Predictors of medication discontinuation by patients with first-episode schizophrenia and schizoaffective disorder

BACKGROUND: Enhancing medication adherence early in the course of schizophrenia and schizoaffective disorder may substantially improve long-term course. Although extensively studied in multi-episode patients, little data exist on medication adherence by first-episode patients. METHOD: Medication adherence was assessed during the first year of treatment and following recovery from the first relapse in patients treated by a standardized medication algorithm. RESULTS: During the first year of treatment, patients with poorer premorbid cognitive functioning were more likely to stop antipsychotics (t=-2.54, df=75, p=0.01). Parkinsonian side effects increased the likelihood (hazard ratio=41.22; 95% CI=2.30, 737.89; p=0.01), and better executive function decreased the likelihood (hazard ratio=0.40; 95% CI=0.18, 0.88; p=0.02) that patients discontinued maintenance medication after a first relapse. CONCLUSION: Interventions to ameliorate cognitive deficits and Parkinsonian side effects may enhance treatment adherence.     

Rehabilitation after proximal femur fracture surgery in the oldest old

OBJECTIVE: To assess the course and results of rehabilitation after proximal femur fracture (PFF) in patients 85 years of age or older, compared with younger elderly patients, with an emphasis on functional status. DESIGN: Prospective cohort study. SETTING: A rehabilitation geriatric ward in a tertiary university hospital in southern Israel. PARTICIPANTS: The study group included 127 elderly patients 85 years of age or older who were hospitalized for rehabilitation following surgery for PFF. The comparison group was comprised of 297 patients aged 75 to 84 years who were hospitalized for the same indication in the same time period. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional studies by FIM trade mark instrument, mental status by the Folstein Mini-Mental State Examination, Geriatric Depression Screening (GDS) scale, length of rehabilitation, and complications and mortality during rehabilitation. RESULTS: Compared with patients aged 75 to 84 years, the older study group was in a worse mental state (P=.00005), even though the groups did not differ in their GDS scores. There were no significant differences between the groups in rehabilitation length of stay, in the rate of most postoperative complications, or in death rates during rehabilitation. FIM values before PFF, at the beginning of rehabilitation and at its end, and the difference between the beginning and end of rehabilitation were lower in the older group (P<.00001 for all tests). CONCLUSIONS: From the functional standpoint, rehabilitation after PFF surgery is much less successful in the 85+ age group than in the 75-to-84 age group but did not differ in its duration, rates of most complications, or mortality. Nonetheless, a significant percentage of patients in this age group have successful rehabilitation so they should not be deprived the chance.     

Alterations in regional brain metabolism in genetic and pharmacological models of reduced NMDA receptor function

A mouse line has been developed that expresses low levels of the NMDA R1 (NR1) subunit of the NMDA receptor [Cell 98 (1999) 427]. These NR1 hypomorphic mice represent an experimental model of reduced NMDA receptor function that may be relevant to the pathophysiology of schizophrenia. To further characterize the neurobiological phenotype resulting from developmental NMDA receptor hypofunction, regional brain metabolic activity was assessed by autoradiographic analysis of 14C-2-deoxyglucose (2-DG) uptake. In addition, ligand binding to NMDA, AMPA, and kainate receptors was measured by quantitative autoradiography. MK-801 binding to NMDA receptors was reduced markedly throughout the brain of the NR1 hypomorphic mice. However, no alteration in 3H-AMPA or 3H-kainate binding was apparent in any region examined. Neuroanatomically specific alterations in regional 2-DG uptake were observed in the NR1 hypomorphic animals. Reduced relative 2-DG uptake was observed in the medial prefrontal and anterior cingulate cortices. Altered patterns of 2-DG uptake were also found in neocortical regions, with selective reductions of uptake in layer 6 in frontal regions of somatosensory and motor cortices. These data indicate alterations in cortical circuitry in the NR1 hypomorphic animals and are consistent with functional imaging studies in chronic schizophrenia patients which typically show reduced frontal cortical metabolic activity. Reduced relative 2-DG uptake was also found in the caudate, accumbens, hippocampus, and select thalamic regions in the NR1-deficient mice. However, in many other brain regions no alteration in 2-DG uptake was observed. The alterations in 2-DG uptake in the NR1 hypomorphic mice were distinctly different compared to those observed after acute challenge with the selective NMDA antagonist MK-801 in wild-type mice. The altered patterns of brain 2-DG uptake in the NR1 hypomorphic mice found in the present work, together with the altered behavioral phenotypes previously described, suggest that the mice may provide a valuable model to study novel therapeutic strategies to counteract the neurobiological consequences of chronic developmental NMDA receptor hypofunction.     

Procedural success and complications of large-scale screening colonoscopy

BACKGROUND: Indirect evidence and modeling analyses suggest that colonoscopy may be the most cost-effective way to screen the average-risk population for colorectal neoplasia. However, the success and safety of primary colonoscopic screening has not been prospectively evaluated in a multicenter trial. METHODS: Asymptomatic subjects age 50 to 75 years who had not undergone examination of the colon within 10 years were recruited from the general medicine clinics of 13 Department of Veterans Affairs Medical Centers. Eligible patients underwent colonoscopy by study coinvestigators, at which time all polyps were measured, photographed, and removed. Patients were contacted at 24 hours and 1 week to track procedure-related complications. RESULTS: Primary screening colonoscopy was performed in a cohort of 3196 asymptomatic subjects. A "good" preparation was reported in 81% of patients, and colonoscopy to the cecum was successful in 97.2% of cases. Mean insertion time to the cecum and total procedure times were 10.5 (8.7) and 30.6 (19.1) minutes, respectively. No preprocedural patient characteristics were identified that were predictive of an incomplete procedure. At least one polyp was resected in 1672 patients. There was no perforation and no death attributed to colonoscopy. Major morbidity considered to be definitely related to colonoscopy occurred in 9 of 3196 procedures (0.3%): lower GI bleeding requiring intervention (6), myocardial infarction and/or cerebrovascular accident (2), and thrombophlebitis (1). In subjects undergoing only diagnostic procedures, the major complication rate was 0.1%. CONCLUSIONS: Screening colonoscopy can be performed in multiple centers with a high degree of success and safety in large numbers of asymptomatic, average-risk men.     

Perinatal substance abuse intervention in obstetric clinics decreases adverse neonatal outcomes.

OBJECTIVE: To evaluate the effect of Early Start, a managed care organization's obstetric clinic-based perinatal substance abuse treatment program, on neonatal outcomes. STUDY DESIGN: Study subjects were 6774 female Kaiser Permanente members who delivered babies between July 1, 1995 and June 30, 1998 and were screened by completing prenatal substance abuse screening questionnaires and urine toxicology screening tests. Four groups were compared: substance abusers screened, assessed, and treated by Early Start ("SAT," n=782); substance abusers screened and assessed by Early Start who had no follow-up treatment ("SA," n=348); substance abusers who were only screened ("S," n=262); and controls who screened negative ("C," n=5382). RESULTS: Infants of SAT women had assisted ventilation rates (1.5%) similar to control infants (1.4%), but lower than the SA (4.0%, p=0.01) and S groups (3.1%, p=0.12). Similar patterns were found for low birth weight and preterm delivery. CONCLUSION: Improved neonatal outcomes were found among babies whose mothers received substance abuse treatment integrated with prenatal care. The babies of SAT women did as well as control infants on rates of assisted ventilation, low birth weight, and preterm delivery. They had lower rates of these three neonatal outcomes than infants of either SA or S women.     

"Real World" compliance with strategies to prevent early-onset group B streptococcal disease.

OBJECTIVE: To assess the "real-world" compliance with risk- and culture-based strategies to prevent early-onset group B streptococcal disease. STUDY DESIGN: We retrospectively reviewed the medical records of consecutive term pregnancies delivered at three institutions (a subset of practices at an academic hospital using the culture-based strategy, an academic hospital using the risk-based strategy, and a community hospital using both) between January and March 1998. We abstracted demographic data and risk factors for group B streptococcus, group B streptococcal culture information, documentation of intrapartum antibiotic prophylaxis, and adverse drug reactions. We compared intrapartum compliance with the intended strategy. RESULTS: There were a total of 505 women managed with the risk-based strategy. Of those, 79 had a risk factor for group B streptococcal disease and 72/79 (91.1%) received intrapartum antibiotic prophylaxis. There were a total of 428 women managed with the culture-based strategy. Of those, 70 had positive cultures and 67 (95.7%) received intrapartum antibiotic prophylaxis. An additional 39 women in the culture-based group had no documentation that cultures had been done. Of those, eight (20.5%) had risk factors and all eight received intrapartum antibiotic prophylaxis. Compliance with the risk-based strategy was 91.1 versus 96.2% with the culture-based strategy (p=0.3). Among women managed using the risk-based strategy, 5/426 (1.2%) received intrapartum antibiotic prophylaxis without an identifiable risk factor. Among women in the culture-based strategy, 5/359 (1.4%) received intrapartum antibiotic prophylaxis with documented negative group B streptococcal cultures (p=0.5). When examined by site, compliance with the intended strategy was 91.2% at the academic hospital using the risk-based strategy, 100% at the academic hospital using the culture-based strategy, 90.9% at the community practices using the risk-based strategy, and 82.4% at the community practices using the culture-based strategy. CONCLUSION: Overall, intrapartum compliance with the risk-based approach was similar to the culture-based approach. However, there were more cultures not done and cultures done at inappropriate gestations at the community hospital practice.     

Infectious aetiologies in elderly patients hospitalised with non-pneumonic lower respiratory tract infection

OBJECTIVE: to identify the infectious aetiologies of non-pneumonic lower respiratory tract infections in hospitalised elderly patients, and to characterise the patients in terms of demographic, clinical and therapeutic variables. DESIGN:a prospective, non-interventional, purely serologically based diagnostic study. SETTING: a tertiary university hospital in southern Israel. SUBJECTS:133 elderly patients hospitalised for non-pneumonic lower respiratory tract infections. METHODS: paired sera were obtained for each of the hospitalisations and were tested using immunofluorescence or enzyme immunoassay methods to identify 13 different pathogens. Only significant changes in antibody titers or levels between the paired sera were considered diagnostic. RESULTS: at least one infectious aetiology was identified in 77 patients (58%). At least one of seven viral aetiologies was identified in 52 patients (39%). A bacterial aetiology was identified in 27 patients (20%) including Streptococcus pneumoniae in 24 (18%). An atypical bacterium was found in 27 patients (20%) including Mycoplasma pneumoniae in 15 (11%) and Legionella spp. in nine (7%). More than one aetiology was found in 23 patients (17%). One hundred and twenty nine patients (96%) suffered from serious chronic co-morbidity. One hundred and twenty one patients received antibiotics during their hospitalisation, 106 (80%) with a beta-lactam and 42 (31%) with another antibiotic. CONCLUSIONS: non-pneumonic lower respiratory tract infection is caused in hospitalised elderly patients by a broad spectrum of aetiological agents, primarily respiratory viruses with a significant, though lesser, prevalence of classical and atypical bacteria. Despite this distribution of aetiologies, most patients are treated with beta-lactam antibiotics. The indication for antibiotic therapy in these patients and the choice of antibiotic preparation should be addressed in further studies.     

Purified particulate methane monooxygenase from Methylococcus capsulatus (Bath) is a dimer with both mononuclear copper and a copper-containing cluster

Particulate methane monooxygenase (pMMO) is a membrane-bound enzyme that catalyzes the oxidation of methane to methanol in methanotropic bacteria. Understanding how this enzyme hydroxylates methane at ambient temperature and pressure is of fundamental chemical and potential commercial importance. Difficulties in solubilizing and purifying active pMMO have led to conflicting reports regarding its biochemical and biophysical properties, however. We have purified pMMO from Methylococcus capsulatus (Bath) and detected activity. The purified enzyme has a molecular mass of approximately 200 kDa, probably corresponding to an alpha(2)beta(2)gamma(2) polypeptide arrangement. Each 200-kDa pMMO complex contains 4.8 +/- 0.8 copper ions and 1.5 +/- 0.7 iron ions. Electron paramagnetic resonance spectroscopic parameters corresponding to 40-60% of the total copper are consistent with the presence of a mononuclear type 2 copper site. X-ray absorption near edge spectra indicate that purified pMMO is a mixture of Cu(I) and Cu(II) oxidation states. Finally, extended x-ray absorption fine structure data are best fit with oxygennitrogen ligands and a 2.57-A Cu-Cu interaction, providing direct evidence for a copper-containing cluster in pMMO.     

Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of recurrent glioblastoma: preliminary observations in a patient with a favorable response to therapy

Summary We designed a phase I clinical trial of vaccinations with autologous glioma cells expressing transgene-derived interleukin-4 (IL-4), and treated one patient with a right temporal lobe recurrent glioblastoma. This 62-year-old man underwent crainotomy and partial tumor removal, at which time autologous tumor cells were obtained for vaccine preparation. After confirming the patient’s cellular immune function by skin test, two cycles of vaccination with irradiated autologous glioma cells admixed with gene transfected fibroblasts were given intradermally. The patient demonstrated no evidence of allergic encephalitis throughout this course. Immunohistochemistry with biopsy samples taken from the vaccine sites demonstrated that the infiltration level of CD4, CD8 and CD1a positive cells increased proportionally to the amount of IL-4 produced at the each site, suggesting that there was local immune response induced at the vaccine site. While it is premature to assess effectiveness of the vaccine, this initial patient’s course suggested a transient response to the vaccine, and he survived 10 months after treatment.     

Electronic support groups for breast carcinoma: a clinical trial of effectiveness

BACKGROUND: A recent Pew Charitable Trust study found that 52,000,000 individuals used the Internet to obtain health/medical information. Clinical trials of face-to-face breast carcinoma support groups show evidence of 1) improvement in quality of life, 2) reduction of psychologic symptoms, 3) improvement in coping responses, and 4) a reduction in pain. To the authors' knowledge, a few studies published to date have investigated Internet-delivered electronic support groups (ESGs) for cancer. The most sophisticated is the Comprehensive Health Enhancement Support System (CHESS) program, which provides integrated information, referral, and a newsgroup-based social support program. However, to the authors' knowledge, no studies published to date have examined the impact of a breast carcinoma ESG in a clinical trial. METHODS: Sixty-seven women completed the initial baseline questionnaires, 32 of whom accepted the authors' invitation and began the groups. With regard to geographic location, 49% lived in rural/small towns, 41% lived in medium-sized cities, and 10% lived in large cities. Diagnostic stages of disease were: Stage I, 22%; Stage II, 56%; Stage III, 12%; and other forms, 10%. There were 4 intervention groups, of which 8 participants led by trained Wellness Community (TWC) (a national agency) leaders met for 1.5 hours once a week for 16 weeks. Student t tests for paired outcome data were computed using baseline and postgroup scores. RESULTS: The results of the current study indicated that breast carcinoma patients significantly reduced depression (Center for Epidemiologic Studies-Depression [CES-D] scale) and Reactions to Pain. They also demonstrated a trend toward increases on The Posttraumatic Growth Inventory (PTGI) in two subscales: New Possibilities and Spirituality. Counterintuitively, breast carcinoma patients appeared to demonstrate an increase in emotional suppression. Postinterview results indicated that approximately 67% of patients found the group to be beneficial. Those who withdrew from the groups (20%) demonstrated low scores in their ability to contain anxiety and appeared to be more likely to suppress their thoughts and feelings regarding their illness. CONCLUSIONS: The findings of the current study are encouraging, particularly because it was conducted through TWC, a national agency willing to make this type of intervention readily available at no cost. A limitation of the current study was the lack of randomization and a control group comparison. Although the authors were not able to demonstrate effectiveness without the addition of a control condition, the analysis of pregroup and postgroup outcomes suggests that a randomized trial is worthwhile. Women with a devastating disease will join and commit themselves to an online support group. In addition, because a large percentage of these women were from rural locations, this type of intervention may hold promise for those who have limited access to support groups.