Nidotherapy compared with enhanced care programme approach training for adults with aggressive challenging behaviour and intellectual disability (NIDABID): cluster-randomised controlled trial.

BACKGROUND: Aggressive challenging behaviour is very common in care homes for people with intellectual disability, and better psychological treatments are needed. Nidotherapy aims to change the environment of people with mental illness and is an appropriate treatment for this group of disorders. METHOD: The design was a cluster randomised trial of 20 care homes in which the staff either received training in nidotherapy or the enhanced care programme approach (ECPA), with equivalent duration of treatment in each arm. Cluster randomisation of care homes was carried out at the beginning of the study by an independent statistician. Primary and secondary outcomes were not specified exactly in view of absence of previous study data, but changes over time in scores on two scales, the Modified Overt Aggression Scale and the Problem Behaviour Check List were the main outcome measures. Serious violent incidents were recorded using the Quantification of Violence Scale. All these measures were recorded monthly by research assistants who were carefully kept blind to the allocation of treatment. RESULTS: A total of 200 residents entered the trial, 115 allocated to the ECPA arm and 85 to the nidotherapy one. Seven residents left the care homes in the course of the study, and six were replaced; these were included 79 in the analysis as the trial was a pragmatic one. There were no material reductions in challenging behaviour in the first 8 months of the trial in either group, but in the last 7 months, those allocated to nidotherapy had a 33% reduction in Modified Overt Aggression Scale (MOAS) scores and a 43% reduction in Problem Behaviour Check List scores compared with 5% and 13%, respectively, for the ECPA group, differences which for the MOAS were close to statistical significance. DISCUSSION: Nidotherapy shows promise in the management of aggressive challenging behaviour in care homes, but a delay in its benefit might be expected if given to staff only. The treatment is worthy of further evaluation and development.

Homology of complete genome sequences for dengue virus type-1, from dengue-fever- and dengue-haemorrhagic-fever-associated epidemics in Hawaii and French Polynesia.

Dengue epidemic virulence is thought to be conferred by various factors, including the genotype of the virus involved. Increased or decreased epidemic virulence has been associated not only with the introduction of type-2 (DENV-2) strains into the South Pacific, the Caribbean and South America, but also with newly emergent DENV-3 genotypes in Sri Lanka, and the year-to-year variation in the DENV-4 strains circulating in Puerto Rico. These observations indicate that there are inherent differences among viral genotypes in their capacity to induce severe disease, that is, their virulence potential. The present study involved a comparison of the complete genome sequences of DENV-1 viruses that had been isolated from cases of dengue fever (DF) or dengue haemorrhagic fever (DHF) that occurred in French Polynesia or Hawaii in 2001, when a virulent DHF-associated dengue epidemic was occurring throughout the Pacific region. Previous studies have identified putative virulence-associated motifs and substitutions in the DENV-2 genome, and the main aim of the present study was to identify similar changes in DENV-1 that may be associated with viral virulence. As no virulence determinants were seen, however, in any gene or untranslated region, it appears that genotype is not the sole determinant of virulence in DENV-1. Further studies, to compare DF- and DHF-associated strains of DENV-1 isolated from epidemics of variable virulence, in the same eco-biological context, are needed.

Zidovudine in the management of primary HIV-1 infection.

Eleven subjects who presented with a clinical illness characteristic of primary HIV-1 infection were treated with 1 g zidovudine daily for a median period of 56 days (range, 28-111 days). Primary HIV-1 infection was confirmed in each subject by seroconversion and virus isolation. The acute phase of the illness resolved a median of 4 days (range, 3-14 days) from commencement of zidovudine. Six subjects reported symptoms that may have been side-effects of zidovudine, the most common being nausea in four subjects and headache in two. Treatment was discontinued in one subject who had persistent headache and nausea. Haemoglobin, haematocrit and erythrocyte counts decreased and mean corpuscular volume increased significantly during the treatment. None of the subjects developed anaemia and none required dose modification or blood transfusion as a result of haematological side-effects. There were no significant differences in the granulocyte count or the lymphocyte count during any week of treatment when compared with baseline levels. There were no significant differences in T-cell subset numbers of the subjects during treatment compared with a group of historical controls. HIV-1 was isolated from several subjects during and after termination of zidovudine treatment. The results of this investigation indicate that zidovudine is a safe drug to administer to people with primary HIV-1 infection. There was no clear evidence, however, of any clinical benefit in terms of resolution of the acute illness and no indication that the treatment would prevent development of persistent infection.(ABSTRACT TRUNCATED AT 250 WORDS)

A controlled trial of nevirapine plus zidovudine versus zidovudine alone in p24 antigenaemic HIV-infected patients. The Dutch-Italian-Australian Nevirapine Study Group.

OBJECTIVES: Nevirapine is a non-nucleoside reverse transcriptase inhibitor of HIV-1 which exhibits synergy in vitro with zidovudine (ZDV) and also is active against ZDV-resistant HIV. We evaluated the activity and safety of nevirapine in combination with ZDV in patients receiving long-term ZDV therapy. METHODS: We conducted a randomized, open-label, controlled 28-week study of nevirapine (200 mg daily for 2 weeks followed by 200 mg twice daily for 26 weeks) and continued ZDV (500-600 mg daily) versus continued ZDV alone in 49 HIV-1 p24 antigenaemic patients with CD4+ lymphocyte counts < 500 x 10(6)/l and who had been treated with ZDV for at least 6 months. RESULTS: Addition of nevirapine to ZDV resulted in a significant and rapid reduction in circulating RNA load (mean, 0.65), a mean CD4+ lymphocyte rise of 34 x 10(6)/l, a reduction in serum beta 2-microglobulin and a median fall in immune complex dissociated p24 antigen levels of 69%. These changes remained statistically significant for 4, 4, 12 and at least 28 weeks, respectively. The principal adverse event due to nevirapine was a hypersensitivity reaction comprising rash with or without fever and mucositis in eight (32%) patients, which was dose-limiting in seven patients. CONCLUSION: Nevirapine exhibits significant although transient anti-HIV activity in ZDV-pretreated patients but its use is frequently associated with a hypersensitivity reaction.

Fasting hyperinsulinemia and increased waist-to-hip ratios in non-wasting individuals with AIDS.

OBJECTIVE: To identify metabolic and body composition changes associated with HIV-1 infection in a cross-sectional study of individuals stratified by immunologic status and body mass. DESIGN: Metabolic abnormalities including glucose intolerance and changes in body morphology have recently been described in HIV-1-infected individuals following therapy with protease inhibitor-containing highly active anti-retroviral therapy. Although this is suggestive of a direct drug effect, the possibility that HIV infection may induce a tendency towards such underlying derangements should be considered. HIV-infected patients are heterogeneous with respect to immunologic status and body mass. In examining the underlying effect of HIV-1 on metabolic and body composition parameters, stratification by various immunologic and body mass categories may give divergent results that would not be detected otherwise. METHODS: Thirty male participants were categorized into four cohorts: non-wasting HIV-seronegative controls, non-wasting HIV-infected patients with relatively intact immune function (CD4 cell count > 500 x 10(6)/l); non-wasting individuals with AIDS (CD4 cell count < 200 x 10(6)/l); and individuals with AIDS wasting. RESULTS: Increased fasting plasma insulin and waist-to-hip ratios were found specifically in non-wasting individuals with AIDS compared with HIV-negative controls. CONCLUSIONS: Our study emphasises the importance of both body mass and immune function in studying metabolic and body composition abnormalities associated with HIV-1 infection. The association of increased waist-to-hip ratios and hyperinsulinemia suggestive of insulin resistance in non-wasting individuals with AIDS suggest that the tendency towards these metabolic abnormalities may be related to the HIV infectious process or to factors associated with immunologic dysfunction.

HIV-1 western blot: development and assessment of testing to resolve indeterminate reactivity.

OBJECTIVE: To reduce the number of HIV-1 Western blot (WB)-indeterminates requiring follow-up and the time taken to provide a clear positive or negative result. DESIGN: In the first of two stages, a testing and follow-up strategy was developed to resolve anti-HIV-1 status of WB-indeterminates. In the second stage, implementation of this strategy was assessed. METHODS: After dividing indeterminates into four groups according to WB profile, samples were tested for anti-HIV-1, anti-HIV-2, anti-HTLV-I antibodies, and HIV-1 antigen using the most sensitive assays available. When testing failed to clarify anti-HIV-1 status, follow-up samples were taken to monitor changes in antibody status. RESULTS: Samples in two out of the four indeterminate groups were negative for anti-HIV-1. The other two groups required additional testing and/or follow-up to distinguish reactivity caused by anti-HIV-1 from cross-reactivity. CONCLUSION: Grouping HIV-1 WB-indeterminates according to profile allows a significant percentage to be reported as anti-HIV-1-negative, while additional testing may allow others to be reported as anti-HIV-1-positive. The remainder require a maximum of 3 months' follow-up to resolve anti-HIV-1 status.

Seroimmunology of AIDS retrovirus infection. I. Use of immunofluorescence assay to confirm sera with ELISA reactivity.

One thousand sera shown to be reactive by one of two commercial enzyme linked immunosorbent assays (ELISA) for antibodies to the AIDS virus were referred to the NSW State Reference Laboratory for confirmatory assays. Each serum was retested by two commercial ELISA systems (Abbott and ENI), the ENI exclusionary H9 ELISA and an immunofluorescence assay. Three hundred and twenty four sera were reactive by all 3 tests whereas 244 demonstrated concordant non-reactivity. Three hundred and seventy seven sera were reactive by Abbott EIA only and could not be confirmed positive by the ENI ELISA incorporating exclusionary testing, immunofluorescence or Western immunoblot of representative sera. Sera obtained from teaching hospital laboratories were more likely to be positive and less likely to be negative by all 3 tests, and were also less likely to be Abbott EIA reactive only compared with sera obtained from the blood transfusion service. Of the remaining 55 sera, 52 demonstrated a negative immunofluorescent reaction or a pattern of equal fluorescence on AIDS virus infected and control cells. Representative sera were shown to be negative on Western immunoblot analysis. Of the 3 sera which demonstrated immunofluorescence reactivity, one was positive and one was negative by Western immunoblot, and one could not be determined. We conclude that a combination of two ELISAs, one with an exclusionary ELISA test and an immunofluorescence assay is a reliable and simple means of confirming reactive sera for AIDS virus antibodies.

Molecular epidemiology of dengue in the Pacific: introduction of two distinct strains of dengue virus type-1 [corrected] into Hawaii.

In 2000, a major dengue epidemic, caused by the type-1 virus (DENV-1), began in the Pacific and Asia, with cases still being reported in 2006. The phylogenetic analysis of full-length sequences of the envelope-protein gene of DENV-1 isolates recovered during outbreaks in Hawaii and Tahiti in 2001-2002 indicated that most Hawaiian isolates were Tahitian in origin. All the Hawaiian and Tahitian isolates were identified as the Pacific subtype (i.e. subtype IV) of DENV-1. A Hawaiian isolate, collected from a resident who had travelled to Samoa, differed significantly at the nucleotide level, however, from all the other Hawaiian strains, clustering, in the phylogenetic analysis, with a virus previously isolated from another visitor to Samoa. These results not only indicate that two distinct strains of DENV-1 were introduced into Hawaii in 2001 but also illustrate the ease with which dengue can be carried across distances of many thousands of miles.

Severe intravascular coagulation preceding severe pre-eclampsia.

A patient is described in whom clinical and laboratory evidence of intravascular coagulation preceded the development of fulminating pre-eclampsia necessitating the delivery of a fresh stillbirth by Caesarean section at 31 weeks.

Antibody response to human immunodeficiency virus after primary infection.

The antibody response to human immunodeficiency virus (HIV) after primary infection was monitored in eight homosexual men with the acute mononucleosis-like illness associated with seroconversion. Multiple sera from each subject, taken at frequent intervals after onset of acute illness, were tested for antibody to HIV by IgM and IgG immunofluorescent assays (IFAs), four commercial enzyme-linked immunosorbent assays (ELISAs), and Western immunoblot (WB). Antibody to HIV was detected first by IgM IFA (mean +/- SD, 5 +/- 3 days), followed by IgG IFA (11 +/- 3 days); the IgM antibody titer peaked at 24 +/- 17 days and disappeared by 81 +/- 27 days, whereas the IgG antibody titer peaked at 133 +/- 63 days and has not disappeared in any subject. Antibody to HIV was first detected by ELISA from 31 +/- 14 to 58 +/- 32 days, depending on the assay kit used. Antibody to p24 and gp41 was first detected by WB at 24 +/- 10 days, followed by antibody to p55 (40 +/- 20 days), p68 (57 +/- 19 days), and p34 (71 +/- 22 days).

Falling incidence of HIV infection in a cohort of clinic attenders.

It is widely accepted that changes in sexual behaviour in the mid-1980s drastically reduced the spread of human immunodeficiency virus (HIV) through male homosexual contact in Western countries, but documentation of changes in infection rates has been based on observation of subjects enrolled in cohort studies, who may be highly selected and motivated. In this study, the incidence of HIV seroconversion was investigated among people attending a major site of HIV testing, counselling and patient care in Sydney. Over the period March 1985 to June 1990, 2,301 people were tested for HIV antibody on more than one occasion, following a negative result at the first test. On the basis of subsequent tests, 107 were found to have seroconverted during the study period, including 91 men who reported homosexual or bisexual contact as their only exposure to HIV. Overall, the incidence rate of HIV infection among men reporting homosexual or bisexual contact was 404 per 100 person-years of follow-up. Under various methods of calculation, the incidence was estimated to have declined between 1985 and 1989-1990. However, there was continuing HIV seroconversion in 1989-1990 and no indication of declining incidence in younger men. The fall in HIV incidence documented in this study supports the role of HIV prevention programs aimed at homosexual and bisexual men.

Early teenage pregnancies in Hull.

OBJECTIVES: To determine the pattern, obstetric outcome and factors that predispose to pregnancies in young teenagers in Hull. DESIGN: Retrospective study of case records of pregnancies from 1977 to 1988 in girls aged 16 years or less and in a control group of nulliparous women aged 20-24 years. SETTING: Hull health district hospitals. SUBJECTS: 1,660 pregnant teenagers and 3,576 nulliparas aged 20-24 years. MAIN OUTCOME MEASURES: Ages at pregnancy, number of pregnancies per year, gestational age at booking and delivery, antenatal complications, mode of delivery, utilization of contraceptives and some social factors. RESULTS: Of the 1,660 pregnancies in the young adolescents, 59-6% were terminations. The youngest girl was 11. The average annual incidence of early teenage pregnancies was 10.5 per 1,000 girls aged 10-16 compared to 6.4 per 1,000 in England and Wales. Physical characteristics and pattern of antenatal care were similar in the study and control groups. Anaemia was 2.53 times as common in teenagers (95% CI 2.19-2.9; P < 0.0001) while hypertension alone was 1.7 times as frequent (95% CI 1.28-2.4; P = 0.002). Pre-eclampsia and proteinuric disorders were similar in the two groups. Apart from prolonged pregnancy, which was significantly less common in the index group, other gestational ages at delivery and birthweights were the same in both groups. The caesarean section rate in the index group was 0.56 times that in the control group (95% CI 0.4-0.75; P < 0.0001) but forceps deliveries were 2.37 times as common in the index group (95% CI 1.80-3.12; P < 0.0001). The uncorrected perinatal mortality rates were 13.6/1000 and 15.7/1000 in the index and control groups respectively. CONCLUSION: Early teenage pregnancies are common in Hull and, contrary to previous reports, are physically well tolerated by the early adolescents who book early and attend antenatal clinics regularly. Ineffective utilization and ignorance of contraceptive methods are contributory factors. We recommend that emphasis should be placed on providing contraceptive services for teenagers and adopting a more purposeful and holistic approach to sex education.

Characterization of T lymphocyte responses during primary infection with human immunodeficiency virus.

The present study was undertaken to determine T cell response to primary human immunodeficiency virus (HIV) infection. No significant difference in T cell subsets was found between subjects who later seroconverted and a group of controls. Six subjects had multiple enumerations of T cell subsets done at the time of seroconversion. Initially, total lymphocyte and T cell subset counts were reduced. An inversion of the CD4+:CD8+ ratio due to a rise in the level of CD8+ cells was found later, followed by an appreciable increase in the number of CD8+ cells and further inversion of the CD4+:CD8+ ratio. Finally, the CD8+ cell count returned toward normal but remained higher than the CD4+ cell count; the inverted ratio was maintained. Lymphocyte hyporesponsiveness to mitogens and antigens was found during the seroconversion illness in one subject. In three of five subjects for whom data were available, an increase in the absolute number of CD8+ cells followed a decrease in the serum HIV antigen level.

Transmission of human immunodeficiency virus type 1 resistant to nevirapine and zidovudine. Sydney Primary HIV Infection Study Group.

Human immunodeficiency virus type 1 (HIV-1) resistant to the nonnucleoside reverse transcriptase inhibitor nevirapine and to the nucleoside analogue zidovudine was transmitted from a homosexual man to his sex partner. The virus source patient had commenced combination zidovudine and nevirapine therapy 2.5 years prior to his partner's primary HIV infection. He received both therapies for 7 months, then discontinued nevirapine treatment, continuing to receive zidovudine monotherapy for a further 16 months. He had ceased zidovudine therapy 6 months before the time of his partner's seroconversion. Analysis of major and minor isolates obtained from both patients soon after onset of the recipient's primary HIV infection illness confirmed that an HIV-1 variant mutant at codons 70, 98, and 181 of the viral reverse transcriptase was transmitted. This is the first documented case of transmission of HIV-1 resistant to two antiretroviral compounds.

Oxybutynin hydrochloride (3 mg) in the treatment of women with idiopathic detrusor instability.

Oxybutynin hydrochloride (3 mg) was compared with placebo by randomised, double-blind crossover trial in 53 females with idiopathic detrusor instability. Symptoms were cured or markedly improved in 60% of patients on oxybutynin and 2.3% on placebo. During the first treatment period, oxybutynin reduced the frequency of voiding by 35%, compared with 9% for placebo. Oxybutynin gave a significantly greater improvement than placebo in volume at the first desire to void (70 ml increase versus 7.7 ml), maximum filling-phase detrusor pressure (17 cm H2O reduction versus no benefit) and cystometric capacity (104 ml increase versus 7.0 ml). A marked oxybutynin carry-over effect was seen during the second treatment period. Side effects from the 3 mg dose of oxybutynin caused 7.5% of subjects to discontinue therapy.

Crouching over the toilet seat: prevalence among British gynaecological outpatients and its effect upon micturition.

This study investigated whether British women prefer to crouch over public toilet seats, and measured the effect of such a voiding position on urine flow rate and residual urine volume. Of 528 consecutive women who attended a general gynaecological clinic and completed an anonymous questionnaire, 85% usually crouched over the toilet when using a public convenience, 12% applied paper to the seat and 2% sat directly on public toilet seats. When using a friend's bathroom 38% of the women voided by crouching. Results were similar for 155 patients attending a urodynamic clinic, 80 of whom were studied while voiding in both positions. There was a 21% reduction in average urine flow rate and a 149% increase in residual urine volume in the crouching position. Women undergoing urodynamic tests should be asked which voiding position they used before abnormal results are interpreted. Patients with a reduced functional bladder capacity may benefit from being encouraged to sit comfortably on the toilet whenever possible.

Antibodies to the human immunodeficiency virus in needles and syringes used by intravenous drug abusers.

The sharing of needles and syringes by intravenous drug abusers has been recognized as a critical factor in the transmission of the human immunodeficiency virus (HIV). In an attempt to reduce the sharing of needles and syringes among intravenous drug abusers, a pilot sterile needle-and-syringe exchange programme was established in an inner city neighbourhood in Sydney. The contents of exchanged syringes were screened for antibody to HIV by the enzyme-linked immunosorbent assay (ELISA); reactive and borderline samples were tested further by the Western Blot method. Of a sample of 300 needles-and-syringes that were exchanged, three (1%) needles-and-syringes were confirmed as containing antibody-seropositive blood by both ELISA and Western Blot methods and thus as being potentially infectious. As only 70% of known positive-control syringes were detected in this study, the proportion of potentially infectious needles-and-syringes that was found may have underestimated the proportion of infectious injection equipment that was returned. These findings highlight the importance of the removal of used needles and syringes from circulation in addition to the supply of sterile equipment. This method of monitoring exchanged needles-and-syringes is suggested as a means to evaluate measures that are designed to reduce the transmission of HIV among intravenous drug abusers. The rapid implementation of sterile needle-and-syringe exchange programmes is imperative to stem the spread of HIV infection.

Prevalence of maternal HIV infection based on anonymous testing of neonates, Sydney 1989.

The presence of antibody to human immunodeficiency virus (HIV) in post-partum women may be inferred by screening the blood of their newborn babies, since maternal IgG antibodies freely cross the placenta. We tested a sample of 10,217 newborns from 10 hospitals covering three areas in Sydney and other metropolitan centres in New South Wales from April to July, 1989. None of the specimens gave a positive test for antibody to HIV. Thus, the prevalence of HIV positive serology in this sample of newborns was found to be zero. It was estimated that the seroprevalence of antibody to HIV among all neonates in the study area was between zero and 0.045% (99% confidence interval). Because newborns are an accessible group for the study of HIV, and can act as surrogates for their mothers, anonymous testing of this sentinel group will remove some of the limitations generalizing the information in the present database of HIV infection in Australia. This study provides baseline data and suggests that there is not a widespread epidemic of HIV infection among heterosexual persons in Australia at the present time and that routine antenatal testing of women for antibody to HIV may not be cost-effective. However, it will be important to repeat this study at regular intervals to detect any increase in HIV seroprevalence.