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Background: Huntington disease (HD) is a genetic neurodegenerative disease leading to progressive motor, cognitive, and behavioral decline. Subtle changes in these domains are detectable up to 15 years before a definitive motor diagnosis is made. This period, called prodromal HD, provides an opportunity to examine lifestyle behaviors that may impact disease progression., Theoretical Framework: Physical activity relates to decreased rates of brain atrophy and improved cognitive and day-to-day functioning in Alzheimer disease and healthy aging populations. Previous research has yielded mixed results regarding the impact of physical activity on disease progression in HD and paid little attention to the prodromal phase., Methods: We conducted analyses of associations among current physical activity level, current and retrospective rate of change for hippocampus and striatum volume, and cognitive, motor, and day-to-day functioning variables. Participants were 48 gene-expanded cases with prodromal and early-diagnosed HD and 27 nongene-expanded control participants. Participants wore Fitbit Ultra activity monitors for three days and completed the self-reported International Physical Activity Questionnaire (IPAQ). Hippocampal and striatal white matter volumes were measured using magnetic resonance imaging. Cognitive tests included the Stroop Color and Word Test, and the Symbol Digit Modalities Test (SDMT). Motor function was assessed using the Unified Huntington's Disease Rating Scale total motor score (TMS). Day-to-day functioning was measured using the World Health Organization Disability Assessment Schedule (WHODAS) version 2.0., Results: Higher Fitbit activity scores were significantly related to better scores on the SDMT and WHODAS in case participants but not in controls. Fitbit activity scores tracked better with TMS scores in the group as a whole, though the association did not reach statistical significance in the case participants. Higher Fitbit activity scores related to less day-to-day functioning decline in retrospective slope analyses. Fitbit activity scores did not differ significantly between cases and controls., Conclusions: This is the first known study examining the associations between activity level and imaging, motor, cognitive, and day-to-day functioning outcomes in prodromal and early HD. Preliminary results suggest physical activity positively correlates with improved cognitive and day-to-day functioning and possibly motor function in individuals in the prodromal and early phase of the condition.

The Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5), recommends the World Health Organization Disability Assessment Schedule (WHODAS) 2.0 for routine clinical use. We tested the utility of the 12-item WHODAS 2.0 in prodromal Huntington disease. Using data from 726 participants and 630 companions over a 3-year follow-up, linear mixed models were fitted to test (1) baseline and longitudinal differences by progression group; (2) participant and companion differences within each group; and (3) sensitivity of the 12-item WHODAS in comparison to the 36-item WHODAS and the Total Functional Capacity (TFC) score from the Unified Huntington's Disease Rating Scale. Participants showed baseline group differences whereas companions showed baseline and longitudinal group differences. Companions reported worse functional decline over time than participants as the disease progresses. The 12-item WHODAS detected longitudinal change better than the 36-item WHODAS and the TFC in the medium progression group. Results suggest the 12-item WHODAS 2.0 can detect baseline and longitudinal differences in prodromal HD and may be useful in HD clinical trials.

Background: Spironolactone, the only aldosterone antagonist available in China, improves outcomes in acute myocardial infarction (AMI) among patients with systolic dysfunction and either diabetes or heart failure (HF). However, national practice patterns in the use of spironolactone in China are unknown., Methods and Results: From a nationally representative sample of AMI patients from in 2001, 2006, and 2011, we identified 6906 patients with either diabetes or HF and classified them into 1 of 4 groups according to their eligibility for spironolactone-"ideal"(left ventricular ejection fraction [LVEF] ≤40% and without contraindications), "contraindicated," "not indicated" (neither ideal nor contraindicated), and "unknown indications" (LVEF unmeasured)-to determine how frequently patient eligibility for this drug is assessed in the hospital, how it is used in several groups, and to identify factors associated with the use in these groups. From 2001 to 2011, the proportion of patients whose eligibility for spironolactone was not assessed decreased (66.9% in 2001 to 32.8% in 2011). Spironolactone use significantly increased among ideal patients over this period (28.6% to 72.4%; P<0.001 for trend), but also in contraindicated patients (11.4% to 27.5%; P=0.002 for trend) and in other patients groups (not indicated: 27.5% to 38.3%; unknown indications: 21.3% to 35.1%; both P<0.01 for trend). In all 4 groups, patients presenting with HF on admission were more likely to receive spironolactone., Conclusions: Although the appropriate use of spironolactone and assessment of eligibility increased in China over the past decade, there remains marked opportunities for improvement., Clinical Trial Registration: URL: http://www.clinicaltrials.gov Unique identifier: NCT01624883., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc, by Wiley Blackwell.)

Objective: Assessment of daily functions affected by cognitive loss in prodromal Huntington's disease (HD) is necessary in practice and clinical trials. We evaluated baseline and longitudinal sensitivity of the Everyday Cognition (ECog) scales in prodromal HD and compared self- and companion-ratings., Method: Everyday cognition was self-assessed by 850 participants with prodromal HD and 768 companions. We examined internal structure using confirmatory factor analysis (CFA) on baseline data. For longitudinal analysis, we stratified participants into Low, Medium, and High disease progression groups. We examined ECog scores for group differences and participant-and-companion differences using linear mixed effects regression (LMER). Comparison with the Total Functional Capacity (TFC) scale was made., Results: CFA revealed good fit of a 5-factor model having a global factor (total score), and subfactors (subscales) of memory, language, visuospatial perception, and executive function. At study entry, participants and companions in the Medium and High groups reported significantly worsened everyday cognition as well as significant functional decline over time. Losses became more pronounced and participant and companion ratings diverged as individuals progressed. TFC showed significant functional loss over time in the High group but not in the Medium group., Conclusions: Disease progression is associated with reduced self- and companion-reported everyday cognition in prodromal HD participants who are less than 13 years to estimated motor onset. Our findings suggest companion ratings are more sensitive than participants' for detecting longitudinal change in daily cognitive function. ECog appears more sensitive to specific functional changes in the prodrome of HD than the TFC., (PsycINFO Database Record (c) 2015 APA, all rights reserved.)

In the United States, the ability to securely exchange health information between organization has been limited by technical interoperability, patient identity matching, and variable institutional policies. Here, we examine the regional experience in a national health information exchange network by examining clinical data sharing between eleven Northern California organizations using the same health information exchange (HIE) platform between 2013-2014. We identify key policies and technologies that have led to a dramatic increase in health information exchange.

Background: The European Medicines Agency (EMA) and national regulators share the responsibility to communicate to healthcare providers postmarketing safety events but little is known about the consistency of this process. We aimed to compare public availability of safety-related communications and drug withdrawals from the EMA and European Union member countries for novel medicines., Methods and Findings: We performed a cross-sectional analysis using public Dear Healthcare Professional Communications (DHPCs) for all novel medicines authorized between 2001 and 2010 by the EMA and available for use in France, Netherlands, Spain, and the United Kingdom. Between 2001 and 2010, the EMA approved 185 novel medicines. DHPCs could not be ascertained for the EMA. Among the 4 national regulators, as of April 30, 2013, at least one safety DHPC or withdrawal occurred for 53 (28.6%) medicines, totaling 90 DHPCs and 5 withdrawals. Among these 53 medicines, all 4 national agencies issued at least one communication for 17 (32.1%), three of the four for 25 (47.2%), two of the four for 6 (11.3%), and one of the four for 5 (9.4%). Five drugs were reported to be withdrawn, three by all four countries, one by three and one by two. Among the 95 DHPCs and withdrawals, 20 (21.1%) were issued by all 4 national regulators, 37 (38.9%) by 3 of the 4, 22 (23.2%) by 2 of the 4, and 16 (16.8%) by one. Consistency of making publicly available all identified safety DHPC or withdrawal across regulator pairs varied from 33% to 73% agreement., Conclusions: Safety communications were not made publicly available by the EMA. Among the 4 European member countries with national regulators that make DHPCs publicly available since at least 2001, there were substantial inconsistencies in safety communications for novel medicines. The impact of those inconsistencies in terms of public health remains to be determined.

Purpose: Determine availability of emergency contraception (EC) at rural and urban pharmacies in Kansas., Methods: A sample of 201 Kansas pharmacies was selected using a random integer generator. We measured ability to dispense EC within 24 hours and whether it was in stock at the time of the survey call. We examined EC availability based on geographic differences and pharmacy type., Findings: Of the sample, 186 pharmacists agreed to be interviewed. Of these, 19% (n = 36) were unable to provide EC within 24 hours. There were essentially no differences in availability of EC between rural (75% could dispense in 24 hours) and urban pharmacies (85% could dispense in 24 hours) (P= .105). Corporate pharmacies were more likely to be able to provide EC within 24 hours compared to independent pharmacies (OR = 3.79, CI 1.71-8.43). Thirty-one percent (n = 57) of pharmacists did not carry EC at the time of the survey call. With this sample, urban pharmacies were more than twice as likely to report carrying EC compared to rural pharmacies (OR = 2.47, CI 1.31-4.68), and corporate pharmacies were also more likely to report carrying EC compared to independent pharmacies (OR = 7.77, CI 3.72-16.21)., Conclusions: In a sample of Kansas pharmacies, there were no differences between rural and urban pharmacies in 24-hour EC availability; however, there were differences in those who stocked EC at the time of the survey call. Corporate pharmacies were more likely to dispense EC within 24 hours and have it in stock compared to independent pharmacies, suggesting differences in availability of EC., (© 2012 National Rural Health Association.)

Although there are numerous position papers on the issues and challenges surrounding disclosure of incidental genomic findings involving children, there is very little research. To fill this gap, the purpose of this study was to explore the perspectives of multiple professional (N = 103) and public (N = 63) stakeholders using both interviews and focus groups. Using qualitative analysis, we identified one overarching theme, "It's hard for us; it's hard for them," and three subthemes/questions: "What to disclose?," "Who gets the information?," and "What happens later?" Perspectives differed between professional (Institutional Review Board chairs, clinicians, and researchers) and public stakeholders. While professionals focused on the complexities of what to disclose, the lay public stated that parents should have all information laid out for them. Professionals pondered multiple parent and child situations, while the public identified parents as informational gatekeepers who know their children best. Professionals described the potential requirement for follow-up over time as a logistical "nightmare," while the public believed that parents have the responsibility for managing their children's health information over time. However, the parent role as gatekeeper was seen as time limited and in need of professional support and backup. Our findings present a case for needed dialogue around what we propose as an "ethically important moment," with the goal of protecting and respecting the viewpoints of all stakeholders when policies regarding children are developed.

Depression causes significant morbidity and mortality, and this also occurs in Huntington Disease (HD), an inherited neurodegenerative illness with motor, cognitive, and psychiatric symptoms. The presentation of depression in this population remains poorly understood, particularly in the prodromal period before development of significant motor symptoms. In this study, we assessed depressive symptoms in a sample of 803 individuals with the HD mutation in the prodromal stage and 223 mutation-negative participants at the time of entry in the Neurobiological Predictors of HD (PREDICT-HD) study. Clinical and biological HD variables potentially related to severity of depression were analyzed. A factor analysis was conducted to characterize the symptom domains of depression in a subset (n=168) with clinically significant depressive symptoms. Depressive symptoms were found to be more prevalent in HD mutation carriers but did not increase with proximity to HD diagnosis and were not associated with length of the HD mutation. Increased depressive symptoms were significantly associated with female gender, self-report of past history of depression, and a slight decrease in functioning, but not with time since genetic testing. The factor analysis identified symptom domains similar to prior studies in other populations. These results show that individuals with the HD mutation are at increased risk to develop depressive symptoms at any time during the HD prodrome. The clinical presentation appears to be similar to other populations. Severity and progression are not related to the HD mutation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: A work function measure specific for persons with prodromal Huntington disease (HD) was created to assist with workplace accommodations., Methods: A self-report HD Work Function (HDWF) measure was developed from focus group and expert validation., Results: Pilot studies with 238 people with prodromal HD, and 185 companions; and 89 people without prodromal HD, and 70 companions indicate that HDWF has acceptable internal consistency (Cronbach α = 0.77), acceptable interrater reliability (r = 0.58), and acceptable convergent validity with selected items from the Endicott Work Productivity Scale (r = -0.56), Social Adjustment Scale-Self Report (r = -0.29), and Everyday Cognition (r = -0.70). The HDWF can distinguish between people with prodromal HD and people with an HD family history who do not have prodromal HD (P < 0.0001)., Conclusions: The HDWF is a brief self-assessment that may be used to monitor work function.

Aims: Genomic research can produce findings unrelated to a study's aims. The purpose of this study was to examine researcher and Institutional Review Board (IRB) chair perspectives on genomic incidental findings (GIFs)., Methods: Nineteen genomic researchers and 34 IRB chairs from 42 institutions participated in semi-structured telephone interviews. Researchers and chairs described GIFs within their respective roles. Few had direct experience with disclosure of GIFs. Researchers favored policies where a case by case determination regarding whether GIF disclosure would be offered after discovery, whereas IRB chairs preferred policies where procedures for disclosure would be determined prior to approval of the research., Conclusions: Researcher and IRB chair perspectives on management of GIFs overlap, but each group provides a unique perspective on decisions regarding disclosure of GIFs in research. Engagement of both groups is essential in efforts to provide guidance for researchers and IRBs regarding disclosure of GIFs in research.

This study examines perceived stress and its relationship to depressive symptoms, life changes and functional capacity in a large sample of individuals who are positive for the Huntington disease (HD) gene expansion but not yet diagnosed. Participants were classified by estimated proximity to HD diagnosis (far, mid, near) and compared with a non-gene-expanded comparison group. Persons in the mid group had the highest stress scores. A significant interaction between age and time since HD genetic testing was also found. Secondary analyses using data from a different data collection point and including a diagnosed group showed the highest stress scores in the diagnosed group. Possible explanations and implications are discussed.

Day-to-day functioning is a component of health-related quality of life and is an important end point for therapies to treat Huntington Disease (HD). Specific areas of day-to-day function changes have not been reported for prodromal or very early stages of HD. An exploratory self-report telephone interview was conducted with sixteen people with prodromal HD or early HD who met criteria designed to capture research participants most near to motor diagnosis. All completed semi-structured interviews on function in nine aspects of day-to-day life. Out of 16, 14 reported changes in at least one area. All day-to-day function areas were endorsed by at least one participant with driving being the most common area endorsed by 11/16. Changes in ability to perform some day-to-day tasks are experienced by people who are close to the time of clinical diagnosis for HD. Functional ability is likely to be an important component of outcome assessments of clinical trials and in ongoing clinical management.

This study assessed whether nonunion of displaced scaphoid waist fractures with nonoperative treatment could be predicted from 4 week CT scans. Thirty-one patients with unilateral displaced scaphoid waist fractures and adequate follow-up were included. CT scans in the longitudinal axis of the scaphoid with sagittal and coronal slices were done 4 weeks after the index injury. The effects of fracture gap, sclerosis and bone resorption on union were assessed. Fracture union was observed in all 13 displaced fractures with a < 2 mm gap, four of the seven with a gap of 2-3 mm and only four of the 11 with a gap > 3 mm (p = 0.01). Bone resorption involving more than 50% of the fracture cross-section was also associated with nonunion, but sclerosis was not.

This prospective study investigated a cohort of 59 scaphoid waist fractures which were treated nonoperatively in a below-elbow plaster cast for 4 weeks and then underwent a Week 4 CT scan to assess displacement and progress to union. Forty-three were classed as undisplaced and 37 of these 43 were also classed as 'united'. All the 37 undisplaced and 'united' fractures united with up to 8 weeks' cast immobilisation, including 26 which were taken out of plaster at 4 weeks and mobilised. We conclude that scaphoid waist fractures which appear to be undisplaced and united on a week 4 CT scan will unite, and may not need to be immobilised in a plaster cast for more than 4 weeks. Such a treatment policy may reduce the period of disability and time off work associated with nonoperative treatment.

Intramedullary stabilization of metacarpal shaft and neck fractures is a relatively simple, cost-effective, and safe technique with good published outcomes (Fig. 9); however definite advantages over other techniques of fracture stabilization, or indeed simple early mobilization in some instances, have not been clearly demonstrated. A recent publication does suggest that the technique is comparable to percutaneous transverse fixation in the context of fifth metacarpal neck fractures.

Changes in reef benthos were assessed at Aldabra Atoll following the mass coral bleaching event of 1998. Video transects were used to survey the benthos and analysed using the Australian Institute of Marine Science five-dot method. Comparison of coral cover data collected by the Cambridge Southern Seychelles Atoll Research Programme with data collected during this study revealed that mortality of coral at Aldabra following the bleaching event was approximately 66% at 10 m depth and 38% at 20 m depth. Five years on, there are signs of hard coral recovery at some locations, but in spite of several years of high coral recruitment (7-9 recruits per m2 at 10 m depth, 4-6 recruits per m2 at 20 m depth, where recruits are defined as any colony under 5 cm maximum diameter), recovery of hard coral has not occurred at a significant level. There has been a considerable increase in soft coral cover at some locations, which was dominated by the genus Rhytisma. Macro algal cover did not increase following the bleaching event, although, as would be expected, dead corals have been colonized by coralline algae. There have been no further events leading to large-scale coral mortality at Aldabra since 1998.

Quantitative surveys of fish-species diversity were undertaken at 10 m and 20 m water depth on the outer reef at Aldabra Atoll, southern Seychelles, between November 1999 and May 2003. No significant changes in total fish-species diversity, numbers of families represented by these species, or numbers of pomacentrid or chaetodontid species were seen, contrary to fish-diversity changes seen on coral bleaching-impacted reefs elsewhere. The lack of additional anthropogenic pressures at remote Aldabara may make this system, and others like it, more tolerant of bleaching-related population changes.

This study investigated whether the outcome of bone graft and internal fixation surgery for nonunion of scaphoid fractures could be predicted by gadolinium-enhanced MR assessments of proximal fragment vascularity. Sixteen established scaphoid fracture nonunions underwent gadolinium-enhanced MR scanning before surgical treatment with bone grafting and internal fixation. No relationship was found between MR enhancement and the outcome of surgery. Union was achieved in eight of the 12 nonunions with more than 50% enhancement, and three of the four with less than 50% enhancement, of the proximal pole. Furthermore, union was achieved in both of the nonunions which had less than 25% enhancement of the proximal pole. We conclude that enhanced MR assessments of the vascularity of the proximal fragment of a scaphoid fracture nonunion do not accurately predict the outcome of reconstructive surgery.

Seventy-three thumbs in 67 women with osteoarthritis of the trapeziometacarpal joint were assessed prospectively. The patients were randomly allocated for treatment by either trapeziectomy alone (n = 26) or trapeziectomy with tendon interposition (n = 23) or ligament reconstruction (n = 24). A K-wire was passed through the thumb metacarpal base and across the trapezial space into the distal pole of the scaphoid in all procedures; this held the base of the metacarpal away from the scaphoid for 4 weeks. Standard thumb radiographs were used to calculate the trapezial space ratio before surgery and at 1-year follow-up examination. The trapezial space ratio decreased significantly from a preoperative mean of 0.40 (range, 0.20-0.56) to a mean of 0.18 (range, 0.08-0.30) after trapeziectomy, 0.16 (range, 0.07-0.30) after trapeziectomy with tendon interposition, and 0.20 (range, 0.00-0.33) after trapeziectomy with ligament reconstruction. There was no significant difference between these 1-year follow-up trapezial space ratios, suggesting that the placement of a K-wire across the trapezial void is as effective as tendon interposition or ligament reconstruction in creating a trapezial space in the short term at least. However, the need to create a trapezial space and maintain thumb length is questioned because the trapezial space height did not correlate with thumb strength at 1-year follow-up examination.

Contact with rat saliva or faeces can lead to infection with Streptobacillus moniliformis and the condition known as 'rat bite fever'. We report a case of septic arthritis of the hip due to this organism following a bite on the finger of a 14-year-old boy from a rat for sale in a pet shop. The case was successfully treated by arthrotomy, drainage and joint lavage followed by administration of penicillin. Septic arthritis of the hip due to S. moniliformis has not been previously described and this case highlights a possible danger of keeping rats as pets.

We studied the hip abductor strength and Trendelenburg test prospectively in 100 patients undergoing total hip replacement via a lateral or posterior approach. In 49 patients, we used the lateral approach to implant the Charnley total hip replacement, and in 51 patients, the posterior approach to implant the Exeter total hip. Isometric abductor strength was measured with the kinetic communicator device and the Trendelenburg test was recorded preoperatively and at 3 and 12 months postoperatively. Of the original 100 patients, 83 were available for study at 3 months and 73 at 12 months. Hip abductor strength and the Trendelenburg test improved postoperatively in both groups, but we found no difference in hip abductor strength recovery at 3 and 12 months between the lateral approach and the posterior approach. Similarly there was no difference in the Trendelenburg test between the two groups 3 and 12 months following hip replacement.

A new method is described for the histochemical localization of acid phosphatase. Naphthol AS BI, enzymatically released from naphthyl AS BI phosphoric acid, is coupled with diazotized 2,5-dibromoaniline to produce a fine insoluble red azo dye. The histochemical and cytochemical localization of this final reaction product in rat liver is described. In the electron microscope, sites of the azo dye can be detected by X-ray microanalysis of ultrathin cryosections of reactive tissue.