Cholinesterase inhibitor to prevent falls in Parkinson's disease (CHIEF-PD) trial: a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson's disease.

BACKGROUND: Falls are a common complication of Parkinson's disease. There is a need for new therapeutic options to target this debilitating aspect of the disease. Cholinergic deficit has been shown to contribute to both gait and cognitive dysfunction seen in the condition. Potential benefits of using cholinesterase inhibitors were shown during a single centre phase 2 trial. The aim of this trial is to evaluate the effectiveness of a cholinesterase inhibitor on fall rate in people with idiopathic Parkinson's disease. METHODS: This is a multi-centre, double-blind, randomised placebo-controlled trial in 600 people with idiopathic Parkinson's disease (Hoehn and Yahr stages 1 to 4) with a history of a fall in the past year. Participants will be randomised to two groups, receiving either transdermal rivastigmine or identical placebo for 12 months. The primary outcome is the fall rate over 12 months follow-up. Secondary outcome measures, collected at baseline and 12 months either face-to-face or via remote video/telephone assessments, include gait and balance measures, neuropsychiatric indices, Parkinson's motor and non-motor symptoms, quality of life and cost-effectiveness. DISCUSSION: This trial will establish whether cholinesterase inhibitor therapy is effective in preventing falls in Parkinson's disease. If cost-effective, it will alter current management guidelines by offering a new therapeutic option in this high-risk population. TRIAL REGISTRATION: REC reference: 19/SW/0043. EudraCT: 2018-003219-23. ISCRTN: 41639809 (registered 16/04/2019). ClinicalTrials.gov Identifier: NCT04226248 PROTOCOL AT TIME OF PUBLICATION: Version 7.0, 20th January 2021.

The Lombard effect in singing humpback whales: Source levels increase as ambient ocean noise levels increase.

Many animals increase the intensity of their vocalizations in increased noise. This response is known as the Lombard effect. While some previous studies about cetaceans report a 1 dB increase in the source level (SL) for every dB increase in the background noise level (NL), more recent data have not supported this compensation ability. The purpose of this study was to calculate the SLs of humpback whale song units recorded off Hawaii and test for a relationship between these SLs and background NLs. Opportunistic recordings during 2012-2017 were used to detect and track 524 humpback whale encounters comprised of 83 974 units on the U.S. Navy's Pacific Missile Range Facility hydrophones. Received levels were added to their estimated transmission losses to calculate SLs. Humpback whale song units had a median SL of 173 dB re 1 µPa at 1 m, and SLs increased by 0.53 dB/1 dB increase in background NLs. These changes occurred in real time on hourly and daily time scales. Increases in ambient noise could reduce male humpback whale communication space in the important breeding area off Hawaii. Since these vocalization changes may be dependent on location or behavioral state, more work is needed at other locations and with other species.

Lombard effect: Minke whale boing call source levels vary with natural variations in ocean noise.

Minke whales were acoustically detected, localized, and tracked on the U.S. Navy's Pacific Missile Range Facility from 2012 to 2017. Animal source levels (SLs) were estimated by adding transmission loss estimates to measured received levels of 42 159 individual minke whale boings. Minke whales off Hawaii exhibited the Lombard effect in that they increased their boing call intensity in increased background noise. Minke whales also decreased the variance of the boing call SL in higher background noise levels. Although the whales partially compensated for increasing background noise, they were unable or unwilling to increase their SLs by the same amount as the background noise. As oceans become louder, this reduction in communication space could negatively impact the health of minke whale populations. The findings in this study also have important implications for acoustic animal density studies, which may use SL to estimate probability of detection.

A multicentre, clinical evaluation of a hydro-responsive wound dressing: the Glasgow experience.

OBJECTIVE: Our aim was to assess the effectiveness of hydro-responsive wound dressing (HRWD) in debridement and wound bed preparation of a variety of acute and chronic wounds that presented with devitalised tissue needing removal so that healing may proceed. METHOD: This was a non-comparative evaluation of acute and chronic wounds that required debridement as part of their normal treatment regimen. Clinicians recorded wound changes including a subjective assessment level of devitalised tissue and wound bed preparation, presence of pain, wound status (e.g., wound size) and periwound skin condition. Data was also collected from clinicians and patients to provide information on clinical performance of the dressing. RESULTS: We recruited 100 patients with a variety of wound types into the study. Over 90% of the clinicians reported removal of devitalised tissue to enable a healing response in both chronic and acute wounds. Specifically, over the course of the evaluation period, levels of devitalised tissue (necrosis and slough) reduced from 85.5% to 26.3%, and this was accompanied by an increase in wound bed granulation from 12.0% to 33.7%. Correspondingly, there was a 40% reduction in wound area, hence a clinically relevant healing response was seen upon treatment with HRWD. It is also noteworthy that this patient population included a significant proportion of chronic wounds (51.4%) that showed no signs of wound progression within <4 weeks before study inclusion. Of these chronic wounds, 93% demonstrated wound progression upon treatment with HRWD. Despite reported pain levels being low pre- and post-dressing change, overall wound pain improved (reduced) in 48% of patients. Periwound skin condition showed a tendency towards improvement, and the fluid management capabilities of the HRWD was reported as good to excellent in the majority of cases. Wound infections were reduced by at least 60% over the evaluation period. A simple cost-effective analysis demonstrated significant savings using HRWD (£6.33) over current standard practice regimens of a four-step debridement process (£8.05), larval therapy (£306.39) and mechanical pad debridement (£11.46). CONCLUSION: HRWD was well tolerated and was demonstrated to be an efficient debridement tool providing rapid, effective and pain free debridement in a variety of wound types.

Comparing the epidemiology of hospital-acquired methicillin-resistant Staphylococcus aureus clone groups in Alberta, Canada.

Patients with methicillin-resistant Staphylococcus aureus (MRSA) clones, which were traditionally seen in the community setting (USA400/CMRSA7 and USA300/CMRSA10), are often identified as hospital-acquired (HA) infections using Infection Prevention and Control (IPC) surveillance definitions. This study examined the demographics and healthcare risk factors of patients with HA-MRSA to help understand if community MRSA clones are from a source internal or external to the hospital setting. Despite USA300/CMRSA10 being the predominant clone in Alberta, hospital clones (USA100/CMRSA2) still dominated in the acute care setting. In the Alberta hospitalized population, patients with USA400/CMRSA7 and USA300/CMRSA10 clones were significantly younger, had fewer comorbidities, and a greater proportion had none or ambulatory care-only healthcare exposure. These findings suggest that there are two distinct populations of HA-MRSA patients, and the patients with USA400/CMRSA7 and USA300/CMRSA10 clones identified in hospital more greatly resemble patients affected by those clones in the community. It is possible that epidemiological assessment overidentifies HA acquisition of MRSA in patients unscreened for MRSA on admission to acute care.

Swim track kinematics and calling behavior attributed to Bryde's whales on the Navy's Pacific Missile Range Facility.

Time difference of arrival methods for acoustically localizing multiple marine mammals have been applied to recorded data from the Navy's Pacific Missile Range Facility in order to localize and track calls attributed to Bryde's whales. Data were recorded during the months of August-October 2014, and 17 individual tracks were identified. Call characteristics were compared to other Bryde's whale vocalizations from the Pacific Ocean, and locations of the recorded signals were compared to published visual sightings of Bryde's whales in the Hawaiian archipelago. Track kinematic information, such as swim speeds, bearing information, track duration, and directivity, was recorded for the species. The intercall interval was also established for most of the tracks, providing cue rate information for this species that may be useful for future acoustic density estimate calculations.

Minke whales (Balaenoptera acutorostrata) respond to navy training.

Minke whales (Balaenoptera acutorostrata) were acoustically detected and localized via their boing calls using 766 h of recorded data from 24 hydrophones at the U.S. Navy's Pacific Missile Range Facility located off Kauai, Hawaii. Data were collected before, during, and after naval undersea warfare training events, which occurred in February over three consecutive years (2011-2013). Data collection in the during periods were further categorized as phase A and phase B with the latter being the only period with naval surface ship activities (e.g., frigate and destroyer maneuvers including the use of mid-frequency active sonar). Minimum minke whale densities were estimated for all data periods based upon the numbers of whales acoustically localized within the 3780 km(2) study area. The 2011 minimum densities in the study area were: 3.64 whales [confidence interval (CI) 3.31-4.01] before the training activity, 2.81 whales (CI 2.31-3.42) for phase A, 0.69 whales (CI 0.27-1.8) for phase B and 4.44 whales (CI 4.04-4.88) after. The minimum densities for the phase B periods were highly statistically significantly lower (p < 0.001) from all other periods within each year, suggesting a clear response to the phase B training. The phase A period results were mixed when compared to other non-training periods.

Delphinid behavioral responses to incidental mid-frequency active sonar.

Opportunistic observations of behavioral responses by delphinids to incidental mid-frequency active (MFA) sonar were recorded in the Southern California Bight from 2004 through 2008 using visual focal follows, static hydrophones, and autonomous recorders. Sound pressure levels were calculated between 2 and 8 kHz. Surface behavioral responses were observed in 26 groups from at least three species of 46 groups out of five species encountered during MFA sonar incidents. Responses included changes in behavioral state or direction of travel, changes in vocalization rates and call intensity, or a lack of vocalizations while MFA sonar occurred. However, 46% of focal groups not exposed to sonar also changed their behavior, and 43% of focal groups exposed to sonar did not change their behavior. Mean peak sound pressure levels when a behavioral response occurred were around 122 dB re: 1 µPa. Acoustic localizations of dolphin groups exhibiting a response gave insight into nighttime movement patterns and provided evidence that impacts of sonar may be mediated by behavioral state. The lack of response in some cases may indicate a tolerance of or habituation to MFA sonar by local populations; however, the responses that occur at lower received levels may point to some sensitization as well.

Why go online when you have pain? A qualitative analysis of teenagers' use of the Internet for pain management advice.

BACKGROUND: Adolescents are routinely recognized as native to online technologies. However, we know from previous research that this familiarity does not often translate into its use for help-seeking around health. We designed this study to examine the experience of adolescents in using the Internet to access pain management information, specifically why some adolescents may be reluctant to use these resources. METHODS: Twenty-six healthy, school attending, adolescents aged between 14 and 17 years old were recruited to a qualitative study of focus groups. Seventeen participants were female and nine were male. Participation was limited to those who self-selected as frequent users of the Internet, but who were loath to use it as a resource for health information as we wished to explore reasons for non-use. All data were thematically analysed. RESULTS: Most participants reported using the Internet to seek health information at least once. Experiences with online content were typically negative and drawn on only when all other sources of information and pain coping were exhausted. Three themes emerged, Drivers of Internet use, Barriers, and Anxiety around use. Adolescent health websites were reported to be confusing, anxiety provoking and hard to negotiate. The Internet was judged to be less accessible than other forms of pain and health coping information. Secondary themes related to topic embarrassment, the strive for independence and reassurance, preferred information source failure, curiosity, website design, availability of OTC analgesics, effort, fear-provoking narratives, mistrust of quality of online content and pain-related anxiety. CONCLUSIONS: Counter to many positive reports of the health benefits of Internet use during information seeking, its value is questionable to some adolescents. Typical experience was anxiety provoking, unlikely to yield helpful results, and wasteful comparative to off-line resources for pain.

Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino population.

IMPORTANCE: Latino populations have one of the highest prevalences of type 2 diabetes worldwide. OBJECTIVES: To investigate the association between rare protein-coding genetic variants and prevalence of type 2 diabetes in a large Latino population and to explore potential molecular and physiological mechanisms for the observed relationships. DESIGN, SETTING, AND PARTICIPANTS: Whole-exome sequencing was performed on DNA samples from 3756 Mexican and US Latino individuals (1794 with type 2 diabetes and 1962 without diabetes) recruited from 1993 to 2013. One variant was further tested for allele frequency and association with type 2 diabetes in large multiethnic data sets of 14,276 participants and characterized in experimental assays. MAIN OUTCOME AND MEASURES: Prevalence of type 2 diabetes. Secondary outcomes included age of onset, body mass index, and effect on protein function. RESULTS: A single rare missense variant (c.1522G>A [p.E508K]) was associated with type 2 diabetes prevalence (odds ratio [OR], 5.48; 95% CI, 2.83-10.61; P = 4.4 × 10(-7)) in hepatocyte nuclear factor 1-α (HNF1A), the gene responsible for maturity onset diabetes of the young type 3 (MODY3). This variant was observed in 0.36% of participants without type 2 diabetes and 2.1% of participants with it. In multiethnic replication data sets, the p.E508K variant was seen only in Latino patients (n = 1443 with type 2 diabetes and 1673 without it) and was associated with type 2 diabetes (OR, 4.16; 95% CI, 1.75-9.92; P = .0013). In experimental assays, HNF-1A protein encoding the p.E508K mutant demonstrated reduced transactivation activity of its target promoter compared with a wild-type protein. In our data, carriers and noncarriers of the p.E508K mutation with type 2 diabetes had no significant differences in compared clinical characteristics, including age at onset. The mean (SD) age for carriers was 45.3 years (11.2) vs 47.5 years (11.5) for noncarriers (P = .49) and the mean (SD) BMI for carriers was 28.2 (5.5) vs 29.3 (5.3) for noncarriers (P = .19). CONCLUSIONS AND RELEVANCE: Using whole-exome sequencing, we identified a single low-frequency variant in the MODY3-causing gene HNF1A that is associated with type 2 diabetes in Latino populations and may affect protein function. This finding may have implications for screening and therapeutic modification in this population, but additional studies are required.