Real Time-PCR HBV-DNA Analysis: Significance and First Experience in Armed Forces

Background

HBV DNA quantitation is used extensively world wide for the diagnosis and monitoring of treatment of Hepatitis B virus (HBV) infection. However, it has still to be popular in India. The aim of this study was to quantitate HBV – DNA by Real time – PCR method in Hepatitis B and in immuno-compromised patients, to compare the results with HBeAg detection and to monitor the response to therapy of chronic Hepatitis B patients to antivirals.

Methods

Ninety one serum samples of Hepatitis group of patients (all HBsAg positive), 41 samples from immuno-compromised patients (all HBsAg negative) and 49 patients of Chronic Hepatitis B group (all HBsAg positive) were the subjects of this first ever study in Armed Forces. Twenty serum samples from healthy volunteers and non-hepatitis B patients served as negative controls. The amplification detection was carried out in a Rotor-Gene 2000-sequence detector

Results

Amongst Hepatitis B group, 33% (30/91) of the samples were positive for HBV-DNA and 26% (24/91) of samples were positive for HBeAg. In the immuno-compromised group of patients 14.6% (6/11) of samples were positive for HIV-DNA and 9.7% (4/41) were positive for HBeAg. Of the Chronic Hepatitis B patients on treatment, all (100%) were positive by HBV-DNA, whereas 29/49 (59.2%) were positive by HBeAg before treatment. After treatment with antivirals, 06/49 (12.2%) were positive by both tests and 11/49 (22.5%) were positive only by HBV-DNA. 32/49 (65.3%) patients became negative serologically after therapy.

Conclusion

HBeAg status did not necessarily reflect HBV-DNA level in the serum, as 10/91 (11%) in the Hepatitis B group, 2/41 (4.9%) in the immuno compromised group and 20/49 (40.8%) patients in the Chronic Hepatitis B group were positive for HBV-DNA but negative for HBeAg. HBV-DNA was not found to be positive amongst any of the negative controls. Real time – PCR is a sensitive and reproducible assay for HBV-DNA quantitation and may be started in Armed Forces referral centers in the near future.Key Words: Real time – PCR, Chronic Hepatitis B, HBV – DNA, Antivirals     

High utilizers of psychiatric emergency services

OBJECTIVE: The purpose of this study was to examine the sociodemographic and clinical characteristics of high utilizers of psychiatric emergency services. METHODS: Data were collected over four years for 761 patients who were identified as high utilizers according to three definitions (two standard deviations above the mean number of visits to an urban psychiatric emergency service, six visits in a year, and four visits in a quarter) and for 1,585 nonfrequent utilizers (control group). Univariate analysis of variance and logistic regression models were used to determine group differences. RESULTS: Two distinct groups of high utilizers emerged: high utilizers by quarter and high utilizers by standard deviation. Compared with the control group, the high utilizers were more likely to be homeless, to have developmental delays, to be enrolled in a mental health plan, to have a history of voluntary and involuntary hospitalizations, to be uncooperative, to have personality disorders, to have unreliable social support, and to have a lifetime history of incarceration and detoxification. Compared with the high utilizers by quarter, the high utilizers by standard deviation had more visits and were more likely to have a history of incarceration and psychiatric hospitalization, more likely to be enrolled in mental health plan, and less likely to be homeless. CONCLUSIONS: High utilizers make up a small percentage of individuals who seek care in psychiatric emergency services and disproportionately use resources. It may be helpful to use two definitions of high utilizer to identify patients at different phases of their illness and to guide clinical interventions and mental health policies.     

Perceived unmet need for mental health treatment and barriers to care among patients with panic disorder

OBJECTIVE: This study estimated the extent of perceived unmet need for mental health treatment among individuals with panic disorder in primary care settings, investigated the determinants of unmet need, and assessed barriers to care. METHODS: Data were from baseline interviews in a clinical trial that investigated primary care treatment of panic disorder. Participants were asked whether there was any time in the past three months when they did not get as much care for emotional or personal problems as they needed or whether they had delays in getting care. Patients who endorsed unmet need were asked about specific perceived barriers. Logistic regression was used to investigate the determinants of unmet need. RESULTS: Of the 231 patients eligible for the study, 88 (38 percent) endorsed unmet need for emotional or mental health problems. Individuals with worse mental health, those who were more worried about panic, and those without sick pay were significantly more likely to report unmet need. Commonly reported barriers included being unable to find out where to go for help (43 percent), worry about cost (40 percent), lack of coverage by health plan (35 percent), and being unable to get an appointment soon enough (35 percent). CONCLUSIONS: The relatively low level of patient-reported unmet need for mental health treatment among primary care patients with panic disorder suggests that efforts to improve treatment of panic disorder should include patient education about mental illness and the effective treatments available. Although discussion of barriers to care has traditionally centered on stigma and economic factors, the results of this study suggest that simple logistic factors, such as not knowing whom to call for help, are also important barriers.     

The impact of comorbid posttraumatic stress disorder on short-term clinical outcome in hospitalized patients with depression

OBJECTIVE: Posttraumatic stress disorder (PTSD) is often comorbid with other psychiatric disorders but often goes unrecognized. The effects of PTSD comorbidity are unclear, especially in patients with severe mental illness. The authors assessed short-term clinical outcome in severely depressed psychiatric inpatients with and without comorbid PTSD. METHOD: From patients hospitalized between 1995 and 2000, all patients with depression and comorbid PTSD (N=587) were selected and matched with depressed patients without PTSD (N=587). Clinical outcome was assessed with a semistructured, physician-administered battery. Differences between the two groups were examined, with overall burden of psychiatric illness entered as a covariate in the analyses. RESULTS: Relative to depressed patients without PTSD, depressed patients with PTSD had, at discharge, greater psychiatric symptom severity and higher levels of depression and hostility. Depressed patients with comorbid PTSD also had a significantly higher rate of being discharged against medical advice (odds ratio=6.10, 95% CI 2.96-12.57). CONCLUSIONS: PTSD comorbidity correlates with poorer short-term clinical outcome and greater likelihood of discharge against medical advice in severely depressed psychiatric inpatients. Better recognition of PTSD comorbidity may improve overall care of these patients.     

A randomized effectiveness trial of cognitive-behavioral therapy and medication for primary care panic disorder

BACKGROUND: Panic disorder is a prevalent, often disabling condition among patients in the primary care setting. Although numerous studies have assessed the effectiveness of treatments for depression in primary care, few such studies have been conducted for panic disorder. OBJECTIVE: To implement and test the effectiveness of a combined pharmacotherapy and cognitive-behavioral intervention for panic disorder tailored to the primary care setting. DESIGN: Randomized, controlled study comparing intervention to treatment as usual. SETTING: Six primary care clinics associated with 3 university medical schools, serving an ethnically and socioeconomically diverse patient population. PARTICIPANTS: Two hundred thirty-two primary care patients meeting DSM-IV criteria for panic disorder. Comorbid mental and physical disorders were permitted, provided these did not contraindicate the treatment to be provided and were not acutely life threatening. INTERVENTION: Patients were randomized to receive either treatment as usual or an intervention consisting of a combination of up to 6 sessions (across 12 weeks) of cognitive-behavioral therapy (CBT) modified for the primary care setting, with up to 6 follow-up telephone contacts during the next 9 months, and algorithm-based pharmacotherapy provided by the primary care physician with guidance from a psychiatrist. Behavioral health specialists, the majority inexperienced in CBT for panic disorder, were trained to deliver the CBT and coordinated overall care, including pharmacotherapy. MAIN OUTCOMES MEASURES: Proportion of subjects remitted (no panic attacks in the past month, minimal anticipatory anxiety, and agoraphobia subscale score <10 on Fear Questionnaire) and responding (Anxiety Sensitivity Index score <20) and change over time in World Health Organization Disability Scale and short form 12 scores. RESULTS: The combined cognitive-behavioral and pharmacotherapeutic intervention resulted in sustained and gradually increasing improvement relative to treatment as usual, with significantly higher rates at all points of both the proportion of subjects remitted (3 months, 20% vs 12%; 12 months, 29% vs 16%) and responding (3 months, 46% vs 27%; 12 months, 63% vs 38%) and significantly greater improvements in World Health Organization Disability Scale (all points) and short form 12 mental health functioning (3 and 6 months) scores. These effects were obtained in spite of similar rates of delivery of guideline-concordant pharmacotherapy to the 2 groups. CONCLUSION: Delivery of evidence-based CBT and medication using the collaborative care model and a CBT-naive, midlevel behavioral health specialist is feasible and significantly more effective than usual care for primary care panic disorder.     

Medical illness and response to treatment in primary care panic disorder

OBJECTIVE: Although studies have suggested that comorbid medical illness can affect the outcome of patients with depression, little is known about whether medical illness comorbidity affects treatment outcome in patients with anxiety. METHOD: Primary care patients with panic disorder (n=232), participating in a randomized collaborative care intervention of CBT and pharmacology, were divided into those above (n=125) and below (n=107) the median for burden of chronic medical illness and assessed at 3, 6, 9 and 12 months. RESULTS: Subjects with a greater burden of medical illness were more psychiatrically ill at baseline, with greater anxiety symptom severity, greater disability and more psychiatric comorbidity. The intervention produced significant and similar increases in amount of evidence-based care, and reductions in clinical symptoms and disability that were comparable in the more and less medically ill groups. CONCLUSIONS: The comparable response of individuals with more severe medical illness suggests that CBT and pharmacotherapy for panic disorder work equally well regardless of medical illness comorbidity. However, the more severe psychiatric illness both at baseline and follow-up in these same individuals suggest that treatment programs may need to be extended in time to optimize treatment outcome.     

Predicting rehospitalization and outpatient services from administration and clinical databases

The study tests whether psychiatric services utilization may be predicted from administrative databases without clinical variables equally as well as from databases with clinical variables. Persons with a psychiatric hospitalization at an urban medical center were followed for 1 year postdischarge (N=1384.) Dependent variables included statewide rehospitalization and the number of hours of outpatient services received. Three linear and logistic regression models were developed and cross-validated: a basic model with limited administrative independent variables, an intermediate model with diagnostic and limited clinical indicators, and a full model containing additional clinical predictors. For rehospitalization, the clinical cross-validated model accounted for twice the variance accounted by the basic model (adjusted R²=.13 and .06, respectively). For outpatient hours, the basic cross-validated model performed as well as the clinical model (adjusted R²=.36 and .34, respectively.) Clinical indicators such as assessment of functioning and co-occurring substance use disorder should be considered for inclusion in predicting rehospitalization.     

Moving treatment research from clinical trials to the real world

Recently the National Institutes of Health has been emphasizing research that takes findings generated by clinical research and translates them into treatments for patients who are seen in day-to-day nonresearch settings. This translational process requires a series of steps in which elements of both efficacy and effectiveness research are combined into successively more complex designs. However, there has been little discussion of exactly how to develop and operationalize these designs. This article describes an approach to the development of these hybrid designs. Their operationalization is illustrated by using the design of an ongoing effectiveness treatment study of panic disorder in primary care. Experts in both efficacy and effectiveness research collaborated to address the methodologic and data collection issues that need to be considered in designing a first-generation effectiveness study. Elements of the overall study design, setting or service delivery context, inclusion and exclusion criteria, recruitment and screening, assessment tools, and intervention modification are discussed to illustrate the thinking behind and rationale for decisions about these different design components. Although the series of decisions for this study were partly influenced by considerations specific to the diagnosis of panic disorder and the context of the primary care setting, the general stepwise approach to designing treatment interventions using an effectiveness model is relevant for the development of similar designs for other mental disorders and other settings.