Cost-effectiveness of varicella vaccination of healthcare workers

OBJECTIVE: Although transmission of VZV is recognized as an important cause for morbidity in health care workers (HCWs), there is no general agreement on the recommended immunization policy. This study aimed to evaluate several of such prevention policies in economic terms. SETTINGS: Analysis of the cost per avoided future varicella cases among HCWs in Israel. METHODS: A cost-effectiveness analysis was performed by comparing the cost per avoided case of varicella among a theoretical cohort of 63,353 physician and nurses aged less than 45 years in Israel. Four policies were examined: (a) do nothing (status quo); (b) vaccination of susceptible workers using VZV serotesting; with (c) or without anamnestic history of chickenpox; and (d) presumptive mass vaccination of all eligible workers. A Markov-based model was developed using data from our recent seroepidemiological study in target population and from the literature. RESULTS: Screening and vaccination of susceptible workers using anamnestic selection is expected to reduce future cases, within 20 years since vaccination, from 58.3 to 33.0 with an incremental cost of 23,713 US dollars per avoided cases. Using only serological tests to detect susceptible workers would prevent additional 5.7 cases with an incremental cost of 206,692 US dollars per avoided case. Vaccinating all HCWs without serotesting, raises the costs markedly, with almost identical effectiveness, resulting in an incremental cost of 10.4 million US dollars per avoided case. Sensitivity analyses do not alter the ranking of the options. CONCLUSION: From the employer's perspective, routine varicella vaccination program for HCWs with or without selection of susceptible workers is extremely expensive compared to other high-cost practiced approaches. Substantial reduction in cost of vaccination may alter this conclusion.     

Adiponectin and future coronary heart disease events among men with type 2 diabetes

Adiponectin, predominantly synthesized in the adipose tissue, seems to have substantial anti-inflammatory properties and to be a major modulator of insulin resistance and dyslipidemia, mechanisms that are associated with an increased atherosclerotic risk in diabetic patients. However, it is unknown whether higher levels of adiponectin are associated with a reduced risk for coronary heart disease (CHD) among diabetic individuals. We investigated the association between plasma adiponectin levels and incidence of CHD among 745 men with confirmed type 2 diabetes in the Health Professionals Follow-up Study. Participants were aged 46-81 years and were free of diagnosed cardiovascular disease at the time of blood draw in 1993/1994. During an average of 5 years of follow-up (3,980 person-years), we identified 89 incident cases of CHD (19 myocardial infarction and 70 coronary artery bypass surgery), confirmed by medical records. Levels of adiponectin were inversely associated with BMI and directly associated with age, alcohol intake, and duration of diabetes (P < 0.05). After adjustment for age, BMI, smoking, alcohol consumption, duration of diabetes, and other lifestyle factors, adiponectin was associated with a decreased risk for CHD events. The multivariate relative risk for CHD for a doubling of adiponectin was 0.71 (95% CI 0.53-0.95). Further adjustment for HDL cholesterol attenuated this association (0.78 [0.57-1.06]). The inverse association between adiponectin and CHD was consistent across strata of aspirin use, family history of myocardial infarction, alcohol consumption, insulin use, duration of diabetes, and levels of HbA(1c), triglycerides, C-reactive protein, and HDL cholesterol. Our study suggests that increased adiponectin levels are associated with a moderately decreased CHD risk in diabetic men. This association seems to be mediated in part by effects of adiponectin on HDL cholesterol levels.     

Changes in astigmatism after congenital cataract surgery and foldable intraocular lens implantation

PURPOSE: To evaluate the changes in astigmatism after cataract extraction and implantation of a foldable intraocular lens (IOL) in children. Only eyes with astigmatism of 3.0 D or more were included in the study. METHODS: The charts of children who had undergone surgery for nontraumatic cataract using a foldable IOL were retrospectively reviewed. In 13 eyes with astigmatism of 3.0 D or more, the refraction was tested and recorded at 1 week, 3 months, and 5 months postoperatively. A paired t test was used to compare the variables. RESULTS: Mean astigmatism 1 week postoperatively was 4.7 +/- 1.9 D (range, 3.0-10.0 D). Thereafter, the astigmatic component of the refractive error underwent a spontaneous steady decline, reaching a mean value of 0.9 +/- 0.9 D (range, 0-2.25 D) 5 months after surgery. The difference between the mean values at 1 week and 5 months was statistically significant (P < .0001). CONCLUSION: Children who underwent congenital cataract surgery and IOL implantation showed a significant spontaneous reduction in astigmatism postoperatively.     

Time course and predictors of median nerve conduction after carpal tunnel release

PURPOSE: To identify predictors of outcome and of electrophysiologic recovery in patients with carpal tunnel syndrome (CTS) treated by endoscopic carpal tunnel release using a nerve conduction testing system (NC-Stat; NEUROMetrix, Inc, Waltham, MA). METHODS: Validity of the automated nerve conduction testing system was shown by comparing presurgical distal motor latencies (DMLs) against a reference obtained by referral to an electromyography laboratory. The DML was evaluated in 48 patients with CTS. Measurements were obtained within 1 hour of surgery and at 2 weeks, 6 weeks, 3 months, and 6 months after carpal tunnel release. Presurgical and postsurgical DMLs were then compared and correlated with variables and possible predictors of outcome including age, body mass index, gender, and presurgical DMLs. RESULTS: The automated nerve conduction testing system DMLs matched those of reference electromyography/nerve conduction study values with high correlation. Sensitivity of the automated nerve conduction testing system when compared with a standardized CTS case definition was 89%, with a specificity of 95%. A significant correlation was found between the DML before release and the DML 1 hour after release. Moreover, maximal postsurgical DML improvement was highly dependent on the presurgical DML, with no improvement shown for the <4-ms group, mild improvement for the 4-to-6-ms group, and maximal improvement in the >6-ms group. Among the clinical variables of age, gender, and body mass index only age was mildly predictive of postrelease DML changes at 6 months. No other correlations between clinical variables and postsurgical DMLs were significant. In addition the predictive value of age was lost when combined with the presurgical DML in a multivariate analysis. CONCLUSIONS: Postsurgical changes in the median nerve DML were highly dependent on the prerelease latency. The sensitivity and specificity of a nerve conduction monitoring system in detecting and aiding in the diagnosis of CTS is useful in the long-term management of patients with CTS and can aid in determining the level of improvement in median nerve function after endoscopic carpal tunnel release.     

Sil overexpression in lung cancer characterizes tumors with increased mitotic activity

Sil (SCL interrupting locus) was cloned from the most common chromosomal rearrangement in T-cell acute lymphoblastic leukemia. It is an immediate early gene whose expression is associated with cell proliferation. Sil protein levels are tightly regulated during the cell cycle, reaching peak levels in mitosis and disappearing on transition to G1. A recent study found Sil to be one of 17 genes whose overexpression in primary adenocarcinomas predicts metastatic spread. We hypothesized that Sil might have a role in carcinogenesis. To address this question, we utilized several approaches. Using a multitumor tissue array, we found that Sil protein expression was increased mostly in lung cancer, but also at lower levels, in a subset of other tumors. Microarray gene expression analysis and immunohistochemistry of lung cancer samples verified these observations. Sil gene expression in lung cancer correlated with the expression of several kinetochore check-point genes and with the histopathologic mitotic index. These observations suggest that overexpression of the Sil gene characterizes tumors with increased mitotic activity.     

Mitochondrial pro-apoptotic ARTS protein is lost in the majority of acute lymphoblastic leukemia patients

Acquired resistance towards apoptosis is the hallmark of most if not all types of cancer. We have previously identified and characterized ARTS, a broadly expressed protein localized to mitochondria. ARTS was initially shown to mediate TGF-beta induced apoptosis. Recently, we have found that high levels of ARTS induce apoptosis without additional pro-apoptotic stimuli. Further, ARTS promotes apoptosis in response to a wide variety of pro-apoptotic stimuli. Here, we report that the expression of ARTS is lost in all lymphoblasts of more than 70% of childhood acute lymphoblastic leukemia (ALL) patients. The loss of ARTS is specific, as the related non-apoptotic protein H5, bearing 83% identity to ARTS, is unaffected. During remission, ARTS expression is detected again in almost all patients. Two leukemic cell lines, ALL-1 and HL-60 lacking ARTS, were resistant to apoptotic induction by ara-C. Transfection of ARTS into these cells restored their ability to undergo apoptosis in response to this chemotherapeutic agent. We found that methylation process contributes to the loss of ARTS expression. We conclude that the loss of ARTS may provide a selective advantage for cells to escape apoptosis thereby contributing to their transformation to malignant lymphoblasts. We therefore propose that ARTS can function as a tumor suppressor protein in childhood ALL.     

Adverse events due to discontinuations in drug use and dose changes in patients transferred between acute and long-term care facilities

BACKGROUND: Care transitions are commonplace for ill older adults, but no studies to our knowledge have examined the occurrence of iatrogenic harm from medication changes during patient transfer. OBJECTIVES: To identify medication changes during transfer between hospital and nursing home and adverse drug events (ADEs) caused by these changes. METHODS: Participants were residents of 4 nursing homes in the New York City metropolitan area admitted to 2 academic hospitals. Nursing home and hospital medical records were reviewed to identify changes in medication regimens between sites. Medications were matched and compared regarding dosage, route, and frequency of administration. Two physician investigators used structured implicit review to identify ADEs attributable to transfer-related medication changes. RESULTS: During a total of 122 admissions, the mean numbers of medications altered during transfer from nursing home to hospital and hospital to nursing home were 3.1 and 1.4, respectively (P<.001 for comparison). Most changes in drug use were discontinuations, followed by dose changes and class substitutions. Of 71 bidirectional transfers that were reviewed by 2 physician investigators, ADEs attributable to medication changes occurred during 14 (20%). The overall risk of ADE per drug alteration (n = 320) was 4.4% (95% confidence interval, 2.5%-7.4%). Although most medication changes (8/14) implicated in causing ADEs occurred in the hospital, most ADEs (12/14) occurred in the nursing home after nursing home readmission. CONCLUSIONS: Medication changes are common during transfer between hospital and nursing home and are a cause of ADEs. Research is needed on interinstitutional patient care and systems interventions designed to prevent ADEs.