Profile of Acute Asthma Exacerbation in Drug Users.

The characteristics of patients who use heroin, cocaine, or both and present with acute asthma exacerbations have not been well studied. In this retrospective study, we aimed to study the demographic characteristics of this patient population, the characteristics of their asthma attack, and the risk factors for the need for invasive mechanical ventilation in this patient population. We reviewed the charts of patients discharged from an inner-city hospital with a diagnosis of acute asthma exacerbation. Individuals who used either heroin or cocaine or both within 24 hours of presenting to the emergency department were identified as a cohort of drug users. The rest were classified as non-drug users. Both groups were compared, and a univariate analysis was performed. To assess the predictive value of drug use for the need for intubation in the presence of confounding factors, logistic regression analysis was performed to identify whether using cocaine or heroin or both was an individual predictor for the need for invasive ventilation. Data from 218 patients were analyzed. Drug users (n = 85) were younger (mean age in years 43.9 vs. 50.5, P < 0.01), predominantly male (63.5% vs. 33.8%, P < 0.01), and more likely to be cigarette smokers (90.6% vs. 57.6%, P < 0.01). A medical history of intubation and admissions to the intensive care unit (ICU) was more common among drug users (56.5% vs. 29.3%, P < 0.01 and 54.1% vs. 38.3%, P < 0.03, respectively). Drug use was associated with increased need for invasive mechanical ventilation (35% vs. 23.3%, P = 0.05). Non-drug users were more likely to be using inhaled corticosteroids (48.9% vs. 32.9%, P = 0.03) and had longitudinal care established with a primary care provider (50.6% vs. 68.9%, P < 0.01). After adjusting for a history of mechanical ventilation, history of ICU admission, use of systemic corticosteroids, smoking, and acute physiological assessment and chronic health evaluation 2 score, drug use remained predictive for the need for mechanical ventilation (P = 0.026). Acute asthma exacerbations triggered by cocaine and heroin should be treated aggressively because they represent a cohort with poor follow-up and undertreated asthma as outpatients and are associated with increased need for invasive mechanical ventilation and ICU admission during acute exacerbation.

Efficacy of Intravenous and Oral Sotalol in Pharmacologic Conversion of Atrial Fibrillation: A Systematic Review and Meta-Analysis.

OBJECTIVES: The role of sotalol is well established for the maintenance of sinus rhythm after successful conversion of atrial fibrillation (AF). However, its role in pharmacologic conversion of AF is poorly defined. The purpose of this study is to compare the efficacy of sotalol to that of other antiarrhythmic agents for AF conversion. METHODS: Standard methods of meta-analysis were employed. Full-text publications of clinical trials in English that compared the efficacy of sotalol to that of other antiarrhythmics or placebo/no treatment were eligible for inclusion. RESULTS: A systematic review revealed 10 eligible publications. Sotalol was superior to placebo and/or no antiarrhythmic therapy in AF conversion, with a relative success of 24 (95% CI 4.7-119, p < 0.001). Sotalol was not significantly different from class IA antiarrhythmic drugs. Similarly, sotalol was not different from class IC antiarrhythmic drugs or amiodarone in terms of conversion efficacy. In one study, sotalol was less effective than high-dose ibutilide (2 mg), with a relative success of 0.248 (95% CI 0.128-0.481, p < 0.001). Ibutilide caused more proarrhythmia. CONCLUSIONS: Sotalol is as effective as class IA and class IC antiarrhythmic agents, and it is also as effective as amiodarone for pharmacologic conversion of AF. Only ibutilide at a high dose showed a greater conversion rate of AF.

The unfulfilled gene and nervous system development in Drosophila.

The unfulfilled gene of Drosophila encodes a member of the NR2E subfamily of nuclear receptors. Like related members of the NR2E subfamily, UNFULFILLED is anticipated to function as a dimer, binding to DNA response elements and regulating the expression of target genes. The UNFULFILLED protein may be regulated by ligand-binding and may also be post-transcriptionally modified by sumoylation and phosphorylation. unfulfilled mutants display a range of aberrant phenotypes, problems with eclosion and post-eclosion behaviors, compromised fertility, arrhythmicity, and a lack of all adult mushroom body lobes. The locus of the fertility problem has not been determined. The behavioral arrhythmicity is due to the unfulfilled-dependent disruption of gene expression in a set of pacemaker neurons. The eclosion and the mushroom body lobe phenotypes of unfulfilled mutants are the result of developmental problems associated with failures in axon pathfinding or re-extension. Interest in genes that act downstream of unfulfilled has resulted in the identification of a growing number of unfulfilled interacting loci, providing the first glimpse into the composition of unfulfilled-dependent gene networks. This article is part of a Special Issue entitled: Nuclear receptors in animal development.

Cardiac-resynchronization therapy in patients with systolic heart failure and QRS interval ≤130 ms: insights from a meta-analysis.

AIMS: Cardiac-resynchronization therapy (CRT) reduces morbidity and mortality in patients with chronic systolic heart failure (SHF) and a wide QRS complex. It is unclear whether the same benefit extends to patients with QRS duration (QRSd) <130 ms. METHODS AND RESULTS: Our aim was to perform a meta-analysis of all randomized controlled trial (RCTs) and to evaluate the effect of implantable CRT defibrillator(CRTD) on all-cause mortality, HF mortality, and HF hospitalization in patients with QRSd <130 ms. We performed a systematic literature search to identify all RCTs, comparing CRTD therapy with implantable cardiac defibrillator (ICD) therapy in patients with SHF (ejection fraction <35%) and QRS ≤130 ms, published in Pubmed, Medline, EMBASE, Cochrane library, and Google scholar from June 1980 through June 2013. The search terms included CRT, QRS duration, narrow QRS, clinical trial, RCT, biventricular pacing, heart failure, systolic dysfunction, dyssynchrony, left ventricular remodelling, readmission, mortality, survival, and various combinations of these terms. We studied the trends of overall mortality, SHF mortality, and hospitalizations due to SHF between the two groups. Heterogeneity of the studies was analysed by Q statistic. A fixed-effect model was used to compute the relative risk (RR) of mortality due to SHF, while a random-effects model was used to compare hospitalization due to SHF. Out of a total of 12 100 citations, four RCTs comparing CRTD vs. ICD therapy in patients with SHF and QRS ≤130 ms fulfilled the inclusion criteria. The median follow-up was 12 months and the cumulative number of patients was 1177. Relative Risk for all-cause mortality in patients treated with CRTD was 1.66 with a 95% CI of 1.096-2.515 (P = 0.017) while for SHF mortality was 1.29 with 95% CI of 0.68-2.45 (P = 0.42). Relative risk for HF hospitalization in patients treated with CRTD was 0.94 with 95% CI of 0.50-1.74 (P = 0.84) in comparison to the ICD group. CONCLUSION: Cardiac-resynchronization therapy defibrillator has no impact on SHF mortality and SHF hospitalization in patients with systolic HF with QRS duration ≤130 ms and is associated with higher all-cause mortality in comparison with ICD therapy.

Retrospective Evaluation on the Analgesic Activities of 2 Compounded Topical Creams and Voltaren Gel in Chronic Noncancer Pain.

Pharmacologic treatment of chronic pain is challenging. Oral therapy may require multiple medications; each has side effects, dose limitations, and limited efficacy. Compounded topical formulations have evolved as potential treatment options. The objective of this study was to evaluate the efficacy of 2 compounded topical creams, "Cream I" and "Cream II," in patients with chronic extremity, joint, musculoskeletal, neuropathic, or other chronic topical pain conditions and compare their efficacy with Voltaren gel. The primary efficacy outcome was the change in visual numeric pain intensity score from pretreatment to posttreatment. The Cream I contained Flurbiprofen (20%), Tramadol (5%), Clonidine (0.2%), Cyclobenzaprine (4%), and Bupivacaine (3%). The Cream II contained Flurbiprofen (20%), Baclofen (2%), Clonidine (0.2%), Gabapentin (10%), and Lidocaine (5%). The Voltaren gel contained 1% diclofenac sodium. A total of 2177 patients were evaluated, 826 males and 1351 females. During their medical treatment, 1141 patients received Cream I, 527 patients received Cream II, and 509 patients received Voltaren gel. After treatment, the pain intensity score decreased by 3.11 ± 1.65 (37%) with Cream I (from 8.44 ± 1.19 to 5.33 ± 2.0, P < 0.001), by 2.93 ± 1.58 (35%) with Cream II (from 8.42 ± 1.27 to 5.50 ± 1.96, P < 0.001), and by 1.49 ± 0.73 (19%) with Voltaren gel (from 7.93 ± 0.81 to 6.44 ± 1.14, P < 0.001). Cream I and Cream II did not differ significantly in efficacy, and both were significantly more effective than Voltaren gel (P < 0.001). It is concluded that Voltaren gel had less efficacy than the compounded creams, which were effective and provided pain relief in the majority of the patients studied.

Retrospective Study on the Analgesic Activity of a Topical (TT-CTAC) Cream in Patients With Diabetic Neuropathy and Other Chronic Pain Conditions.

Treatment of chronic pain in diabetic neuropathy or neuropathic pain of other origins is challenging. Compounded topical formulations have evolved as potential treatment options. The objective of this retrospective study was to evaluate the efficacy of a compounded topical cream (Transdermal Therapeutics). Two versions of TT-CTAC cream were evaluated: cream 6B and cream 7B. Both creams contain ketamine (10%), baclofen (2%), gabapentin (6%), amitriptyline (4%), bupivacaine (2%), and clonidine (0.2%). Additionally, one cream (7B) contains nifedipine (2%). The primary efficacy outcome was the change in numeric pain intensity score from pretreatment to posttreatment. Secondary outcomes were qualitative grading (excellent, good, poor, or no effect), reduction in oral medication, and avoiding referral to a pain specialist. Information on 283 patients was evaluated, 205 received the 7B and 78 received 6B creams. The pain score decreased by 2.4 ± 2.4 (35%) with the 6B cream (from 7.8 ± 1.6 to 5.4 ± 2.0, P < 0.001) and by 3.0 ± 2.4 (40%) with the 7B cream (from 7.5 ± 1.7 to 4.5 ± 2.2, P < 0.001). Excellent or good effects were reported in 82% of the patients in the 6B and in 70% in the 7B groups. Reduction in oral pain medication was seen in 35% of the patients in the 7B and in 20% in the 6B groups. In the opinion of the treating physicians, the cream therapy caused the avoidance of a pain specialist referral in 53% of the patients in the 6B and in 39% in the 7B groups. The creams were equally effective in diabetic neuropathy, neuropathic pain, or other chronic pain states. We conclude that both creams provided excellent pain relief in the majority of the patients studied and may be a useful modality for pain therapy.

Use of noninvasive ventilation in adult patients with acute asthma exacerbation.

Noninvasive ventilation (NIV) has been found to be beneficial for respiratory failure in many disease states; however, limited data are available supporting its use in acute asthma exacerbation. A retrospective chart analysis of adult patients admitted for acute asthma exacerbation and treated with NIV between January 2007 and December 2009 at a tertiary care community hospital was done. Ninety-eight patient encounters were identified. Mean age of the patients was 48.3 years, and 46% were male. Nineteen patients failed NIV and required invasive ventilation. There was no significant difference in the mean age, sex, race, and initial blood gas between patients with successful versus failed NIV. Usage of drugs, smoking, and history of past hospital or intensive care unit admission or intubation did not significantly influence the rate of failure of NIV. Patients who needed higher initial FiO2 were more likely to get intubated during their hospital stay (46.2 vs. 20.4%, P = 0.019). Patients who failed NIV were found to have longer duration of hospital stay (6.8 vs. 3.9 days, P= 0.016) and longer intensive care unit stay (4 vs. 0.9 days, P = 0.002). Use of inhalers and other medications was not found to significantly influence the rate of failure of NIV. NIV can be used initially in patients with acute asthma exacerbation, as it is associated with shorter duration of hospital stay and can prevent the morbidity of mechanical intubation. Patients with initial requirement of higher FiO2 were more likely to fail NIV and should be carefully monitored.

Role of Anemia in Home Oxygen Therapy in Chronic Obstructive Pulmonary Disease Patients.

Anemia is a known comorbidity found in chronic obstructive pulmonary disease (COPD) patients. Hypoxemia is common and basically due to ventilation/perfusion (V/Q) mismatch in COPD. Anemia, by decreasing arterial oxygen content, may be a contributing factor for decreased delivery of oxygen to tissues. The objective of this study is to determine if anemia is a factor in qualifying COPD patients for home oxygen therapy. The study was designed as a retrospective, cross-sectional, observational chart review. Patients who were referred for home oxygen therapy evaluation were selected from the computerized patient record system. Demographic data, oxygen saturation at rest and during exercise, pulmonary function test results, hemoglobin level, medications, reason for anemia, comorbid diseases, and smoking status were recorded. The χ tests, independent sample t tests, and logistic regression were used for statistical analysis. Only 356 of total 478 patient referrals had a diagnosis of COPD over a 2-year period. Although 39 of them were excluded, 317 patients were included in the study. The overall rate of anemia was 38% in all COPD patients. Anemia was found significantly more frequent in COPD patients on home oxygen therapy (46%) than those not on home oxygen therapy (18.5%) (P < 0.0001). Mean saturation of peripheral oxygen values were significantly lower in anemic COPD patients both at rest and during exercise (P < 0.0001). Also, in COPD patients, age, Global Initiative for Chronic Obstructive Lung Disease class, smoking status, hemoglobin level, hematocrit, percent of forced expiratory volume in first second, forced expiratory volume in first second/forced vital capacity, residual volume/total lung volume, percent of carbon monoxide diffusion capacity were significantly different between home oxygen therapy and those not on home oxygen therapy (P < 0.05). Multivariate logistic regression showed that anemia remained a strong predictor for long-term oxygen therapy use in COPD patients after adjusting for other significant parameters. Anemic COPD patients are more hypoxic especially during exercise than those who are not anemic. We conclude that anemia is a contributing factor in qualifying COPD patients for home oxygen therapy.

A Rapid Method to Evaluate Cardiac Repolarization Changes: The Effect of Two Coffee Strengths on the QT Interval.

OBJECTIVES: To assess the effect of coffee on ventricular repolarization as measured by an electrocardiogram. METHODS: Fifty-four healthy volunteers (34 males and 20 females, age 23 ± 5 years) received 1 cup of coffee (caffeine content 120 mg) and 11 participants received 2 cups. Blood pressure and heart rate were measured prior to coffee and every hour thereafter for 5 h. A 12-lead digital Holter recorded continuously, and RR, QT, and QTc intervals were obtained every 30 min. RESULTS: Following coffee, RR increased from 802 ± 102 to 873 ± 126 ms (p = 0.001), QT increased from 359 ± 26 to 367 ± 27 ms at 1.5 h (p = 0.047), and QTc decreased from 387 ± 21 to 381 ± 23 ms at 30 min (p = 0.001), with no changes noted at other time points. Caffeine users and caffeine-naive subjects did not differ in QTc effects (p = 0.971). Females had longer QTc at each time point than males (p = 0.037), but neither had QTc prolongation following coffee. The heart rate decreased from 73 ± 9 to 69 ± 11 bpm at 1 h (p = 0.018), and no significant changes in blood pressure were noted. The effects of 1 or 2 cups of coffee did not differ in terms of QTc (p = 0.663), heart rate (p = 0.161), diastolic (p = 0.250), or systolic blood pressure (p = 0.168). CONCLUSION: Neither 1 nor 2 cups of coffee increased ventricular repolarization.

Potential Augmentation of the Risk of Ischemic Cerebrovascular Accident by Chronic Obstructive Pulmonary Disease in Patients with Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a potent risk factor for ischemic cerebrovascular accident (ICVA). Inflammation is a potential pathogenic factor for atherosclerosis and ICVA. Chronic obstructive pulmonary disease (COPD) is associated with increased inflammatory markers. Subjects who frequently experience COPD and AF together may have higher risk of ICVA. The objective of the study is to compare the prevalence of ICVA in patients with atrial fibrillation and COPD together versus atrial fibrillation alone. METHODS: Subjects diagnosed with COPD, AF, and ICVA were categorized into 3 groups: COPD, AF, and COPD plus AF. Prevalence of ICVA was compared. Confounding factors affecting ICVA risk were recorded: age, diabetes, hypertension, peripheral vascular disease, dyslipidemia, and congestive cardiac failure. RESULTS: Total charts reviewed were 500: COPD alone 244, AF alone 188, and both together 68. ICVA was documented in 132 (26.4%) subjects. Prevalence of ICVA was 11.8% (COPD alone), 29.8% (AF alone), and 39.7% (AF plus COPD). COPD plus AF group had ICVA 2.05 (95% confidence interval [CI], 1.203-3.94; P = .007) times compared with others. ICVA was also higher in patients with AF only versus COPD only (P < .001). Logistic regression showed AF plus COPD was a stronger predictor of ICVA (P = .001) than AF only (P = .07) or COPD only (P = .8). Odds ratio for ICVA was 2.85 (CI, 1.57-5.16; P = .001) for AF plus COPD versus 1.81 (CI, .94-3.47; P = .71) for AF only and 1.08 (CI, .58-2.10; P = .8) for COPD only. CONCLUSIONS: COPD may increase the risk of ischemic stroke in subjects with AF. Presence of COPD may increase the risk of ischemic stroke in subjects with AF.

Genome sequencing and analysis of Mangalica, a fatty local pig of Hungary.

BACKGROUND: Mangalicas are fatty type local/rare pig breeds with an increasing presence in the niche pork market in Hungary and in other countries. To explore their genetic resources, we have analysed data from next-generation sequencing of an individual male from each of three Mangalica breeds along with a local male Duroc pig. Structural variations, such as SNPs, INDELs and CNVs, were identified and particular genes with SNP variations were analysed with special emphasis on functions related to fat metabolism in pigs. RESULTS: More than 60 Gb of sequence data were generated for each of the sequenced individuals, resulting in 11× to 19× autosomal median coverage. After stringent filtering, around six million SNPs, of which approximately 10% are novel compared to the dbSNP138 database, were identified in each animal. Several hundred thousands of INDELs and about 1,000 CNV gains were also identified. The functional annotation of genes with exonic, non-synonymous SNPs, which are common in all three Mangalicas but are absent in either the reference genome or the sequenced Duroc of this study, highlighted 52 genes in lipid metabolism processes. Further analysis revealed that 41 of these genes are associated with lipid metabolic or regulatory pathways, 49 are in fat-metabolism and fatness-phenotype QTLs and, with the exception of ACACA, ANKRD23, GM2A, KIT, MOGAT2, MTTP, FASN, SGMS1, SLC27A6 and RETSAT, have not previously been associated with fat-related phenotypes. CONCLUSIONS: Genome analysis of Mangalica breeds revealed that local/rare breeds could be a rich source of sequence variations not present in cosmopolitan/industrial breeds. The identified Mangalica variations may, therefore, be a very useful resource for future studies of agronomically important traits in pigs.

Genome-wide hypermethylation coupled with promoter hypomethylation in the chorioamniotic membranes of early onset pre-eclampsia.

Pre-eclampsia is the leading cause of fetal and maternal morbidity and mortality. Early onset pre-eclampsia (EOPE) is a disorder that has severe maternal and fetal outcomes, whilst its etiology is poorly understood. We hypothesize that epigenetics plays an important role to mediate the development of EOPE and conducted a case-control study to compare the genome-wide methylome difference between chorioamniotic membranes from 30 EOPE and 17 full-term pregnancies using the Infinium Human Methylation 450 BeadChip arrays. Bioinformatics analysis tested differential methylation (DM) at CpG site level, gene level, and pathway and network level. A striking genome-wide hypermethylation pattern coupled with hypomethylation in promoters was observed. Out of 385 184 CpG sites, 9995 showed DM (2.6%). Of those DM sites, 91.9% showed hypermethylation (9186 of 9995). Over 900 genes had DM associated with promoters. Promoter-based DM analysis revealed that genes in canonical cancer-related pathways such as Rac, Ras, PI3K/Akt, NFκB and ErBB4 were enriched, and represented biological functional alterations that involve cell cycle, apoptosis, cancer signaling and inflammation. A group of genes previously found to be up-regulated in pre-eclampsia, including GRB2, ATF3, NFKB2, as well as genes in proteasome subunits (PSMA1, PMSE1, PSMD1 and PMSD8), harbored hypomethylated promoters. Contrarily, a cluster of microRNAs, including mir-519a1, mir-301a, mir-487a, mir-185, mir-329, mir-194, mir-376a1, mir-486 and mir-744 were all hypermethylated in their promoters in the EOPE samples. These findings collectively reveal new avenues of research regarding the vast epigenetic modifications in EOPE.

Clinical outcomes after percutaneous coronary intervention in patients with mild versus moderate renal insufficiency at 30-day and 1-year follow-up.

Percutaneous coronary intervention (PCI) is a standard of care in the management of coronary artery disease in patients with renal insufficiency (RI). However, outcomes of PCI in these patients remain suboptimal with high cardiovascular morbidity and mortality. The studies comparing target vessel revascularization (TVR) after PCI in patients with mild and moderate RI have shown conflicting results. Hence, a meta-analysis of these studies comparing 30-day and 1-year outcomes after PCI was performed. A systematic review of literature revealed 5 studies involving 16,262 patients. Based on the creatinine clearance (CrCl), patients were divided into 2 groups (mild RI, CrCl > 60 mL/min and moderate RI, CrCl of 30-60 mL/min). End points extracted were all-cause mortality, TVR, myocardial infarction, and major adverse cardiac events at 30-day and 1-year follow-up. Combined relative risks (RR) across all the studies and 95% confidence intervals (CIs) were computed. A 2-sided alpha error of <0.05 was considered statistically significant. Both groups had similar baseline characteristics. Rate of TVR at 30 days was significantly lower in the mild RI group than in the moderate RI group (RR, 1.45; 95% CI, 1.04-2.02; P < 0.05). However, rate of TVR at 1-year follow-up was similar in both groups (RR, 1.02; 95% CI, 0.94-1.11; P, nonsignificant). Incidence of all-cause mortality, TVR, myocardial infarction, and major adverse cardiac events remained higher in the moderate RI group both at 30-day and 1-year follow-up (P < 0.05 for all outcomes). Patients with moderate RI have higher morbidity and mortality at 30 days and 1 year after PCI compared with patients with mild RI. However, there is no difference in the incidence of TVR after PCI at 1 year between the 2 groups.

The role of severity of obstructive sleep apnea measured by apnea-hypopnea index in predicting compliance with pressure therapy, a meta-analysis.

Obstructive sleep apnea (OSA) is associated with diabetes, hypertension, stroke, coronary artery disease, and premature death. Positive airway pressure (PAP) is the mainstay of therapy. Despite its effective treatment with PAP therapy, noncompliance remains high. Many factors determine compliance. The role of severity of OSA measured by the apnea-hypopnea index (AHI) remains controversial. Meta-analysis of studies examining this role of AHI was performed. A systematic review of the medical literature was conducted using PubMed and Cochrane library by utilizing different combinations of key words: sleep apnea, AHI, compliance, and nonadherence. Inclusion criteria were English articles; Studies with adult population; with 2 groups of patients (compliant and noncompliant); Studies utilizing objective definition of compliance (PAP usage of >4 hours per night for 70% of days or usage >5 d/wk and for >4 hours per night). Studies were analyzed by standard methods of meta-analysis. The studies were heterogeneous for AHI; therefore, the random effect model was used. Six hundred forty-one manuscripts were found. Of these, 230 were found to be appropriate for full text evaluation. Thirty-one met inclusion criteria. Twelve of these studies used objective criteria for PAP compliance and were hence included in meta-analysis. All the subjects had OSA determined by polysomnography, for whom PAP was employed. Compliance to PAP therapy was evaluated after a period of time ranging from 4 weeks to 8 years. There were 1438 subjects included in the meta-analysis; 886 subjects were PAP compliant, whereas 552 subjects were noncompliant. A greater AHI was found in PAP compliant patients. The mean difference between compliant and noncompliant groups was 5.9 (95% confidence interval: 0.19-11.67, P < 0.05). Patients with mild OSA are less likely to be compliant with PAP therapy. These patients should receive aggressive management particularly at the start of therapy with close follow-up to increase compliance.

Effect of the full moon on mortality among patients admitted to the intensive care unit.

OBJECTIVE: To determine the lunar effect on mortality among patients admitted to the intensive care unit. METHODS: The retrospective study conducted at Rosalind Franklin University of Medicine and Science, North Chicago, and comprised data of 4387 patients in intensive care unit from December 2002 to November 2004. The subjects were divided into two groups: patients who died on full moon days (the 14th, 15th, and 16th days of the lunar month); and patients who died on the other days of the month. The mortality rates were calculated for patients in both groups. Parameters including patients' age, gender, acute physiology and chronic health evaluation scores, predicted mortality rates, type of intensive care unit, and actual mortality were compared, and non-parametric tests were performed to determine whether there were any differences between the groups. RESULTS: Of the 4387 patients who were followed for 23 months, 297 patients died, including 31 on full moon days and 266 patients on the other days of the month. Both groups were similar in terms of mean age (73.6 +/- 14.59 vs. 71.07 +/- 16.13 years; p = 0.599), acute physiology and chronic health evalutation scores (82.06 +/- 24.19 vs. 76.52 +/- 27.42; p = 0.258), and predicted mortality (0.405 +/- 0.249 vs. 0.370 +/- 0.268; p = 0.305). There was no difference in the frequency of death between the full moon days and the other days (10.33 +/- 0.58 vs. 9.8 +/- 3.46; p = 0.845). CONCLUSIONS: The full moon does not affect the mortality of the patients in intensive care unit.

Introgression and isolation contributed to the development of Hungarian Mangalica pigs from a particular European ancient bloodline.

BACKGROUND: Mangalica breeds are indigenous to Hungary and their breeding history dates back to about 200-250 years ago. They are fat-type pigs and have a rare curly hair phenotype. The aim of our study was to establish the relationships between these unique breeds and other European breeds. RESULTS: Based on a core sequence of 382 bp present in 2713 mitochondrial D-loop sequences from pigs belonging to 38 local breeds from nine countries, five cosmopolitan breeds and wild boars from 14 countries, we identified 164 haplotypes. More than half of the 2713 sequences belonged to either four haplotypes characteristic of continental European breeds or two haplotypes characteristic of British/cosmopolitan breeds; each haplotype is present in more than 100 individuals. Most Mangalica individuals belonged either to one of these common continental European haplotypes or to two Mangalica-specific haplotypes that were absent in all other breeds. In addition, we identified the ancestral mitochondrial D-loop signature present in these 2713 sequences and found that ~ 80% carried the European ancient signatures, ANC-Aside and ANC-Cside or their closely related signatures, while most of the remaining sequences carried a modern Asian signature, ANC-Easia. Mangalica individuals carried the ANC-Aside signature, but not the ANC-Cside or ANC-Easia signatures. CONCLUSIONS: In all the Mangalica individuals, a unique ancient European signature was found in the mitochondrial DNA D-loop region, but they belonged almost exclusively to either certain very abundant European or two Mangalica-specific D-loop haplotypes. This indicates that the present-day Mangalica population in Hungary evolved either by introgression of other European breeds and wild boars or via total isolation after the divergence of European ancient porcine bloodlines.

The Efficacy of Nitric Oxide-Generating Lozenges on Outcome in Newly Diagnosed COVID-19 Patients of African American and Hispanic Origin.

BACKGROUND: The study was initiated in 2020 to test the efficacy of a nitric oxide-generating lozenge (NOL) in outpatients with newly diagnosed COVID-19 to mitigate disease severity. The study enrolled high-risk patients, African American and Latino. METHODS: This was a randomized, double-blinded, prospective, placebo-controlled trial. The primary endpoint was hospitalization, intensive care unit admission, intubation, dialysis, and death. The secondary endpoints were time to symptom resolution and the effect on oxygen saturation. Patients ages 50-85 years with recent COVID-19 diagnosis with at least one risk factor were recruited. Patients were randomized to either active treatment or placebo using block randomization. Blood pressure and oxygen saturation (SpO2) was measured prior to and after the first dose and each morning thereafter. RESULTS: A total of 840 patients was planned, half in each of the lozenge and placebo groups. An interim review of data was prespecified. Of 524 patients, the composite endpoint occurred in 6 patients, 3 (1.1%) in each group. The time to symptom resolution was 1 day shorter on active treatment (8.7 ± 6.6 vs 9.8 ± 6.8 days) (P = .3). There was no change in SpO2 on placebo (0.0 ± 2.0%) and no significant change on treatment (0.14 ± 0.9%), P = .3. All events occurred in the first year (2020). CONCLUSIONS: This study did not find a benefit of NOL therapy in COVID-19 patients and was terminated for futility. NOL treatment did not reduce mortality, hospitalization, intubation, or a reduction in symptoms duration. The study did find the NO lozenges were well tolerated in high-risk patients, without reported side effects.

CYP2C19*2/ABCB1-C3435T polymorphism and risk of cardiovascular events in coronary artery disease patients on clopidogrel: is clinical testing helpful?

BACKGROUND: Studies evaluating CYP2C19*2 and ABCB1-C3435T polymorphisms have shown conflicting results. We performed this meta-analysis to evaluate role of clinical testing for these polymorphisms in CAD patients on clopidogrel. METHODS: 19,601 patients from 14 trials were analyzed. The endpoints were major adverse cardiovascular events (MACE), cardiovascular (CV) death, stent thrombosis (ST), myocardial infarction (MI), stroke and major bleeding. Combined relative risks (RR) with 95% confidence intervals (CI) were computed for each outcome by using standard methods of meta-analysis and test parameters were computed. RESULTS: CYP2C19*2 polymorphism was associated with higher risk of MACE [RR: 1.28, CI: 1.06-1.54; p=0.009], CV death [RR: 3.21, CI: 1.65-6.23; p=0.001], MI [RR: 1.36, CI: 1.12-1.65; p=0.002], ST [RR: 2.41, CI: 1.69-3.41; p<0.001]. No difference was seen in major bleeding events [RR: 1.02, CI: 0.86-1.20; p=0.83]. Subgroup analysis showed similar results for elective PCI [RR: 1.34, CI: 1.01-1.76; p=0.03], and PCI with DES [RR: 1.53, CI: 1.029-1.269; p=0.03]. CYP2C19*2 polymorphism has very low sensitivity (28-58%), specificity (71-73%), positive predictive value (3-10%) but good negative predictive value (92-99%). ABCB1-C3435T polymorphism analysis revealed similar MACE [RR: 1.13, CI: 0.99-1.29; p=0.06], ST [RR: 0.88, CI: 0.52-1.47; p=0.63] and major bleeding [RR: 1.04, CI: 0.87-1.25; p=0.62] in both groups. CONCLUSION: In CAD patients on clopidogrel therapy, CYP2C19*2 polymorphism is associated with significantly increased adverse cardiovascular events. However, due to the low positive predictive value, routine genetic testing cannot be recommended at present.

Effects of music on systolic blood pressure, diastolic blood pressure, and heart rate: a meta-analysis.

There are a handful of studies that have been done investigating the effect of music on various vital signs, namely systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR). Many studies have also assessed effects of music on self-reported anxiety level, attributing some degree of music-induced anxiety relief to the beneficial impacts of music on vital signs. Several randomised studies have shown varying effects of music on these vital parameters and so a meta-analysis was done to compare the effect of music on them. The fixed effects model was used as studies were homogenous. A two-sided alpha error < 0.05 was considered to be statistically significant. Compared to those who did not receive music therapy, those who did receive music therapy had a significantly greater decrease in SBP before and after (difference in means, -2.629, confidence interval (CI), -3.914 to -1.344, P < 0.001), a significantly greater decrease in DBP (difference in means, -1.112, CI, -1.692 to -0.532, P < 0.001), and a significantly greater decrease in HR (difference in means, -3.422, CI, -5.032 to -1.812, P < 0.001).