[Preventing chronicity in mental health: being present earlier within the network]. / Voorkómen chroniciteit: er eerder bij zijn binnen het netwerk.

BACKGROUND: Despite the increase in treatment options, mental illness is still too often evolving into chronic serious mental illness.
AIM: To describe concrete interventions aimed at the life structure and early detection within and outside mental health care to prevent chronicity in mental health.
METHOD: According to a quadrant, evidence-based interventions to prevent chronicity are proposed. These interventions can focus on the life structure of the patient and on early identification and intervention. They can take place both inside and outside mental health care.
RESULTS: Important interventions within mental health care include complete and repeated diagnostics, including staging, profiling and somatic screening, Mental health care must also focus on early detection and early treatment for all mental illnesses and apply concrete interventions such as IPS, lifestyle interventions, shared decision-making and low threshold anti-stigma actions. Outside of mental health services, mental health first aid (MHFA), housing first, alcohol prevention and mental gymnastics can be used.
CONCLUSION: Preventing chronicity requires an integrated cross-sectoral approach and a gatekeeper approach with active and responsive mental health care. Tijdschrift voor Psychiatrie 63(2021)2, 142-149.

[Using resource groups in assertive community treatment; literature review and recommendation]. / De inzet van resourcegroepen voor gedeelde besluitvorming bij assertive community treatment; literatuuroverzicht en aanbevelingen.

BACKGROUND: In psychiatry there is an increasing interest in giving patients and their relatives control over the goals of treatment and the way in which treatment is carried out. A structural method of organising this within assertive community treatment (ACT) is to let patients and their relatives participate in what is known as a resource group (RG).
AIM: To provide a systematic view of the advantages of giving patients control over their treatment and the way in which it is carried out via ACT, particularly if this control is organised in the form of an RG.
METHOD: We reviewed the relevant literature on the basis of search instructions in the databases of PubMed and Cochrane Library. We found nine trials that had a randomised controlled design (RCT). Only one of these RCTs involved the use of an RG in ACT.
RESULTS: The approaches used in ACT, whereby patients with schizophrenia had control over their treatment, led to significant improvements that were considerably greater than those achieved in standard care. Improvements were found in symptomatology, social functioning and in the quality of life. There are indications that treatment satisfaction and social functioning improve still further if patients' control over their treatment is organised in an RG.
CONCLUSION: Research demonstrates that positive results are achieved with ACT whereby patients have control over their treatment and the way in which it is carried out. However, further research is needed to determine whether this addition to ACT in the form of an RG is superior to other approaches used previously in ACT, particularly if it concerns the inclusion of an RG.

[Functional remission of people with serious mental illness (SMI): psychometric properties of a new ROM-instrument]. / Functionele remissie bij mensen met een ernstige psychiatrische aandoening; psychometrische eigenschappen van een nieuw ROM-instrument.

BACKGROUND: Instruments are used for routine outcome monitoring of patients with severe mental illness in order to measure psychiatric symptoms, care needs and quality of life. By adding an instrument for measuring functional remission a more complete picture can be given of the complaints, the symptoms and general functioning, which can give direction to providing care for patients with severe mental illness. AIM: To describe the development and testing of a new instrument of functional remission (FR) among people with a psychotic disorder or another serious mental disorder (SMI) as an addition to the symptomatic remission (SR), according to international criteria. METHOD: The FR-assessment involves assessment by a mental health professional who conducts a semi-structured interview with the patient and his or her family and/or uses patient files relating to the three areas of functioning: daily living and self-care; work, study and housekeeping; and social contacts. These areas are rated on a three-point scale of 0: independent; 1: partially independent; 2: dependent. The assessment covers a period of six months, in accordance with the measurement of symptomatic remission and should be part of regular routine outcome monitoring (ROM) procedures. The FR-instrument was used in 2012 with 840 patients from eight Dutch mental care institutions and included a one-year follow-up among 523 patients (response 62%). RESULTS: The results showed that the instrument is relatively easily to complete. It was also relevant for clinical practice, although further research is needed because of the raters' low response. Intra- and inter-rater reliability, discriminating and convergent validity, and sensitivity to change were rated sufficient to good. CONCLUSION: If the FR-instrument becomes part of regular ROM-procedures and is used as a measure of societal participation, it could be a useful addition to current measures of symptomatic remission.

[Delirium on re-starting clozapine after a short break in treatment]. / Delirium bij herstart clozapine na korte onderbreking.

Extra care must be taken in treating patients with clozapine because of the serious side-effects. A 44-year-old man with schizophrenia developed delirium on two occasions immediately after restarting clozapine at the dosage he had previously tolerated well; the clozapine-free periods had lasted 2 and 10 days respectively. Because of this 're-challenge' it seems very likely that there is a causal relation between the direct resumption of treatment with clozapine and delirium. Even if clozapine treatment is interrupted for only a short time it is important that the 'new' course begins with a low dosage and is increased very cautiously until it reaches the former, tolerated level.

Lymphoproliferative response to HIV type 1 p24 in long-term survivors of HIV type 1 infection is predictive of persistent AIDS-free infection.

To establish immunologic correlates of progression to AIDS in long-term survivors of HIV-1 infection, HIV-1-specific T cell-mediated responses, together with T cell reactivity to recall antigens, were studied in frozen samples collected after 5 and 8 years of documented HIV-1 infection. Eight of 21 homosexual men, who remained asymptomatic and maintained CD4+ T cell numbers >400 cells/microl for 9 years of HIV-1 infection, progressed to AIDS (CDC 1993 definition) within 12.5 years of infection (late progressors, LPs). The remainders showed minimal deterioration of immune parameters (long-term nonprogressors, LTNPs). CD4+ T cell numbers and T cell function measured at years 5 and 8 of follow-up were comparable in the two groups. At both time points responses to recall antigens did not significantly differ between the two groups, although a significant decline of lymphoproliferative responses to Candida and tetanus toxoid was observed in LPs. Circulating HIV-1-specific cytotoxic T lymphocyte precursors were found in broad frequency ranges in both LPs and LTNPs and, similarly, no significant differences were found in comparing the breadth of serum neutralizing activity against heterologous HIV-1 primary isolates. In contrast, lymphoproliferative responses to p24gag, but not p17gag or gp160env, were detected only in LTNPs and were totally absent in LPs at both time points (p < 0.01). Our data suggest that the presence of circulating p24-specific CD4+ T cells may reflect effective viral control and be predictive of subsequent favorable clinical course in long-term asymptomatic individuals.

Consistent associations of HLA class I and II and transporter gene products with progression of human immunodeficiency virus type 1 infection in homosexual men.

Polymorphic products of genes in the HLA region contributing to variability in the course of human immunodeficiency virus type 1 (HIV-1) infection were identified by screening 375 Caucasian seroconverters who were aggregated from 3 cohorts. AIDS-free time was related to numerous (15) class I alleles, alone or in conjunction with transporter protein variants, to homozygosity at the A or B locus, and to alleles of two class II haplotypes. A prognostic scoring algorithm derived from the 3 cohorts captured multiple HLA contributions to protection or to risk (relative hazard=0.57-60 per unit increase in score, all P<<.001). The impact of HLA was strong and appeared independent of the effects of chemokine receptor/ligand polymorphisms and antiretroviral treatment. The algorithm also predicted divergent rates of CD4+ cell decline in 2 other groups, totaling 227 seropositive persons (P=.06 - <.001). Confirmation of these relationships should encourage investigation of HIV-1 antigen processing and presentation mediated by polymorphisms in the HLA region.

HLA class I homozygosity accelerates disease progression in human immunodeficiency virus type 1 infection.

Polymorphic products of HLA class I genes restrict cytotoxic T lymphocyte responses to the constantly evolving spectrum of HIV-1 antigens. Accordingly, homozygosity at class I loci can reduce the repertoire for such HLA-dependent interactions, leading to accelerated disease progression. To test this hypothesis we studied subjects from two distinct HIV/AIDS cohorts: 140 Dutch homosexual men and 202 Rwandan heterosexual women followed up to 13 years from HIV-1 seroconversion. We performed intermediate- and selective high-resolution molecular typing at HLA class I (A, B, and C) and high-resolution typing at HLA class II DRB1 and DQB1. Homozygosity at the HLA-A or -B locus or both was found at increasingly high frequency among individuals with successively more rapid progression to late-stage HIV-1-related conditions. In the combined cohorts (n = 342) the odds ratio (OR) due to HLA-A or -B antigen homozygosity in rapid versus slow progressors was 3.8 (p = 0.003); for Dutch men alone the OR was 3.5 (p = 0.102), and for Rwandan women the OR was 4.1 (p = 0.009). In contrast, homozygous genotypes at either HLA-C, DRB1, or DQB1 alone, or DRB1-DQB1 haplotypes, did not exert any deleterious effect on HIV-1 disease progression. These findings suggest strongly that diversity in addition to sequence specificity at HLA-A and -B loci can influence the rate of disease progression following HIV-1 infection.

Conversion rate towards a syncytium-inducing (SI) phenotype during different stages of human immunodeficiency virus type 1 infection and prognostic value of SI phenotype for survival after AIDS diagnosis.

The presence of syncytium-inducing (SI) human immunodeficiency virus type 1 (HIV-1) variants is predictive for accelerated progression to AIDS. This study showed that a 4-year survival with AIDS also occurred significantly more often for patients who lacked SI variants. However, multivariate Cox analysis excluded the predictive value of SI viruses for rapid death as being independent from low CD4+ T cell counts. Incidence of appearance of SI variants was increased in persons with CD4+ T cell counts <500/microliter but remained constant in the strata of CD4+ T cell counts <500/microliter, excluding the possibility that loss of immune control is the only prerequisite for the development of SI HIV-1 variants.

Body mass index course in asymptomatic HIV-infected homosexual men and the predictive value of a decrease of body mass index for progression to AIDS.

Weight loss is a common characteristic of advanced stages of HIV infection. Weight changes during the asymptomatic stage of HIV infection have not been well documented and the possible predictive value of early weight loss for progression to AIDS is unknown. In 122 HIV seroconverters, the natural course of body mass index (BMI) following seroconversion was studied. No BMI decline was seen immediately following seroconversion. In the 56 AIDS cases, however, a steep BMI decline of 1.14 kg/m2 occurred 6 months before AIDS. This BMI decline was more pronounced in those with low CD4+ T cell counts (<100 x 10(6)/L) at the time of AIDS diagnosis (1.8 kg/m2). The relative hazard for progression to AIDS of a BMI decline of 1.14 kg/m2 per 6 months was 3.1, which remained similar after adjustment for CD4 count and p24 antigenemia. We conclude that the course of BMI in HIV-1 infection is biphasic: a relatively stable period is followed by a rapid decline in the 6 months preceding onset of AIDS. Furthermore, we found that this steep BMI decline was associated with faster progression to AIDS.

PIP: The possible predictive value of weight loss during the asymptomatic stage of HIV infection for progression to AIDS was assessed in 122 HIV seroconverters from the Netherlands. Study subjects were part of a broader cohort study initiated in 1984 of initially seronegative homosexuals from Amsterdam. The mean age of seroconverters was 35.8 years, with a mean follow-up time between seroconversion and AIDS diagnosis of 5.3 years (range, 0.6-10.8 years). The mean body mass index (BMI) was 22.2 kg/sq. mm at the first HIV-positive visit and 21.0 kg/sq. mm at AIDS diagnosis. Overall, there was no immediate decline in BMI in the immediate postseroconversion period. However, in the 56 men who progressed to AIDS, a BMI decline of 1.14 kg/sq. mm occurred 6 months before diagnosis. This decline was even more pronounced (1.8 kg/sq. mm) in those with CD4 T cell counts under 100 at the time of AIDS diagnosis. The relative hazard of progression to AIDS of a BMI decline of 1.14 kg/sq. mm per 6 months was 3.1. This rate persisted after adjustment for CD4 count and p24 antigenemia. Although the sensitivity of weight loss is only about one third, when weight loss is present, it can be considered a useful marker of progression to AIDS. It could not be established from this study whether weight loss was an early manifestation of an AIDS-defining illness or a true pre-AIDS decline. Initiation of antiretroviral therapy should be considered before the first signs of weight loss appear.

In vivo delayed-type hypersensitivity skin test anergy in human immunodeficiency virus type 1 infection is associated with T cell nonresponsiveness in vitro.

In a cross-sectional study, the prevalence of delayed-type hypersensitivity skin test anergy (DTHA) was examined in 136 asymptomatic human immunodeficiency virus-infected participants in relation to immunologic and virologic parameters. DTHA was assessed with a multitest cell-mediated immunity skin test. Of the 136 participants, with a mean CD4 T cell count of 335 x 10(6)/L, 25 were anergic (18.4%). In the stepwise forward multivariate logistic regression models, after adjustment for CD4 T cell counts, depending on whether it was analyzed continuously or after dichotomization (20th percentile), both T cell reactivity to CD2 plus CD28 antibodies or to CD3 antibodies were the most predictive markers of DTHA (odds ratio, 0.80; 95% confidence interval, 0.67-0.94; and odds ratio, 2.97; 95% confidence interval, 1.1-8.3, respectively). This study shows a strong correlation between the decreased T cell responses in vitro and DTHA. Therefore, next to DTHA testing, T cell function assays may be useful to test immune reconstitution observed during antiretroviral treatment.

An open randomized controlled trial of zidovudine plus lamivudine versus stavudine plus lamivudine.

OBJECTIVE: To compare the antiretroviral effect and safety of zidovudine (ZDV)-lamivudine (3TC) with that of stavudine (d4T)-3TC. METHODS: In an open randomized controlled trial antiretroviral therapy-naive patients who had CD4+ counts > or = 200 x 10(6)/l and plasma HIV RNA load > or = 10000 copies/ml were randomized to receive ZDV-3TC (200 mg three times daily and 150 mg twice daily, respectively) or d4T-3TC (40 mg and 150 mg, both twice daily). If the plasma HIV RNA level at week 8 or thereafter was > 500 copes/ml, indinavir was added at the next scheduled visit. Genotypic resistance analysis of the reverse transcriptase gene was performed at week 0 and 12. Results over 24 weeks were reported. RESULTS: Forty-seven patients were treated (24 took ZDV-3TC; 23 took d4T-3TC). Plasma HIV RNA levels decreased from median 4.80 to 3.15 log10 copies/ml (ZDV-3TC, P < 0.0001) and from 4.98 to 3.03 log10 copies/ml (d4T-3TC, P < 0.0001) after 12 weeks of treatment. Indinavir was added at week 12 in 11 out of 21 patients with ZDV-3TC and in 10 out of 22 patients with d4T-3TC. Median virus load at week 24 was 2.41 log10 and 2.29 log10 copies/ml (P=0.14), respectively. Seventy-five per cent (15 out of 20; ZDV-3TC) and 95% (18 out of 19; d4T-3TC) of patients had a virus load of < 500 copies/ml. Genomic evidence for 3TC resistance was found in all patients tested (11/11 ZDV-3TC and 12/12 d4T-3TC). At week 12, CD4 cell counts had increased with a median of 110 x 10(6)/l in the ZDV-3TC group (baseline, 315 x 10(6)/l) and a median of 115 x 10(6)/l in the d4T-3TC group (baseline 290 x 10(6)/l). At week 24, the median increases were 90 and 120 x 10(6)/l, respectively. Overall the increase of CD4+ cells was higher in the d4T-3TC group (P=0.02). CONCLUSION: d4T-3TC is at least as effective as ZDV-3TC, but 3TC resistance emerged in all patients investigated. The virological response of the dual nucleoside combination is of short duration. However, after addition of indinavir the virus load could be reduced to < 500 copies/ml in the majority of patients. The increase in CD4+ cell count was significantly greater in the d4T-3TC group. To prevent 3TC resistance, the drug should not be used in regimens containing only two nucleosides, irrespective the virus load at baseline.

Cerebrospinal-fluid HIV-1 RNA and drug concentrations after treatment with lamivudine plus zidovudine or stavudine.

BACKGROUND: Treatment and prevention of HIV-1-related central-nervous-system disease may be dependent on penetration of antiretroviral drugs into the central nervous system. Few data are available about cerebrospinal-fluid penetration and concomitant changes of HIV-1-RNA concentrations during treatment with antiretroviral agents. We investigated these effects in HIV-1-infected people. METHODS: 28 antiretroviral-naive individuals with CD4 cell counts of 200/microL or more and plasma HIV-1-RNA concentrations of 10,000 or more copies/mL who were free of neurological symptoms were randomly assigned lamivudine plus either stavudine (n = 17) or zidovudine (n = 11). We did lumbar punctures on 28 individuals before and 22 individuals after 12 weeks of treatment to assess HIV-1-RNA and drug concentrations in cerebrospinal fluid. FINDINGS: All 28 individuals had detectable HIV-1-RNA concentrations in the cerebrospinal fluid (median 4.64 log10 copies/mL and 4.20 log10 copies/mL in the lamivudine plus zidovudine and lamivudine plus stavudine groups, respectively). There was no correlation between plasma and cerebrospinal-fluid HIV-1-RNA concentrations (r = 0.18, p = 0.35). After 12 weeks of treatment none of the individuals had detectable HIV-1-RNA concentrations in the cerebrospinal fluid. The highest drug concentration in the cerebrospinal fluid was for lamivudine followed by stavudine and zidovudine. Concentrations were consistent over time, unlike plasma concentrations. Therefore, we found time-dependent cerebrospinal-fluid to plasma drug-penetration ratios, which were highest for zidovudine followed by stavudine and lamivudine. INTERPRETATION: The two drug combinations were equally effective in the decrease of cerebrospinal fluid HIV-1-RNA concentrations. All drugs penetrated the cerebrospinal fluid. Antiretroviral drugs other than zidovudine might be useful in the prevention of AIDS dementia complex.

Longitudinal analysis of CD4 T cell counts, T cell reactivity, and human immunodeficiency virus type 1 RNA levels in persons remaining AIDS-free despite CD4 cell counts <200 for >5 years.

CD4 cell count, T cell reactivity, and human immunodeficiency virus type 1 (HIV-1) RNA load were examined in 10 persons remaining free of AIDS while CD4 cell counts were <200/mm3 for >5 years, so-called low CD4 cell count long-term survivors (low CD4 LTS), and 10 matched rapid and 10 matched intermediate progressors (AIDS within 1 and 1-3 years). Longitudinal analysis of CD4 cell count and T cell reactivity revealed slower declines in low CD4 LTS. HIV-1 RNA load was 1 log/mL lower in the low CD4 LTS compared with the rapid progressors, with a similar linear increase over time in low CD4 LTS and progressors of 0.1 log/year. There was considerable overlap between groups. The constant difference between low CD4 LTS and progressors probably reflects HIV RNA load early after infection, but low CD4 LTS and progressors show similar slopes of HIV-1 RNA load rise.