Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe.

OBJECTIVES: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. METHODS: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15-29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. RESULTS: The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4-111) vs. 8 (IQR 2-38) weeks, respectively], and highest in perinatally infected participants aged 10-14 years [49 (IQR 9-267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0-12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9-5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10-14 years when starting ART (27.7%; 95% CI 13.2-42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10-14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. CONCLUSIONS: The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development.

Antiretroviral therapy for prevention of HIV transmission: implications for Europe.

The aim of this review is to summarise the evidence on the population-level effect of antiretroviral therapy (ART) in preventing HIV infections, and to discuss potential implications in the European context of recommending starting ART when the CD4 count is above 350 cells/mm3. The ability of ART to reduce the risk of HIV transmission has been reported in observational studies and in a randomised controlled trial (HPTN 052), in which ART initiation reduced HIV transmission by 96% within serodiscordant couples. As yet, there is no direct evidence for such an effect among men having sex with men or people who inject drugs. HPTN 052 led international organisations to develop recommendations with a higher CD4 threshold for ART initiation. However, there remains a lack of strong evidence of clinical benefit for HIV-positive individuals starting ART with CD4 count above 350 cells/mm3. The main goal of ART provision should be to increase ART coverage for all those in need, based on the current guidelines, and the offer of ART to those who wish to reduce infectivity; increased HIV testing is therefore a key requirement. Other proven prevention means such as condom use and harm reduction for people who inject drugs remain critical.

Use of a prescription-based measure of antiretroviral therapy adherence to predict viral rebound in HIV-infected individuals with viral suppression.

OBJECTIVE: The aim of the study was to assess whether a simple, routinely available measure of antiretroviral therapy (ART) adherence predicts viral rebound at the next HIV viral load (VL) measurement in virally suppressed patients. METHODS: The analysis was performed on the Royal Free HIV Cohort, London, UK. Each 'drug coverage-viral load episode' (DCVL episode) was defined as a 6-month period immediately prior to a VL < or =50 HIV-1 RNA copies/mL (time-zero), during which the patient had been continuously on HAART, with all measured VLs < or =50 copies/mL. The next VL after time-zero was used to assess whether VL rebound (defined as >200 copies/mL) had occurred. Drug coverage, our measure of adherence, was calculated as the proportion of days in the 6-month period covered by a valid prescription for at least three antiretroviral drugs. RESULTS: A total of 376 (2.4%) VL rebounds occurred in 15 660 DCVL episodes among 1632 patients. Drug coverage was 100% for 32% of episodes, 95-99% for 16% of episodes and < or =60% for 10% of episodes. The risk ratio of rebound associated with a 10% increase in drug coverage, adjusted for potential confounding variables, was 0.93 (95% confidence interval 0.88-0.98). CONCLUSIONS: Antiretroviral drug coverage assessed at the time of VL measurement in patients with undetectable VL is potentially clinically useful for predicting VL rebound at the next VL measurement.

Hemodialysis-induced hypoglycemia in diabetic patients.

BACKGROUND: The authors have previously reported asymptomatic hypoglycemia in non-diabetic patients on hemodialysis. The present study was designed to assess the effect of hemodialysis on plasma glucose, glucagon, cortisol and catecholamines in diabetic patients. METHODS: Eighteen diabetic patients with chronic renal failure were hemodialyzed using a glucose-free dialysis fluid. They did not take any medication prior to dialysis and were asked not to eat during the first hour on hemodialysis. Blood and dialysate were sampled at regular intervals during the first hour of dialysis for analysis. RESULTS: Plasma glucose fell below 4.0 mmol/l (72 mg/dl) in 7 of the 18 patients, below 3.5 mmol/l (63 mg/dl) in 3 and below 3.0 mmol/l (54 mg/dl) in one. The lowest recorded value was 2.8 mmol/l (50 mg/dl). The mean glucose loss in the waste dialysate was 9.2 g/h. In none of the group of 7 patients whose plasma glucose fell below 4.0 mmol/l (72 mg/dl) did symptoms of hypoglycemia occur. When 6 patients from this group were subsequently dialyzed with a dialysis fluid containing 5.5 mmol/l (100 mg/dl) glucose, their plasma glucose became stabilized within the fasting reference range. There were no significant hormonal changes during the dialysis or between non-hypoglycemic and hypoglycemic patients. CONCLUSIONS: Patients undergoing hemodialysis may become hypoglycemic and not be aware of it. There is no hormonal imbalance causing the hypoglycemia and the hormonal response to the hypoglycemia is blunted. Patients with an initial plasma glucose of 5.5 mmol/l (100 mg/dl) or less who are hemodialyzed and who do not eat during dialysis may be particularly at risk, especially if they are on insulin or taking glucose-lowering medication. These should be dialyzed with a dialysis fluid containing at least 5.5 mmol/l (100 mg/dl) glucose.

Occult hypoglycemia caused by hemodialysis.

BACKGROUND: Previous studies have ignored hypoglycemia in patients undergoing hemodialysis. The fall in plasma glucose may not have been considered to be clinically relevant because the patients were asymptomatic. The present study was designed to assess the effect of hemodialysis on plasma glucose, insulin, glucagon, cortisol and catecholamines in non diabetic patients. METHODS: 21 non diabetic patients with chronic renal failure were hemodialyzed using a glucose-free dialysis fluid. They did not take any medication prior to dialysis and were asked not to eat during the first hour on hemodialysis. Blood and dialysate fluid was sampled at regular intervals during the first hour of dialysis for analysis. RESULTS: Plasma glucose fell below 4.0 mmol/l (72 mg/dl) in 9 of the 21 patients, below 3.5 mmol/l (63 mg/dl) in 6 and below 3.0 mmol/l (54 mg/dl) in 3. The lowest recorded value was 2.1 mmol/l (38 mg/dl). The mode glucose loss in the waste dialysate fluid was 6 g/h. In the group of 9 patients whose plasma glucose fell below 4.0 mmol/l (72 mg/dl), no symptoms of hypoglycemia were shown but 4 of the 7 patients who felt very hungry and ate were in this group. When 7 patients from this group were subsequently dialysed with a dialysis fluid containing 5.5 mmol/l (100 mg/dl) glucose, their plasma glucose became stabilized within the fasting reference range. There were no significant hormonal changes during the dialysis or between euglycemic and hypoglycemic patients. CONCLUSIONS: Patients undergoing hemodialysis may become hypoglycemic and not be aware of it. There is no hormonal imbalance causing the hypoglycemia and the hormonal response to the hypoglycemia is blunted. Patients with an initial plasma glucose of 4.5 mmol/l (81 mg/dl) or less who are hemodialyzed and who do not eat during dialysis may be particularly at risk. They should be dialysed with a dialysis fluid containing at least 5.5 mmol/l (100 mg/dl) glucose.

A comparison of presenting characteristics of patients with intracapsular and extracapsular proximal femoral fractures.

The presenting characteristics of 1423 consecutive admissions with proximal femoral fractures were prospectively studied, to determine any differences that may exist between patients, dependent on the radiological site of the fracture. Patients with intracapsular fractures were of a lower average age, more mobile, less likely to use walking aids or live in residential accommodation, they also had a considerably shorter length of hospital stay than for those patients with extracapsular fractures. Comparison against previous series shows that the average age of hip fracture patients and the proportion of trochanteric fractures is increasing.

Proximal femoral fractures: prevalence in different racial groups.

This paper describes the methodology and the results of a study performed in Central England. The predominant racial group here is "White European" (Europid). There are smaller numbers of people of Indian origin (Indids) and still smaller numbers of Afro-Caribbean and of Mongolian ancestry (Mongoloids). We found no significant differences in the incidence of hip fractures in the first two groups. The study population was 1600 consecutive patients with proximal femoral fractures (PFF). The difficulties of racial classification are discussed. To elucidate the predisposing factors for PFF, large scale collaborative studies between medical centres in the major European, Asian, African and American conurbations are suggested. Racial burden may be one such factor; osteoporosis may be another.

Evaluation of the penetration of ciprofloxacin and amoxycillin into the bronchial mucosa.

The concentrations of two antibiotics, amoxycillin and ciprofloxacin, were measured by microbiological assay in serum and in bronchial mucosa obtained at fibreoptic bronchoscopy in 38 patients undergoing diagnostic bronchoscopy for a range of respiratory symptoms. Patients had taken one of the two drugs orally for four days before bronchoscopy. The percentage penetration of antibiotic from serum to bronchial mucosa was calculated as the ratio of drug concentration in bronchial tissue to that in serum x 100. Of the nine patients who took amoxycillin 500 mg thrice daily the mean (SD) percentage penetration was 75. This was significantly lower than the mean percentage penetration of 147 in 29 patients who took ciprofloxacin 500 mg twice daily. Ten patients were given a single intravenous dose of ciprofloxacin 200 mg one hour before bronchoscopy and the mean percentage penetration was 231. This study has shown that the quinolone antibiotic ciprofloxacin is concentrated in the bronchial mucosa.

Effect of naproxen on renal haemodynamics in elderly patients with arthritis.

The effects of naproxen on renal haemodynamics were observed in ten elderly arthritic patients who were otherwise healthy and without clinical evidence of renal disease. Glomerular filtration rate (GFR,51Cr-EDTA clearance) and effective renal plasma flow (ERPF, 125I-iodohippurate clearance) were measured after 2 weeks' treatment with naproxen 500 mg twice daily and again after 2 weeks off the drug, in random order. Baseline values for GFR and ERPF were within normal limits (mean 72 ml/min/1.73 m2, 110% predicted and 326 ml/min/1.73 m2, 111% predicted, respectively). On naproxen, ERPF and renal blood flow decreased by 10% and 9%, respectively (-32 ml/min/1.73 m2; p = 0.05 and -49 ml/min/1.73 m2; p less than 0.01). These events produced no untoward clinical effects. Nevertheless, this response might impair the kidney's ability to preserve GFR if a further stress were to supervene. Consequently, temporary withdrawal of non-steroidal anti-inflammatory drugs from elderly patients should be considered in response to intercurrent illness or drug therapy likely to compromise renal blood flow.

The destination and dependency of patients discharged from care of the elderly units in the West Midlands.

Between November 1988 and January 1989 a prospective survey was undertaken on patients aged 65 years and over who were discharged from the care of geriatricians in seven District General Hospitals. The survey aimed to provide a regional perspective on patient dependency by relating dependency at discharge to the discharge destination. The findings show that the majority of patients were relatively independent and most returned home. A significant number of the very dependent patients were discharged to the community with private residential and nursing homes making an important contribution to the placement of highly dependent patients.