Nonbiological pharmacotherapies for the treatment of diabetic macular edema

Introduction: During the past decade, there have been significant advances in the pharmacotherapies for the treatment of diabetic macular edema (DME). Among the presently available treatment options, anti-vascular endothelial growth factors (anti-VEGF) agents are the most favored agents due to their efficacy and safety. The index review focuses on nonbiological therapies that have entered in phase 3 clinical trials for DME.

Areas covered: An extensive review of the literature was performed to identify various nonbiological immunotherapies i.e., drugs other than ‘-mAbs’ (monoclonal antibodies including anti-VEGF agents), ‘-mibs’ (proteasome inhibitors), ‘-NAbs’ (nanoparticle albumin-bound), and ‘-nibs’ (small molecule inhibitor/tyrosine kinase inhibitors), among others. Extended-release low-dose corticosteroid devices have been recently approved for the treatment of DME. Other compounds such as non-steroidal anti-inflammatory drugs, antibody mimetic proteins, nonbiological growth factor inhibitors, and inhibitors of protein kinase C have been described.

Expert opinion: A number of therapies are under development for the pharmacological management of DME. Due to the rising healthcare costs associated with anti-VEGF agents, a number of alternate treatment options have been explored recently. Some of these agents have reached phase 3 in clinical trials and appear to have a promising role in the management of DME. As further research is conducted, the role of each individual agent will become more defined, alone or in combination therapy.     

A computer-managed clinical evaluation system: implications for competency-based dietetic education programs

Instruments for evaluating clinical performance of students were developed, tested, and designed for a computer-managed evaluation system for the competency-based dietetic internship program at Emory University, Atlanta. The development, evaluation, and utilization of the instruments are described. The method of development included: (a) analysis of validated competencies and performance criteria to determine aspects of behavior appropriate to measure in clinical settings, (b) specification of major areas to be evaluated, (c) specification of component behaviors within each of the major areas, (d) specification of criteria to be used in evaluating component behaviors, and (e) definition of the rating continuum. Validation of the instruments consisted of determinations of content validity, interrater reliability, and practicality. Results of the use of the computer-managed evaluation system indicated that the instruments were valid, reliable, and practical to use for evaluating students' clinical performance.     

Predictors of exercise capacity and everyday activity in older heart failure patients

BACKGROUND: Exercise capacity and daily activity are key outcomes for older, frail heart failure patients. Little is known about the determinants of these outcomes in this patient group. AIMS: To explore predictors of exercise capacity and daily activity in older, frail heart failure patients. METHODS: Analysis of prospectively collected data from a cohort of 82 patients aged 70 years and over, enrolled in a randomised controlled trial of exercise in heart failure patients. Pathophysiological, demographic, psychological and social factors were analysed by multivariate regression to determine predictors of exercise capacity (6-min walk distance) and daily activity (daily accelerometer counts). RESULTS: Between 49% and 55% of the variance in 6-min walk distance was explained by variables including New York Heart Association class, depression score, attitude to ageing and use of walking aids. Only 11% to 26% of the variance in accelerometer scores was explained by the model; 6-min walk distance was the only consistent predictor of daily activity. CONCLUSIONS: Physical, psychological and attitudinal variables contribute to variance of the 6-min walk. Six-minute walk distance predicts a small amount of the variance in daily activity, but the majority of variance in daily activity remains unexplained and requires further investigation.     

Effect of a seated exercise program to improve physical function and health status in frail patients > or = 70 years of age with heart failure

Eighty-two patients aged > or = 70 years with heart failure were randomized to a gentle, seated exercise program or to usual care. Six-minute walk distance and quality of life did not change between groups, but daily activity as measured by accelerometry increased in the exercise group relative to the control group.     

The association of weight gain and olanzapine plasma concentrations

Atypical antipsychotics, including olanzapine, have been associated with clinically significant weight gain in some patients. The purpose of this study was to determine if weight gain was associated with increasing plasma concentrations during olanzapine treatment in subjects with schizophrenia. This study included 39 acutely ill subjects with schizophrenia, schizoaffective disorder, or schizophreniform disorder (DSM-III-R or DSM-IV). Assessments included the Brief Psychiatric Rating Scale (BPRS), the Scale for Assessment of Negative Symptoms (SANS), and weight measurements. Olanzapine was titrated to a dose of 5 to 20 mg/d for 2 to 6 weeks. A 24-hour plasma concentration was obtained after 6 weeks of treatment. Analysis using a receiver operator characteristic curve identified a threshold dose-weighted plasma concentration of 20.6 ng/mL being associated with an increased likelihood of clinically significant weight gain (> or =7% baseline weight) during olanzapine treatment. The associations remained significant after adjusting for age, gender, baseline body mass index, baseline symptom severity, and symptom improvement (OR = 10.1; 95% CI, 1.3-75.0; P = 0.024). Similar analysis determined that a threshold olanzapine dose of 13.3 mg/d was associated with > or =7% weight gain. However, after adjusting for potential confounders, the results did not remain significant. The association of weight gain with plasma concentrations during treatment with olanzapine may support the utilization of plasma drug concentration as a marker for antipsychotic-induced weight gain in the treatment of schizophrenia.     

Analysis of penetrance and expressivity during ontogenesis supports a stochastic choice of zebrafish odorant receptors from predetermined groups of receptor genes

Olfactory receptor neurons select a single odourant receptor gene for expression out of a large gene family. The mechanisms of this extreme selectivity are largely unknown. We have determined in detail the developmental expression dynamics of a representative subset of the zebrafish odourant receptor repertoire, using in situ hybridization analysis. We have thus generated a dataset, which allows us to test hypotheses of odourant receptor gene regulation. The receptors chosen belong to four different groups with respect to ontogenetic onset of expression (onset groups). Statistical analysis of the data supports a model in which the final choice of an individual odourant receptor gene occurs stochastically from within a group of genes sharing a deterministically defined onset of expression. Genomic mapping revealed a pronounced correlation of onset of expression with genomic neighbourhood. During a protracted juvenile developmental period individual regulatory influences seem to modify the expression of odourant receptor genes, a notable example being a transient decrease in expressivity of two odourant receptor genes.     

A model for competency-based, computer-managed instruction in allied health

A competency-based, computer-managed instruction model was developed and used in revising and managing the curricula of dietetic internship and physical therapy certificate programs. Use of the model resulted in identification and validation of program competencies and performance criteria, revision of curricula, and implementation of a computer-managed instructional support system to record, store, and provide feedback to students and instructors about performance on the competency measures. Improvements in the quality of the curricula and in the ability to manage student performance information have resulted from these efforts. The computer-managed instruction system has been well received by instructors and students. The most obvious benefits include savings in time for instructors and immediate feedback on performance for students. Results indicate that a competency-based, computer-managed approach to curriculum development and implementation is desirable and practical and has the potential for effectively serving future developments in allied health education.     

A comparison of decisions to discharge committed psychiatric patients between treating physicians and district psychiatric committees: an outcome study

Background

The Israel Mental Health Act of 1991 stipulates a process for involuntary psychiatric hospitalization (IPH). A patient thus hospitalized may be discharged by either the treating psychiatrist (TP) or the district psychiatric committee (DPC). The decision rendered by the DPC is often at odds with the recommendation of the TP. Although much has been written about the ethical issues of restricting patients’ rights and limiting their freedom, far less attention has been devoted to the psychiatric, medical, and social outcome of legal patient discharge against the doctor’s recommendation.

Methods

In our study we examined the outcomes of the decisions made by the DPC using readmission data, an internationally recognized indicator of the quality of hospital care, and compared them to the outcomes of patients discharged by the TP. All IPH discharges resulting from the DPC’s determination for the year 2013 (N = 972) were extracted from the Israel national register. We also collected all IPH discharges owing to the TP’s decision for 2013 (N = 5788). We defined “failure” as readmission in less than 30 days, involuntary civil readmission in less than 180 days, and involuntary readmission under court order in less than 1 year.

Results

The rehospitalization pattern was compared in the two groups of patients discharged from their psychiatric hospitalization during 2013 (index discharges) and followed up individually for a year.We found a statistically significant difference between the DPC and the TP group for each of the time frames, with the DPC group returning to IPH much more frequently than the TP group.Using cross-sectional comparison with logistic regression adjusted for age, gender, diagnosis and length of hospitalization, we found the probability of a decision failure in the TP group was significantly less with an OR of 0.7 (95% CI .586–.863), representing a 30% adjusted decrease in the probability for failure in the TP group.

Conclusions

The results we present show that the probability of decision “failure” (readmission) was found to be significantly higher in the DPC group than in the TP group. It is often assumed that IPH patients will fare better at home in their communities than in a protracted hospitalization. This is frequently the rationale for early discharge by the DPC (30.1 days vs. 75.9 DPC and TP groups, respectively). Our results demonstrate that this rationale may well be a faulty generalization.

     

Cervical necrotizing fasciitis and descending necrotizing mediastinitis in a patient affected by neglected peritonsillar abscess: a case of medical negligence

We report a case of fatal cervical necrotizing fasciitis (CNF) and descending necrotizing mediastinitis (DNM) due to primary peritonsillar abscess in 60-year-old male patient with no history or evidence of immunocompromising disorders. The patient was treated with antibiotic and corticosteroid drugs but he developed mediastinitis and septic shock and died of multiple organ failure six days later from recovery in hospital. After a clinical, diagnostic and therapeutical consideration of the cervical necrotizing fasciitis and some related risks of a delayed diagnosis and treatment, the authors analysed the clinical history of the patient and of the medical conduct pointing out professional malpractice chargeable to doctors.