Feline Hypertrophic Cardiomyopathy: A Spontaneous Large Animal Model of Human HCM.

Hypertrophic cardiomyopathy (HCM) is a common disease in pet cats, affecting 10-15% of the pet cat population. The similarity to human HCM, the rapid progression of disease, and the defined and readily determined endpoints of feline HCM make it an excellent natural model that is genotypically and phenotypically similar to human HCM. The Maine Coon and Ragdoll cats are particularly valuable models of HCM because of myosin binding protein-C mutations and even higher disease incidence compared to the overall feline population. The cat overcomes many of the limitations of rodent HCM models, and can provide enhanced translation of information from in vitro and induced small animal models to human clinical trials. Physicians and veterinarians working together in a collaborative and interdisciplinary approach can accelerate the discovery of more effective treatments for this and other cardiovascular diseases affecting human and veterinary patients

Influences of Labour Participation Among Persons With Disabilities: A Systematic Review and Best Evidence Synthesis

A systematic literature review was conducted to assess the individual, organisation, societal, and legal influences of labour participation among individuals with a disability. Methods: Nine databases were searched, for peer-reviewed studies of individual, organisation, societal, and legal influences among disabled populations published between 1990 and 2010. Results: Of a total of 809 papers initially selected, only 46 studies were deemed to be of sufficient quality to be included in the review. Conclusions: Numerous studies have examined labour participation among persons with physical disabilities, some among persons with chronic disabilities, and few among persons with mental disabilities. Strong evidence was found for individual and organisation influences of labour participation among persons with physical disabilities in particular pain, catastrophising, job strain, and support. Only individual influences provided strong evidence among persons with chronic disabilities and no influences provided strong evidence among those with mental disabilities. The results are presented along with methodological weaknesses and future recommendations

A Pilot Investigation of Acute Inhibitory Control Training in Cocaine Users

Background—Disrupted response inhibition and presence of drug-cue attentional bias in cocaine-using individuals have predicted poor treatment outcomes. Inhibitory control training could help improve treatment outcomes by strengthening cognitive control. This pilot study assessed the effects of acute inhibitory control training to drug- and non-drug-related cues on response inhibition performance and cocaine-cue attentional bias in cocaine-using individuals. Methods—Participants who met criteria for a cocaine-use disorder underwent five sessions of inhibitory control training to either non-drug-related cues (i.e., rectangles) or cocaine cues (n=10/condition) in a single day. Response inhibition and attentional bias were assessed prior to and following training using the stop-signal task and visual-probe task with eye tracking, respectively. Results—Training condition groups did not differ on demographics, inhibitory control training performance, response inhibition, or cocaine-cue attentional bias. Response inhibition performance improved as a function of inhibitory control training in both conditions. Cocaine-cue attentional bias was observed, but did not change as a function of inhibitory control training in either condition. Conclusions—Response inhibition in cocaine-using individuals was augmented by acute inhibitory control training, which may improve treatment outcomes through better behavioral inhibition. Future studies should investigate longer-term implementation of inhibitory control training, as well as combining inhibitory control training with other treatment modalities

Buspirone Maintenance Does Not Alter the Reinforcing, Subjective, and Cardiovascular Effects of Intranasal Methamphetamine

Background—Medications development efforts for methamphetamine-use disorder have targeted central monoamines because these systems are directly involved in the effects of methamphetamine. Buspirone is a dopamine autoreceptor and D3 receptor antagonist and partial agonist at serotonin 1A receptors, making it a logical candidate medication for methamphetamine-use disorder. Buspirone effects on abuse-related behaviors of methamphetamine have been mixed in clinical and preclinical studies. Experimental research using maintenance dosing, which models therapeutic use, is limited. This study evaluated the influence of buspirone maintenance on the reinforcing effects of methamphetamine using a self-administration procedure, which has predictive validity for clinical efficacy. The impact of buspirone maintenance on the subjective and cardiovascular response to methamphetamine was also determined. Methods—Eight research participants (1 female) reporting recent illicit stimulant use completed a placebo-controlled, crossover, double-blind protocol in which the pharmacodynamic effects of intranasal methamphetamine (0, 15, and 30 mg) were assessed after at least 6 days of buspirone (0 and 45 mg/day) maintenance. Results—Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like subjective (e.g., increased ratings of Good Effects and Like Drug) and cardiovascular (e.g., elevated blood pressure) effects. These effects of methamphetamine were similar under buspirone and placebo maintenance conditions. Maintenance on buspirone was well tolerated and devoid of effects when administered alone. Conclusions—These data suggest that buspirone is unlikely to be an effective pharmacotherapy for methamphetamine-use disorder. Given the central role of monoamines in methamphetamine-use disorder, it is reasonable for future studies to continue to target these systems

N-Acetylcysteine Reduces Cocaine-Cue Attentional Bias and Differentially Alters Cocaine Self-Administration Based on Dosing Order

Background—Disrupted glutamate homeostasis is thought to contribute to cocaine-use disorder, in particular, by enhancing the incentive salience of cocaine stimuli. n-Acetylcysteine might be useful in cocaine-use disorder by normalizing glutamate function. In prior studies, n-acetylcysteine blocked the reinstatement of cocaine seeking in laboratory animals and reduced the salience of cocaine stimuli and delayed relapse in humans. Methods—The present study determined the ability of maintenance on n-acetylcysteine (0 or 2400 mg/day, counterbalanced) to reduce the incentive salience of cocaine stimuli, as measured by an attentional bias task, and attenuate intranasal cocaine self-administration (0, 30, and 60 mg). Fourteen individuals (N = 14) who met criteria for cocaine abuse or dependence completed this within-subjects, double-blind, crossover-design study. Results—Cocaine-cue attentional bias was greatest following administration of 0 mg cocaine during placebo maintenance, and was attenuated by n-acetylcysteine. Cocaine maintained responding during placebo and n-acetylcysteine maintenance, but the reinforcing effects of cocaine were significantly attenuated across both maintenance conditions in participants maintained on n-acetylcysteine first compared to participants maintained on placebo first. Conclusions—These results collectively suggest that a reduction in the incentive salience of cocaine-related stimuli during n-acetylcysteine maintenance may be accompanied by reductions in cocaine self-administration. These results are in agreement with, and link, prior preclinical and clinical trial results suggesting that n-acetylcysteine might be useful for preventing cocaine relapse by attenuating the incentive salience of cocaine cues

Retrospective evaluation of hypertrophic cardiomyopathy in 68 dogs

BACKGROUND: There is a lack of clinical data on hypertrophic cardiomyopathy (HCM) in dogs. HYPOTHESIS/OBJECTIVES: To investigate signalment, clinical signs, diagnostic findings, and survival in dogs with HCM. ANIMALS: Sixty-eight client-owned dogs. METHODS: Retrospective multicenter study. Medical records were searched between 2003 and 2015. The diagnosis of left ventricular (LV) hypertrophy was made by echocardiographic examination. RESULTS: Three hundred and forty-five dogs with LV hypertrophy were identified, of which 277 were excluded. The remaining 68 dogs were 0.3 to 14 years old and predominantly <10 kg (85%), and without a sex predilection. Twenty-four % were Shih Tzu and 24% terrier breeds. Most (80%) had a systolic heart murmur. Owner-determined exercise intolerance (37%) and syncope (18%) were most commonly reported signs. The majority (84%) of dogs had symmetrical LV hypertrophy, whereas asymmetrical septal and LV free wall hypertrophy was observed in 9% and 6% of dogs, respectively. Isolated basal interventricular septal hypertrophy was not observed. Commonly recorded were systolic anterior motion of the mitral valve (60%) and LV diastolic dysfunction (89% of dogs where diastolic function was evaluated). Six dogs died unexpectedly, and 3 developed congestive heart failure. Known survival times were between 1 day and 114 months after diagnosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Hypertrophic cardiomyopathy in dogs should be considered as a differential diagnosis if LV hypertrophy is identified. Small breed dogs are overrepresented, and it is uncommon for dogs with HCM to develop CHF although sudden death can occur

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24&nbsp;months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500&nbsp;steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30&nbsp;minutes spent performing activities ≥500&nbsp;counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24&nbsp;months), both the number of steps per day (per 500&nbsp;steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500&nbsp;counts per minute (per 30&nbsp;minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score &gt;10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research