Vaccination of health care workers to protect patients at increased risk for acute respiratory disease.

Health care workers (HCWs) may transmit respiratory infection to patients. We assessed evidence for the effectiveness of vaccinating HCWs to provide indirect protection for patients at risk for severe or complicated disease after acute respiratory infection. We searched electronic health care databases and sources of gray literature by using a predefined strategy. Risk for bias was assessed by using validated tools, and results were synthesized by using a narrative approach. Seventeen of the 12,352 identified citations met the full inclusion criteria, and 3 additional articles were identified from reference or citation tracking. All considered influenza vaccination of HCWs, and most were conducted in long-term residential care settings. Consistency in the direction of effect was observed across several different outcome measures, suggesting a likely protective effect for patients in residential care settings. However, evidence was insufficient for us to confidently extrapolate this to other at-risk patient groups.

The Trier Social Stress Test in first episode psychosis patients: Impact of perceived stress, protective factors and childhood trauma.

Psychosis has been associated with abnormalities in hypothalamic-pituitary-adrenal axis functioning, which may emerge through heightened stress sensitivity following early life adversity - ultimately resulting in illness onset and progression. The present study assessed cortisol levels during an established psychosocial stress task and their association with current stress perception, putative protective factors and adverse childhood experiences in patients with a first episode of psychosis (FEP). A total of 100 volunteers participated in the study, 57 of whom were patients with a FEP (mean age 23.9 ± 3.8) and 43 healthy community controls (mean age 23.2 ± 3.9). Salivary cortisol, heart rate and blood pressure were measured at eight time points before and after the Trier Social Stress Test. Subjective stress and protective factors were assessed with the Perceived Stress Scale, the Self-Esteem Rating Scale and the Brief COPE. Early life adversity was assessed with the Childhood Trauma Questionnaire. Patients compared to controls showed significantly lower cortisol levels (F = 7.38; p = .008) throughout the afternoon testing period, but no difference in the cortisol response to the TSST. Heart rate was elevated and protective factors were lower in patients compared to controls. Attenuated cortisol levels were associated with higher levels of perceived stress, poor protective factors and more physical neglect during childhood. Our results suggest that attenuated baseline cortisol levels and not a blunted response during an acute stress task might be an indicator of heightened stress vulnerability and poor resilience in psychosis. The possible influence of childhood adversity and antipsychotic medication is discussed.

Sex differences in the cortisol response to awakening in recent onset psychosis.

A dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been suggested as a factor in the etiology and exacerbation of psychosis, but has not been reported consistently. Sex differences are apparent in many aspects of psychotic disorders and may explain some of the equivocation associated with the regulation of the HPA axis in the illness. The present study compared the cortisol response to awakening (CRA) in 27 patients (16 men and 11 women) with recent onset of psychosis (within the past 2 years) and 40 age and gender matched controls. Within the patient group, we also assessed the relationship between the CRA and positive and negative symptoms of psychosis, anxiety and depression. The CRA in patients was not significantly different from controls. However, within the patient group, we observed a significant sex difference, with a blunted cortisol response to awakening in men but not in women (F=7.26; p<0.002). This difference could not be explained by differences between male and female patients in awakening time, medication, or diagnosis of schizophrenia vs. affective psychosis. Cortisol levels were not related to symptom measures. Our findings demonstrate a dysregulation of the HPA axis in male patients with recent onset of psychosis. This sex specificity might be related to and explain in part the unfavorable course of the illness observed in men.

Determinants of help-seeking and system related components of delay in the treatment of first-episode psychosis.

INTRODUCTION: Knowledge about factors that influence different components of duration of untreated psychosis (DUP) is important for designing interventions to reduce DUP. METHOD: We tested associations between help-seeking and referral components of DUP (DUP-H and DUP-R, respectively) and the following predictor variables: age, gender, ethnicity, living arrangement, pre-morbid adjustment, age at onset of psychosis, diagnosis, level of symptoms, type of first and total number of mental health contacts prior to and after the onset of psychosis in a sample of 98 first-episode psychosis patients (FEP). RESULTS: Longer DUP-HS was significantly associated with earlier age at onset, diagnosis of schizophrenia spectrum psychosis and poor pre-morbid adjustment during adolescence. Longer DUP-R was associated with earlier age at onset and first help-seeking contact having been made with a non-medical professional. CONCLUSIONS: Relatively non-malleable patient characteristics are likely to influence delay in help-seeking while more malleable systemic characteristics influence delay associated with referral for specialized treatment.

Time to all-cause treatment discontinuation of olanzapine compared to other antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis.

OBJECTIVE: This comprehensive review and meta-analysis compared the effectiveness of olanzapine and other antipsychotics in schizophrenia treatment, defining effectiveness as time to all-cause medication discontinuation (primary) and as all-cause treatment discontinuation rates. This study examined randomized clinical trials (RCTs) and observational non-interventional studies. EXPERIMENTAL PROCEDURES: Schizophrenia studies that compared olanzapine with individual first- (FGAs) and/or second-generation antipsychotics (SGAs) were included in the meta-analyses. Hazard ratios (HR), risk ratios (RR), and their associated 95% confidence intervals were extracted for RCTs and observational studies. Sensitivity analyses assessed the impact of sources of funding, dose of olanzapine, and allocation concealment method on final results. RESULTS: There were 60 RCTs (N=33,360) and 27 observational studies (N=202,591) included. On time to all-cause medication discontinuation, olanzapine was significantly better than aripiprazole, quetiapine, risperidone, ziprasidone and perphenazine for RCTs and better than amisulpride, risperidone, haloperidol, and perphenazine for observational studies. There were no significant differences between olanzapine and clozapine in RCTs or observational studies. All-cause discontinuation rates in RCTs were significantly lower for olanzapine compared to all comparators except amisulpride and clozapine. In observational studies, olanzapine was less effective than clozapine. Industry-sponsored studies favored olanzapine when compared to haloperidol and perphenazine; higher dose of olanzapine favored quetiapine and perphenazine when compared to olanzapine; method of allocation concealment did not generally affect the results. CONCLUSION: Using a global measure of medication effectiveness (time to all-cause medication discontinuation), olanzapine appears to be more effective - in both RCTs and observational studies - than most SGAs and FGAs, except for clozapine.

Attenuated cortisol response to acute psychosocial stress in individuals at ultra-high risk for psychosis.

We recently reported that individuals at ultra-high risk for the development of psychosis (UHR) have elevated levels of chronic stress and deficits in the putative protective factors self-esteem, social support and coping skills. The aim of the present study was to assess endocrine and autonomic responses to acute psychosocial stress and their associations with self-ratings of stress and protective factors in individuals at UHR. Twenty-one patients diagnosed with an "at risk mental state" (12 male, 9 female; mean age 20.8 ± 3.27) and 21 healthy age and gender matched community controls were exposed to the Trier Social Stress Test (TSST). Saliva samples for cortisol assessment and measurements of heart rate and blood pressure were taken throughout the testing period. Levels of perceived chronic stress, protective factors and depression were assessed with reference to the preceding month and year (stress only). Compared to healthy controls, individuals at UHR reported significantly higher levels of depression, deficits in protective factors, and a trend for higher chronic stress levels. Cortisol levels and systolic blood pressure during the TSST were significantly lower in the UHR group, while heart rate changes were comparable to controls. Lower cortisol levels in the UHR group were associated with higher self-ratings of stress in the past year and a lower level of education. Attenuated cortisol responses to acute psychosocial stress in the presence of high chronic stress could indicate a desensitization of the HPA axis. Associated poor metabolic and psychological adjustment to stress might increase vulnerability for the development of psychosis.

Vaccination of healthcare workers to protect patients at increased risk of acute respiratory disease: summary of a systematic review.

Healthcare workers (HCWs) are at increased risk of exposure to respiratory pathogens and may transmit infection to vulnerable patients. This study summarises a recent systematic review, which aimed to assess evidence that influenza or pneumococcal vaccination of HCWs provides indirect protection for those patients most at risk of severe or complicated acute respiratory infection. A number of healthcare databases and sources of grey literature were searched using a predefined strategy, and citations screened for eligibility in accordance with specified inclusion criteria. Risk of bias was assessed using validated tools and results summarised qualitatively. Twenty papers were included in the final review, all of which considered influenza vaccination of HCW. As such, planned subanalysis of pneumococcal vaccination was discarded. The majority of primary research studies included (11/14) were conducted in long-term care facilities, but there was marked heterogeneity in terms of the population, intervention/exposure and outcomes considered. Consistency in the direction of effect was observed across several different outcome measures, suggesting that influenza vaccination of HCWs is likely to offer some protection. Further evidence is, however, required from acute care settings.

Influenza vaccination for immunocompromised patients: summary of a systematic review and meta-analysis.

Vaccination of immunocompromised patients is recommended in many national guidelines to protect against severe or complicated influenza infection. However, due to uncertainties over the evidence base, implementation is frequently patchy and dependent on individual clinical discretion. We conducted a systematic review and meta-analysis to assess the evidence for influenza vaccination in this patient group. Healthcare databases and grey literature were searched and screened for eligibility. Data extraction and assessments of risk of bias were undertaken in duplicate, and results were synthesised narratively and using meta-analysis where possible. Our data show that whilst the serological response following vaccination of immunocompromised patients is less vigorous than in healthy controls, clinical protection is still meaningful, with only mild variation in adverse events between aetiological groups. Although we encountered significant clinical and statistical heterogeneity in many of our meta-analyses, we advocate that immunocompromised patients should be targeted for influenza vaccination.

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

BACKGROUND: Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events. METHODOLOGY/PRINCIPAL FINDINGS: Electronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I(2) and publication bias was assessed using Begg's funnel plot and Egger's regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR]=0.23; 95% confidence interval [CI]=0.16-0.34; p<0.001) and laboratory confirmed influenza infection (OR=0.15; 95% CI=0.03-0.63; p=0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. We found no difference in the odds of influenza-like illness compared to vaccinated immunocompetent controls. The pooled odds of seroconversion were lower in vaccinated patients compared to immunocompetent controls for seasonal influenza A(H1N1), A(H3N2) and B. A similar trend was identified for seroprotection. Meta-analyses of seroconversion showed higher odds in vaccinated patients compared to placebo or unvaccinated controls, although this reached significance for influenza B only. Publication bias was not detected and narrative synthesis supported our findings. No consistent evidence of safety concerns was identified. CONCLUSIONS/SIGNIFICANCE: Infection prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified.

Early predictors of nonadherence to antipsychotic therapy in first-episode psychosis.

OBJECTIVE: To examine the hypothesis that poorer social and family support, identifiable at the onset of treatment, is associated with nonadherence in the first 6 months of treatment of patients with first-episode psychosis (FEP), independent of other patient-related factors. METHOD: Consecutive patients (n = 100) admitted to a specialized early intervention service for FEP who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for either a schizophrenia spectrum disorder or an affective psychosis were evaluated monthly for 6 months regarding their adherence to medications. Using sociodemographic and illness-related factors, including social and family support, as independent variables and adherence as the dependent variable, univariate analyses were followed by logistic regression. RESULTS: Fifty-six patients (54.9%) were adherent (76% to 100% of doses taken) and 46 (45.1%) nonadherent (less than 76% of doses taken). Nonadherent patients were less likely to have received a good level of social support (chi (2) = 5.89, df = 1, P = 0.02), as rated by their respective case manager, and more likely to be single (Fisher exact test, P = 0.019) and to have refused medication at the first offer of treatment (chi (2) = 19.70, df = 1, P = 0.001). Using logistic regression, both the level of social support (OR = 3.552, P = 0.03) and early medication acceptance (OR = 11.092, P < 0.001) were significant as predictors of adherence. CONCLUSION: These results suggest the significance of social and family support in achieving adherence to medications very early in the course of treatment of FEP, in addition to the influence of early acceptance or rejection of medication.

Predictors of rate and time to remission in first-episode psychosis: a two-year outcome study.

BACKGROUND: The evidence regarding the independent influence of duration of untreated psychosis (DUP) on rate and time to remission is far from unequivocal. The goal of the current study was to examine the role of predictors for rate and time to remission in first-episode psychosis (FEP). METHOD: The differential effect of age, gender, age of onset, duration of untreated psychosis (DUP), duration of untreated illness (DUI), pre-morbid adjustment, co-morbid diagnosis of substance abuse and adherence to medication on the rate of and time to remission were estimated using a logistic and Poisson regression, and survival analysis respectively, in FEP patients. RESULTS: In a sample of 107 FEP patients 82.2% achieved remission over a period of 2 years after a mean of 10.3 weeks (range 1-72). Regression analysis, based on complete data on all variables of interest (n=80), showed status of remission to be positively influenced by better pre-morbid adjustment (RR 0.57, 95% CI 0.34-0.95, p<0.05), later age of onset (RR 1.09, 95% CI 1.05-1.13, p<0.0001), higher level of adherence to medication (RR 1.96, 95% CI 1.38-2.76, p<0.001) and shorter DUI (RR 0.99, 95% CI 0.997-0.999, p<0.005). Time to remission was influenced by age of onset (HR 1.04, 95% CI 1.00-1.08, p<0.04) and adherence to medication (HR 1.58, 95% CI 1.11-2.23, p<0.01). CONCLUSIONS: Improving adherence to medication early in the course of treatment may be an important intervention to improve short-term outcome.