Assessing the potential for precision medicine in body weight reduction with regard to type 2 diabetes mellitus therapies: A meta-regression analysis of 120 randomized controlled trials.

Aims: To assess the potential for precision medicine in type 2 diabetes by quantifying the variability of body weight as response to pharmacological treatment and to identify predictors which could explain this variability.

Methods: We used randomized clinical trials (RCTs) comparing glucose-lowering drugs (including but not limited to sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and thiazolidinediones) to placebo from four recent systematic reviews. RCTs reporting on body weight after treatment to allow for calculation of its logarithmic standard deviation (log[SD], i.

Risk-adjusted management in catheterization procedures for non-ST-segment elevation myocardial infarction: A standard operating procedure pilot study.

Background: The effects of standardized risk-adjusted periprocedural management of cardiac catheterization procedures in Non-ST segment elevation myocardial infarction (NSTEMI) remain unknown. We implemented a standard operating procedure (SOP) specifying risk assessment (RA, using National Cardiovascular Data Registry (NCDR) risk models) and risk-adjusted management (RM, e.g.

Meta-analysed numbers needed to treat of novel antidiabetic drugs for cardiovascular outcomes.

Aims: Absolute treatment effects-i.e. numbers needed to treat (NNTs)-of novel antidiabetic drugs for cardiovascular outcomes have not been comprehensively evaluated.

Predicting exon criticality from protein sequence.

Alternative splicing is frequently involved in the diversification of protein function and can also be modulated for therapeutic purposes. Here we develop a predictive model, called Exon ByPASS (predicting Exon skipping Based on Protein amino acid SequenceS), to assess the criticality of exon inclusion based solely on information contained in the amino acid sequence upstream and downstream of the exon junctions. By focusing on protein sequence, Exon ByPASS predicts exon skipping independent of tissue and species in the absence of any intronic information.

Endogenous ADAR-mediated RNA editing in non-human primates using stereopure chemically modified oligonucleotides.

Technologies that recruit and direct the activity of endogenous RNA-editing enzymes to specific cellular RNAs have therapeutic potential, but translating them from cell culture into animal models has been challenging. Here we describe short, chemically modified oligonucleotides called AIMers that direct efficient and specific A-to-I editing of endogenous transcripts by endogenous adenosine deaminases acting on RNA (ADAR) enzymes, including the ubiquitously and constitutively expressed ADAR1 p110 isoform. We show that fully chemically modified AIMers with chimeric backbones containing stereopure phosphorothioate and nitrogen-containing linkages based on phosphoryl guanidine enhanced potency and editing efficiency 100-fold compared with those with uniformly phosphorothioate-modified backbones in vitro.

Control of backbone chemistry and chirality boost oligonucleotide splice switching activity.

Although recent regulatory approval of splice-switching oligonucleotides (SSOs) for the treatment of neuromuscular disease such as Duchenne muscular dystrophy has been an advance for the splice-switching field, current SSO chemistries have shown limited clinical benefit due to poor pharmacology. To overcome limitations of existing technologies, we engineered chimeric stereopure oligonucleotides with phosphorothioate (PS) and phosphoryl guanidine-containing (PN) backbones. We demonstrate that these chimeric stereopure oligonucleotides have markedly improved pharmacology and efficacy compared with PS-modified oligonucleotides, preventing premature death and improving median survival from 49 days to at least 280 days in a dystrophic mouse model with an aggressive phenotype.

Receiving Recognition: A Case for Occupational Therapy Practitioners as Mental and Behavioral Health Providers.

Importance: An analysis by the Substance Abuse and Mental Health Services Administration (SAMHSA; 2015a) found that an additional 10,000 mental health care providers will be needed by 2025 to meet the expected growth in demand for treatment of people with mental illness, substance use disorder, or both. Despite being the largest payer of mental health services in the United States, the Medicaid program has extremely low numbers of mental health providers (Frank et al., 2003).

National Cardiovascular Data Registry-Acute Kidney Injury (NCDR) vs. Mehran risk models for prediction of contrast-induced nephropathy and need for dialysis after coronary angiography in a German patient cohort.

Background: Contrast-induced nephropathy (CIN) is a major adverse event in patients undergoing coronary angiography. The Mehran risk model is the gold-standard for CIN risk prediction. However, its performance in comparison to more contemporary National Cardiovascular Data Registry-Acute Kidney Injury (NCDR-AKI) risk models remains unknown.

Federal Indian Law as a Structural Determinant of Health.

Federal Indian law is the body of law that defines the rights, responsibilities, and relationships between three sovereigns, Tribes, states, and the federal government. This area of law has defined, oftentimes poorly, the contours of treaty rights, criminal and civil jurisdiction, economic development, among other issues. Much has been documented in terms of the implications of social, legal, political, and economic systems that perpetuate inequities amongst American Indian and Alaska Native populations.

State statutes and regulations related to human papillomavirus vaccination.

A cross-sectional analysis of human papillomavirus (HPV) vaccine statutes and regulations from states and the District of Columbia in the United States (U.S.) was conducted from September-November 2018 to advance analyses of policy impact on HPV vaccination uptake.

Integration of genomic and clinical data augments surveillance of healthcare-acquired infections.

Background: Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.

Objective: To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.

Association of State Laws With Influenza Vaccination of Hospital Personnel.

Introduction: Healthcare personnel influenza vaccination can reduce influenza illness and patient mortality. State laws are one tool promoting healthcare personnel influenza vaccination.

Methods: A 2016 legal assessment in 50 states and Washington DC identified (1) assessment laws: mandating hospitals assess healthcare personnel influenza vaccination status; (2) offer laws: mandating hospitals offer influenza vaccination to healthcare personnel; (3) ensure laws: mandating hospitals require healthcare personnel to demonstrate proof of influenza vaccination; and (4) surgical masking laws: mandating unvaccinated healthcare personnel to wear surgical masks during influenza season.

Evolution and mutations predisposing to daptomycin resistance in vancomycin-resistant Enterococcus faecium ST736 strains.

We recently identified a novel vancomycin-resistant Enterococcus faecium (VREfm) clone ST736 with reduced daptomycin susceptibility. The objectives of this study were to assess the population dynamics of local VREfm strains and genetic alterations predisposing to daptomycin resistance in VREfm ST736 strains. Multilocus sequence typing and single nucleotide variant data were derived from whole-genome sequencing of 250 E.

[Changes in Patient and Disease Characteristics in a Psychiatric Clinic After Adopting the Model of Sectorized Mandatory Care].

Background: Regional mandatory care is a special feature of psychiatric inpatient care in Germany. There is practically no systematic information on the changes in patient and disease characteristics a clinic is confronted with when adopting regional mandatory care.

Method: Changes in inpatient characteristics were assessed by analyzing the whole set of the basic documentation inpatient data (BADO) of 2 years at Schlosspark-Klinik in Berlin (SPK) which switched to mandatory care in one regional sector in the year between the 2 years.

Clinical relevance of copeptin plasma levels as a biomarker of disease severity and mortality in critically ill patients.

Background: Copeptin, also termed C-terminal pre-pro-vasopressin or CTproAVP, mirrors endogenous vasopressin (anti-diuretic hormone, ADH) activity and might thereby serve as a biomarker reflecting the biological stress level. We therefore hypothesized that copeptin plasma concentrations are associated with disease severity in critically ill patients and could predict mortality.

Methods: We analyzed plasma copeptin levels in a prospective, single-center, observational study comprising 218 critically ill patients at admission to the medical intensive care unit (ICU).

Predicting pharmacy naloxone stocking and dispensing following a statewide standing order, Indiana 2016.

Background: While naloxone, the overdose reversal medication, has been available for decades, factors associated with its availability through pharmacies remain unclear. Studies suggest that policy and pharmacist beliefs may impact availability. Indiana passed a standing order law for naloxone in 2015 to increase access to naloxone.

The Latest in Vaccine Policies: Selected Issues in School Vaccinations, Healthcare Worker Vaccinations, and Pharmacist Vaccination Authority Laws.

This paper discusses recent changes to state legal frameworks for mandatory vaccination in the context of school and healthcare worker vaccination. It then discusses state laws that allow pharmacists the authority to vaccinate.

miR-149 and miR-29c as candidates for bipolar disorder biomarkers.

Bipolar disorder (BD) is a common, recurring psychiatric illness with unknown pathogenesis. Recent studies suggest that microRNA (miRNA) levels in brains of BD patients are significantly altered, and these changes may offer insight into BD pathology or etiology. Previously, we observed significant alterations of miR-29c levels in extracellular vesicles (EVs) extracted from prefrontal cortex (Brodmann area 9, BA9) of BD patients.

State Laws Requiring Hand Sanitation Stations at Animal Contact Exhibits-United States, March-April 2016.

In the United States, animal contact exhibits, such as petting zoos and agricultural fairs, have been sources of zoonotic infections, including infections with Escherichia coli, Salmonella, and Cryptosporidium (1-4). The National Association of State Public Health Veterinarians recommends handwashing after contact with animals as an effective prevention measure to disease transmission at these exhibits (4). This report provides a list of states that have used law, specifically statutes and regulations, as public health interventions to increase hand sanitation at animal contact exhibits.

Novel microRNA discovery using small RNA sequencing in post-mortem human brain.

Background: MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression mainly through translational repression of target mRNA molecules. More than 2700 human miRNAs have been identified and some are known to be associated with disease phenotypes and to display tissue-specific patterns of expression.

Methods: We used high-throughput small RNA sequencing to discover novel miRNAs in 93 human post-mortem prefrontal cortex samples from individuals with Huntington's disease (n = 28) or Parkinson's disease (n = 29) and controls without neurological impairment (n = 36).

State Public Health Enabling Authorities: Results of a Fundamental Activities Assessment Examining Core and Essential Services.

Context: Public health enabling authorities establish the legal foundation for financing, organizing, and delivering public health services. State laws vary in terms of the content, depth, and breadth of these fundamental public health activities. Given this variance, the Institute of Medicine has identified state public health laws as an area that requires further examination.