Long-Term Impact of a Low-Cost Paediatric Intussusception Air Enema Reduction Simulation-Based Education Programme in a Low-Middle Income Country.

INTRODUCTION: Intussusception is one of the commonest causes of bowel obstruction in infants. Most infants in Low- and Middle-Income Countries (LMICs) undergo an invasive operative intervention. Supported by simulation-based education (SBE), the Air Enema (AE) non-operative technique was introduced in 2016 in Myanmar. This study assesses the long-term outcomes. METHODS: Mixed methods study design over 4 years including clinical outcomes and surgeon's attitudes towards the AE technique and SBE. Prospectively collected clinical outcomes and semi-structured interview with reflexive thematic analysis (RTA). Primary outcome measure was a long-term shift to non-operative intervention. SECONDARY OUTCOMES: Length of Stay (LoS), recurrence rates, intestinal resection rates, compared to the operative group. The data was analysed according to intention to treat. Quantitative data analysis with Mann-Whitney U test, Fisher's exact test, Student's T-Test or Wilcoxon Signed-Rank Test utilised. A p-value of <.05 was considered significant. RESULTS: A total of 311 infants with intussusception were included. A sustained shift to AE was revealed with high success rates (86.1-91.2%). AE had a reduced LoS (4 vs. 7 days p ≤ 0.0001), Duration of Symptoms (DoS) was lower with AE (1.9/7 vs. 2.5/7, p = 0.002). Low recurrence rates (0-5.8%) and intestinal resection rates stabilised at 30.5-31.8% vs.15.3% pre-intervention. Four RTA themes were identified: Expanding conceptions of healthcare professional education and training; realising far reaching advantages; promoting critical analysis and reflective practice of clinicians; and adapting clinical practice to local context. RTA revealed an overall positive paradigm shift in attitudes and application of SBE. CONCLUSIONS: A sustained change in clinical outcomes and appreciation of the value of SBE was demonstrated following the intervention.

The Effects of Different Aspirin Dosing Frequencies and the Timing of Aspirin Intake in Primary and Secondary Prevention of Cardiovascular Disease: A Systematic Review.

Enhancing the effectiveness of aspirin by tailoring administration regimens is an important question among health professionals. We conducted a systematic review to evaluate the evidence on the effects of different aspirin regimens in terms of timing (chronotherapy) or frequency of dosing in the prevention of cardiovascular disease. Only two out of the 28 included studies reported long-term cardiovascular outcomes, highlighting an evidence gap that future research should address. The remaining 26 studies used surrogate outcomes.

Mindfulness training for smokers via web-based video instruction with phone support: a prospective observational study.

BACKGROUND: Many smokers are unable to access effective behavioral smoking cessation therapies due to location, financial limitations, schedule, transportation issues or other reasons. We report results from a prospective observational study in which a promising novel behavioral intervention, Mindfulness Training for Smokers was provided via web-based video instruction with telephone-based counseling support. METHODS: Data were collected on 26 low socioeconomic status smokers. Participants were asked to watch eight video-based classes describing mindfulness skills and how to use these skills to overcome various core challenges in tobacco dependence. Participants received eight weekly phone calls from a smoking cessation coach who provided general support and answered questions about the videos. On the quit day, participants received two weeks of nicotine patches. RESULTS: Participants were a mean of 40.5 years of age, smoked 16.31 cigarettes per day for 21.88 years, with a mean of 6.81 prior failed quit attempts. Participants completed a mean of 5.55 of 8 online video classes with a mean of 23.33 minutes per login, completed a mean of 3.19 of 8 phone coach calls, and reported a mean meditation practice time of 12.17 minutes per day. Smoking abstinence was defined as self-reported abstinence on a smoking calendar with biochemical confirmation via carbon monoxide breath-test under 7 parts per million. Intent-to-treat analysis demonstrated 7-day point prevalence smoking abstinence at 4 and 6-months post-quit of 23.1% and 15.4% respectively. Participants showed a significant pre- to post-intervention increase in mindfulness as measured by the Five-Factor Mindfulness Questionnaire, and a significant pre- to post-intervention decrease in the Anxiety Sub-scale of the Depression Anxiety and Stress Scale. CONCLUSIONS: Results suggest that Mindfulness Training for Smokers can be provided via web-based video instruction with phone support and yield reasonable participant engagement on intervention practices and that intervention efficacy and mechanism of effect deserve further study. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02164656 , Registration Date June 13, 2014.

Randomized trial comparing mindfulness training for smokers to a matched control.

Smoking continues to take an enormous toll on society, and although most smokers would like to quit, most are unsuccessful using existing therapies. These findings call on researchers to develop and test therapies that provide higher rates of long-term smoking abstinence. We report results of a randomized controlled trial comparing a novel smoking cessation treatment using mindfulness training to a matched control based on the American Lung Association's Freedom From Smoking program. Data were collected on 175 low socioeconomic status smokers in 2011-2012 in a medium sized midwestern city. A significant difference was not found in the primary outcome; intent-to-treat biochemically confirmed 6-month smoking abstinence rates were mindfulness=25.0%, control=17.9% (p=0.35). Differences favoring the mindfulness condition were found on measures of urges and changes in mindfulness, perceived stress, and experiential avoidance. While no significant differences were found in quit rates, the mindfulness intervention resulted in positive outcomes.

Hair cortisol as a biomarker of stress in mindfulness training for smokers.

OBJECTIVES: Stress is a well-known predictor of smoking relapse, and cortisol is a primary biomarker of stress. The current pilot study examined changes in levels of cortisol in hair within the context of two time-intensity matched behavioral smoking cessation treatments: mindfulness training for smokers and a cognitive-behavioral comparison group. PARTICIPANTS: Eighteen participants were recruited from a larger randomized controlled trial of smoking cessation. OUTCOME MEASURES: Hair samples (3 cm) were obtained 1 month after quit attempt, allowing for a retrospective analysis of hair cortisol at preintervention and post-quit attempt time periods. Self-reported negative affect was also assessed before and after treatment. INTERVENTION: Both groups received a 7-week intensive intervention using mindfulness or cognitive-behavioral strategies. RESULTS: Cortisol significantly decreased from baseline to 1 month after quit attempt in the entire sample (d=-0.35; p=.005). In subsequent repeated-measures analysis of variance models, time by group and time by quit status interaction effects were not significant. However, post hoc paired t tests yielded significant pre-post effects among those randomly assigned to the mindfulness condition (d=-0.48; p=.018) and in those abstinent at post-test (d=-0.41; p=.004). Decreased hair cortisol correlated with reduced negative affect (r=.60; p=.011). CONCLUSIONS: These preliminary findings suggest that smoking cessation intervention is associated with decreased hair cortisol levels and that reduced hair cortisol may be specifically associated with mindfulness training and smoking abstinence. RESULTS support the use of hair cortisol as a novel objective biomarker in future research.

Randomized trial on mindfulness training for smokers targeted to a disadvantaged population.

We report the results of a randomized trial comparing a novel smoking cessation treatment Mindfulness Training for Smokers (MTS) to a usual care therapy (Controls), which included the availability of a tobacco quit line and nicotine patches. Data were collected from 196 low socioeconomic status smokers in 2010-2011 in Madison, Wisconsin. Participants were randomized to either MTS or a telephonic quit line. The primary outcome was 6-month smoking abstinence measured by carbon monoxide breath testing and Time-Line Follow-Back. Among treatment initiators (randomized participants who participated in the intervention), abstinence rates were significantly different between the MTS (38.7%) and control (20.6%, p = .05) groups. Study limitations are also discussed. Results suggest that further study is warranted.

Pilot randomized trial on mindfulness training for smokers in young adult binge drinkers.

BACKGROUND: We report results of a pilot study designed to test a novel smoking cessation intervention, Mindfulness Training for Smokers (MTS), in smokers age 18-29 years with regular episodes of binge drinking. Mindfulness is a cognitive skill of applying close moment-to-moment attention to experience with a mental posture of acceptance and non-reactivity. The MTS intervention consisted of six weekly classes that provided instruction on how to use mindfulness to manage known precursors of smoking relapse including smoking triggers, strong emotions, stressful situations, addictive thoughts, urges, and withdrawal symptoms. METHODS: The MTS intervention was compared to Interactive Learning for Smokers (ILS), a time/intensity matched control group using daily non-directed walking instead of mindfulness meditation. Recruitment was conducted primarily at local technical colleges. Primary outcome measures included biochemically-confirmed smoking abstinence and reduction in alcohol use at the end of treatment (2-weeks post-quit attempt). RESULTS: The sample (N = 55) was 70.9% male, with a mean age of 21.9 years, and a mean of 11.76 alcoholic drinks consumed per week. Intent-to-treat analysis showed biochemically-confirmed 7-day point prevalence abstinence rates at 2-weeks post-quit for MTS = 20.0% and ILS = 4.0%, p = .08. Secondary analysis showed number of drinks per week in the first 2-weeks post-quit correlated with smoking relapse at 2-weeks post-quit (p < .01). CONCLUSIONS: This pilot study demonstrated that Mindfulness Training for Smokers shows promise for smoking cessation and alcohol use reduction in treating young adult smokers with alcohol abuse. Results suggest the need for a study with larger sample size and methods that reduce attrition. TRIAL REGISTRATION: ClnicalTrial.gov, NCT01679236.

Description of the Efficacy and Safety of Three New Biologics in the Treatment of Rheumatoid Arthritis

English articles on abatacept, golimumab, and tocilizumab in rheumatoid arthritis published between 2002 and 2009 were reviewed systematically. All randomized clinical trials, open-label extensions, meta-analyses, and reviews were examined. There were thirteen articles on abatacept, four on golimumab, and seven on tocilizumab. All three drugs were effective in methotrexate-naive, methotrexate-incomplete responders, and tumor-necrosis-factor-failure rheumatoid arthritis patients. Of the three, only abatacept has been tested in a head-to-head trial with infliximab, in which it was found to be equivalent to infliximab. Golimumab resulted in a more modest improvement than the others in methotrexate-naive patients, although no direct comparisons among the three drugs were possible or appropriate. Descriptive analysis of adverse events showed that patients receiving abatacept, golimumab, and tocilizumab were subject to more adverse events than controls overall, as expected. In the abatacept studies, a few cases of tuberculosis, more cardiovascular events and gastrointestinal bleedings and more basal cell carcinoma were seen. Golimumab was associated with more skin rashes and pneumonia, while tocilizumab was associated with increased lipids, more liver-function abnormalities, and neutropenia. These new medications are useful additions to the rheumatologic armamentarium and represent greater convenience (golimumab) or different mechanisms of action (abatacept and tocilizumab) than tumor-necrosis-factor inhibitors for treating rheumatoid arthritis. As expected, some adverse events occur when using these drugs and patients need to be watched carefully.

Hyperalgesia, synovitis and multiple biomarkers of inflammation are suppressed by interleukin 1 inhibition in a novel animal model of gouty arthritis.

BACKGROUND: Monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystal-induced interleukin 1 beta (IL1beta) release contributes to inflammation in subcutaneous air pouch and peritoneal models of acute gout and pseudogout. However, consequences of IL1 inhibition have not been explored in more clinically relevant models of crystal-induced arthritis. OBJECTIVE: To develop a novel mouse model of acute gouty ankle arthritis and use it to assess the effects of genetic deletion of IL1 receptor type (IL1R1) and of exogenous mIL1 Trap (a high-affinity blocker of mouse IL1alpha and IL1beta) on pain, synovitis and systemic inflammatory biomarkers. METHODS: MSU crystals were injected into the mouse ankle joint and pain and ankle swelling were measured over 4 days. The effects of IL1 inhibition were determined in this model, and in the comparator models of crystal-induced peritonitis and subcutaneous air pouch inflammation. RESULTS: Both IL1R1-null mice and mice pretreated with mIL1 Trap showed reduced neutrophil influx in MSU and CPPD crystal-induced peritonitis and air pouch models (p<0.05). In the ankle joint model, both IL1R1 knockout mice and pretreatment with mIL1 Trap were associated with significant reductions in MSU crystal-induced elevations in hyperalgesia, inflammation, serum amyloid A and the levels of multiple inflammatory cytokines and chemokines (p<0.05). Additionally, it was found that administration of mIL1 Trap after MSU crystal injection reduced established hyperalgesia and ankle swelling. CONCLUSIONS: IL1 inhibition both prevented and relieved pain and ankle joint inflammation in response to intra-articular MSU crystals in mice. Results suggested that IL1 Trap has the potential to both prevent and treat gouty arthritis.

Atopic dermatitis management: comparing the treatment patterns of dermatologists in Japan, U.S.A. and U.K.

BACKGROUND: The incidence of atopic dermatitis (AD) is increasing worldwide. No large-scale study has previously compared the therapeutic management of this condition in different countries. OBJECTIVES: The purpose of this study was to determine the treatment preferences of dermatologists in Japan, the U.S.A. and the U.K., and investigate their relationship with certain factors pertaining to the physician and his practice. METHODS: A questionnaire was sent to all registered members of dermatological societies in Japan, the U.S.A. and the U.K. Responses were collated and statistical analysis performed using chi2, Mantel-Haenszel and Breslow heterogeneity tests. RESULTS: Three thousand six hundred and eighty-eight completed surveys were returned. U.S.A. and U.K. physicians were significantly more aggressive in prescribing systemic medications, such as steroids, antibiotics and immunosuppressants, compared with those in Japan. Japanese dermatologists also utilized topical steroids significantly less. The use of alternative remedies was highest in Japan. All three countries had a relatively high degree of optimism for topical immunosuppressants, but less so for other emerging therapies. CONCLUSIONS: Both similarities and differences in the therapy of AD exist in the three countries studied. Factors related to the physician, patient population and culture may influence these observations.

Region-specific alterations in the concentrations of catecholamines and indoleamines in the brains of young and old F344 rats after L-deprenyl treatment.

The effects of L-deprenyl, a monoamine oxidase-B (MAO-B) inhibitor, on the concentrations of norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-hydroxytryptamine), and 5-hydroxyindoleacetic acid (5-HIAA) in medial basal hypothalamus (MBH), substantia nigra (SN), striatum (Str), and nucleus accumbens (NAc) of young (3 month) and old (21 month) male F344 rats were examined after a 7-day wash-out period following 1, 15, or 30 days of deprenyl treatment in young rats and a 9-day wash-out period after a 10-week deprenyl treatment in old rats. The brain areas were microdissected and the concentrations of neurotransmitters were measured by High Performance liquid chromatography with electrochemical detection (HPLC-EC). Deprenyl administration following the drug wash-out period increased the concentrations of DOPAC in the SN, Str, and in the NAc of young rats but it was decreased in the NAc of old rats. The concentration of HVA was lower in the Str of young deprenyl-treated rats, and in the Str and NAc of old deprenyl-treated rats, but it was higher in the SN of young deprenyl-treated rats. The concentration of 5-HIAA was increased in the MBH, SN, and in the NAc of young deprenyl-treated rats, but it was decreased in the Str and NAc of old deprenyl-treated rats. The concentration of NE was increased in the MBH, SN, Str, and in the NAc of young rats treated with deprenyl and in the MBH of old deprenyl-treated rats. The concentration of 5-HT was increased in the SN of young deprenyl-treated rats. The concentration of DA increased in the Str of both young and old deprenyl-treated rats. We concluded that a drug wash-out period after deprenyl treatment differentially affects the metabolism of catecholamines and indoleamine depending on the region of the brain and that this effect may be due to variation in the kinetics of MAO inhibition.

Psychosocial predictors of natural killer cell mobilization during marital conflict.

This study examined how specific emotions relate to autonomic nervous and immune system parameters and whether cynical hostility moderates this relationship. Forty-one married couples participated in a 15-min discussion about a marital problem. Observers recorded spouses' emotional expressions during the discussion, and cardiovascular, neuroendocrine, and immunologic parameters were assessed throughout the laboratory session. Among men high in cynical hostility, anger displayed during the conflict was associated with greater elevations in systolic and diastolic blood pressure, cortisol, and increases in natural killer cell numbers and cytotoxicity. Among men low in cynical hostility, anger was associated with smaller increases in heart rate and natural killer cell cytotoxicity. These findings suggest that models describing the impact of stress on physiology should be refined to reflect the joint contribution of situational and dispositional variables.

Effect of anesthetic technique on cardiac morbidity following carotid artery surgery.

PURPOSE: To investigate the effect of anesthetic technique on cardiac morbidity after carotid artery surgery. PATIENTS AND METHODS: From 1991 to 1994, 266 consecutive carotid endarterectomies were performed under local/regional (n=140) or general anesthesia (n=126). The effects of anesthetic technique on postoperative adverse cardiac events were assessed retrospectively. RESULTS: Preoperative cardiac testing was performed in all patients undergoing general or local/regional anesthesia. Medical characteristics were similar among patients in both groups. Forty-seven adverse cardiac events (4 myocardial infarction, 9 congestive heart failure, 7 angina, and 27 new ventricular dysrhythmias) occurred postoperatively in 38 patients (14.3%). There were no deaths. The relative risks of general anesthesia for dysrhythmias, myocardial infarction, angina, congestive heart failure, and total adverse cardiac events were 2.22, 0.37, 0.83, 1.38, and 1.5, respectively. The only statistically significant differential was the increased risk of postoperative dysrhythmias after general anesthesia (P<0.03). CONCLUSIONS: Major cardiac morbidity following carotid endarterectomy is independent of anesthetic technique.

Lasers in endoscopic gastrointestinal surgery.

Lasers have been used for endoscopic gastrointestinal surgery at our institution since 1977. The argon and Nd-YAG lasers are valuable for coagulating upper gastrointestinal hemorrhage, arteriovenous malformations, and benign and malignant lesions, as well as a variety of anatomic anomalies. Between December 1977 and September 1983, 222 procedures were performed in 122 patients. Hospital charts were reviewed and a scale constructed to assess the results of treatment. When information was available, a comparison of transfusion requirements before and after laser therapy was made. Success was achieved in 84 percent of the patients regardless of initial diagnosis. Laser therapy was not effective in 12 patients (10 percent). In 27 patients with gastrointestinal atrioventricular malformations, transfusion requirements fell from a mean of 17 +/- 5.9 units in the year before laser therapy to 1 +/- 0.8 units in the year after laser phototherapy (p less than 0.01). Complications rarely occurred (6 percent of all procedures). There were no perforations of the gastrointestinal tract and only one death (0.8 percent) partially attributable to laser application. Endoscopic laser surgery is minimally invasive and can be performed on an outpatient basis without anesthesia. It is especially valuable in patients with a high operative risk.

Crigler-Najjar Type 1 syndrome: absence of hepatic bilirubin UDP-glucuronyl transferase activity and therapeutic responses to light.

A 16-year-old boy with severe congenital unconjugated hyperbilirubinaemia is described in whom mental retardation occurred as an isolated neurological deficit. The diagnosis of Crigler-Najjar type 1 syndrome was supported by an extreme and persistent elevation of serum unconjugated bilirubin (650 mumol/l), failure of administered phenobarbitone to lower serum bilirubin concentration and family history of a similarly affected sibling. Hepatic bilirubin UDP-glucuronyl transferase activity determined in vitro by a sensitive new enzyme assay was found to be absent using bilirubin or bilirubin monoglucuronide as substrate. Phototherapy for 12 hours each night produced a partial but highly significant reduction in serum bilirubin concentration, which was not influenced further by the administration of cholestyramine.