Effects of the advent of disease on smoking habit

A study was undertaken to determine the effect of the development or disease on patients' smoking habits. Interviews with 841 subjects (591 smokers) were conducted following a standard protocol. Of the 841 subjects, 96 (61 smokers) had hydroceles or hernias and were considered a control group; the remainder had neoplastic diseases, respiratory disorders, diabetes, cardiovascular diseases, psychiatric illnesses, peripheral vascular diseases, and gastrointestinal and liver disorders. Patients with cardiovascular, pulmonary, and neoplastic diseases, diabetes, gastrointestinal diseases, and cirrhosis of the liver significantly reduced or stopped smoking because of medical advice (19%), socioeconomic factors (8%), or aggravation of disease (24%). The advent of disease was associated with an increase in smoking in several patients (including 2 with bronchial asthma and 12 with peripheral vascular disease) because of the apparent belief that smoking is beneficial in overcoming the disease or in controlling pain. Additional long-term studies are needed to explore the relationship between disease and smoking habits.     

Passage of intravenously administered tubocurarine into the liquor space in man and dog

1. In anaesthetized patients under controlled respiration, samples of lumbar cerebrospinal fluid were withdrawn 15 and 60 min after an intravenous injection of 30 mg tubocurarine. When tested on the frog rectus muscle preparation contracted by acetylcholine, they exerted curare-like activity which corresponded to between 0.05 and 0.33 mug/ml tubocurarine.2. In dogs anaesthetized with pentobarbitone sodium and artificially ventilated, two procedures were adopted to find out if tubocurarine passes into the liquor space after an intravenous injection of 0.3 or 3 mg/kg and during its intravenous infusion at a rate of 10 (mug/kg)/minute. Either samples of cisternal cerebrospinal fluid (c.s.f.) were collected, or different regions of the liquor space were perfused with artificial c.s.f. and the effluent was collected. The samples of c.s.f. and the effluent were assayed for curare-like activity on the frog rectus muscle.3. After the intravenous injection of tubocurarine samples of cisternal effluent collected during perfusion from lateral ventricle to cisterna exerted curare-like activity. It corresponded to 20 ng/min tubocurarine in the sample collected during the first 15 min after the injection of 0.3 mg/kg and to 40-60 ng/min in the samples collected up to 2 h after the injection of 3 mg/kg.4. During intravenous infusion of tubocurarine the cisternal c.s.f. as well as the effluent from the perfused regions of the liquor space exhibited curare-like activity. Expressed in equivalents of tubocurarine, the activity in the cisternal c.s.f. ranged from between 0.1 and 0.75 mug/ml. On perfusion from lateral ventricle to aqueduct or cisterna, the activity ranged from between 3 and 25 ng/min in the aqueductal and from between 4 and 40 ng/min in the cisternal effluent. On perfusion from the lumbar-spinal subarachnoid space to cisterna it ranged from between 6 and 55 ng/min in the cisternal effluent.     

Cognitive enhancement therapy for schizophrenia: effects of a 2-year randomized trial on cognition and behavior

BACKGROUND: Deficits in social cognition and neurocognition are believed to underlie schizophrenia disability. Attempts at rehabilitation have had circumscribed effects on cognition, without concurrent improvement in broad aspects of behavior and adjustment. OBJECTIVE: To determine the differential effects of cognitive enhancement therapy (a recovery-phase intervention) on cognition and behavior compared with state-of-the-art enriched supportive therapy. DESIGN: A 2-year, randomized controlled trial with neuropsychological and behavioral assessments completed at baseline and at 12 and 24 months. SETTING: An outpatient research clinic housed in a medical center's comprehensive care service for patients with severe mental illness. PATIENTS: A total of 121 symptomatically stable, non-substance-abusing but cognitively disabled and chronically ill patients with schizophrenia or schizoaffective disorder. INTERVENTIONS: Cognitive enhancement therapy is a multidimensional, developmental approach that integrates computer-assisted training in neurocognition with social cognitive group exercises. Enriched supportive therapy fosters illness management through applied coping strategies and education. MAIN OUTCOME MEASURES: Six highly reliable summary measures--Processing Speed, Neurocognition, Cognitive Style, Social Cognition, Social Adjustment and Symptoms--were tested using analysis of covariance and linear trend analysis. RESULTS: At 12 months, robust cognitive enhancement therapy effects were observed on the Neurocognition and Processing Speed composites (P<.003), with marginal effects observed on the behavioral composites. By 24 months, differential cognitive enhancement therapy effects were again observed for the 2 neuropsychological composites and for Cognitive Style (P=.001), Social Cognition (P=.001), and Social Adjustment (P=.01). As expected, no differences were observed on the residual Symptoms composite. Effects were unrelated to the type of antipsychotic medication received. Enriched supportive therapy also demonstrated statistically significant within-group effect sizes, suggesting that supportive psychotherapy can also have positive, although more modest, effects on cognitive deficits. CONCLUSION: Many cognitive deficits and related behaviors of patients with stable schizophrenia are improved when sufficient exposure to relevant rehabilitation is provided.     

Oxide terpenes as human skin penetration enhancers of haloperidol from ethanol and propylene glycol and their modes of action on stratum corneum

In this study, two terpenes with the same functional group; limonene oxide and pinene oxide were used at 5% w/v concentration in 50% v/v ethanol and 100% v/v propylene glycol (PG) to enhance the in vitro permeation of haloperidol (HP) through the human epidermis (or stratum corneum, SC). The enhancement mechanism of terpenes from both solvents was elucidated with HP-SC binding studies, Fourier transform infrared spectroscopy and differential scanning calorimetry. The enhancement activity of these terpenes was higher in 50% v/v ethanol than in 100% v/v PG. These terpenes in 50% v/v ethanol were predicted to provide the required therapeutic plasma concentration and daily-permeated amounts of the drug. Limonene oxide showed higher enhancement in both solvents, which was attributed to its less bulky structure. The terpenes in both solvents did not increase the partition of HP. Instrumental studies showed that these terpenes in 50% v/v ethanol extracted the SC lipids, disrupted the bilayer packing and partially fluidised the lipids. Limonene oxide in 100% v/v PG possibly disrupted the lipid bilayer, whilst leaving the overall bilayer structure intact and pinene oxide in the same vehicle fluidised the lipids within the ordered environment. This study showed that the mode of interactions of terpenes with SC were different in two solvent systems.     

Human skin permeation of 3-O-alkyl carbamate prodrugs of naltrexone

N-Monoalkyl and N,N-dialkyl carbamate prodrugs of naltrexone (NTX), an opioid antagonist, were synthesized and their in vitro permeation across human skin was determined. Relevant physicochemical properties were also determined. Most prodrugs exhibited lower melting points, lower aqueous solubilities, and higher oil solubilities than NTX. The flux values from N-monoalkyl carbamate prodrugs were significantly higher than those from NTX and N,N-dialkyl carbamates. The melting points of N-monoalkyl carbamate prodrugs were quite low compared to the N,N-dialkyl carbamate prodrugs and NTX. Heats of fusion for the N,N-dialkyl carbamate prodrugs were higher than that for NTX. N-Monoalkyl carbamate prodrugs had higher stratum corneum/vehicle partition coefficients than their N,N-dialkyl counterparts. Higher percent prodrug bioconversion to NTX in skin appeared to be related to increased skin flux. N,N-Dialkyl carbamate prodrugs were more stable in buffer and in plasma than N-monoalkyl carbamate prodrugs. In conclusion, N-monoalkyl carbamate prodrugs of NTX improved the systemic delivery of NTX across human skin in vitro. N,N-Dialkyl substitution in the prodrug moiety decreased skin permeation and plasma hydrolysis to the parent drug. The cross-sectional area of the carbamate head group was the major determinant of flux of the N-monoalkyl and N,N-dialkyl carbamate prodrugs of NTX.     

Consensus Development and Application of ICD-9-CM Codes for Defining Chronic Illnesses and their Complications

Background

One particularly difficult challenge in evaluating disease management (DM) programs is defining the scope of economic outcomes to include in the evaluation. Measuring ‘all-cause utilization’ or ‘total costs‘ assumes that a DM intervention impacts the entire spectrum of services rendered and reduces total medical costs, while limiting the evaluation to ‘disease-specific’ costs of the conditions under management may fail to capture any effect the program may have on complications directly related to that primary condition. An acceptable compromise between the two options is to include costs associated with diagnostic codes for the primary condition and those of medical complications directly related to that condition.

Objective

To develop consensus on the International Classification of Diseases, ninth revision, Clinical Modification (ICD-9-CM) codes defining the primary conditions and complications of coronary artery disease (CAD), congestive heart failure (CHF), asthma, and chronic obstructive pulmonary disease.

Methods

A modified Delphi technique, involving two panels of three physicians each (one consisting of cardiologists and the other of pulmonologists) and a physician consultant, was conducted via email and used to establish 100% consensus on the ICD-9-CM codes to be included in order to capture the appropriate costs for each of the primary conditions considered and their complications. The codes for primary conditions included by the panel were compared with those included in industry references.

Results

Total consensus on the codes to be included for each of the primary conditions was reached within three rounds. Near-consensus on the codes to be used for complications for conditions was reached after the first round; however, four additional rounds were required for total consensus. Regarding the primary conditions, greatest agreement between the codes included by the panel and the various industry references was seen for asthma, with poor agreement observed between sources of codes for CAD and CHF.

Conclusion

It is suggested that these lists of ICD-9-CM codes developed by consensus be used in evaluations across the industry to define the utilization and/or costs associated with DM interventions. The consistent use of these codes will greatly strengthen the validity of the current evaluation approach and consequently substantiate the value proposition offered by the industry.