Qualitative Study of the Patient Experience with Venglustat for Gaucher Disease Type 3 in a Phase 2 Open-Label, Multicenter, Multinational Study (LEAP).

Introduction: Gaucher disease type 3 (GD3) is a genetic, progressive lysosomal storage disorder characterized by visceral manifestations and chronic neurologic symptoms (e.g., horizontal ophthalmoplegia/supranuclear gaze palsy, ataxia, dystonia).

Validation of reference genes for quantitative PCR in the forest pest, Ips calligraphus.

The six-spined ips, Ips calligraphus, is a North American bark beetle that can exploit most eastern North American Pinus species and can cause mortality. Biotic and abiotic disturbances weaken trees, creating breeding substrate that promotes rapid population growth. Management historically relied on silvicultural practices, but as forests become increasingly stressed, innovative management is needed.

Fixing a Fragmented System: Impact of a Comprehensive Geriatric Hip Fracture Program on Long-Term Mortality.

Context: Geriatric hip fractures are increasingly common and confer substantial morbidity and mortality. Fragmentation in geriatric hip fracture care remains a barrier to improved outcomes.

Objective: To evaluate the impact of a comprehensive geriatric hip fracture program on long-term mortality.

Training Emergency Physicians in Ultrasound-guided Fascia Iliaca Compartment Blocks: Lessons in Change Management.

Study objectives Older adults who sustain hip fractures are susceptible to high rates of morbidity and mortality. The systemic administration of opioids is associated with side effects disproportionately affecting the elderly. The ultrasound-guided fascia iliaca compartment block procedure (FICB) is associated with a reduced patient need for oral and parenteral opioids and with improved functional outcomes.

Opioid Utilization and Perception of Pain Control in Hospitalized Patients: A Cross-Sectional Study of 11 Sites in 8 Countries.

Background: Hospitalized patients are frequently treated with opioids for pain control, and receipt of opioids at hospital discharge may increase the risk of future chronic opioid use.

Objective: To compare inpatient analgesic prescribing patterns and patients' perception of pain control in the United States and non-US hospitals.

Design: Cross-sectional observational study.

Reducing Firearm Injuries and Deaths in the United States: A Position Paper From the American College of Physicians.

For more than 20 years, the American College of Physicians (ACP) has advocated for the need to address firearm-related injuries and deaths in the United States. Yet, firearm violence continues to be a public health crisis that requires the nation's immediate attention. The policy recommendations in this paper build on, strengthen, and expand current ACP policies approved by the Board of Regents in April 2014, based on analysis of approaches that the evidence suggests will be effective in reducing deaths and injuries from firearm-related violence.

Association of Crohn's disease-related chromosome 1q32 with ankylosing spondylitis is independent of bowel symptoms and faecal calprotectin.

Background: Genome-wide association studies have identified a plethora of risk genes for both Crohn's disease (CD) and ankylosing spondylitis (AS). A subset of genes found to be risk factors for CD have also been found to be risk factors for AS. The objective of our study was to assess whether CD risk genes were associated with non-invasive clinical markers of gut inflammation in patients with AS, indicating a potential subset of patients with clinical as well as genetic overlap.

Nonsynonymous Polymorphism in Guanine Monophosphate Synthetase Is a Risk Factor for Unfavorable Thiopurine Metabolite Ratios in Patients With Inflammatory Bowel Disease.

Background: Up to 20% of patients with inflammatory bowel disease (IBD) who are refractory to thiopurine therapy preferentially produce 6-methylmercaptopurine (6-MMP) at the expense of 6-thioguanine nucleotides (6-TGN), resulting in a high 6-MMP:6-TGN ratio (>20). The objective of this study was to evaluate whether genetic variability in guanine monophosphate synthetase (GMPS) contributes to preferential 6-MMP metabolizer phenotype.

Methods: Exome sequencing was performed in a cohort of IBD patients with 6-MMP:6-TGN ratios of >100 to identify nonsynonymous single nucleotide polymorphisms (nsSNPs).

Association between ABCG2 rs2231142 and poor response to allopurinol: replication and meta-analysis.

Objective: ABCG2 rs2231142 (Q141K) has been reported to be associated with poor response to allopurinol, while there are conflicting data on the association between the genetically independent ABCG2 rs10011796 variant and allopurinol response. The aim of this study was to replicate the association of ABCG2 rs2231142 and rs10011796 with allopurinol response and perform a meta-analysis.

Methods: Participants in the Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) (n = 299) were studied.

A double-blind, placebo-controlled trial of triheptanoin in adult polyglucosan body disease and open-label, long-term outcome.

Background: Adult polyglucosan body disease (APBD) is a progressive neurometabolic disorder caused by a deficiency of glycogen branching enzyme. We tested the efficacy of triheptanoin as a therapy for patients with APBD based on the hypothesis that decreased glycogen degradation leads to brain energy deficit.

Methods And Results: This was a two-site, randomized crossover trial of 23 patients (age 35-73 years; 63% men) who received triheptanoin or vegetable oil as placebo.

The role of neutrophil gelatinase-associated lipocalin (NGAL) in the detection of blast lung injury in a military population.

Purpose: To study the relationship between serum neutrophil gelatinase-associated lipocalin (NGAL) and military blast and gunshot wound (GSW) to establish whether potential exists for NGAL as a biomarker for blast lung injury (BLI).

Method: Patients from the intensive care unit (ICU) of the Role 3 Medical Treatment Facility at Camp Bastion, Helmand Province, Afghanistan were studied over a five month period commencing in 2012. Age, mechanism, trauma injury severity score (TRISS) and serum NGAL were recorded on ICU admission (NGAL1).

Reduction of Central Line-Associated Bloodstream Infection Rates in Patients in the Adult Intensive Care Unit.

Central line-associated bloodstream infections (CLABSIs) prolong hospital stays and increase cost, morbidity, and mortality. An intensive care unit (ICU) in a suburban Baltimore hospital reduced CLABSI rates to zero in 2012, by revising central venous access device policies and initiatives, which included a bloodstream infection alert system, bundle compliance monitoring and routine evaluation, and use of positive displacement needleless connectors. The hospital's ICU infection rate decreased from 2.

A human leukocyte antigen locus haplotype confers risk for allopurinol-related adverse effects in Caucasian patients with gout.

A human leukocyte antigen haplotype comprising six single-nucleotide polymorphisms (SNPs) confers risk for allopurinol hypersensitivity syndrome in Caucasians. The objective of the current study was to test for association of this haplotype with other, less severe adverse effects (AEs) of allopurinol therapy in a large New Zealand gout cohort. A total of 626 Caucasian and 766 Polynesian patients were genotyped for six SNPs (rs2844665, rs9263715, rs3130931, rs3130501, rs3094188, rs9469003) using TaqMan SNP assays.

Deep intronic GBE1 mutation in manifesting heterozygous patients with adult polyglucosan body disease.

Importance: We describe a deep intronic mutation in adult polyglucosan body disease. Similar mechanisms can also explain manifesting heterozygous cases in other inborn metabolic diseases.

Objective: To explain the genetic change consistently associated with manifesting heterozygous patients with adult polyglucosan body disease.

Correlation between trough plasma dabigatran concentrations and estimates of glomerular filtration rate based on creatinine and cystatin C.

Aims: Dabigatran is largely cleared by renal excretion. Renal function is thus a major determinant of trough dabigatran concentrations, which correlate with the risk of thromboembolic and haemorrhagic outcomes. Current dabigatran dosing guidelines use the Cockcroft-Gault (CG) equation to gauge renal function, instead of contemporary equations including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations employing creatinine (CKD-EPI_Cr), cystatin C (CKD-EPI_Cys) and both renal biomarkers (CKD-EPI_CrCys).

Identification of a novel thiopurine S-methyltransferase allele (TPMT*37).

Thiopurine S-methyltransferase (TPMT) is a key enzyme in the methylation of the thiopurine drugs azathioprine and 6-mercaptopurine. TPMT is subject to genetic polymorphism that results in a trimodal distribution of enzyme activity. All poor methylators (PMs) and 30-60% of intermediate methylators develop potentially life-threatening myelosuppression on standard doses of azathioprine and 6-mercaptopurine because of excess production of the thioguanine nucleotides (6-TGNs).

Prevalence of HLA-B27 in the New Zealand population: effect of age and ethnicity.

Introduction: HLA-B27 genotyping is commonly used to support a diagnosis of ankylosing spondylitis (AS). A recent study has suggested that HLA-B27 may adversely affect longevity. The objectives of this study were to determine, for the first time, the prevalence of HLA-B27 in the New Zealand population, and to test whether HLA-B27 prevalence declines with age.

Association of the HLA locus and TNF with type I autoimmune hepatitis susceptibility in New Zealand Caucasians.

Purpose: The precise etiology of autoimmune hepatitis (AIH) remains unknown, although a number of genetic loci have been implicated in the susceptibility of type 1 AIH. The purpose of this study was to test for association of these loci with type 1 AIH in New Zealand Caucasians.

Methods: 77 AIH patients and 485 healthy controls were genotyped for the SNPs rs2187668 (HLA-DRB*03:01), rs660895 (HLA-DRB*04:01), rs3749971 (HLA-A1-B8-DR3), rs231775 (CLTLA4), rs1800629 (TNF), and rs1800682 (FAS) using predesigned TaqMan SNP genotyping assays.

Frequency of CYP2C9 polymorphisms in Polynesian people and potential relevance to management of gout with benzbromarone.

Objectives: Gout is a major health problem in Polynesians and allopurinol, the drug of choice for the management gout, appears to be less effective in Polynesian patients. The uricosuric drug benzbromarone is an alternative treatment but CYP2C9 poor metabolisers (PMs) may be at a heightened risk of benzbromarone-induced hepatotoxicity. The objectives of this study were to determine the frequency of the PM alleles CYP2C9*2 and CYP2C9*3 in New Zealand (NZ) Caucasian and Polynesian gout cohorts; and then to test for novel CYP2C9 polymorphisms in Polynesians.

Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings.

Objective: Adult polyglucosan body disease (APBD) is an autosomal recessive leukodystrophy characterized by neurogenic bladder, progressive spastic gait, and peripheral neuropathy. Polyglucosan bodies accumulate in the central and peripheral nervous systems and are often associated with glycogen branching enzyme (GBE) deficiency. To improve clinical diagnosis and enable future evaluation of therapeutic strategies, we conducted a multinational study of the natural history and imaging features of APBD.

Adult Polyglucosan Body Disease (APBD): Anaplerotic diet therapy (Triheptanoin) and demonstration of defective methylation pathways.

APBD is a rare disorder most often affecting adults of Ashkenazi Jewish origin due to partial deficiency of the glycogen brancher enzyme (GBE). It is characterized by progressive involvement of both the central and peripheral nervous systems and deposition of amylopectin-like polyglucosan bodies. There have been no metabolic derangements that might suggest effective therapy nor have there been any clinical improvements for control of its relentless progression.

Choice of oils for essential fat supplements can enhance production of abnormal metabolites in fat oxidation disorders.

Patients with mitochondrial long-chain fat oxidation deficiencies are usually treated with diets containing reduced fat and increased carbohydrate, at times via gastrostomy feeding. To ensure adequate intake of essential fatty acids, supplements are provided to their diets using commercially available oils. These oils contain large quantities of non-essential fats that are preferentially oxidized and produce disease-specific metabolites (acyl-CoA intermediates) due to the genetic defect.