Sustained-release naltrexone for opioid dependence.

BACKGROUND: Naltrexone is an opioid antagonist which effectively blocks heroin effects. Since opioid dependence treatment with naltrexone tablets suffers from high dropout rates, several depot injections and implants are under investigation. Sustained-release formulations are claimed to be effective, but a systematic review of the literature is lacking. OBJECTIVES: To evaluate the effectiveness of sustained-release naltrexone for opioid dependence and its adverse effects in different study populations. SEARCH STRATEGY: The following databases were searched from their inception to November 2007: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, LILACS, PsycINFO, ISI Web of Science, trial database at http://clinicaltrials.gov, available NIDA monographs, CPDD and AAAP conference proceedings. The reference lists of identified studies, published reviews and relevant web sides were searched manually. Study authors and drug companies were contacted to obtain any unpublished material or missing data. SELECTION CRITERIA: To evaluate effectiveness only RCTs were included. To evaluate safety, any clinical trial reporting adverse effects was assessed. Treatment condition was extended to include alcohol dependent subjects and healthy volunteers. DATA COLLECTION AND ANALYSIS: Reviewers independently evaluated the reports, rated methodological quality and extracted data. Analyses were performed separately for opioid dependent, alcohol dependent and healthy participants. MAIN RESULTS: Foe effectiveness, one report met inclusion criteria. Two dosages of naltrexone depot injections (192 and 384 mg) were compared to placebo. High-dose significantly increased days in treatment compared to placebo (WMD 21.00, 95% CI 10.68 to 31.32, p<0.0001). High-dose compared to low-dose significantly increased days in treatment (WMD 12.00, 95% CI 1.69 to 22.31, p=0.02). Number of patients retained in treatment did not show significant differences between groups. For adverse effects, seventeen reports met inclusion criteria analyses, six were RCTs. Side effects were significantly more frequent in naltrexone depot groups compared to placebo. In alcohol dependent samples only, adverse effects appeared to be significantly more frequent in the low-dose naltrexone depot groups compared to placebo (RR 1.18, 95% CI 1.02 to 1.36, p=0.02). In the opioid dependent sample, group differences were not statistically significant. Reports on systematic assessment of side effects and adverse events were scarce. AUTHORS' CONCLUSIONS: There is insufficient evidence to evaluate the effectiveness of sustained-release naltrexone for treatment of opioid dependence. For naltrexone injections, administration site-related adverse effects appear to be frequent, but of moderate intensity and time limited. For a harm-benefit evaluation of naltrexone implants, more data on side effects and adverse events are needed.

Integrated Health Care for People with Chronic Conditions: a policy brief

Clinical research has led to spectacular developments in health care. It has provided us with knowledge about how to prevent diseases, like heart disease, how to reduce the consequences of disease, such as complications of diabetes, and to alleviate symptoms, such as those of lung disease, and how to rehabilitate people who have suffered a disabling event, such as a stroke. Healthcare systems have the potential to deliver interventions that save lives and improve the quality of life. We know this from well designed research and systematic reviews of that research. Unfortunately, we also know that patients often do not receive effective care when they should, that they sometimes receive care that is not effective or safe, and that not all of the money we spend on health care is well spent. This comes from a different type of research ­ health services research. In the same way that clinical research is essential for informing how best to care for patients clinically, health services research is essential to inform decisions about how best to organise, finance and govern our healthcare system. This policy brief is a good example of both the potential for health services research to inform healthcare policies and management, and an example of the limitations of health services research to inform decisions.

Impact of antenatal HIV screening to prevent HIV infection in children in Norway 1987-99.

OBJECTIVE: To assess the impact of the antenatal HIV screening programme in Norway in preventing HIV infection in children. SETTING: Norway, 1987-99. METHODS: In a simulated retrospective cohort design data were used from the mandatory HIV surveillance system to compare the observed number of children born infected with HIV in Norway 1987-99 to the expected number without the antenatal screening programme. The main measures were relative and absolute performance of the screening programme. Other measures were uptake and false positive rate of screening, and number and exposure category of screen positive women. RESULTS: 96% of 961 000 eligible pregnant women were tested. 0.1% had an indeterminate test result and 46 women (5.0/100 000) were confirmed screen positive. 27 were African or south east Asian women infected before immigration to Norway. Nine out of 739 000 live born children (1.2/100 000) were infected compared with the expected 18 with no screening. The absolute impact of the screening programme was 1.3 (95% confidence interval (95% CI) -0.1 to 2.7) prevented infections in 100 000 women screened. The relative preventive impact was 51% (-15% to 81%). CONCLUSIONS: The limited absolute impact is because of the very low prevalence of undetected HIV infection among pregnant women in Norway.

Length variation of glycoprotein 120 V2 region in relation to biological phenotypes and coreceptor usage of primary HIV type 1 isolates.

Conflicting data have been published concerning the correlation between the length of the second variable region (V2) in the HIV-1 envelope and the biological phenotype of the virus. Here the V2 region length of primary HIV-1 isolates was compared with biological phenotype and coreceptor usage. The V2 region variation was determined by DNA fragment length analysis, virus biological phenotype by the MT-2 cell assay, and coreceptor usage by infection of U87.CD4 cells expressing CCR3, CCR5, or CXCR4. Ninety-three primary virus isolates from 40 patients were analyzed. This panel of viruses included sequential isolates obtained from patients who progressed to AIDS with or without a virus phenotypic switch. We found that NSI MT-2-negative isolates had significantly shorter V2 regions than SI MT-2-positive isolates. However, when V2 region lengths of viruses were analyzed in more detail, we observed that NSI isolates obtained from patients shortly before the phenotypic switch had V2 region lengths similar to those of SI isolates. V2 regions of NSI isolates obtained from patients who progressed to AIDS without a virus phenotypic switch had, in contrast, shorter V2 region than isolates obtained just before virus phenotypic switch. Coreceptor analysis revealed that CCR5-using (R5) isolates generally had shorter V2 regions than virus isolates with the ability to enter CXCR4-expressing cells. Moreover, no significant difference in V2 region length was observed between monotropic SI isolates, that is, X4 isolates, and multitropic SI isolates, that is, R3R5X4 or R5X4 isolates. Thus, we conclude that R5 NSI isolates obtained from patients with stable virus phenotype through the whole disease course display shorter V2 regions than isolates obtained from patients at switch of virus phenotype, suggesting that V2 region length may influence virus coreceptor usage.

The potential for research-based information in public health: identifying unrecognised information needs.

OBJECTIVE: To explore whether there is a potential for greater use of research-based information in public health practice in a local setting. Secondly, if research-based information is relevant, to explore the extent to which this generates questioning behaviour. DESIGN: Qualitative study using focus group discussions, observation and interviews. SETTING: Public health practices in Norway. PARTICIPANTS: 52 public health practitioners. RESULTS: In general, the public health practitioners had a positive attitude towards research-based information, but believed that they had few cases requiring this type of information. They did say, however, that there might be a potential for greater use. During five focus groups and six observation days we identified 28 questions/cases where it would have been appropriate to seek out research evidence according to our definition. Three of the public health practitioners identified three of these 28 cases as questions for which research-based information could have been relevant. This gap is interpreted as representing unrecognised information needs. CONCLUSIONS: There is an unrealised potential in public health practice for more frequent and extensive use of research-based information. The practitioners did not appear to reflect on the need for scientific information when faced with new cases and few questions of this type were generated.

[Observational units--same good service to lower costs?]. / Observasjonsposter--like godt tilbud til lavere kostnader?

BACKGROUND: With increased demand for hospital services and limited resources in the health sector, modes of organisation of services which give the same health outcome, but at lower cost, are of interest. Observation units in hospitals imply rapid diagnostic procedures and/or brief, but adequate treatment. We looked at the evidence for whether stays in observational units provide similar health outcome and reduce the admissions costs for hospitals compared to standard inpatient stays. MATERIAL AND METHODS: We systematically evaluated four randomized controlled studies that have compared the outcome for chest pain and asthma patients admitted to either observational units or directly to ordinary hospital units. The outcomes in focus were health effects measured as mortality and/or complications, length of stay and direct hospital costs. RESULTS: The studies indicate that for the conditions included, there are no health outcome differences between patients treated in observational units on one hand or in ordinary hospital units on the other. Stays in observational units do not seem to imply increased risk of complication. Furthermore, the studies show a reduction in length of stay and hospital costs associated with the use of observational units. INTERPRETATION: The main reason for the reduction in length of stay and cost is quicker diagnosis in observational units than in the ordinary hospital units. The preconditions for these results are clear by defined criteria for selection of patients to the different units and well-defined protocols for making diagnoses and treating patients. If many patients after staying in observational units are transferred to ordinary hospital units or are discharged and then readmitted, the economic benefits of observational units could be undermined.

A population study of factors associated with general practitioner consultation for non-inflammatory musculoskeletal pain.

OBJECTIVE: To investigate factors associated with visiting a general practitioner (GP) for non-inflammatory musculoskeletal pain, and to examine whether these factors were affected by duration (chronic v non-chronic) or location (widespread v regional) of pain. METHODS: From a cross sectional postal survey of 20 000 (response rate 59%) randomly selected adults in two counties of Norway, 6408 subjects who had experienced musculoskeletal pain during the past month were included. Patients who reported inflammatory rheumatic diagnoses made by a doctor were excluded. RESULTS: 2909 (45%) had consulted a GP for their musculoskeletal pain during the past 12 months. The odds of consulting were significantly increased by being a woman, by having a higher age and lower education, and by being a pensioner or on sick leave. Patients with widespread pain were more likely to consult than those with regional pain, as were patients with chronic compared with non-chronic pain. Greater than median pain intensity was the factor most prominently associated with consultation for men (odds ratio (OR)=2.4; 95% confidence interval (95% CI) 2.0 to 2.9) and for women (OR=2.6; 95% CI 2.3 to 2.9). Overall, consultation was significantly associated with mental distress for women but not for men. Subgroup analyses showed that consultation for chronic pain was significantly associated with greater than median mental distress for both women (OR=1.3; 95% CI 1.1 to 1.6) and men (OR=1.2; 95% CI 1. 0 to 1.4), whereas consultation for non-chronic pain was not. CONCLUSION: The results show that about half of the patients with musculoskeletal pain consult a general practitioner (GP) each year, that demographic factors are associated with consulting, and that the role of mental distress for consulting a GP varies with duration of pain.

Rapid changes in the prevalence of obesity and known diabetes in an adult Norwegian population. The Nord-Trøndelag Health Surveys: 1984-1986 and 1995-1997.

OBJECTIVE: To determine whether changes in mean BMI and the prevalence of obesity in a total adult population during a short (11-year) period were associated with changes in the prevalence of diabetes. RESEARCH DESIGN AND METHODS: This study involved cross-sectional surveys of all inhabitants aged > or = 20 years of the county of Nord-Trøndelag from 1984 to 1986 (n = 85,100) and from 1995 to 1997 (n = 92,434). Attendance rates were 88.1 and 71.3%, respectively, and 90.0% in an additional survey of people aged 13-19 years from 1995 to 1997 (n = 9,593). Main outcome measures were age-specific mean BMI for the diabetic and nondiabetic subgroups and the prevalence of obesity and diabetes. For comparison, mean BMIs from 18 of 19 Norwegian counties for the group aged 40-42 years were examined. RESULTS: Mean BMI increased from 27.2 to 29.0 kg/m2 in the diabetic population and from 25.1 to 26.3 kg/m2 in the nondiabetic population. The BMI distribution curve shifted to the right, but homogeneity was also reduced. A comparison with other Norwegian counties indicated that this increase occurred during the last 6 years between the surveys. The prevalence of obesity (BMI > or = 30 kg/m2) increased from 7.5 to 14% in nondiabetic men and from 13 to 18% in nondiabetic women. The increase was particularly great in men aged < 60 years and in women aged < 50 years. The overall prevalence of known diabetes increased between the two surveys (from 2.9 to 3.2%) but only in men. The largest increase was observed in the corresponding younger sex and age-groups. CONCLUSIONS: A substantial increase in mean BMI and the prevalence of obesity occurred in the younger age-groups at the same time as an increase in the prevalence of diabetes. A greater increase in diabetes prevalence in this ethnically stable Western European population may follow if effective primary preventive strategies are not undertaken.

[Do public health practitioners have satisfactory access to important information sources?]. / Har samfunnsmedisinere tilfredsstillende tilgang til viktige informasjonskilder?

We asked Norwegian public health practitioners which information sources they used as support for their professional medical counselling, how they gathered their information, and how they evaluated the validity of the information. 348 (67%) questionnaires were returned. Legal sources, other types of reference books/textbooks, different types of expertise from other institutions, and colleagues were considered the most important information sources. The majority had difficulties accessing libraries. Bibliographic databases were used very little. 30% often had problems finding relevant information, while 56% had problems occasionally. Many respondents felt that it was too difficult to get hold of information, that it was difficult to know where to search and that it was difficult to find the time to do it. In judging the scientific validity of an article the majority compared the content with their own experience. Relevant scientifically based medical information was seldom obtained and utilized. Public health practitioners were surprisingly homogeneous in their description of their handling of information. We found for instance almost no differences between specialists and non-specialists. The survey shows that public health practitioners do not have satisfactory access to potentially important information sources. The type of barriers many of them meet when searching for information, indicates that public health physicians would benefit from tailored information services.

Phenotypic characteristics of human immunodeficiency virus type 1 subtype C isolates of Ethiopian AIDS patients.

It has been estimated that, to date, about 48% of all HIV-infected people in the world carry HIV-1 subtype C virus. Therefore, it is of great importance to gain better knowledge about the genetic and biological characteristics of this virus subtype. In the present study, the biological properties of HIV-1 isolates obtained from nine Ethiopian patients with AIDS were studied. DNA sequencing of the V3 loop of gp120 classified the isolates as subtype C. In primary isolation cultures, virus infection was accompanied by syncytium formation and cell lysis. Interestingly, when examining the growth in primary monocyte-macrophage cultures, initial low-level virus replication was followed by a nonproductive state, from which virus could be rescued by cocultivation with Jurkat(tat) cells. Furthermore, none of the isolates replicated in T cell lines (CEM, MT-2, HuT-78, and H9) or in the promonocytic cell line U937 clone 2. All isolates could use CCR5 as coreceptor, whereas no isolates could use CCR2b, CCR3, CCR5, CXCR4, Bonzo/STRL33, or BOB/GPR15. The genotype of the V3 region correlated with the MT-2 negative/non-syncytium-inducing (NSI) phenotype. Comparative studies revealed that the scarcity of CXCR4 usage as well as other phenotypic characteristics of subtype C isolates distinguish this subtype. On the basis of these data, we suggest that in addition, factors other than viral phenotype may govern the pathogenic potential of subtype C isolates.

Primary human immunodeficiency virus type 2 (HIV-2) isolates, like HIV-1 isolates, frequently use CCR5 but show promiscuity in coreceptor usage.

Coreceptor usage of primary human immunodeficiency virus type 1 (HIV-1) isolates varies according to biological phenotype. The chemokine receptors CCR5 and CXCR4 are the major coreceptors that, together with CD4, govern HIV-1 entry into cells. Since CXCR4 usage determines the biological phenotype for HIV-1 isolates and is more frequent in patients with immunodeficiency, it may serve as a marker for viral virulence. This possibility prompted us to study coreceptor usage by HIV-2, known to be less pathogenic than HIV-1. We tested 11 primary HIV-2 isolates for coreceptor usage in human cell lines: U87 glioma cells, stably expressing CD4 and the chemokine receptor CCR1, CCR2b, CCR3, CCR5, or CXCR4, and GHOST(3) osteosarcoma cells, coexpressing CD4 and CCR5, CXCR4, or the orphan receptor Bonzo or BOB. The indicator cells were infected by cocultivation with virus-producing peripheral blood mononuclear cells and by cell-free virus. Our results show that 10 of 11 HIV-2 isolates were able to efficiently use CCR5. In contrast, only two isolates, both from patients with advanced disease, used CXCR4 efficiently. These two isolates also promptly induced syncytia in MT-2 cells, a pattern described for HIV-1 isolates that use CXCR4. Unlike HIV-1, many of the HIV-2 isolates were promiscuous in their coreceptor usage in that they were able to use, apart from CCR5, one or more of the CCR1, CCR2b, CCR3, and BOB coreceptors. Another difference between HIV-1 and HIV-2 was that the ability to replicate in MT-2 cells appeared to be a general property of HIV-2 isolates. Based on BOB mRNA expression in MT-2 cells and the ability of our panel of HIV-2 isolates to use BOB, we suggest that HIV-2 can use BOB when entering MT-2 cells. The results indicate no obvious link between viral virulence and the ability to use a multitude of coreceptors.

Coreceptor usage and RANTES sensitivity of non-syncytium-inducing HIV-1 isolates obtained from patients with AIDS.

OBJECTIVES: The biologic phenotype of HIV-1 primary isolates obtained from approximately 50% of patients who progress to AIDS switches from non-syncytium-inducing (NSI) to syncytium-inducing (SI). We evaluated possible associations between virus coreceptor usage, sensitivity to inhibition by beta-chemokines, and disease progression of patients who continue to yield NSI isolates after developing AIDS. STUDY DESIGN/METHODS: Sequential virus isolates were analyzed for biologic phenotype using the MT-2 cell assay, for sensitivity to beta-chemokines using RANTES inhibition, and for coreceptor usage using U87.CD4 and GHOST.CD4 cells expressing different chemokine/orphan receptors or donor peripheral blood mononuclear cells (PBMC) defective in CCR5 expression. In addition, the env V3 region was sequenced and the length of the V2 region determined. RESULTS: All NSI isolates, regardless of patient status at time of isolation, were dependent on CCR5 expression for cell entry. Furthermore, there was no indication of broadened coreceptor usage of NSI isolates obtained from persons with late-stage AIDS. A majority of NSI isolates remained RANTES sensitive; however, virus variants with reduced sensitivity were observed. The V2 lengths and the V3 sequences exhibited no or minor changes at analysis of sequential NSI isolates. CONCLUSIONS: Our data suggest that NSI isolates obtained from AIDS patients remain CCR5 dependent (ie, R5) and, in many cases, also remain sensitive to RANTES inhibition. However, virus variants with decreased sensitivity to RANTES inhibition may evolve during disease progression, not only as a result of a switch from NSI to SI but also in patients who develop AIDS while continuing to maintain R5 isolates.

Ex-smokers and risk of hip fracture.

OBJECTIVES: The purpose of this study was to examine the reversibility of the effect of smoking on hip fracture incidence rates. METHODS: A 3-year follow-up cohort study was conducted involving 35,767 adults 50 years of age or older. Of these individuals, 421 suffered a hip fracture. RESULTS: Among participants less than 75 years of age, the relative risk (RR) of hip fracture was elevated for ex-smokers, even for those who had quit smoking more than 5 years previously (men: RR = 4.4, 95% confidence interval [CI] = 1.2, 15.3; women: RR = 1.3, 95% CI = 0.6, 3.0), but was not as high as that for current smokers (men: RR = 5.0, 95% CI = 1.5, 16.9; women: RR = 1.9, 95% CI = 1.2, 3.1). CONCLUSIONS: The effect of smoking on risk of hip fracture was not reversed completely 5 years after smoking cessation.

The limits of leadership: opinion leaders in general practice.

OBJECTIVE: To explore the importance and characteristics of opinion leaders in general practice, particularly in relationship to the use of laboratory tests. DESIGN: Focus group discussions and a mailed survey. SUBJECTS: Five focus groups (n = 29 participants) in four different municipalities and a random sample of 85 general practitioners (GPs) in Norway. RESULTS: While Norwegian GPs recognised colleagues who were influential in determining how they practised, they found it difficult to identify opinion leaders specifically with respect to the use of laboratory tests. Opinion leaders were thought to be less important in influencing the use of laboratory tests than continuing medical education activities and practice guidelines, but more important than industry, patients or personal financial interests. Norwegian GPs recognised and characterised opinion leaders in much the same way as physicians in the USA. Influential colleagues were characterised as being good conveyers of information and willing to take time, as well as being up-to-date and having a high level of clinical expertise. GPs expressed a negative attitude towards 'superspecialists' who give advice without knowing the epidemiology of general practice, people who are arrogant and people who do not show respect towards GPs. CONCLUSIONS: The potential to identify and use opinion leaders to improve the use of laboratory tests by GPs in Norway appears to be limited.