James Young

Prevalence of unsafe sexual behavior among HIV-infected individuals: the Swiss HIV Cohort Study

Sexual contact is the major mode of HIV transmission. Increased sexual risk taking has been described in HIV-infected individuals receiving potent antiretroviral therapy. A new questionnaire on sexual behavior was introduced into the Swiss HIV Cohort Study on April 1, 2000. We evaluated sexual behavior in all individuals who completed the questionnaire for the first time within 1 year after its introduction. Our primary hypothesis was that self-reported unsafe sexual behavior would be more prevalent among individuals with optimal viral suppression. On April 1, 2000, 4948 individuals were registered in the study, and 4723 (95%) completed the questionnaire. Of these individuals, 12% reported unsafe sex, 78% received antiretroviral therapy, and 25% had optimal viral suppression (HIV RNA level always <50 copies/mL during the preceding 12 months). During the preceding 6 months, 55% of individuals had stable and 19% had occasional partners, and 6% had both types of partners. Sexual intercourse was reported by 82% of individuals with stable and 87% of individuals with occasional partners, and of those reporting sexual intercourse in each group, 76% and 86%, respectively, said that they always used condoms. After adjustment for covariates, reported unsafe sex was not associated with optimal viral suppression (odds ratio, 1.04; 95% confidence interval, 0.81-1.33) or antiretroviral therapy (odds ratio, 0.83; 95% confidence interval, 0.65-1.07), but it was associated with gender, age, ethnicity, HIV transmission group, HIV status of partner, having occasional partners, and living alone. There is no evidence that self-reported unsafe sexual behavior is more prevalent among HIV-infected individuals with optimal viral suppression. However, unsafe sex is associated with other factors.

Stable partnership and progression to AIDS or death in HIV infected patients receiving highly active antiretroviral therapy: Swiss HIV cohort study

Abstract Objectives To explore the association between a stable partnership and clinical outcome in HIV infected patients receiving highly active antiretroviral therapy (HAART). Design Prospective cohort study of adults with HIV (Swiss HIV cohort study). Setting Seven outpatient clinics throughout Switzerland. Participants The 3736 patients in the cohort who started HAART before 2002 (median age 36 years, 29% female, median follow up 3.6 years). Main outcome measures Time to AIDS or death (primary endpoint), death alone, increases in CD4 cell count of at least 50 and 100 above baseline, optimal viral suppression (a viral load below 400 copies/ml), and viral rebound. Results During follow up 2985 (80%) participants reported a stable partnership on at least one occasion. When starting HAART, 52% (545/1042) of participants reported a stable partnership; after five years of follow up 46% (190/412) of participants reported a stable partnership. In an analysis stratified by previous antiretroviral therapy and clinical stage when starting HAART (US Centers for Disease Control and Prevention group A, B, or C), the adjusted hazard ratio for progression to AIDS or death was 0.79 (95% confidence interval 0.63 to 0.98) for participants with a stable partnership compared with those without. Adjusted hazards ratios for other endpoints were 0.59 (0.44 to 0.79) for progression to death, 1.15 (1.06 to 1.24) for an increase in CD4 cells of 100 counts/μl or more, and 1.06 (0.98 to 1.14) for optimal viral suppression. Conclusions A stable partnership is associated with a slower rate of progression to AIDS or death in HIV infected patients receiving HAART.

Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: study protocol for a randomised controlled trial and baseline characteristics of participating general practitioners [ISRCTN73182671]

BackgroundAcute respiratory tract infections (ARTI) are among the most frequent reasons for consultations in primary care. Although predominantly viral in origin, ARTI often lead to the prescription of antibiotics for ambulatory patients, mainly because it is difficult to distinguish between viral and bacterial infections. Unnecessary antibiotic use, however, is associated with increased drug expenditure, side effects and antibiotic resistance. A novel approach is to guide antibiotic therapy by procalcitonin (ProCT), since serum levels of ProCT are elevated in bacterial infections but remain lower in viral infections and inflammatory diseases.The aim of this trial is to compare a ProCT-guided antibiotic therapy with a standard approach based on evidence-based guidelines for patients with ARTI in primary care.Methods/DesignThis is a randomised controlled trial in primary care with an open intervention. Adult patients judged by their general practitioner (GP) to need antibiotics for ARTI are randomised in equal numbers either to standard antibiotic therapy or to ProCT-guided antibiotic therapy. Patients are followed-up after 1 week by their GP and after 2 and 4 weeks by phone interviews carried out by medical students blinded to the goal of the trial.Exclusion criteria for patients are antibiotic use in the previous 28 days, psychiatric disorders or inability to give written informed consent, not being fluent in German, severe immunosuppression, intravenous drug use, cystic fibrosis, active tuberculosis, or need for immediate hospitalisation.The primary endpoint is days with restrictions from ARTI within 14 days after randomisation. Secondary outcomes are antibiotic use in terms of antibiotic prescription rate and duration of antibiotic treatment in days, days off work and days with side-effects from medication within 14 days, and relapse rate from the infection within 28 days after randomisation.DiscussionWe aim to include 600 patients from 50 general practices in the Northwest of Switzerland. Data from the registry of the Swiss Medical Association suggests that our recruited GPs are representative of all eligible GPs with respect to age, proportion of female physicians, specialisation, years of postgraduate training and years in private practice.

MATERNAL MORTALITY IN ROCHDALE: AN ACHIEVEMENT IN A BLACK AREA

Dr. F. A. HORT (London, N.W.8) writes: Any apparatus designed to wash out bo-wel contents by irrigation will inevitably tend-the more so the more effective the apparatus-to lead to constipation, inasmuch as (1) the normal protective residual debris is thereby washed away, and (2) the natural function of defaccationl is su)p)lanted by artificial means. The glass contrivance shown in the accompanying figure, which differs from those commonly used in irrigationi only in that the vertical limb is curved instea(l of straight, enables the operator to watch the effects of w%!hat he is doinlg, as the tide alternately ebbs and flows before him. By this means he is able to form some idea of the activity and general

Low levels of mannan-binding lectin or ficolins are not associated with an increased risk of cytomegalovirus disease in HIV-infected patients

Background In HIV-infected patients, prediction of Cytomegalovirus (CMV) disease remains difficult. A protective role of mannan-binding lectin (MBL) and ficolins against CMV disease has been reported after transplantation, but the impact in HIV-infected patients is unclear. Methods In a case-control study nested within the Swiss HIV Cohort Study, we investigated associations between plasma levels of MBL/ficolins and CMV disease. We compared HIV-infected patients with CMV disease (cases) to CMV-seropositive patients without CMV disease (controls) matched for CD4 T-cells, sampling time, and use of combination antiretroviral therapy. MBL and M-ficolin, L-ficolin, and H-ficolin were quantified using ELISA. Results We analysed 105 cases and 105 matched controls. CMV disease was neither associated with MBL (odds ratio [OR] 1.03 per log10 ng/mL increase (95% CI 0.73–1.45)) nor with ficolins (OR per log10 ng/mL increase 0.66 (95% CI 0.28–1.52), 2.34 (95% CI 0.44–12.36), and 0.89 (95% CI 0.26–3.03) for M-ficolin, L-ficolin, and H-ficolin, respectively). We found no evidence of a greater association between MBL and CMV disease in patients with low CD4 counts; however in the multivariable analysis, CMV disease was more likely in patients with an increased HIV RNA (OR 1.53 per log10 copies/mL; 95% CI 1.08–2.16), or a shorter duration of HIV-infection (OR 0.91 per year; 95% CI 0.84–0.98). Conclusions CMV disease is not associated with low levels of MBL/ficolins, suggesting a lack of a protective role in HIV-infected patients.

EDUCATION OF THE PUBLIC AS TO CANCER

if he couldl give me details of the methods w-hicll were being a(lolted for the treatmeiit of cancer by lead under his directioni, but lie answered in a letter of October 17tll that thle preparation of lead which they were using liad lnot been brought to the level of perfection whiclh tlley hoped to achieve: le adlded that any-one who was unw-illing to go to Liverpool to learin the methods, dangers, etc., at first hand they could not help. I at once wrote offerincg to visit the Researlch Department at any time conveniient to Professor Blair Bell, but was then told that individuals (couldinot be giveln tho informatioln, but only delegates from isistitutionis. From other sources I understand that the colloidal preparationl of lead whicll is being used can be manufactured in London, anid I therefore fail to understalnd why full details of the mlietlhods of treatment of these cases could not have been given to the profession lonig enough ago. There are admiiirable and efficient organizations in several towi-nis in Englanid, where the testing of any preparationls for the treatmeent of cancer can be calried out, and it seems to me a very great pity that Professor Blair Bell has not seen fit to give the fullest information he has to the rest of tlho profession as sooln as it was available.-I am, etc.,

Dynamic models for estimating the effect of HAART on CD4 in observational studies: Application to the Aquitaine Cohort and the Swiss HIV Cohort Study

Highly active antiretroviral therapy (HAART) has proved efficient in increasing CD4 counts in many randomized clinical trials. Because randomized trials have some limitations (e.g., short duration, highly selected subjects), it is interesting to assess the effect of treatments using observational studies. This is challenging because treatment is started preferentially in subjects with severe conditions. This general problem had been treated using Marginal Structural Models (MSM) relying on the counterfactual formulation. Another approach to causality is based on dynamical models. We present three discrete-time dynamic models based on linear increments models (LIM): the first one based on one difference equation for CD4 counts, the second with an equilibrium point, and the third based on a system of two difference equations, which allows jointly modeling CD4 counts and viral load. We also consider continuous-time models based on ordinary differential equations with non-linear mixed effects (ODE-NLME). These mechanistic models allow incorporating biological knowledge when available, which leads to increased statistical evidence for detecting treatment effect. Because inference in ODE-NLME is numerically challenging and requires specific methods and softwares, LIM are a valuable intermediary option in terms of consistency, precision, and complexity. We compare the different approaches in simulation and in illustration on the ANRS CO3 Aquitaine Cohort and the Swiss HIV Cohort Study.

An Address on MATERNAL MORTALITY FROM PUERPERAL SEPSIS : AN ANALYSIS OF THE FACTORS OF CONTAGION, TRAUMA, AND AUTO-INFECTION.

young women which is incurred yearly through childbearing and childbirth. In these islands the maternal dteath rate is about 4,000 each year; between 1911 and 1926 inclusive there were 66,421 deaths from these causes in England and Wales. Septic infection is by far the most important single cause. According to the official figures for 1926 the total maternal mortality for England and Wales was 5.14, and the sepsis mortality 1.60, per 1,000 live births. This loss bv death, however, is in some ways not the gravest consequence of child-bearing, for we have come to iealize that, for each mother so lost, there are many more Wliose health is in varying degrees chronically undermined by the d-amage they have stustained in childbed. Infection and mechanical damage thus acquired are amongst the main causes of the frequent chronic ill health which dates from childbirth. We can assess within accurate limits the loss by death, but of the incidence of persisting invalidism of child-bearing origin we have no exact knowledge.We_ know with certainty, however, that many of the common gyn-aecological disorders, the uterine haemorrhages, the leucorrhoeas, the pelvic pains, the displacements, etc., and many general disturbances, debility, indigestion, neurasthenia, rhieumiiatism, etc., are to be traced to the lesions of childbirth. It is probably not an over-statement to sav that abouit 60 per cent. of hospital g-naecology is a legacy from vitiated child-bearing, and of this a very large part falls into the category of infection. Septic inflammationi of the genital canal during labour or in the pluerperiulm may, as a useful basis for analysis, be considered as falling into one or other of three clinical types according as it is caused by (1) contagion, (2) trauma,

AVERTIN IN GYNAECOLOGY

All who have had experience of arthroplasty are agreed that the most successful cases are those in which the ankylosis is bony, with comparatively normal-shaped bones. This will include traumatic joints, and those the result of pyaemia. We may exclude tuberculous joints, which so often and for years contain foci of infection. The operation is contraindicated in the presence of active disease, and should be delayed until at least two years after its complete cessation. It should never be performed in the presence of sinuses, nor where the soft tissues are infiltrated and tense, nor where muscles are atrophied and adherent; nor should it be performed until growth is ended. The joint which responds most favourably to an arthroplasty is the elbow; the knee, although technique has improved, mainly by the excellent work of Putti, is still in the experimen-tal stage. It is an operation which requires the highest judgement and skill on the part of the surgeon, and fortitude on the part of the patient, for the after-treatment is very painful. The elbow is a joint where we can almost promise a satisfactory result-good movement and fair stability; but the ankle-joint, if stiff and painless, should not be mobilized if painful it should be arthrodesed.

THE CHRONIC PELVIC WOMAN

of lactic acid in normal and pathological gastric contents, and their main thesis-namely, that the lactic acid content varies roughly inversely with the HCI content-has been known for a great many years. In 1886 Ewald (Berl. klin. Woch., 1886, xxiii, 825) demonstrated that if a healthy man took m roll of bread on an empty stomach then lactic acid appeared in the gastric contents in the first half-hour after the meal. On dissolving bread in water and digesting at body temperature he found no lactic acid to be present, and he writes: