Exploring Hong Kong nurses' decision-making processes around presenteeism.

BACKGROUND: Presenteeism among nurses is the common behaviour of being physically present at work when one should not be due to personal health and well-being, a stressful work environment, lack of work-life balance, or a sense of professional identity or obligation. AIMS: To explore nurses' decision-making process related to presenteeism in a large Hong Kong public hospital. METHODS: As part of a larger study on nurse presenteeism in Hong Kong, we conducted focus groups with nurses to understand their considerations related to working sick. RESULTS: Eleven major themes emerged from the focus groups, which we grouped into three organizational domains reflecting nurses' decision-making process around presenteeism: consideration for colleagues, organizational factors and professional identity. CONCLUSIONS: Presenteeism was a familiar behaviour among Hong Kong nurses in our study. We found both overlap and divergence with prior presenteeism research in the domains and themes identified. Loyalty to colleagues, written and unwritten rules and professional identity as nurses all seemed to encourage presenteeism among Hong Kong nurses. Organizations seeking to discourage presenteeism should evaluate policies such as sick leave certificates, ensure appropriate coverage for all nurse ranks and address subcultural norms encouraging presenteeism.

Acute intermittent hypoxia enhances regeneration of surgically repaired peripheral nerves in a manner akin to electrical stimulation.

The intrinsic repair response of injured peripheral neurons is enhanced by brief electrical stimulation (ES) at time of surgical repair, resulting in improved regeneration in rodents and humans. However, ES is invasive. Acute intermittent hypoxia (AIH) - breathing alternate cycles of regular air and air with ~50% normal oxygen levels (11% O2), considered mild hypoxia, is an emerging, promising non-invasive therapy that promotes motor function in spinal cord injured rats and humans. AIH can increase neural activity and under moderately severe hypoxic conditions improves repair of peripherally crushed nerves in mice. Thus, we posited an AIH paradigm similar to that used clinically for spinal cord injury, will improve surgically repaired peripheral nerves akin to ES, including an impact on regeneration-associated gene (RAG) expression-a predictor of growth states. Alterations in early RAG expression were examined in adult male Lewis rats that underwent tibial nerve coaptation repair with either 2 days AIH or normoxia control treatment begun on day 2 post-repair, or 1 h ES treatment (20 Hz) at time of repair. Three days post-repair, AIH or ES treatments effected significant and parallel elevated RAG expression relative to normoxia control at the level of injured sensory and motor neuron cell bodies and proximal axon front. These parallel impacts on RAG expression were coupled with significant improvements in later indices of regeneration, namely enhanced myelination and increased numbers of newly myelinated fibers detected 20 mm distal to the tibial nerve repair site or sensory and motor neurons retrogradely labeled 28 mm distal to the repair site, both at 25 days post nerve repair; and improved return of toe spread function 5-10 weeks post-repair. Collectively, AIH mirrors many beneficial effects of ES on peripheral nerve repair outcomes. This highlights its potential for clinical translation as a non-invasive means to effect improved regeneration of injured peripheral nerves.

Treatment-induced remission of medulloblastoma using a chemotherapeutic regimen devoid of vincristine in a child with Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (cmt) disease is the most common form of inherited neuropathy. Core features include peripheral neuropathy and secondary axonal degeneration, with a noted distal predominance of limb-muscle wasting, weakness, and sensory loss. Given the significant prevalence of cmt, superimposed neoplastic disease can be encountered within this patient population. Malignancies that are treated with vincristine (a microtubule-targeting agent), even at low doses as part of standard treatment, pose a significant challenge for patients with cmt. Here, we present the case of a child with cmt who was successfully treated for medulloblastoma without vincristine, a standard drug used for treatment of that disease, to avoid the risk of severe debilitating neuropathy. This report is the first of a patient successfully treated for medulloblastoma without vincristine.

Demonstration of differences in colonic volumes, transit, chyme consistency, and response to psyllium between healthy and constipated subjects using magnetic resonance imaging.

BACKGROUND: In functional gastrointestinal disorders a lack of objective biomarkers limits evaluation of underlying mechanisms. We aimed to demonstrate the utility of magnetic resonance imaging for this task using psyllium, an effective constipation treatment, in patients and controls. METHODS: Two crossover studies: (i) adults without constipation (controls, n = 9) took three treatments in randomized order for 6 days - maltodextrin (placebo), psyllium 3.5 g t.d.s and 7 g t.d.s., (ii) adults with chronic constipation (patients, n = 20) took placebo and psyllium 7 g t.d.s. for 6 days. MRI was performed fasting and postprandially on day 6. Measurements included small bowel and ascending colon water content, colonic volume, transit time, and MR relaxometry (T1, T2) to assess colonic chyme. Stool water percentage was measured. RESULTS: 7 g psyllium t.d.s. increased fasting colonic volumes in controls from median 372 mL (IQR 284-601) to 578 mL (IQR 510-882), and in patients from median 831 mL (IQR 745-934) to 1104 mL (847-1316), P < .05. Mean postprandial small bowel water was higher in controls and patients after 7 g psyllium t.d.s. vs placebo. Whole gut transit was slower in patients than controls (P < .05). T1 of the descending colon chyme (fasting) was lower in patients (213 ms, 176-420) than controls (440 ms, 352-884, P < .05) on placebo, but increased by 7 g psyllium t.d.s. (590 ms, 446-1338), P < .001. Descending colon T1 correlated with baseline stool water content and stool frequency on treatment. CONCLUSIONS AND INFERENCES: MRI measurements can objectively demonstrate the mode of action of therapy targeting intestinal fluid content in constipation.

Differences in the diagnosis and management of systemic lupus erythematosus by primary care and specialist providers in the American Indian/Alaska Native population.

Objectives The objective of this study is to investigate differences in the diagnosis and management of systemic lupus erythematosus (SLE) by primary care and specialist physicians in a population-based registry. Methods This study includes individuals from the 2009 Indian Health Service lupus registry population with a diagnosis of SLE documented by either a primary care provider or specialist. SLE classification criteria, laboratory testing, and medication use at any time during the course of disease were determined by medical record abstraction. Results Of the 320 individuals with a diagnosis of SLE, 249 had the diagnosis documented by a specialist, with 71 documented by primary care. Individuals with a specialist diagnosis of SLE were more likely to have medical record documentation of meeting criteria for SLE by all criteria sets (American College of Rheumatology, 79% vs 22%; Boston Weighted, 82% vs 32%; and Systemic Lupus International Collaborating Clinics, 83% vs 35%; p < 0.001 for all comparisons). In addition, specialist diagnosis was associated with documentation of ever having been tested for anti-double-stranded DNA antibody and complement 3 and complement 4 ( p < 0.001). Documentation of ever receiving hydroxychloroquine was also more common with specialist diagnosis (86% vs 64%, p < 0.001). Conclusions Within the population studied, specialist diagnosis of SLE was associated with a higher likelihood of having SLE classification criteria documented, being tested for biomarkers of disease, and ever receiving treatment with hydroxychloroquine. These data support efforts both to increase specialist access for patients with suspected SLE and to provide lupus education to primary care providers.

Determining an optimal dose of linaclotide for use in Japanese patients with irritable bowel syndrome with constipation: A phase II randomized, double-blind, placebo-controlled study.

BACKGROUND: Clinical testing to determine a suitable dose of linaclotide for Japanese patients with irritable bowel syndrome with constipation (IBS-C) was needed. METHODS: This was a randomized, double-blind, placebo-controlled, dose-finding trial. Japanese patients with IBS-C diagnosed using Rome III criteria (n = 559, men/women: 49/510) were randomly assigned to 1 of 4 linaclotide doses (0.0625, 0.125, 0.25, or 0.5 mg) or placebo for the 12-week treatment period. The primary endpoint was responder rate of global assessment of relief of IBS symptoms during 12 weeks. The secondary endpoints included responder rates of complete spontaneous bowel movement (CSBM), SBM and abdominal pain/discomfort relief and others. KEY RESULTS: The primary endpoint was 23.2%, 36.2%, 38.7%, 34.8%, and 38.3% in placebo (n = 112), 0.0625 (n = 116), 0.125 (n = 111), 0.25 (n = 112), and 0.5 (n = 107) mg of linaclotide groups with the difference from the placebo group in each linaclotide group (13.0%, 15.5%, 11.6%, 15.1%, P > .05). Monthly responder rate of global assessment of relief of IBS symptoms at month 3 (48.6%), responder rate of CSBM during 12 weeks (45.8%), and responder rate of abdominal pain/discomfort relief during 12 weeks (32.7%) in the 0.5 mg were significantly higher than those in placebo group (29.5%, P < .01; 25.9%, P < .01; and 18.8%, P < .05 respectively). The most frequent adverse event in the linaclotide groups was diarrhea. CONCLUSIONS & INFERENCES: This study suggests that a linaclotide dose of 0.5 mg may be appropriate in Japanese patients with IBS-C.

Crystal structure of a bicupin protein HutD involved in histidine utilization in Pseudomonas.

Cupins form one of the most functionally diverse superfamilies of proteins, with members performing a wide range of catalytic, non-catalytic, and regulatory functions. HutD is a predicted bicupin protein that is involved in histidine utilization (Hut) in Pseudomonas species. Previous genetic analyses have suggested that it limits the upper level of Hut pathway expression, but its mechanism of action is unknown. Here, we have determined the structure of PfluHutD at 1.74 Å resolution in several crystallization conditions, and identified N-formyl-l-glutamate (FG, a Hut pathway intermediate) as a potential ligand in vivo. Proteins 2017; 85:1580-1588. © 2017 Wiley Periodicals, Inc.

Diabetes incidence and prevalence in Hong Kong, China during 2006-2014.

AIMS: To estimate recent secular changes in the incidence and prevalence of diabetes and pre-diabetes among Hong Kong Chinese adults, and thus show possible future trends for developing mainland China. METHODS: Based on a complete census of the public sector health records of 6.4 million people from 2006 to 2014, diabetes cases were ascertained using different methods including the World Health Organization (WHO) 2011 guidelines (HbA1c , fasting plasma glucose and glucose tolerance test), American Diabetes Association (ADA) 2015 guidelines (plus random plasma glucose), and additionally recorded diagnosis codes and medication dispensation. Pre-diabetes was defined using ADA 2015 guidelines. RESULTS: We identified 697 201 people with diabetes (54.2% were incident cases); and 1 229 731 people with diabetes or pre-diabetes. In 2014, the overall incidence of diabetes was 9.46 per 1000 person-years [95% confidence interval (CI): 9.38 to 9.54], and overall prevalence was 10.29% (95% CI: 10.27% to 10.32%). Incidence of diabetes decreased significantly from 2007 to 2014 (quadratic trend, P < 0.001). From 2006 to 2014, the prevalence of diabetes increased significantly in both sexes and across all age groups (quadratic trend, P < 0.001). The overall incidence of pre-diabetes in 2014 was 18.88 per 1000 person-years (95% CI: 18.76 to 18.99), and the overall prevalence of pre-diabetes was 8.90% (95% CI: 8.87% to 8.92%). CONCLUSIONS: Similar to other developed western and Asian populations, diabetes (and pre-diabetes) incidence in Hong Kong Chinese appeared to have stabilized and there have been small declines during the period of observation. Ageing and survivorship will likely drive a continued increase in the prevalence of diabetes and pre-diabetes, albeit with a decelerating growth rate if past trends persist.

The impact of abdominal pain on global measures in patients with chronic idiopathic constipation, before and after treatment with linaclotide: a pooled analysis of two randomised, double-blind, placebo-controlled, phase 3 trials.

BACKGROUND: Few clinical trials in chronic idiopathic constipation (CIC) patients have evaluated abdominal symptom severity and whether CIC patients with abdominal symptoms respond similarly to patients with limited abdominal symptoms. AIMS: To examine abdominal symptom severity and relationships between symptoms and global measures at baseline; compare linaclotide's effect on symptoms in subpopulations with more or less abdominal pain; and assess relationships between symptom improvement and global measures in these two subpopulations. METHODS: In two phase 3 trials, patients meeting modified Rome II CIC criteria were assigned to linaclotide 145 µg, 290 µg, or placebo once daily. Patients rated abdominal and bowel symptoms daily during 2-week pre-treatment and 12-week treatment periods. Linaclotide's effect on symptoms and global measures [constipation severity, health-related quality of life (HRQOL), treatment satisfaction] and their inter-relationships were assessed in post hoc analyses of abdominal pain subpopulations. RESULTS: Of 1271 CIC patients, 23%, 32%, and 43% reported moderate-to-severe abdominal pain, discomfort, and bloating, respectively, during baseline. In more-severe abdominal pain patients, abdominal symptoms were more strongly correlated than bowel symptoms with global measures, but in less-severe abdominal pain patients, abdominal and bowel symptoms were similarly correlated with global measures, at baseline and post-treatment. Linaclotide significantly improved all symptoms and global measures in both subpopulations. CONCLUSIONS: When abdominal pain is present in CIC, abdominal and not bowel symptoms may drive patient assessments of constipation severity, HRQOL, and treatment satisfaction. Linaclotide (145 µg and 290 µg) is an effective treatment for both abdominal and bowel symptoms, even in CIC patients with more severe abdominal pain at baseline. (Clinicaltrials.gov: NCT00765882, NCT00730015).

High-throughput screening identifies compounds that enhance lentiviral transduction.

A difficulty in the field of gene therapy is the need to increase the susceptibility of hematopoietic stem cells (HSCs) to ex vivo genetic manipulation. To overcome this obstacle a high-throughput screen was performed to identify compounds that could enhance the transduction of target cells by lentiviral vectors. Of the 1280 compounds initially screened using the myeloid-erythroid-leukemic K562 cell line, 30 were identified as possible enhancers of viral transduction. Among the positive hits were known enhancers of transduction (camptothecin, etoposide and taxol), as well as the previously unidentified phorbol 12-myristate 13-acetate (PMA). The percentage of green fluorescent protein (GFP)-positive-expressing K562 cells was increased more than fourfold in the presence of PMA. In addition, the transduction of K562 cells with a lentiviral vector encoding fVIII was four times greater in the presence of PMA as determined by an increase in the levels of provirus in genetically modified cells. PMA did not enhance viral transduction of all cell types (for example, sca-1(+) mouse hematopoietic cells) but did enhance viral transduction of human bone marrow-derived CD34(+) cells. Notably, the percentage of GFP-positive CD34(+) cells was increased from 7% in the absence of PMA to greater than 22% in the presence of 1 nM PMA. PMA did not affect colony formation of CD34(+) cells or the expression of the hematopoietic markers CD34 and CD45. These data demonstrate that high-throughput screening can be used to identify compounds that increase the transduction efficiency of lentiviral vectors, identifying PMA as a potential enhancer of lentiviral HSC transduction.

Psychometric validation of symptom severity measures in irritable bowel syndrome with constipation.

BACKGROUND: Historically, measures of symptom severity of irritable bowel syndrome with constipation (IBS-C) in clinical trials have not met the evidence requirements described in the FDA guidance on patient-reported outcomes (PROs), which describes the evidentiary requirements and review criteria for patient-reported outcome measures intended to support product approval or labelling claims. AIM: Data from two phase 3 trials (N = 1608) of linaclotide for the treatment of IBS-C were analysed to evaluate the psychometric properties of patient-reported outcome measures assessing changes in the severity of abdominal and bowel symptoms. METHODS: A set of patient-reported outcome assessments addressing abdominal and bowel symptoms, the IBS-C Symptom Severity Measures, were administered daily using interactive voice response system technology. Intraclass correlation coefficients (ICCs), Pearson correlations, factor analyses, F-tests and effect sizes were computed to evaluate the reliability, construct validity, discriminating ability and responsiveness of the IBS-C Symptom Severity Measures in a clinical trial context. RESULTS: The IBS-C Symptom Severity Measures showed highly satisfactory test-retest reliability (ICCs ranging from 0.79 to 0.95) and construct validity. Factor analyses indicated one factor for abdominal symptoms and another for bowel symptoms. Known-groups F-tests comparing subgroups based on various responder definitions were statistically significant and in the expected direction, substantiating the discriminating ability of the IBS-C Symptom Severity Measures. Responsiveness statistics (ranging from 0.6 to 2.1) demonstrated these measures are also capable of detecting change. CONCLUSIONS: The psychometric analysis results strongly support the reliability, construct validity, discriminating ability and responsiveness of the IBS-C Symptom Severity Measures and substantiate the conclusion of linaclotide treatment benefit.

Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C.

BACKGROUND: US Food and Drug Administration (FDA) set a rigorous standard for defining patient responders in irritable bowel syndrome-C (IBS-C; i.e., FDA's Responder Endpoint) for regulatory approval. However, this endpoint's utility for health-care practitioners to assess clinical response has not been determined. We analyzed pooled IBS-C linaclotide trial data to evaluate clinically significant responses in linaclotide-treated patients who did not meet the FDA responder definition. METHODS: Percentages of FDA non-responders reporting improvement in abdominal pain, bowel function and/or global relief measures were determined using pooled data from two linaclotide Phase 3 IBS-C trials. KEY RESULTS: 1602 IBS-C patients enrolled; 34% of linaclotide-treated and 17% of placebo-treated patients met the FDA Responder Endpoint (p < 0.0001). Among FDA non-responders at week 12, 63% of linaclotide-treated patients reported their abdominal pain was at least somewhat relieved, compared with 48% of placebo-treated patients. For stool frequency, 62% of linaclotide-treated patients reported that they were at least somewhat improved at week 12, compared with 46% of placebo-treated patients. For global IBS symptoms, 65% of linaclotide-treated patients reported at least some IBS-symptom relief, 43% reported adequate relief of IBS symptoms, and 57% reported being satisfied with linaclotide treatment, vs placebo rates of 48%, 34%, and 41% respectively. CONCLUSIONS & INFERENCES: Most linaclotide-treated IBS-C patients who were FDA non-responders reported some improvement in abdominal pain and stool frequency, and global relief/satisfaction. In addition to the FDA Responder Endpoint, differing response thresholds and symptom-specific change from baseline should be considered by clinicians for a complete understanding of clinical response to linaclotide and other IBS-C therapies.

Factors affecting implementation of accreditation programmes and the impact of the accreditation process on quality improvement in hospitals: a SWOT analysis.

OBJECTIVES: The objectives of this review were to identify factors that influence implementation of hospital accreditation programmes and to assess the impact of the accreditation process on quality improvement in public hospitals. DATA SOURCES: Two electronic databases, Medline (OvidSP) and PubMed, were systematically searched. STUDY SELECTION: "Public hospital", "hospital accreditation", and "quality improvement" were used as the search terms. A total of 348 citations were initially identified. After critical appraisal and study selection, 26 articles were included in the review. DATA EXTRACTION: The data were extracted and analysed using a SWOT (strengths, weaknesses, opportunities, threats) analysis. DATA SYNTHESIS: Increased staff engagement and communication, multidisciplinary team building, positive changes in organisational culture, and enhanced leadership and staff awareness of continuous quality improvement were identified as strengths. Weaknesses included organisational resistance to change, increased staff workload, lack of awareness about continuous quality improvement, insufficient staff training and support for continuous quality improvement, lack of applicable accreditation standards for local use, and lack of performance outcome measures. Opportunities included identification of improvement areas, enhanced patient safety, additional funding, public recognition, and market advantage. Threats included opportunistic behaviours, funding cuts, lack of incentives for participation, and a regulatory approach to mandatory participation. CONCLUSIONS: By relating the findings to the operational issues of accreditation, this review discussed the implications for successful implementation and how accreditation may drive quality improvement. These findings have implications for various stakeholders (government, the public, patients and health care providers), when it comes to embarking on accreditation exercises.