A Clinical Diagnostic Test for Calcium Release Deficiency Syndrome.

Importance: Sudden death and cardiac arrest frequently occur without explanation, even after a thorough clinical evaluation. Calcium release deficiency syndrome (CRDS), a life-threatening genetic arrhythmia syndrome, is undetectable with standard testing and leads to unexplained cardiac arrest. Objective: To explore the cardiac repolarization response on an electrocardiogram after brief tachycardia and a pause as a clinical diagnostic test for CRDS. Design, Setting, and Participants: An international, multicenter, case-control study including individual cases of CRDS, 3 patient control groups (individuals with suspected supraventricular tachycardia; survivors of unexplained cardiac arrest [UCA]; and individuals with genotype-positive catecholaminergic polymorphic ventricular tachycardia [CPVT]), and genetic mouse models (CRDS, wild type, and CPVT were used to define the cellular mechanism) conducted at 10 centers in 7 countries. Patient tracings were recorded between June 2005 and December 2023, and the analyses were performed from April 2023 to December 2023. Intervention: Brief tachycardia and a subsequent pause (either spontaneous or mediated through cardiac pacing). Main Outcomes and Measures: Change in QT interval and change in T-wave amplitude (defined as the difference between their absolute values on the postpause sinus beat and the last beat prior to tachycardia). Results: Among 10 case patients with CRDS, 45 control patients with suspected supraventricular tachycardia, 10 control patients who experienced UCA, and 3 control patients with genotype-positive CPVT, the median change in T-wave amplitude on the postpause sinus beat (after brief ventricular tachycardia at ≥150 beats/min) was higher in patients with CRDS (P < .001). The smallest change in T-wave amplitude was 0.250 mV for a CRDS case patient compared with the largest change in T-wave amplitude of 0.160 mV for a control patient, indicating 100% discrimination. Although the median change in QT interval was longer in CRDS cases (P = .002), an overlap between the cases and controls was present. The genetic mouse models recapitulated the findings observed in humans and suggested the repolarization response was secondary to a pathologically large systolic release of calcium from the sarcoplasmic reticulum. Conclusions and Relevance: There is a unique repolarization response on an electrocardiogram after provocation with brief tachycardia and a subsequent pause in CRDS cases and mouse models, which is absent from the controls. If these findings are confirmed in larger studies, this easy to perform maneuver may serve as an effective clinical diagnostic test for CRDS and become an important part of the evaluation of cardiac arrest.

Compassionate Use of Remdesivir for Patients with Severe Covid-19.

BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).

Conceptualizing skill mix in nursing and health care: An analysis.

AIM: This paper aims to unpack the concept of "skill mix" into its constituent parts to achieve a better understanding and reduce confusion associated with the term. BACKGROUND: Skill mix is a topic that is widely debated and is foremost on the health policy agenda due to specific local pressures within international health services. At present, however, there is large variation in terms of what is understood by the concept of "skill mix" and there is a paucity of research that attempts to analyse this concept. EVALUATION: Using Rodgers' evolutionary method of concept analysis, this paper provides an analysis of definitions of skill mix, its attributes and associated terms in the literature. KEY ISSUE: Definitions of skill mix are often vague and ambiguous and may refer to one or more attributes of skill mix. CONCLUSION: A lack of understanding of the concept can lead to an ad hoc interpretation of policy recommendations related to skill mix at local level. IMPLICATIONS FOR NURSING MANAGEMENT: A better understanding of the concept of "skill mix" and its attributes can assist both policy makers and stakeholders, including nurse management, to ensure that the potential of skill mix is maximized.

Interventions Supporting Long-term Adherence aNd Decreasing cardiovascular events (ISLAND): Pragmatic randomized trial protocol.

BACKGROUND: Guidelines recommend cardiac rehabilitation and long-term use of cardiac medications for most patients who have had a myocardial infarction (MI), but adherence to these secondary prevention treatments is suboptimal. METHODS: This is a multicenter, pragmatic, 3-arm randomized trial. Eligible patients (n = 2,742) with obstructive coronary artery disease are randomized post-MI to usual care or 1 of 2 intervention arms. Patients in the first intervention arm receive mail-outs sent on behalf of their cardiologist at 4, 8, 20, 32, and 44 weeks post-MI; content is designed to address determinants of adherence and facilitate discussion between the patient and their health care team. Patients in the second intervention arm receive mail-outs plus automated interactive voice response system telephone calls 2 weeks after each letter, as well as a telephone call by trained lay health workers if the interactive voice response system identifies challenges with adherence. Outcomes are assessed 12 months post-MI via patient self-report and administrative data sources. Co-primary outcomes are adherence to cardiac medications and completion of cardiac rehabilitation. Secondary outcomes include cardiovascular events and mortality. An embedded, theory-informed process evaluation will explore the mechanism of action; an economic evaluation is also planned. CONCLUSIONS: We describe a complete program evaluation of a highly pragmatic, health-system intervention to support adherence to recommended treatments. Research ethics boards approved waiver of consent for patients enrolled in the trial with provision of multiple opportunities to opt out and a debrief at the time of outcome assessment. The methods used here may provide a model for similar interventions.

Kinetic and mutational studies of the adenosine diphosphate ribose hydrolase from Mycobacterium tuberculosis.

Mycobacterium tuberculosis represents one of the world's most devastating infectious agents - with one third of the world's population infected and 1.5 million people dying each year from this deadly pathogen. As part of an effort to identify targets for therapeutic intervention, we carried out the kinetic characterization of the product of gene rv1700 of M. tuberculosis. Based on its sequence and its structure, the protein had been tentatively identified as a pyrophosphohydrolase specific for adenosine diphosphate ribose (ADPR), a compound involved in various pathways including oxidative stress response and tellurite resistance. In this work we carry out a kinetic, mutational and structural investigation of the enzyme, which provides a full characterization of this Mt-ADPRase. Optimal catalytic rates were achieved at alkaline pH (7.5-8.5) with either 0.5-1 mM Mg2+ or 0.02-1 mM Mn2+. K m and k cat values for hydrolysis of ADPR with Mg2+ ions are 200 ± 19 µM and 14.4 ± 0.4 s-1, and with Mn2+ ions are 554 ± 64 µM and 28.9 ± 1.4 s-1. Four residues proposed to be important in the catalytic mechanism of the enzyme were individually mutated and the kinetics of the mutant enzymes were characterized. In the four cases, the K m increased only slightly (2- to 3-fold) but the k cat decreased significantly (300- to 1900-fold), confirming the participation of these residues in catalysis. An analysis of the sequence and structure conservation patterns in Nudix ADPRases permits an unambiguous identification of members of the family and provides insight into residues involved in catalysis and their participation in substrate recognition in the Mt-ADPRase.

The Impact of a Cognitive Behavioral Pain Management Program on Sleep in Patients with Chronic Pain: Results of a Pilot Study.

OBJECTIVE: To determine the impact of a cognitive behavioral pain management program on sleep in patients with chronic pain. DESIGN: Prospective nonrandomized controlled pilot study with evaluations at baseline and 12 weeks. SETTING: Out-patient multidisciplinary cognitive behavioral pain management program in a university teaching hospital. SUBJECTS: Patients with chronic pain who fulfilled the criteria for participation in a cognitive behavioral pain management program. METHODS: Patients assigned to the intervention group (n = 24) completed a 4 week cognitive behavioral pain management program, and were compared with a waiting list control group (n = 22). Assessments for both groups occurred at baseline and two months post cognitive behavioral pain management program. Outcome measures included self-report (Pittsburgh Sleep Quality Index) and objective (actigraphy) sleep measures, pain and quality of life measures. RESULTS: Both groups were comparable at baseline, and all had sleep disturbance. The Pittsburgh Sleep Quality Index correlated with only two of the seven objective sleep measures (fragmentation index r = 0.34, P = 0.02, and sleep efficiency percentage r = -0.31, P = 0.04). There was a large treatment effect for cognitive behavioral pain management program group in mean number of wake bouts (d = 0.76), where a significant group*time interaction was also found (P = 0.016), showing that the CBT-PMP group improved significantly more than controls in this sleep variable. CONCLUSIONS: Patients attending a cognitive behavioral pain management program have high prevalence of sleep disturbance, and actigraphy technology was well tolerated by the patients. Preliminary analysis of the impact of a cognitive behavioral pain management program on sleep is promising, and warrants further investigation.

An exogenous chloroplast genome for complex sequence manipulation in algae.

We demonstrate a system for cloning and modifying the chloroplast genome from the green alga, Chlamydomonas reinhardtii. Through extensive use of sequence stabilization strategies, the ex vivo genome is assembled in yeast from a collection of overlapping fragments. The assembled genome is then moved into bacteria for large-scale preparations and transformed into C. reinhardtii cells. This system also allows for the generation of simultaneous, systematic and complex genetic modifications at multiple loci in vivo. We use this system to substitute genes encoding core subunits of the photosynthetic apparatus with orthologs from a related alga, Scenedesmus obliquus. Once transformed into algae, the substituted genome recombines with the endogenous genome, resulting in a hybrid plastome comprising modifications in disparate loci. The in vivo function of the genomes described herein demonstrates that simultaneous engineering of multiple sites within the chloroplast genome is now possible. This work represents the first steps toward a novel approach for creating genetic diversity in any or all regions of a chloroplast genome.

Acceptability and readiness to promote human papillomavirus vaccination at ages 9-10 years: A pilot study among rural North Carolina clinics.

While 9-valent human papillomavirus vaccination (HPV-9) is approved by the U.S. Food and Drug Administration for use in adolescents as young as age 9, providers typically recommend it at ages 11-12 per Centers for Disease Control and Prevention recommendations. Studies suggest that recommending HPV-9 at 9 or 10 years of age could increase up-to-date vaccination by age 13, which could benefit rural populations with reduced access to primary health care and lower HPV-9 coverage than urban areas. This pilot study aimed to assess the feasibility of earlier recommendation of HPV-9 in rural clinics. We conducted in-depth interviews with providers and staff from two primary care clinics in central North Carolina, to understand attitudes toward recommending HPV-9 to 9- and 10-year-olds. All interviewees agreed that HPV-9 was important for cancer prevention and should be recommended before the onset of sexual activity, and agreed that HPV-9 could be initiated before age 11 to improve timeliness and completion of the vaccination series. However, opinions were mixed on whether it should be initiated as young as 9-years-old. Two key informants recruited from two urban clinics described their experiences recommending HPV-9 to 9- and 10-year-olds, including a modified vaccination schedule that promotes HPV-9 during routine well-child visits, prior to pubertal onset, and alongside other recommended adolescent vaccines. Earlier recommendation and administration of HPV-9 is possible with minimal changes to current clinical practices and could increase convenience and acceptability of HPV-9 in under-vaccinated settings.

Acceptability and readiness to promote human papillomavirus vaccination at ages 9-10 years: a feasibility study among North Carolina clinics.

While 9-valent human papillomavirus (HPV) vaccination is approved by the US Food and Drug Administration for use in adolescents as young as age 9, providers typically recommend it at ages 11-12. Studies suggest that recommending HPV vaccination at 9 or 10 years of age could increase up-to-date vaccination by age 13, which could especially benefit rural populations with reduced access to primary health care and lower HPV vaccination coverage than urban areas. This study aimed to assess the feasibility of the age-9 recommendation of HPV vaccination in rural clinics. We conducted in-depth interviews with providers and staff from two primary care clinics in central North Carolina to understand attitudes toward recommending HPV vaccination to 9- and 10-year-olds. All interviewees agreed that HPV vaccination was important for cancer prevention and should be recommended before the onset of sexual activity, agreeing that HPV vaccination could be initiated before age 11 to improve timeliness and completion of the vaccination series. However, opinions were mixed on whether HPV vaccination should be initiated as young as 9 years old. Two key informants recruited from two university-affiliated clinics described their experiences recommending HPV vaccination to 9- and 10-year-olds, including a modified vaccination schedule that promotes HPV vaccination during routine well-child visits, prior to pubertal onset, and alongside other recommended adolescent vaccines. Age-9 recommendation and administration of HPV vaccination is possible with minimal changes to current clinical practices and could increase the convenience and acceptability of HPV vaccination in under-vaccinated settings.

The impact on sleep of a multidisciplinary cognitive behavioural pain management programme: a pilot study.

BACKGROUND: Reduced sleep quality is a common complaint among patients with chronic pain, with 50-80% of patients reporting sleep disturbance. Improvements in pain and quality of life measures have been achieved using a multidisciplinary cognitive behavioural therapy pain management programme (CBT-PMP) that aims to recondition attitudes to pain, and improve patients' self-management of their condition. Despite its high prevalence in patients with chronic pain, there is very limited objective evidence for the effect of this intervention on sleep quality. The primary research objective is to investigate the short-term effect of a multidisciplinary CBT-PMP on subjective (measured by Pittsburg Sleep Quality Index) and objective sleep quality (measured by Actigraphy) in patients with chronic pain by comparison with a control group. The secondary objectives will investigate changes in function and mood, and then explore the relationship between objective and subjective sleep quality and physical and psychological outcome measures. METHODS/DESIGN: Patients who fulfil the inclusion criteria for attendance on the multidisciplinary CBT-PMP in the Adelaide and Meath Hospital, Tallaght, Dublin and are currently listed on the PMP waiting list will be invited to participate in this pilot study. Potential patients will be screened for sleep disturbance [determined by the Pittsburgh Sleep Quality Index (PSQI)]. Those patients with a sleep disturbance (PSQI >5) will be assigned to either the intervention group (immediate treatment), or control group (deferred treatment, i.e. the PMP they are listed for is more than six months away) based on where they appear on the waiting list. Baseline measures of sleep, function, and mood will be obtained using a combination of self-report questionnaires (the Hospital Anxiety and Depression Scale, the Short Form 36 health survey, the Pittsburgh Sleep Quality Index, the Tampa Scale for Kinesiophobia), and functional outcome measures. Sleep will be measured for seven days using actigraphy (Actiwatch 7). These measures will be repeated after the four week multidisciplinary cognitive behavioural therapy pain management programme, and at a two month follow-up. The waiting list control group will be assessed at baseline, and two months later. Analysis for the primary outcome will include between group differences of subjective and objective sleep parameters from baseline to follow-up using Independent T-tests or Mann-Whitney U tests. The secondary outcomes establishing relationships between the sleep variables and physical and psychological outcome measures will be established using multiple linear regression models. DISCUSSION: This pilot study will evaluate the impact of a multidisciplinary CBT-PMP on both subjective and objective measures of sleep in patients with chronic pain and provide guidance for a larger clinical trial. TRIAL REGISTRATION: Current controlled trial ISRCTN: ISRCTN74913595.

Work related stress and European policy--a comparative exploration of contextual stressors in the rehabilitation sector in five European countries.

BACKGROUND: Dealing with work related stress is a declared priority of European Union mental health policy. A particularly under-researched sector in this regard is the community vocational support sector for people with mental health and intellectual disability problems. AIMS: To report on the organisational profile of the vocational support and rehabilitation sector for people with mental health and intellectual disabilities as this relates to occupational stress, in five European countries (Austria, Ireland, Italy, Romania and UK). METHODS: A sector profile questionnaire was distributed to representative organisations in five countries and a short face-to-face survey was conducted with 25 local managers (five from each country) to draw up a profile and facilitate a comparative description and analysis. RESULTS: It was found that there is no national and European data collected at any level in this sector upon which to base effective policy interventions to combat occupational stress specific to professionals working in this sector. Results indicate that the sector in a number of the countries sampled does not have effective mechanisms in place to deal with occupational stress. CONCLUSION: Developing effective transnational occupational stress management policy that supports staff working in this sector and measuring its success is greatly impaired by a failure to effectively define the purpose of the sector and collect and collate national data to support it.

Developing a web-based stress management intervention for occupational support workers.

BACKGROUND: Occupational support workers in the mental healthcare sector are exposed to considerable occupational stress and have little access to stress management facilities. AIMS: This article describes the process behind creating a web-based stress management intervention (SMI) for occupational support workers in the mental healthcare sector. METHOD: Mixed methods were used to inform the content of the web-based SMI, following MRC strategy for designing interventions and PRIMA-EF guidelines for best practice in SMI design. We conducted a literature review to ascertain the content of interventions that had been shown to be successful in reducing stress in mental healthcare populations. In addition, we conducted focus groups in order to assess specific stressors that individuals in the occupational support sector deemed to be important. RESULTS: The literature review showed that a variety of methods had been successful for reducing occupational stress in the mental healthcare sector including: Relaxation and Cognitive Behavioural Therapy techniques, and skills training in; time management, problem-solving and communication. Individuals in the focus groups identified both personal and organisational stressors to be addressed in the intervention. CONCLUSIONS: This intervention was developed with reference to a design strategy, using input from the target population.

Increasing Hepatitis C Screening in a Federally Qualified Health Center: A Quality Improvement Initiative.

ABSTRACT: Hepatitis C virus (HCV) is a chronic infection that can lead to severe liver damage if left untreated. With increased availability and affordability of curative treatments, screening for HCV has become an important first step in reducing morbidity and mortality. At a rural federally qualified health center in North Carolina, two quality improvement initiatives-an electronic health record (EHR) prompt and educational flyers-were implemented to improve HCV screening rates. We compared the proportion of eligible patients born from 1945 to 1965 who received HCV screening before, during, and after the initiatives. HCV screening rates were highest during the two initiatives (30% and 39%, respectively). Screening rates fell in the 6-month period after the initiatives' conclusion (12%) but remained higher than at baseline (6%). Although HCV screening can increase with simple interventions, more durable solutions are needed to maintain screening coverage.

Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019: Crisis Standards of Care.

The coronavirus disease 2019 (COVID-19) pandemic has placed extraordinary strain on global healthcare systems. Use of extracorporeal membrane oxygenation (ECMO) for patients with severe respiratory or cardiac failure attributed to COVID-19 has been debated due to uncertain survival benefit and the resources required to safely deliver ECMO support. We retrospectively investigated adult patients supported with ECMO for COVID-19 at our institution during the first 80 days following New York City's declaration of a state of emergency. The primary objective was to evaluate survival outcomes in patients supported with ECMO for COVID-19 and describe the programmatic adaptations made in response to pandemic-related crisis conditions. Twenty-two patients with COVID-19 were placed on ECMO during the study period. Median age was 52 years and 18 (81.8%) were male. Twenty-one patients (95.4%) had severe ARDS and seven (31.8%) had cardiac failure. Fifteen patients (68.1%) were managed with venovenous ECMO while 7 (31.8%) required arterial support. Twelve patients (54.5%) were transported on ECMO from external institutions. Twelve patients were discharged alive from the hospital (54.5%). Extracorporeal membrane oxygenation was used successfully in patients with respiratory and cardiac failure due to COVID-19. The continued use of ECMO, including ECMO transport, during crisis conditions was possible even at the height of the COVID-19 pandemic.

A randomised controlled trial of bag-valve-mask teaching techniques.

BACKGROUND: Bag-valve-mask (BVM) ventilation is a vital skill in the management of the collapsed patient; however, the quality of BVM ventilation is a cause for concern. Modified techniques, designed to be easier for the novice practitioner, offer an opportunity to improve quality. One such modification is the 'LASOO' (Lift, Apply, Slide, Oppose, Observe) approach, which offers theoretical benefits over the traditionally taught 'CE' (finger shapes) technique. We conducted a randomised controlled trial (RCT) to determine whether LASOO was superior to CE in terms of tidal volume, when taught to novices in the skills-lab setting. We conducted a randomised controlled trial (RCT) to determine whether LASOO was superior to CE in terms of tidal volume, when taught to novices in the skills-lab setting METHODS: A total of 76 undergraduate health care students received a manikin-based teaching session on LASOO or CE. They then delivered 20 breaths (10 with each hand) to a modified airway manikin. The primary outcome was mean tidal volume; secondary outcomes were the proportion of breaths that achieved 150-mL and 400-mL threshold volumes. Subgroup analyses and statistical modelling were conducted for time-point, hand dominance and hand size. RESULTS: The mean tidal volume was 320 mL for CE and 304 mL for LASOO. The median percentage of attempts that exceeded 150 mL was 85 for CE and 82.5 for LASOO. The median percentage of attempts that exceeded 400 mL was 20 for CE and 20 for LASOO. The differences recorded between the techniques were not statistically significant. There was a small, statistically significant increase in tidal volume across both techniques with time-point and holding the mask with the non-dominant hand. DISCUSSION: LASOO is a viable alternative to CE. Educators may opt to teach either or both techniques, allowing students to choose the technique that they prefer.

Safety, Feasibility, and Efficacy of Early Rehabilitation in Patients Requiring Continuous Renal Replacement: A Quality Improvement Study.

INTRODUCTION: Early rehabilitation in critically ill patients is associated with improved outcomes. Recent research demonstrates that patients requiring continuous renal replacement therapy (CRRT) can safely engage in mobility. The purpose of this study was to assess safety and feasibility of early rehabilitation with focus on mobility in patients requiring CRRT. METHODS: Study design was a mixed methods analysis of a quality improvement protocol. The setting was an intensive care unit (ICU) at a tertiary medical center. Safety was prospectively recorded by incidence of major adverse events including dislodgement of CRRT catheter, accidental extubation, bleeding, and hemodynamic emergency; and minor adverse events such as transient oxygen desaturation >10% of resting. Limited efficacy testing was performed to determine if rehabilitation parameters were associated with clinical outcomes. RESULTS: A total of 67 patients (54.0 ± 15.6 years old, 44% women, body mass index 29.2 ± 9.3 kg/m2) received early rehabilitation under this protocol. The median days of CRRT were 6.0 (interquartile range [IQR], 2-11) and 72% of patients were on mechanical ventilation concomitantly with CRRT at the time of rehabilitation. A total of 112 rehabilitation sessions were performed of 152 attempts (74% completion rate). No major adverse events occurred. Patients achieving higher levels of mobility were more likely to be alive at discharge (P = 0.076). CONCLUSIONS: The provision of early rehabilitation in critically ill patients requiring CRRT is safe and feasible. Further, these preliminary results suggest that early rehabilitation with focus on mobility may improve patient outcomes in this susceptible population.

IMAGINE Network's Mind And Gut Interactions Cohort (MAGIC) Study: a protocol for a prospective observational multicentre cohort study in inflammatory bowel disease and irritable bowel syndrome.

INTRODUCTION: Gut microbiome and diet may be important in irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and comorbid psychiatric conditions, but the mechanisms are unclear. We will create a large cohort of patients with IBS, IBD and healthy controls, and follow them over time, collecting dietary and mental health information and biological samples, to assess their gastrointestinal (GI) and psychological symptoms in association with their diet, gut microbiome and metabolome. METHODS AND ANALYSIS: This 5-year observational prospective cohort study is recruiting 8000 participants from 15 Canadian centres. Persons with IBS who are 13 years of age and older or IBD ≥5 years will be recruited. Healthy controls will be recruited from the general public and from friends or relatives of those with IBD or IBS who do not have GI symptoms. Participants answer surveys and provide blood, urine and stool samples annually. Surveys assess disease activity, quality of life, physical pain, lifestyle factors, psychological status and diet. The main outcomes evaluated will be the association between the diet, inflammatory, genetic, microbiome and metabolomic profiles in those with IBD and IBS compared with healthy controls using multivariate logistic regression. We will also compare these profiles in those with active versus quiescent disease and those with and without psychological comorbidity. ETHICS AND DISSEMINATION: Approval has been obtained from the institutional review boards of all centres taking part in the study. We will develop evidence-based knowledge translation initiatives for patients, clinicians and policymakers to disseminate results to relevant stakeholders.Trial registration number: NCT03131414.

Interventions supporting long term adherence and decreasing cardiovascular events after myocardial infarction (ISLAND): pragmatic randomised controlled trial.

OBJECTIVE: To test a scalable health system intervention to improve long term adherence to secondary prevention treatments among patients who have had a recent myocardial infarction. DESIGN: Three arm, pragmatic randomised controlled trial with blinded outcome assessment. SETTING: Nine cardiac centres in Ontario, Canada. PARTICIPANTS: 2632 patients with obstructive coronary artery disease after a myocardial infarction, identified from a centralised cardiac registry. INTERVENTIONS: Participants were randomised 1:1:1 to receive usual care, five mail-outs developed through a user centred design process, or mail-outs plus phone calls. The phone calls were delivered first by an interactive automated system to screen for non-adherence to treatment. Trained lay health workers followed up as necessary. Interventions were coordinated centrally but delivered from each patient's hospital site. MAIN OUTCOME MEASURES: Co-primary outcomes were completion of cardiac rehabilitation and adherence to recommended medication. Data were collected by blinded assessors through patient report and from administrative health databases at 12 months. RESULTS: 2632 patients (mean age 66, 71% male) were randomised: 878 to the full intervention (mail plus phone calls), 878 to mail only, and 876 to usual care. Of the respondents, 174 (27%) of 643 in the usual care group, 200 (32%) of 628 in the mail only group, and 196 (37%) of 531 allocated to the full intervention completed cardiac rehabilitation (adjusted odds ratio 1.55, 95% confidence interval 1.18 to 2.03). In the mail plus phone group, 11.7%, 6.0%, 14.4%, 32.9%, and 35.0% reported adherence to 0, 1, 2, 3, and 4 drug classes after one year, respectively, in comparison with 12.5%, 6.8%, 13.6%, 30.2%, and 36.8% in the mail only group, and 12.2%, 8.4%, 13.1%, 30.3%, and 36.1% in the usual care group, respectively (mail only v usual care, odds ratio 0.98, 95% confidence interval 0.81 to 1.19; full intervention v usual care, 0.99, 0.82 to 1.20). CONCLUSIONS: Scalable interventions delivered by mail plus phone can increase completion of cardiac rehabilitation after myocardial infarction but not adherence to medication. More intensive interventions should be tested to improve adherence to medication and to evaluate the association between attendance at cardiac rehabilitation and adherence to medication. TRIAL REGISTRATION: ClinicalTrials.gov NCT02382731, registered 9 March 2015 before any patient enrolment.

Epidemiology of nontuberculous mycobacteria in patients without HIV infection, New York City.

We reviewed medical records of patients without known HIV and with positive cultures for nontuberculous mycobacteria (NTM) isolated during 2000-2003 from 1 large hospital in New York, New York. Overall, 505 patients had positive NTM cultures; 119 (24%) met the criteria for NTM disease. The difference between demographic characteristics of case-patients in our study (66% female, 61% white, and 59% > 60 years of age) and those of the base population as determined by regional census data was statistically significant. Estimated incidences for positive cultures, all disease, and respiratory tract disease were 17.7, 2.7, and 2.0 per 100,000 persons, respectively. More patients with rapidly growing mycobacteria (61%), Mycobacterium kansasii (70%), or M. marinum (100%) met criteria for disease than did patients with M. avium complex (MAC) (27%, (p < 0.01). NTM disease in patients without HIV is increasing. Laboratory-based surveillance may be useful for detecting non-MAC and non-respiratory tract disease.

Clinical review: airway hygiene in the intensive care unit.

Maintenance of airway secretion clearance, or airway hygiene, is important for the preservation of airway patency and the prevention of respiratory tract infection. Impaired airway clearance often prompts admission to the intensive care unit (ICU) and can be a cause and/or contributor to acute respiratory failure. Physical methods to augment airway clearance are often used in the ICU but few are substantiated by clinical data. This review focuses on the impact of oral hygiene, tracheal suctioning, bronchoscopy, mucus-controlling agents, and kinetic therapy on the incidence of hospital-acquired respiratory infections, length of stay in the hospital and the ICU, and mortality in critically ill patients. Available data are distilled into recommendations for the maintenance of airway hygiene in ICU patients.