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Biomedical subjects

B Broers

Publications and source records attributed to B Broers.

At least 19 recordsLinked to original sources

Inpatient opiate detoxification in Geneva: follow-up at 1 and 6 months.

The aim of this study was to identify predictors of treatment success and of relapse, 1 and 6 months after inpatient opiate detoxification in an 8-bed unit in Geneva. Of all 73 patients admitted between June 1994 and June 1995, a majority (73%) successfully finished opiate detoxification. Detoxification was performed mainly with methadone tapering; the average duration of hospitalisation was 15 days. Factors associated with treatment failure were: cocaine abuse, presence of legal problems, and short duration of hospital stay. After 1 month, 65% of the patients were using drugs (half of them were dependent again, half of them had used occasionally) and 35% were completely abstinent (21% when excluding those in residential treatment). Predictors of rapid relapse were cocaine abuse and little concern with own psychological situation at baseline. After 6 months, 50% were physically dependent again, 13% had lapsed occasionally, 37% were abstinent (28% when excluding those in residential treatment). Only high benzodiazepine use at baseline was associated with medium term abstinence. Addiction severity index composite scores had considerably improved between baseline and 6 months. Prevention of relapse to opiate use after inpatient detoxification, especially for those with a concurrent cocaine abuse, should be improved.

Adolescent↗

Patterns of opiate use in a heroin maintenance programme.

RATIONALE: Little is known about patterns of opiate use by heroin addicts. OBJECTIVES: To describe opiate use over time among heroin addicts who had access to legally prescribed intravenous heroin and oral opiates. METHODS: Analysis of daily drug administration records of 37 patients enrolled in the Geneva heroin maintenance programme for 4-29 months (total 23,136 patient-days). RESULTS: The average dose of intravenous heroin was 466 mg/day; the total opiate dose, after conversion of oral opiates to heroin-equivalents, was 543 mg/day. Patients received intravenous heroin only on 39% of days, oral opiates only on 7% of days, and mixed regimens on 49% of days; the remaining 4% of days were spent outside the programme, usually on oral opiates. The daily dose of heroin-equivalents increased during the first trimester in the programme, by 30 mg/day per month (95% confidence interval 12-46 mg/day per month), but decreased gradually thereafter, by 12 mg/day per month (95% confidence interval, 8-17 mg/day per month). In patients who alternated between heroin and methadone, 1 mg methadone typically replaced 4.1 mg heroin. During follow-up, five patients switched to methadone maintenance, five underwent detoxification, and three were discharged for noncompliance with regulations. CONCLUSIONS: Heroin users who have facilitated access to legally prescribed drugs consume about 0.5 g heroin per day. Consumption patterns vary, but the daily amount of opiates remains stable or decreases over time. A substantial minority of patients elect for alternative treatments after several months of heroin maintenance.

Adult↗

Do gender differences in CD4 cell counts matter?

OBJECTIVE: To examine the effect of gender on disease progression and whether gender differences in CD4 lymphocyte counts persisted for the entire course from HIV seroconversion until (death from) AIDS. METHODS: CD4 lymphocyte counts were modelled in 221 female and 443 male seroconverters following seroconversion, backwards from AIDS and backwards from death using regression analysis for repeated measurements. RESULTS: In the period before use of highly active antiretroviral therapy (HAART), progression to AIDS and to death were marginally slower in women than in men as assessed by proportional hazards analysis. Women seroconverted for HIV, developed AIDS and died at higher CD4 cell counts than men (women: 815, 146 and 44 x 10(6) cells/l, respectively; men: 727, 49 and 22 x 10(6) cells/l, respectively), although differences were only statistically significant at AIDS onset. Declines in CD4 lymphocyte counts were not significantly affected by gender and absolute differences between men and women were stable, with exception for the trajectory close to AIDS when the decline became steeper for men than women. CONCLUSION: These gender differences in CD4 lymphocyte counts suggest a delay of initiation of therapy in women compared with men (our model predicted that women reach the threshold of starting HAART at about 12 months later than men). If this delay unfavourably influences progression, treatment guidelines should be revised so that women can benefit equally from HAART.

Acquired Immunodeficiency Syndrome↗

Substance abuse and drug-related death, suicidal ideation, and suicide: a review.

The high mortality rate among drug users, which is partly due to the HIV epidemic and partly due to drug-related accidental deaths and suicides, presents a major public health problem. Knowing more about prevalence, incidence, and risk factors is important for the development of rational preventive and therapeutic programs. This article attempts to give an overview of studies of the relations between substance abuse, suicidal ideation, suicide, and drug-related death. Research in this field is hampered by the absence of clear definitions, and results of studies are rarely comparable. There is, however, consensus about suicidal ideation being a risk factor for suicide attempts and suicide. Suicidal ideation is also a predictor of suicide, especially among drug users. It is correlated with an absence of family support, with the severity of the psychosocial dysfunctioning, and with multi-drug abuse, but also with requests for treatment. Every clinical examination of a drug user, not only of those who are depressed, should address the possible presence of suicidal ideation, as well as its intensity and duration.

Adolescent↗

Geographical variation in disease progression in HIV-1 seroconverted injecting drug users in Europe?

BACKGROUND: Human immunodeficiency virus (HIV) disease progression might vary by geographical region due to differences in the spectrum of HIV-related illnesses and (access to) health care. Therefore, the effect of geographical region, next to the effect of other potential cofactors, on disease progression in 664 injecting drug users (IDU) with documented HIV seroconversion from eight cohorts in Europe was studied. METHODS: Kaplan-Meier methods and Cox proportional hazards analysis were performed to assess the effect of geographical region, other sociodemographics, drug use and repeated HIV exposure on progression from HIV seroconversion to immunosuppression, AIDS and death with AIDS. We considered the confounding effect of study-design related factors (e.g. setting of follow-up), and accounted for pre-AIDS death from natural causes by imputing when each endpoint would have occurred, had they not died without AIDS. RESULTS: Estimates of progression to AIDS and death with AIDS were substantially faster after taking pre-AIDS mortality into account. Median incubation time from seroconversion to the first CD4 count < 200 cells/microliter was 7.7 years (95% CI: 7.1-8.3) and to AIDS 10.4 years (95% CI: 9.8-infinity). The 10-year survival was 70.3% (95% CI: 62.8-76.6). The relative hazards (RH) of AIDS for IDU from central and southern Europe compared with IDU from northern Europe was 1.9 (95% CI: 1.2-3.0) and 1.2 (95% CI: 0.6-2.3), respectively, before, and 1.5 (95% CI: 0.7-3.2) and 1.1 (95% CI: 0.6-2.3) after taking differences in study-design related factors into account. Accounting for these factors, the RH of death with AIDS was 0.9 (95% CI: 0.3-2.5) for central and 1.2 (95% CI: 0.4-3.4) for southern Europe compared with northern Europe. For the first CD4 count < 200 cells/microliter these figures were 0.8 (95% CI: 0.5-1.4) and 0.8 (95% CI: 0.5-1.4). Age at seroconversion was the strongest predictor of disease progression. No statistically significant differences in disease progression were found by gender, foreign nationality, drug use and potential repeated HIV exposure. CONCLUSIONS: We found no evidence for regional variability in HIV disease progression among European IDU. Future studies evaluating geographical differences should consider the confounding effect of study-design related factors and differential non-AIDS mortality. As age is an important determinant of disease progression, it should be considered in recommending treatment.

Adult↗

Prevalence and incidence rate of HIV, hepatitis B and C among drug users on methadone maintenance treatment in Geneva between 1988 and 1995.

OBJECTIVES: To evaluate the prevalence and incidence rates of infection with HIV, hepatitis B (HBV) and hepatitis C (HCV), in a cohort of drug users (DU) in Geneva, Switzerland. DESIGN: Prospective open cohort study. SETTING: Private methadone maintenance treatment (MMT) programme. PATIENTS, PARTICIPANTS: Over 700 DU in treatment between 1988 and 1995 were tested biannually for HIV, HBV and HCV infection. INTERVENTION: None. MAIN OUTCOME MEASURE: Prevalence for HIV, HBV and HCV at study entry, determined by gender, by injection behaviour, by year of start of MMT and incidence rates for HIV, HBV and HCV, assuming equal risk of seroconversion on each day of the interval between last negative and first positive test. RESULTS: The prevalence at entry into treatment declined dramatically over time for all three viruses. Comparing DU entering treatment before 1988 to those entering treatment after 1993, the prevalence of HIV was 38.2% versus 4.5%, of HBV 80.5% versus 20.1%, and of HCV 91.6% versus 29.8%, respectively. Follow-up rate was 80%. The incidence rates for HIV and HBV were 0.6% and 2.1% per person-year of follow-up, respectively. For HCV the rate was higher (4.2%) especially among women (9.6%). CONCLUSION: These data suggest that DU have changed HIV risk-taking behaviour in response to HIV prevention campaigns. Current prevention efforts should focus on improvement of HCV prevention, identification of high-risk individuals and maintaining safe behaviour.

Cohort Studies↗

Treatment failure and methadone dose in a public methadone maintenance treatment programme in Geneva.

The aim of this study was to identify predictors of treatment failure in a methadone maintenance treatment programme in Geneva. All patients (n = 149) starting treatment between May 1993 and May 1995 were followed until end of treatment or 31st July 1996. The proportion of depressed patients decreased significantly over time, as did the proportion of those injecting illegal drugs. The overall treatment failure was 21%. The probability of treatment failure was higher for women than for men (RR 2.2, P = 0.03) and decreased in successive cohorts. There was no correlation between the methadone dose at 2 months and treatment outcome, probably because doses were individualised and the associated level of psycho-social services high.

Adult↗

Pre-AIDS mortality from natural causes associated with HIV disease progression: evidence from the European Seroconverter Study among injecting drug users.

OBJECTIVES: To study differences in pre-AIDS mortality between European cohorts of injecting drug users (IDU) and to evaluate whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count. METHODS: The study population consisted of 664 IDU with documented intervals of HIV seroconversion from eight cohort studies. Differences in pre-AIDS mortality were studied between European sites; an evaluation of whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count was carried out using Poisson regression. RESULTS: One hundred and seven IDU died, of whom 57 did not have AIDS. Pre-AIDS causes of death were overdose/suicide (49%), natural causes such as bacterial infections/cirrhosis (40%), and unintentional injuries/unknown (11%). Considering pre-AIDS death and AIDS as competing risks, 14.7% were expected to have died without AIDS and 17.3% to have developed AIDS at 7 years from seroconversion. No statistically significant differences in pre-AIDS mortality were found between European regions, men and women, age categories and calendar time periods. Overall pre-AIDS mortality did not increase with time since seroconversion, but did increase with decreasing CD4 count. Evaluating cause-specific mortality, only pre-AIDS mortality from natural causes appeared to be associated with time since seroconversion as well as immunosuppression. For natural causes, the death rate per 100 person-years was 0.13 the first 2 years after seroconversion, 0.73 in years 2-4 [risk relative (RR) to years 0-2, 5.6], 1.83 in years 4-6 (RR, 14.0) and 1.54 for > or = 6 years (RR, 11.7). This rate was 0 for a CD4 cell count > or = 500 x 10(6)/l, 1.06 for 200-500 x 10(6)/l and 4.06 for < 200 x 10(6)/l (RR versus > or = 200 x 10(6)/l, 7.0). In multivariate analysis, both CD4 count and time since seroconversion appeared to be independently associated with death from natural causes; CD4 count appeared to be the strongest predictor (adjusted RR, 5.9). CONCLUSIONS: A high pre-AIDS mortality rate was observed among IDU. No significant differences were observed across European sites. Pre-AIDS mortality from natural causes but not from overdose and suicide was associated with HIV disease progression.

Acquired Immunodeficiency Syndrome↗

Muscle ultrastructure and biochemistry of lowland Tibetans.

Muscle ultrastructure and biochemistry in vastus lateralis muscle biopsies and the response to exercise of 8 lowland Tibetans (T) were compared with those of 8 Nepalese lowlanders (N). Blood hemoglobin was lower in T than in N (119 +/- 3 vs. 131 +/- 2 g/l; P < 0.05). Peak O2 consumption per kilogram of body mass was similar [37.9 +/- 2.2 (T) vs. 40.1 +/- 1.36 ml.min-1.kg body mass-1 (N)]. Maximum exercise blood lactate was the same [11.4 (T) +/- 0.5 vs. 11.3 +/- 0.6 mM (N)]. Muscle fiber type distribution was similar [type I, 58.6 +/- 3.4 (N) vs. 57.0 +/- 3.4% (T); type IIa, 24.1 +/- 3.5 vs. 27.1 +/- 1.6%; type IIb, 17.4 +/- 1.4 vs. 15.9 +/- 2.9%]. T had smaller fiber cross-sectional areas [3,413 +/- 677 (T) vs. 3,895 +/- 447 microns 2 (N); P < 0.05] but had similar number of capillaries per muscle fiber [1.35 +/- 0.23 (T) vs. 1.46 +/- 0.08 (N)] and muscle fiber area supplied per capillary [399 +/- 29 (T) vs. 382 +/- 65 mm2 (N)]. Total mitochondrial volume density was much lower in T (3.99 +/- 0.17%) than in N (5.51 +/- 0.19%) (P < 0.025). Mirroring mitochondrial volume density, citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities were lower in T than in N (P < 0.05). The activities of L-lactate dehydrogenase and hexokinase were the same in both groups. T had significantly less muscle fiber lipid droplets than did N, which correlated with the low activity of 3-hydroxyacyl-CoA dehydrogenase (r = 0.57, P = 0.02). In conclusion, lowland-born T have a low mitochondrial volume-to-specific peak O2 consumption ratio, which, based on previous measurements on altitude-born Sherpas (B. Kayser, H. Hoppeler, H. Claassen and P. Cerretelli. J. Appl. Physiol. 70: 1938-1942, 1991), appears to be an inborn feature.

Adolescent↗

Growth-deficient mycobacteria in patients with AIDS: diagnosis by analysis of DNA amplified from blood or tissue.

Amplification and sequencing of mycobacterial ribosomal RNA genes (16S rDNA) may permit the detection of growth-deficient species (i.e., those exhibiting no growth or those whose growth is delayed for more than 12 weeks). Of blood samples from 26 patients with AIDS and a liver sample from one additional AIDS patient, three samples (two of blood and the one of liver) were positive by polymerase chain reaction only; cultures of these three samples remained negative for more than 12 weeks. Analysis of amplified 16S rDNA from blood revealed a sequence characteristic of Mycobacterium genavense in the first case, in which one of many previous blood cultures had also been positive for M. genavense. The sequences found in the second and third cases were characteristic of Mycobacterium avium. The sample from the second patient was a liver biopsy specimen in which acid-fast bacilli were visualized; the culture of this specimen yielded M. avium after 7 months. The third sample was a blood sample from a patient in whom a relapse of treated M. avium infection was suspected. These results indicate that amplification and sequencing of mycobacterial 16S rDNA may permit early diagnosis and provide a rationale for treatment of infections due to growth-deficient mycobacteria.

Acquired Immunodeficiency Syndrome↗

A cohort study of drug users' compliance with zidovudine treatment.

OBJECTIVES: Determine whether patients who have acquired the human immunodeficiency virus through injecting drug use receive less antiviral medication (zidovudine) than comparable patients of other risk groups considering access to, acceptance of, and compliance with treatment. DESIGN: Historical cohort study. SETTING: Human immunodeficiency virus outpatient clinic. PATIENTS: Human immunodeficiency virus-infected subjects eligible for zidovudine treatment between January 1, 1989, and January 1, 1992, comparing injecting drug users (IDUs) with non-IDUs ("others"). MAIN OUTCOME MEASURES: Proposal, acceptance, start of, and compliance with zidovudine treatment. RESULTS: One hundred fifty-one IDUs and 162 other human immunodeficiency virus-positive subjects became eligible for zidovudine treatment between January 1, 1989, and January 1, 1992. Both groups were proposed zidovudine as often, but zidovudine treatment was refused by 14.9% of IDUs compared with 7.1% of others (P = .029). The IDUs needed considerably more time than other subjects to accept zidovudine therapy (median delay between indication and start of zidovudine treatment, 61 days vs 30 days, P = .0001). After accepting, IDUs were as compliant with treatment as others: 81.3% vs 83.2% were good compliers, and rises of mean corpuscular volume of erythrocytes after 3 and 6 months of treatment were similar in both groups. Former drug users and IDUs receiving methadone were started on zidovudine treatment more often and complied better with treatment than active drug users. Absence of housing and presence of psychiatric diagnosis (both more prevalent in IDUs) were associated with less zidovudine treatment and worse compliance. CONCLUSION: Injecting drug users tend to delay the start of zidovudine treatment. However, once they have started, their compliance is no worse than the compliance of patients from other risk groups. These results have important implications for clinical trials, medical care, and public health.

Adult↗

The metabolic and ventilatory response to exercise in Tibetans born at low altitude.

The exercise response of 20 Tibetans (T) born and living in Kathmandu, Nepal (1300 m) was compared to that of 21 age- and sex-matched local lowlanders. The subjects carried out an incremental exercise protocol on a bicycle ergometer (30 watt steps every 4 min) until exhaustion. The kinetics of readjustment of VO2 measured as half time (t-on) upon a 90 watt constant load exercise was also determined. Breath-by-breath gas exchange, heart rate (HR) and blood lactate concentration ([La]) were measured at rest, at the end of each load and during recovery. The slope of the straight line relating VO2 to work load was 10.8 ml.watt-1 in both groups which corresponds to a mechanical efficiency of 0.26 (assuming a RQ of 0.89 and an energy equivalent of 20.9 kJ.L-1 O2). At submaximal loads T were characterized by higher VE (P < 0.05), VE.VO2(-1) (P < 0.01) and VCO2 levels (P < 0.001) than N. The found higher VE in T, resulting from a lower tidal volume coupled to a higher respiratory frequency, led to higher PETO2 (P < 0.001) and SaO2 (P < 0.001) at all work levels. Absolute VO2max in the two investigated groups were 1977 +/- 72 (T) and 2095 +/- 80 (N) ml.min-1 (NS). Specific (i.e. per kg body weight) VO2max were identical (37.0 +/- 1.1 [T] vs. 36.7 +/- 1.1 ml.kg-1.min-1 [N]). [La]max were 11.4 +/- 0.4 (T) vs. 12.3 +/- 0.4 (N) mM (NS). [La] accumulation in blood as a function of workload and its rate of disappearance during recovery were similar. t-on at 90 watt was 30.7 +/- 2.4 sec in T and 28.9 +/- 2.3 sec in N (NS). The corresponding average contracted O2 deficit were 971 ml for T and 994 ml for N (NS). In conclusion, Tibetans born at low altitude do not seem to differ from lowlanders with regard to their metabolic response whereas their ventilatory response to exercise is greater.

Adolescent↗