Effectiveness of Japanese encephalitis vaccination among children in central India.

Japanese encephalitis (JE) disease among children continues in central India despite vaccination implemented in the routine immunization program. Therefore, we planned to estimate the JE vaccination effectiveness among children by undertaking a 1:2 individually-matched population-based case-control study from August 2018 to October 2020. The laboratory-confirmed JE cases aged 1-15 years were enrolled along with neighborhood controls without fever and encephalitis matched on the residence area, age and sex. The JE vaccination history was enquired from parents and verified independently from the vaccination cards available at home and records at health facilities. We enrolled 35 JE cases and 70 matched controls. The vaccination effectiveness of 86.7% (95% confidence interval [CI]: 30.8-94.7) was estimated on the per-protocol analysis of 31 case-control sets. The screening method provided an effectiveness of 89.5% (CI: 78.9-94.7) on using the population vaccination coverage of 90% reported earlier in the same area. In conclusion, JE vaccination offered a moderate level of protection among children in JE medium-endemic central India, similar to reports from high-endemic areas in India. The operational aspects of vaccination program implementation need to be evaluated to assess the impact of vaccination on the disease burden of JE in medium-endemic regions of India.

Metal transportation mechanism by rainfall runoff as a contribution to the bioaccumulation in seafood.

Trace metal transport mechanism via rainfall runoff from soil to the water body in the context of the bioaccumulation in seafood was unprecedentedly investigated. Instead of a conventional simulation experiment at a laboratory, the twelve soil sampling sites were selected in the region (Windar Valley, Balochistan-Pakistan) reported with high trace metal content, and Threadfin Sea Catfish and Belanger's Croaker were caught from the adjacent coastal water body. The Pb, Cd, Ni, and Zn in soil samples were high in proportion; the average concentrations were 2793.8, 622.44, 331.33, and 440 in mg kg-1, respectively, as per expectations. Using ArcGIS, the soil sample results were extensively illustrated by the spatial distribution in the sampling regions. The Zn > Pb > Ni > Cd was found in pre- and post-rainfall fish flesh samples. Trace metals were higher in post-rain fish flesh samples than pre-rainfall samples, indicating that rainwater runoff could be the significant source for trace metal transport except for Zn. The Pb, Cd, Ni, and Zn elevated results were 0.80828 ± 0.17752, 0.12102 ± 0.03027, 0.71064 ± 0.24188, and 6.49223 ± 3.65094 in mg kg-1, respectively, in post-rainfall fish flesh samples. Appling chemometric tools revealed that Zn content depends on Zn-protein interaction, and Pb, Cd, and Ni contents significantly pertain to the rainwater runoff. Other probable transport routes for trace metals to the water body could be less responsible. The soil sampling region's NOAA HYSPLIT backward air trajectory showed that the air direction was mostly from ocean to land.

Coverage of Japanese encephalitis routine vaccination among children in Central India.

BACKGROUND: We aimed to estimate the coverage of Japanese encephalitis (JE) vaccination in central India to help explain the continued occurrence of JE disease despite routine vaccination. METHODS: We implemented a 30-cluster survey for estimating the coverage of JE vaccination in the medium-endemic areas implemented with JE vaccination in central India. The parents were enquired about the uptake of the JE vaccine by their children aged 2 to 6 years, followed by verification of the immunization cards at home along with reasons for non-vaccination. Vaccination coverage was reported as a percentage with 95% confidence intervals. RESULTS: We estimated high coverage of live-attenuated SA 14-14-2 JE vaccination in Maharashtra (94.8%, 95% CI 92.7-96.3) and Telangana (92.8%, 90.0-94.9). The vaccination card retention was 90.3% in Maharashtra and 70.4% in Telangana state. There were no gender differences in coverage in both states. A similar level of JE vaccination coverage was observed during the year 2013 to 2021 in both states. In Maharashtra, the maximum age-wise coverage was 96.6% in the >60 months age category, whereas in Telangana it was in the <24 months age category (97.2%). The timeliness of JE vaccination was appropriate and similar in both states. We found very good agreement between JE and Measles-Rubella vaccinations administered simultaneously. The reasons for non-vaccination were the shortage of vaccines and the parental migration for work. CONCLUSIONS: The coverage of Japanese encephalitis vaccination was high in medium-endemic regions in central India. Vaccination effectiveness studies may help further explain the continued incidence of Japanese encephalitis. This article is protected by copyright. All rights reserved.

Modelling the lifetime cost-effectiveness of radical prostatectomy, radiotherapy and active monitoring for men with clinically localised prostate cancer from median 10-year outcomes in the ProtecT randomised trial.

BACKGROUND: Optimal management strategies for clinically localised prostate cancer are debated. Using median 10-year data from the largest randomised controlled trial to date (ProtecT), the lifetime cost-effectiveness of three major treatments (radical radiotherapy, radical prostatectomy and active monitoring) was explored according to age and risk subgroups. METHODS: A decision-analytic (Markov) model was developed and informed by clinical input. The economic evaluation adopted a UK NHS perspective and the outcome was cost per Quality-Adjusted Life Year (QALY) gained (reported in UK£), estimated using EQ-5D-3L. RESULTS: Costs and QALYs extrapolated over the lifetime were mostly similar between the three randomised strategies and their subgroups, but with some important differences. Across all analyses, active monitoring was associated with higher costs, probably associated with higher rates of metastatic disease and changes to radical treatments. When comparing the value of the strategies (QALY gains and costs) in monetary terms, for both low-risk prostate cancer subgroups, radiotherapy generated the greatest net monetary benefit (£293,446 [95% CI £282,811 to £299,451] by D'Amico and £292,736 [95% CI £284,074 to £297,719] by Grade group 1). However, the sensitivity analysis highlighted uncertainty in the finding when stratified by Grade group, as radiotherapy had 53% probability of cost-effectiveness and prostatectomy had 43%. In intermediate/high risk groups, using D'Amico and Grade group > = 2, prostatectomy generated the greatest net monetary benefit (£275,977 [95% CI £258,630 to £285,474] by D'Amico and £271,933 [95% CI £237,864 to £287,784] by Grade group). This finding was supported by the sensitivity analysis. Prostatectomy had the greatest net benefit (£290,487 [95% CI £280,781 to £296,281]) for men younger than 65 and radical radiotherapy (£201,311 [95% CI £195,161 to £205,049]) for men older than 65, but sensitivity analysis showed considerable uncertainty in both findings. CONCLUSION: Over the lifetime, extrapolating from the ProtecT trial, radical radiotherapy and prostatectomy appeared to be cost-effective for low risk prostate cancer, and radical prostatectomy for intermediate/high risk prostate cancer, but there was uncertainty in some estimates. Longer ProtecT trial follow-up is required to reduce uncertainty in the model. TRIAL REGISTRATION: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

Direct access CT for suspicion of brain tumour: an analysis of referral pathways in a population-based patient group.

BACKGROUND: Brain tumour patients see their primary care doctor on average three or more times before diagnosis, so there may be an opportunity to identify 'at risk' patients earlier. Suspecting a brain tumour diagnosis is difficult because brain tumour-related symptoms are typically non-specific. METHODS: We explored the predictive value of referral guidelines (Kernick and NICE 2005) for brain imaging where a tumour is suspected, in a population-based patient group referred for direct access CT of the head. A consensus panel reviewed whether non-tumour findings were clinically important or whether further investigation was necessary. RESULTS: Over a 5-year period, 3257 head scans were performed; 318 scans were excluded according to pre-specified criteria. 53 patients (1.8%) were reported to have intracranial tumours, of which 42 were significant (diagnostic yield of 1.43%). There were no false negative CT scans for tumour. With symptom-based referral guidelines primary care doctors can identify patients with a 3% positive predictive value (PPV). 559 patients had non-tumour findings, 31% of which were deemed clinically significant. In 34% of these 559 patients, referral for further imaging and/or specialist assessment from primary care was still thought warranted. CONCLUSION: Existing referral guidelines are insufficient to stratify patients adequately based on their symptoms, according to the likelihood that a tumour will be found on brain imaging. Identification of non-tumour findings may be significant for patients and earlier specialist input into interpretation of these images may be beneficial. Improving guidelines to better identify patients at risk of a brain tumour should be a priority, to improve speed of diagnosis, and reduce unnecessary imaging and costs. Future guidelines may incorporate groups of symptoms, clinical signs and tests to improve the predictive value.

Neuropsychiatric symptoms, seizure severity, employment, and quality of life of Jordanians with epilepsy.

RATIONALE: Depression and anxiety are more strongly associated with quality of life (QOL) than seizure frequency in several populations with epilepsy. However, QOL is culturally determined and may be influenced by cultural values and norms as well as local policies and resources. The goal of this study is to investigate the impact of neuropsychiatric symptoms and seizure severity on QOL and employment in people with epilepsy living in Jordan. METHODS: Seizure severity and complications, antiepileptic drug side effects, social stigma, neuropsychiatric symptoms, and mental health (MH-SF36) and physical health (PH-SF36) domains of QOL were assessed in 45 adult patients with epilepsy in a university neurology clinic. Multivariate regression analysis was used to evaluate the relationship between these variables and the quality of life of Jordanians with epilepsy. RESULTS: Neuropsychiatric symptoms, seizure frequency, and history of injury due to seizure were associated with the MH-SF36. However, earlier age of seizure onset, longer duration of epilepsy, unemployment, and history of chronic disease was associated with lower PH-SF36 scores. Furthermore, there were no differences in QOL, neuropsychiatric symptoms, and seizure frequency in Jordanians who were employed versus unemployed in this study. CONCLUSIONS: Neuropsychiatric symptoms were significantly associated with mental health-related QOL measures, but not with physically-related QOL measures, in Jordanians with epilepsy. For studies across populations, it is critical to separate mental health from physical health QOL measures. Furthermore, regional differences in culture and policy may more strongly influence employment status than individuals' experiences of epilepsy, neuropsychiatric symptoms, or QOL in some populations.

Incidence of Japanese Encephalitis and Acute Encephalitis Syndrome Hospitalizations in the Medium-Endemic Region in Central India.

BACKGROUND: We estimated the incidence of Japanese encephalitis (JE) and acute encephalitis syndrome (AES) following routine immunization with the live-attenuated SA 14-14-2 JE vaccine. METHODS: We implemented enhanced surveillance of AES and JE hospitalizations in endemic districts in Maharashtra and Telangana States during 2015-2016 and 2018-2020. We estimated incidence and compared differences in the incidence of JE and AES between two states, and vaccinated and unvaccinated districts during two study periods. We also considered secondary data from public health services to understand long-term trends from 2007 to 2020. RESULTS: The annual AES incidence rate of 2.25 cases per 100,000 children in Maharashtra during 2018-2020 was significantly lower than 3.36 cases per 100,000 children during 2015-2016. The six JE-vaccinated districts in Maharashtra had significantly lower incidence rates during 2018-2020 (2.03, 95% CI 1.73-2.37) than in 2015-16 (3.26, 2.86-3.70). In addition, the incidence of both JE and AES in two unvaccinated districts was higher than in the vaccinated districts in Maharashtra. Telangana had a lower incidence of both JE and AES than Maharashtra. The AES incidence rate of 0.95 (0.77-1.17) during 2018-2020 in Telangana was significantly lower than 1.67 (1.41-1.97) during 2015-2016. CONCLUSIONS: The annual incidence rate of Japanese encephalitis was < 1 case per 100,000 children. It indicated accelerated control of Japanese encephalitis after routine immunization. However, the annual incidence of acute encephalitis syndrome was still > 1 case per 100,000 children. It highlights the need for improving surveillance and evaluating the impacts of vaccination.

Infectious causes of acute encephalitis syndrome hospitalizations in Central India, 2018-20.

BACKGROUND: We enhanced surveillance of hospitalizations of all ages for acute encephalitis syndrome (AES) along with infectious aetiologies, including the Japanese encephalitis virus (JEV). METHODS: From October 2018 to September 2020, we screened neurological patients for AES in all age groups in Maharashtra and Telangana States. AES cases were enrolled at study hospitals along with other referrals and sampled with cerebrospinal fluid, acute and convalescent sera. We tested specimens for non-viral aetiologies viz. leptospirosis, typhoid, scrub typhus, malaria and acute bacterial meningitis, along with viruses - JEV, Dengue virus (DENV), Chikungunya virus (CHIKV), Chandipura virus (CHPV) and Herpes simplex virus (HSV). RESULTS: Among 4977 neurological hospitalizations at three study site hospitals over two years period, 857 (17.2%) were AES. However, only 287 (33.5%) AES cases were eligible. Among 278 (96.9%) enrolled AES cases, infectious aetiologies were identified in 115 (41.4%) cases, including non-viral in 17 (6.1%) cases - leptospirosis (8), scrub-typhus (3) and typhoid (6); and viral in 98 (35.3%) cases - JEV (58, 20.9%), HSV (22, 7.9%), DENV (15, 5.4%) and CHPV (3, 1.1%). JEV confirmation was significantly higher in enrolled cases than referred cases (10.2%) (p < 0.05). However, the contribution of JEV in AES cases was similar in both children and adults. JE was reported year-round and from adjacent non-endemic districts. CONCLUSIONS: The Japanese encephalitis virus continues to be the leading cause of acute encephalitis syndrome in central India despite vaccination among children. Surveillance needs to be strengthened along with advanced diagnostic testing for assessing the impact of vaccination.

A novel application for single-incision laparoscopic surgery (SILS): SIL jejunostomy feeding tube placement.

BACKGROUND: Single-incision laparoscopic surgery (SILS) is rapidly gaining popularity as the practical alternative to natural orifice transluminal endoscopic surgery (NOTES). Although SILS achieves essentially the same goal as NOTES (a nearly invisible scar in the umbilicus), it does not carry the significant potential risks of a transluminal approach. The SILS approach has been most commonly described for cholecystectomy and appendectomy. The authors describe a novel application for this approach in the placement of a feeding jejunostomy tube. The described application for this technique is the first to be reported. METHODS: The authors describe use of the technique for two intensive care unit (ICU) patients requiring long-term postpyloric tube feeds. Access was obtained through the umbilicus with the SILS port. The selected loop of the jejunum was exteriorized through this incision, and the feeding tube was placed. The loop was returned into the abdomen, and the SILS port was replaced in the incision. Under laparoscopic visualization and guidance, the feeding tube was brought externally through a predetermined site in the left midabdomen. RESULTS: Two patients underwent SILS jejunostomy tube placement. The average operating time was 42.5 min. No intraoperative or immediate postoperative complications occurred. Tube feedings were started on postoperative day 1 for both patients, with good bowel function. CONCLUSION: The SILS technique for jejunostomy placement is a promising and feasible alternative to the current methods. It is less invasive than the open approach while providing complete intraabdominal visualization. It is less technically demanding than the direct percutaneous endoscopic jejunostomy (PEJ) approach and avoids the risks and difficulties associated with it. The same benefits of other SILS procedures are evident in this application. The authors believe a series study will further highlight long-term benefits and any potential complications.

Meckel's diverticulum with small bowel obstruction presenting as appendicitis in a pediatric patient.

BACKGROUND: Meckel's diverticulum is a congenital anomaly resulting from incomplete obliteration of the omphalomesenteric duct. The incidence ranges from 0.3% to 2.5% with most patients being asymptomatic. In some cases, complications involving a Meckel's diverticulum may mimic other disease processes and obscure the clinical picture. METHODS: This case presents an 8-year-old male with abdominal pain, nausea, and vomiting and an examination resembling appendicitis. RESULTS: A CT scan revealed findings consistent with appendicitis with dilated loops of small bowel. During laparoscopic appendectomy, the appendix appeared unimpressive, and an inflamed Meckel's diverticulum was found with an adhesive band creating an internal hernia with small bowel obstruction. The diverticulum was resected after the appendix was removed. CONCLUSION: The incidence of an internal hernia with a Meckel's diverticulum is rare. A diseased Meckel's diverticulum can be overlooked in many cases, especially in those resembling appendicitis. It is recommended that the small bowel be assessed in all appendectomy cases for a pathological Meckel's diverticulum.

The Enhanced Recovery After Surgery (ERAS) Elements that Most Greatly Impact Length of Stay and Readmission.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been shown to decrease length of stay (LOS) and improve patient outcomes in a wide variety of surgical fields; however, barriers exist preventing the implementation of all elements. We hypothesize that a subset of ERAS elements are most influential on LOS and readmission following colorectal surgery. STUDY DESIGN: A retrospective review of 840 patients was performed and their compliance with 24 ERAS components evaluated. Two independent machine-learning statistical algorithms were employed to determine which subset of ERAS elements was most impactful on LOS <3 days and hospital readmission. RESULTS: Increasing compliance with ERAS elements had an inverse linear relationship with LOS. Open (vs minimally invasive) surgery was associated with increased LOS. Early mobilization and multimodal pain management are the elements most protective against increased LOS. Readmissions increase with the number of morphine milligram equivalents (MME)/day. The subset of patients who underwent minimally invasive procedures, had multimodal pain control, and less than 16 MME per day were least likely (23%) to have >3-day LOS. Those patients who underwent an open procedure with less than 15 ERAS elements completed were most likely (84%) to have >3-day LOS. CONCLUSION: While increasing compliance with ERAS protocols and minimally invasive procedures decrease LOS and readmission overall, a subset of components-multimodal pain control, limited opioid use, and early mobilization-was most associated with decreased LOS and readmission. This study provides guidance on which ERAS elements should be emphasized.

Childhood encephalitis hospitalizations associated with virus agents in medium-endemic states in India.

BACKGROUND: Japanese encephalitis (JE) is the leading cause of childhood acute encephalitis syndrome (AES) in India. We enhanced the AES surveillance in sentinel hospitals to determine trends and virus etiologies in central India. METHODS: The neurological hospitalizations among children ≤15 years were tracked by using the AES case definition implemented by the national program. Acute and convalescent sera along with cerebrospinal fluid (CSF) specimens were collected and tested at the strengthened site hospital laboratories for anti-JE, anti-Dengue and anti-Chikungunya virus by IgM ELISA; along with Chandipura virus RT-PCR. Herpes simplex and enterovirus testing was undertaken at the reference laboratory. RESULTS: Among 1619 pediatric neurological hospitalizations reported during 2015-16, AES case definition was fulfilled in 332 (20.5%) cases. After excluding 52 non-AES cases, 280 AES cases resident from study districts were considered eligible for study. The treating physicians diagnosed non-viral causes in 90 cases, therefore 190 (67.9%) of 280 AES cases were suspected with viral etiologies. We enrolled 140 (73.7%) of 190 eligible AES cases. Viral etiologies were confirmed in 31 (22.1%) of 140 enrolled AES cases. JE (n = 22) was the leading cause. Additional non-JE viral agents included Chikungunya (5), Dengue (2) and Chandipura (2). However, only 21 (9.4%) of 222 additional AES cases referred from peripheral hospitals were confirmed as JE. CONCLUSIONS: Japanese encephalitis virus continues to be the leading cause of childhood acute encephalitis syndrome in central India despite vaccination program. Surveillance needs to be intensified for assessing the true disease burden of Japanese encephalitis following vaccination program implementation.

An unusual case of Churg-Strauss syndrome and a shrinking renal mass.

Churg-Strauss syndrome is a multisystem disorder characterized by allergic rhinitis, asthma and eosinophilia [Churg and Strauss 1951, Noth et al. 2003]. We report a case of Churg-Strauss syndrome associated with a complex renal mass, which resolved with immunosuppressive therapy.

Honey modulates oxidative burst of professional phagocytes.

The effects of natural honey and its major sugar constituents (i.e. D-fructose, D-glucose, maltose and sucrose) on phagocytic respiratory burst have been studied. Pre-incubated whole blood and isolated leukocytes with honey samples and sugars were induced for phagocytosis and the level of reactive oxygen species (ROS) was monitored by using chemiluminescence assays. Honey samples were found to decrease the luminol-enhanced chemiluminescence in opsonized zymosan-stimulated whole blood and isolated leukocytes with statistically significant differences; indicating inhibition of ROS production including hydrogen peroxide, hydroxyl free radical and hypochlorous acid. Thus honey appears to modify the oxidative burst process by inhibiting phagocytic myeloperoxidase activity. Chemiluminescence assays further showed that among the major sugar constituents of honey, D-fructose in high concentration exerted an inhibitory effect on exocytosis-associated myeloperoxidase catalyzed ROS formation. These results pointed out an immuno-modulatory potential of honey in the course of phagocytosis.

Opportunistic infections and HIV clinical disease stage among patients presenting for care in Phnom Penh, Cambodia.

This prospective, cross-sectional study sought to assess the spectrum of HIV-associated complications and disease stage among individuals presenting for first-time care in Phnom Penh, Cambodia between November 2001 and September 2002. One hundred patients participated in this study. All study participants presented with advanced stages of HIV disease. Seventy-four percent of the subjects had CD4 cell counts <50 cells/mm3. Tuberculosis was the most common AIDS-defining illness among participants, with a prevalence of 43%. A spectrum of other opportunistic infections, including cryptosporidiosis (13%), severe bacterial infections (12%), cryptococcosis (12%), and Pneumocystis jiroveci pneumonia (10%), was identified. These findings underscore the need for widespread HIV treatment and prevention in this setting. Increased screening for HIV and routine health maintenance for those infected are urgently needed in order to facilitate management of both opportunistic infections and the secondary prevention of HIV infection.

Comparison of adenosine and exercise thallium-201 single-photon emission computed tomography (SPECT) myocardial perfusion imaging. The GE SPECT Multicenter Adenosine Study Group.

Pharmacologic stress with dipyridamole has provided useful diagnostic, as well as prognostic, information in patients undergoing thallium-201 myocardial perfusion imaging. With its ultrashort half-life and a potent and consistent vasodilator effect, adenosine may be the coronary vasodilator of choice with myocardial perfusion imaging. Fifty-one healthy subjects and 93 patients with suspected coronary artery disease constituted the study group. In this multicenter study the comparative safety and diagnostic efficacy of single-photon emission computed tomography (SPECT) thallium imaging during adenosine-induced coronary hyperemia was compared with exercise treadmill stress. There was a mean increase in heart rate of 37% and a mean decrease in diastolic blood pressure of 5% during the adenosine infusion of 140 micrograms/kg per min for 6 min. Adenosine infusion was well tolerated in 95% of the subjects. Side effects requiring intervention occurred in seven subjects (5%). None of the subjects experienced a life-threatening complication. The sensitivity, specificity and predictive accuracy for detection of coronary artery disease with use of quantitative analysis was 83%, 87% and 84% for adenosine SPECT and 82%, 80% and 81% for exercise SPECT studies, respectively. Most false negative results with adenosine, as well as exercise SPECT studies, occurred in patients with single-vessel disease. The first-order concordance (no defect vs. defect) and second-order concordance (no defect vs. irreversible vs. reversible defect) was 89% and 78% between the two studies, respectively. Thus, the results of adenosine SPECT imaging are highly concordant with exercise SPECT thallium imaging. Adenosine SPECT thallium imaging provides a safe and highly accurate imaging mode for the detection of coronary artery disease.

Stress testing with closed-loop arbutamine as an alternative to exercise. The International Arbutamine Study Group.

OBJECTIVES: This study compared exercise and pharmacologic stress testing using arbutamine delivered by a closed-loop device for the detection of coronary artery disease. BACKGROUND: Arbutamine, an agent designed to simulate exercise, has been developed in conjunction with a closed-loop delivery device that modulates the rate of administration on the basis of physiologic feedback. METHODS: Two hundred ten patients (180 men, 30 women) with symptoms and angiographic evidence of coronary artery disease were studied. Ischemia was categorized in three ways: 1) the presence of angina; 2) the occurrence of > or = 0.1-mV horizontal or downsloping ST segment depression or elevation at 60 ms after the J point; or 3) the presence of either condition 1 or 2. RESULTS: In the 210 patients, the mean increase in heart rate and systolic blood pressure evoked by arbutamine and exercise was 51 and 53 beats/min (p = NS) and 36 and 44 mm Hg (p < 0.0001), respectively. Arbutamine detected ischemia more often than exercise with each of the three ischemic end points. Sensitivity for detecting ischemia by either angina or ST segment change was 84% (95% confidence interval ¿ change was 84% (95% confidence interval [CI] 79% to 89%) for arbutamine and 75% (95% CI 69% to 81%) for exercise testing (p = 0.014). For angina alone, sensitivity was 73% (95% CI 67% to 79%) for arbutamine and 64% (95% CI 57% to 71%) for exercise (p = 0.026). For ST segment change alone, sensitivity was 47% (95% CI 40% to 54%) for arbutamine and 44% (95% CI 37% to 51%) for exercise (p = 0.426). Cardiac events occurred in five patients (1.8%) within 24 h of the arbutamine test. CONCLUSIONS: In detecting documented coronary artery disease, the sensitivity of arbutamine testing was equal to that of exercise for the electrocardiographic end point of ST segment change alone. Arbutamine testing was significantly superior to exercise testing for either ST change or angina or for angina alone.

Multiple pulmonary neurofibromas with hypoxemia. Occurrence due to pulmonary arteriovenous shunts within the tumors.

A 62-year-old woman with multiple neurofibromas of the lung was found to have severe hypoxemia due to right-to-left shunting within the tumors. Pulmonary angiograms demonstrated that the major area of shunting was in a large tumor mass in the right lower lobe. Pathologically the neurofibromas were vascular with hyperplastic small arteries and arterioles and large dilated veins. Multiple pulmonary neurofibromas are rare; and, to our knowledge, never previously reported in association with pulmonary arteriovenous shunting.

Effect of buspirone on withdrawal symptoms associated with smoking cessation.

BACKGROUND: Preliminary information suggests that buspirone hydrochloride ameliorates symptoms of nicotine withdrawal. In a double-blind, randomized, placebo-controlled trial, we determined the effects of buspirone on the withdrawal symptoms associated with smoking cessation in 40 long-term cigarette smokers. METHODS: Subjects were randomized to 4 weeks of treatment with either buspirone (n = 20) or placebo (n = 20). Subjects were instructed to maintain their usual cigarette intake during the first 21 days of treatment and to cease smoking on day 22 of treatment. Withdrawal symptoms were subjectively rated before and during smoking cessation. RESULTS: Before smoking cessation, there were no significant differences in the intensity of any withdrawal symptom between the buspirone- and placebo-treated subjects, with the exception of a significantly higher rating for drowsiness in the buspirone group. During the smoking cessation period, the ratings for craving, anxiety, irritability, restlessness, and sadness were significantly lower in the buspirone group than the placebo group. There were no significant differences between the groups in their ratings for hunger, inability to concentrate, or drowsiness. Fifteen buspirone-treated subjects and nine placebo-treated subjects were able to abstain from cigarettes during the entire 7-day smoking cessation period. No subject dropped out of the study for perceived drug side effects. Eight buspirone-treated subjects and five placebo-treated subjects reported side effects, all of which were mild. CONCLUSIONS: Buspirone ameliorated most of the short-term withdrawal symptoms associated with smoking cessation. Further controlled studies will be needed to define the benefit in smoking cessation.

Tocainide kinetics in congestive heart failure.

Our subjects were 20 patients with life-threatening or symptomatic ventricular arrhythmias refractory to standard oral antiarrhythmic drugs but responsive to intravenous lidocaine. After evaluation of arrhythmias and treatment with intravenous lidocaine, oral tocainide dosage regimens were based on age, weight, and clinical status. During initial tocainide treatment, six plasma tocainide concentrations were recorded within a single dosing interval in 17 of 20 patients, by which standard kinetic parameters were calculated. Eventual trough steady-state tocainide plasma concentrations were predicted from the derived patient-specific kinetic parameters. Mean daily tocainide dose was 1800 mg (1200 to 2400). Mean daily tocainide doses (milligram per kilogram) did not differ significantly among responders and nonresponders or among patients with or without congestive heart failure. Mean peak and trough plasma concentrations 48 hr after initiation of therapy were 9.8 and 7.5 mcg/ml. Tocainide plasma concentrations did not correlate with responders and nonresponders or identify patients who were developing adverse reactions to tocainide. There were no significant differences in any of the calculated kinetic parameters as a function of response to tocainide or the presence of congestive heart failure, but there was a trend toward smaller volumes of distribution and higher average plasma concentrations at steady state in patients with congestive heart failure. There were no significant kinetic differences among patients with and without congestive heart failure, but a trend toward higher plasma concentrations in patients with congestive heart failure and the small number of patients suggests that further data collection is necessary before dosage recommendations can be made.