Prevalence of torture and trauma history among immigrants in primary care in Denmark: do general practitioners ask?

BACKGROUND: Torture survivors typically present with varied and complex symptoms, which may challenge assessment by general practitioners (GPs). This study explored the prevalence of torture and trauma history among immigrants born in non-Western countries presenting to GPs in Denmark and the extent to which GPs ask this population about torture or trauma history. METHODS: Based on a self-reported questionnaire among non-western immigrant patients, we used bivariate analyses to determine the prevalence of torture and trauma history and the proportion of patients being asked by their GP about this. Data were analysed using multivariate logistic regression. RESULTS: From 46 GP clinics, 300 questionnaires were finalized by immigrant patients. Twenty-eight percent of the patients had a history of torture. Of these, significantly more were men (70%) than women (29%). About half of the torture survivors (55%) had been asked by their GP about torture history. The odds ratio (OR, 95% confidence interval) for being asked about torture history by the GP was 1.28 (0.46-3.53) among women compared with men. Compared with Southeast Europe, OR for being a torture survivor among male immigrants from Middle East-North African region and South and East Asia was 1.83 (0.81-4.15) and 0.25 (0.08-0.82), respectively. CONCLUSIONS: Our results suggest that torture and trauma are widespread among immigrants presenting to GPs. In our study, the GPs had managed to detect half of the torture survivors. A more systematic approach to detection in General Practice is advisable, and more knowledge on how and when to ask is needed.

Quantitative B-lymphocyte deficiency and increased TCRγδ T-lymphocytes in acute infectious spondylodiscitis.

Acute infectious spondylodiscitis (AIS) is a serious infection of the spine with rising incidence and a mortality of 3-6%. The role of the immune system in AIS is largely unknown. We performed extensive B and T-lymphocyte phenotyping in patients with AIS at diagnosis and after treatment cessation. In this prospective multicentre study, flow cytometric analysis of T and B-lymphocyte subsets was performed in 35 patients at diagnosis and 3 months after treatment cessation. We additionally analysed levels of immunoglobulins and IgG subclasses, serum level and genetic variants of mannose-binding lectin, and somatic hypermutation. A total of 22 (61%) patients had B-lymphocytes below reference limit at baseline, persisting in 7 (30%) patients at follow-up. We found a lower proportion of CD19 + CD27 + IgD+ marginal zone B-lymphocytes and a higher proportion of γδ+ T-lymphocyte receptors compared with controls at both time points. Immunoglobulin levels were elevated at baseline compared to follow-up, and not associated with absolute B-lymphocyte count. In conclusion, a large proportion of AIS patients presented with profound B-lymphocyte deficiency, only partly reversible at follow-up. Identification of immune dysfunction related to AIS may allow for future targeted therapeutic interventions to restore host immunity.

Pharmacokinetics of two randomized trials evaluating the safety and efficacy of indinavir, saquinavir and lopinavir in combination with low-dose ritonavir: the MaxCmin1 and 2 trials.

Our objective was to identify possible differences in protease inhibitor plasma concentrations between and within three protease inhibitor regimens (indinavir, saquinavir and lopinavir all in combination with low-dose ritonavir) and to relate these differences to safety and efficacy. Data originated from pre-defined pharmacokinetic substudies within two randomized 48-week trials evaluating the safety and efficacy of three protease inhibitor regimens. At weeks 4 and 48, plasma was collected and minimum drug plasma concentrations, C(min), were obtained. Out of 656 randomized patients, 283 patients had available C(min) at week 4. Indinavir, saquinavir and lopinavir C(min) were high when combined with low-dose ritonavir. No significant difference in the proportion of patients experiencing treatment failure could be found according to the C(min) within any treatment arm. A saquinavir C(min) > 2000 ng/ml was associated with an increased risk of gastrointestinal grade 3 or 4 adverse events and higher total cholesterol. Overall, there were no changes in C(min) from week 4 to week 48 in patients who remained on therapy. No association between treatment failure and the C(min) could be demonstrated. Associations between high C(min) and toxicity were identified in the saquinavir arm; therefore, dose reductions may be appropriate in certain patients with C(min) several times above the minimum effective concentration.

Reporting and evaluation of HIV-related clinical endpoints in two multicenter international clinical trials.

PURPOSE: The processes for reporting and review of progression of HIV disease clinical endpoints are described for two large phase III international clinical trials. METHOD: SILCAAT and ESPRIT are multicenter randomized HIV trials evaluating the impact of interleukin-2 on disease progression and death in HIV-infected patients receiving antiretroviral therapy. We report definitions used for HIV progression of disease endpoints, procedures for site reporting of such events, processes for independent review of reported events by an Endpoint Review Committee (ERC), and the procedure for adjudication of differences of opinion between reviewers. RESULTS: Of 473 events reported through May 1, 2006, 28% were judged by an ERC to meet "confirmed" criteria and 38% to meet "probable" criteria; 34% were classified "does not meet criteria." For diseases with >5 case reports, the proportion accepted as either "confirmed" or "probable" events was highest for cervical cancer (100%), non-Hodgkin's lymphoma (88%), cryptococcosis (82%), and cryptosporidiosis (80%) and was lowest for HIV encephalopathy (25%), HIV wasting syndrome (33%), and multidermatomal herpes zoster (35%). 25% of cases required adjudication between reviewers before diagnostic certainty was assigned. CONCLUSION: Important requirements for HIV trials using clinical endpoints include objective definitions of "confirmed" and "probable," a formal reporting process with adequate information and supporting source documentation, evaluation by independent blinded reviewers, and procedures for adjudication.

Factors associated with the development of opportunistic infections in HIV-1-infected adults with high CD4+ cell counts: a EuroSIDA study.

BACKGROUND: Limited data exist on factors predicting the development of opportunistic infections (OIs) at higher-than-expected CD4(+) cell counts in human immunodeficiency virus (HIV) type 1-infected adults. METHODS: Multivariate Poisson regression models were used to determine factors related to the development of groups of OIs above their respective traditional upper CD4(+) cell count thresholds: group 1 (>or=100 cells/ microL), OIs caused by cytomegalovirus, Mycobacterium avium complex, and Toxoplasma gondii; group 2 (>or=200 cells/ microL), Pneumocystis pneumonia and esophageal candidiasis; and group 3 (>or=300 cells/ microL), pulmonary and extrapulmonary tuberculosis. RESULTS: In groups 1, 2, and 3, 71 of 9,219, 125 of 7,934, and 36 of 7,838 patients, respectively, developed >or=1 intragroup OI. The strongest predictor of an OI in groups 1 and 2 was current CD4(+) cell count (for group 1, incidence rate ratio [IRR] per 50% lower CD4(+) cell count, 5.37 [95% confidence interval {CI}, 3.71-7.77]; for group 2, 4.28 [95% CI, 2.98-6.14]). Injection drug use but not current CD4(+) cell count predicted risk in group 3. Use of antiretroviral treatment was associated with a lower incidence of OIs in all groups, likely by reducing HIV-1 RNA levels (IRR per 1-log(10) copies/mL higher HIV-1 RNA levels for group 1, 1.50 [95% CI, 1.15-1.95]; for group 2, 1.68 [95% CI, 1.40-2.02]; and for group 3, 1.89 [95% CI, 1.40-2.54]). CONCLUSION: Although the absolute incidence is low, the current CD4(+) cell count and HIV-1 RNA level are strong predictors of most OIs in patients with high CD4(+) cell counts.

A randomized trial to evaluate continuation versus discontinuation of lamivudine in individuals failing a lamivudine-containing regimen: the COLATE trial.

BACKGROUND: Lamivudine (3TC) therapy can cause the emergence of M1841/V. Previous studies suggest a higher fidelity of the mutant reverse transcriptase and lower replication capacity of the mutant virus. No data exist from clinical comparative studies evaluating the benefit of M1841/V in patients receiving combination antiretroviral therapy (cART). METHODS: HIV-1-infected adults failing a 3TC-containing regimen were randomized to continue (On-3TC) or discontinue 3TC (Off-3TC) whilst receiving cART. The primary efficacy measure was the log10 average-area-under-the-curve-minus-baseline reduction in HIV RNA over 48 weeks. Cryopreserved plasma samples from patients with baseline and > or =1 follow-up sample with HIV RNA >500 copies/ml were sequenced for a nucleotide distances substudy. Evolutionary distances were compared between treatment arms and between viruses with and without M1841/V. RESULTS: The overall 48-week log10 HIV RNA change was -1.4 (95% CI: -1.6, -1.1) for On-3TC (n=65) and -1.5 (95% CI: -1.7, -1.2) for Off-3TC (n=66; P=0.51). No difference was seen in the magnitude of the CD4+ T-cell count increases (median increase: 87 vs 76 cells/ml for 3TC vs Off-3TC, respectively). Thirty-seven patients had baseline and follow-up sequencing. Overall, there were 1.2 (95% CI: -2.2, 4.6) more nucleotide substitutions from baseline for Off-3TC patients (P=0.50), and 10.7 (95% CI: 7.5, 14.0) fewer nucleotide changes in viruses containing M18411V (P<0.0001). CONCLUSION: This study found no added virological or immunological benefit of continuing 3TC in patients on cART harbouring M1841/V. Evolutionary distances from baseline were larger in viruses that did not contain M1841/V. More discernable benefits may be seen in patients with fewer drug options as potent cART may eclipse a benefit of M1841/V in COLATE.

A randomized trial to evaluate lopinavir/ritonavir versus saquinavir/ritonavir in HIV-1-infected patients: the MaxCmin2 trial.

OBJECTIVE: To assess the rate of protocol-defined treatment failure and safety of lopinavir/ritonavir (LPV/r) and saquinavir/ritonavir (SAQ/r). DESIGN: Open-label, prospective, randomized (1:1), international multi-centre trial. METHODS: Adult HIV-1-infected patients were assigned LPV/r 400/100 mg twice daily or SAQ/r 1000/100 mg twice daily with two or more nucleoside reverse transcriptase inhibitors (NRTIs)/non-NRTIs. All patients, whether on or off the assigned treatment, were followed for 48 weeks. RESULTS: Of 339 randomized patients, 324 initiated assigned treatment (intention-to-treat/exposed [ITT/e] population). At 48 weeks, treatment failure occurred in 29/163 (18%) and 53/161 (33%) of patients in the LPV/r and SAQ/r arms, respectively (ITT/e, P = 0.002, log rank test). In an analysis that also considered those patients who discontinued treatment as having failed treatment (ITT/e/discontinuation = failure), 40/161 (25%) LPV/r-treated individuals versus 63/161 (39%) SAQ/R-treated individuals failed treatment (P = 0.005, log rank test). Discontinuation of the assigned treatment occurred in 23/163 (14%) patients in the LPV/r-treated group, compared with 48/161 (300%) in the SAQ/r-treated group (ITT/e; P = 0.001). The primary reasons for premature discontinuation were non-fatal adverse events (LPV/r: 12/163; SAQ/r: 21/161) and patients' choice (LPV/r: 7/163; SAQ/r: 8/161). In the on-treatment analysis of time to treatment failure, no difference was observed between the two arms (P = 0.27, log rank test). CONCLUSION: LPV/r had better antiretroviral effects compared with SAQ/r at the doses and in the formulations studied. This may have been a result of patients' preferences and ability to adhere to assigned therapy, rather than a result of differences in the intrinsic potency of the study protease inhibitors.