1000 copies/mL). In 0.6% [95% confidence interval (CI) 0.5–0.8%] of the overall observation time the patients had VL >1000 copies/mL. In the first 6 months this risk was substantially higher (7.9%; 95% CI 4.5–11.0%), but thereafter decreased and was almost negligible after 5 years (0.03%; 95% CI 0.0–0.2%). The risk was higher in injecting drug users, but otherwise did not differ between subgroups of patients.

Conclusion

The risk of viraemia and therefore the risk of transmitting HIV sexually are high in the first 12 months of successful antiretroviral treatment, but thereafter are low.