Behavioural insights and attitudes on community masking during the initial spread of COVID-19 in Hong Kong.

INTRODUCTION: Community face mask use during the coronavirus disease 2019 (COVID-19) pandemic has considerably differed worldwide. Generally, Asians are more inclined to wear face masks during disease outbreaks. Hong Kong has emerged relatively unscathed during the initial outbreak of COVID-19, despite its dense population. Previous infectious disease outbreaks influenced the local masking behaviour and response to public health measures. Thus, local behavioural insights are important for the successful implementation of infection control measures. This study explored the behaviour and attitudes of wearing face masks in the community during the initial spread of COVID-19 in Hong Kong. METHODS: We observed the masking behaviour of 10 211 pedestrians in several regions across Hong Kong from 1 to 29 February 2020. We supplemented the data with an online survey of 3199 respondents' views on face mask use. RESULTS: Among pedestrians, the masking rate was 94.8%; 83.7% wore disposable surgical masks. However, 13.0% wore surgical masks incorrectly with 42.5% worn too low, exposing the nostrils or mouth; 35.5% worn 'inside-out' or 'upside-down'. Most online respondents believed in the efficacy of wearing face mask for protection (94.6%) and prevention of community spread (96.6%). Surprisingly, 78.9% reused their mask; more respondents obtained information from social media (65.9%) than from government websites (23.2%). CONCLUSIONS: In Hong Kong, members of the population are motivated to wear masks and believe in the effectiveness of face masks against disease spread. However, a high mask reuse rate and errors in masking techniques were observed. Information on government websites should be enhanced and their accessibility should be improved.

Heart Failure With Recovered Ejection Fraction in African Americans: Results From the African-American Heart Failure Trial.

BACKGROUND: Recent studies have described the entity of heart failure with recovered ejection fraction (HFrecEF), but population-specific studies remain lacking. The aim of this study was to characterize patients enrolled in the African-American Heart Failure Trial (A-HeFT) who had significant improvement in their ejection fraction (EF) during the 1st 6 months of follow-up. METHODS AND RESULTS: Subjects with HFrecEF (improvement in EF from <35% to >40% in 6 months; n = 59) were compared with 259 subjects with heart failure and persistently reduced EF (HFrEF), defined as EF ≤40% at 6-month follow-up. The effects of improvement in EF on all-cause mortality and 1st and all hospitalizations were analyzed. Compared with HFrEF, subjects with HFrecEF had a nonsignificant trend toward lower mortality (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.02-1.15; P = .068), fewer 1st HF hospitalizations (HR 0.22, 95% CI 0.07-0.71; P = .011), fewer recurrent HF hospitalizations (HR 0.13, 95% CI 0.05-0.37; P <.001), similar 1st all-cause hospitalizations (HR 0.67, 95% CI 0.39-1.15; P = .150), and fewer recurrent all-cause hospitalizations (HR 0.41, 95% CI 0.24-0.68; P <.001). CONCLUSIONS: These data confirm that, as in other populations, a small subgroup of black patients receiving standard care improve their EF with favorable outcomes. Further studies are required to determine whether myocardial recovery is permanent and the best management strategies in such patients.

The first pilot study of expanded newborn screening for inborn errors of metabolism and survey of related knowledge and opinions of health care professionals in Hong Kong.

INTRODUCTION: Newborn screening is important for early diagnosis and effective treatment of inborn errors of metabolism (IEM). In response to a 2008 coroners' report of a 14-year-old boy who died of an undiagnosed IEM, the OPathPaed service model was proposed. In the present study, we investigated the feasibility of the OPathPaed model for delivering expanded newborn screening in Hong Kong. In addition, health care professionals were surveyed on their knowledge and opinions of newborn screening for IEM. METHODS: The present prospective study involving three regional hospitals was conducted in phases, from 1 October 2012 to 31 August 2014. The 10 steps of the OPathPaed model were evaluated: parental education, consent, sampling, sample dispatch, dried blood spot preparation and testing, reporting, recall and counselling, confirmation test, treatment and monitoring, and cost-benefit analysis. A fully automated online extraction system for dried blood spot analysis was also evaluated. A questionnaire was distributed to 430 health care professionals by convenience sampling. RESULTS: In total, 2440 neonates were recruited for newborn screening; no true-positive cases were found. Completed questionnaires were received from 210 respondents. Health care professionals supported implementation of an expanded newborn screening for IEM. In addition, there is a substantial need of more education for health care professionals. The majority of respondents supported implementing the expanded newborn screening for IEM immediately or within 3 years. CONCLUSION: The feasibility of OPathPaed model has been confirmed. It is significant and timely that when this pilot study was completed, a government-led initiative to study the feasibility of newborn screening for IEM in the public health care system on a larger scale was announced in the Hong Kong Special Administrative Region Chief Executive Policy Address of 2015.

Effect of controlled human exposure to diesel exhaust and allergen on airway surfactant protein D, myeloperoxidase and club (Clara) cell secretory protein 16.

BACKGROUND: Air pollution is a major cause of global morbidity and mortality. Air pollution and aeroallergens aggravate respiratory illness, but the variable effects of air pollutants and allergens in the lung are poorly understood. OBJECTIVE: To determine the effects of diesel exhaust (DE) and bronchial allergen challenge as single and dual exposures on aspects of innate immunity in the airway as reflected by surfactant protein D (SPD), myeloperoxidase (MPO) and club (Clara) cell secretory protein 16 (CC16) in 18 atopic individuals. METHODS: In this double-blind, randomized crossover study, atopic individuals were exposed to DE or filtered air, followed by endobronchial allergen or saline 1 hour after inhalational exposure. Bronchoalveolar lavage, bronchial washings, nasal lavage and blood samples were obtained 48 hours after exposures and assayed for CC16, MPO and SPD by ELISA. RESULTS: In bronchial samples, the concentration of SPD increased from 53.3 to 91.8 ng/mL after endobronchial allergen, with no additional contribution from DE. MPO also increased significantly in response to allergen (6.8 to 14.7 ng/mL), and there was a small additional contribution from exposure to DE. The concentration of CC16 decreased from 340.7 to 151.0 ng/mL in response to DE, with minor contribution from allergen. These changes were not reflected in nasal lavage fluid or plasma samples. CONCLUSIONS AND CLINICAL RELEVANCE: These findings suggest that allergen and DE variably influence different aspects of the innate immune response of the lung. SPD and MPO, known markers of allergic inflammation in the lung, are strongly increased by allergen while DE has a minor effect therein. DE induces a loss of CC16, a protective protein, while allergen has a minor effect therein. Results support site- and exposure-specific responses in the human lung upon multiple exposures.

Quantum key distribution over multicore fiber.

We present the first quantum key distribution (QKD) experiment over multicore fiber. With space division multiplexing, we demonstrate that weak QKD signals can coexist with classical data signals launched at full power in a 53 km 7-core fiber, while showing negligible degradation in performance. Based on a characterization of intercore crosstalk, we perform additional simulations highlighting that classical data bandwidths beyond 1Tb/s can be supported with high speed QKD on the same fiber.

High speed prototype quantum key distribution system and long term field trial.

Securing information in communication networks is an important challenge in today's world. Quantum Key Distribution (QKD) can provide unique capabilities towards achieving this security, allowing intrusions to be detected and information leakage avoided. We report here a record high bit rate prototype QKD system providing a total of 878 Gbit of secure key data over a 34 day period corresponding to a sustained key rate of around 300 kbit/s. The system was deployed over a standard 45 km link of an installed metropolitan telecommunication fibre network in central Tokyo. The prototype QKD system is compact, robust and automatically stabilised, enabling key distribution during diverse weather conditions. The security analysis includes an efficient protocol, finite key size effects and decoy states, with a quantified key failure probability of ε = 10⁻¹°.

Screening for dysglycaemia by oral glucose tolerance test should be recommended in all women with polycystic ovary syndrome.

STUDY QUESTION: Should fasting glucose (FG) or an oral glucose tolerance test (OGTT) be used to screen for dysglycaemia in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: A full OGTT should be recommended as the screening method for dysglycaemia in women with PCOS, regardless of BMI or family history of diabetes mellitus (DM). STUDY DESIGN, SIZE, DURATION: A cross-sectional study on 467 Chinese women diagnosed with PCOS by the Rotterdam criteria between January 2010 to December 2013. PARTICIPANTS, SETTING, METHODS: The study was done at a university hospital in Hong Kong. All subjects underwent a 75 g OGTT after overnight fasting. We evaluated the performance of FG alone, when compared with the full OGTT, in identifying subjects with dysglycaemia (prediabetes or DM, according to the 2010 diagnostic criteria of the American Diabetes Association). MAIN RESULTS AND THE ROLE OF CHANCE: Of the 467 subjects, 58 (12.4%) had dysglycaemia, among which 46 (9.8%) had prediabetes and 12 (2.6%) had DM, including 4 with known DM. Of the 46 subjects with prediabetes, 25 (54.3%) had normal FG and of the 8 subjects with screened DM in this study, 1 (12.5%) had normal FG. The sensitivity of FG alone in screening for prediabetes, DM and overall dysglycaemia were 45.7, 87.5 and 48.1%, respectively, i.e. missing 54.3% of prediabetes and 12.5% of DM cases as defined by the OGTT. Among the 54 subjects with screened dysglycaemia, 20 (37.0%) had BMI < 25 kg/m(2) and 35 (64.8%) had no family history of DM. LIMITATIONS, REASONS FOR CAUTION: We only reported on the biochemical diagnosis of DM based on a single time point. In clinical practice, confirmatory results at another time point is required for definitive diagnosis in asymptomatic subjects. WIDER IMPLICATIONS OF THE FINDINGS: There is an ongoing debate as to whether FG or an OGTT should be used as a screening method for dysglycaemia in women with PCOS. Some guidelines also recommend glucose screening only in those who are overweight and/or having family history of diabetes (DM). There have been scarce data on this issue in the Chinese population, which the current study aims at addressing. STUDY FUNDING/COMPETING INTERESTS: The study was supported by a research grant from the Hong Kong Obstetrical and Gynaecological Trust Fund, as well as internal research funding of the Department of Obstetrics and Gynaecology, The University of Hong Kong. All authors have no competing interests.

Cardiometabolic risk profile of participants with prediabetes diagnosed by HbA1c criteria in an urban Hong Kong Chinese population over 40 years of age.

AIMS: To investigate the usefulness of the additional measurement of HbA1c , compared with performing only the oral glucose tolerance test (OGTT), in identifying participants at increased cardiometabolic risk, in an urban Chinese population. METHODS: All participants from the fourth visit of the population-based Hong Kong Cardiovascular Risk Factors Prevalence Study, without known diabetes, were included. All had their glycaemic status assessed by OGTT and HbA1c , according to American Diabetic Association 2010 criteria. RESULTS: Based on OGTT criteria alone, 3.5% of the study cohort (N = 1300) had diabetes and 19.2% had prediabetes. Based on HbA1c criteria only, 6.2% had diabetes and 61.2% had prediabetes. The measurement of HbA1c , in addition to the OGTT, increased the proportion of participants with diabetes to 7.8% and with prediabetes to 65.3%. Subjects with prediabetes having raised HbA1c but normal glycaemia (N = 600) had waist circumference, systolic blood pressure, fasting glucose, insulin resistance index (HOMA-IR), Gutt Index and Framingham 10-year cardiovascular risk scores intermediate between those with both normal HbA1c and glycaemia (N = 350), and those with impaired fasting glucose and/or impaired glucose tolerance (N = 249; all P < 0.01). CONCLUSION: The measurement of HbA1c in our population, in addition to the OGTT, results in the detection of a large number of participants with prediabetes having raised HbA1c but normal glycaemia who have a cardiometabolic risk profile intermediate between impaired fasting glucose and/or impaired glucose tolerance and normal participants, and would benefit from early lifestyle intervention.

Relationship between parathyroid hormone and subclinical myocardial dysfunction in patients with severe psoriasis.

BACKGROUND: Psoriasis is associated with an increased risk of cardiovascular disease although the mechanism remains unclear. Recent studies have shown that such patients have a high prevalence of vitamin D (vit-D) deficiency and elevated parathyroid hormone (PTH) level. We hypothesized that vit-D deficiency and/or elevated PTH in psoriasis may contribute to left ventricular (LV) dysfunction. METHODS: Seventy-four patients with severe psoriasis with no known cardiovascular disease and 53 age- and gender-matched controls were recruited. All patients underwent detailed transthoracic echocardiography, including speckle tracking derived strains, and plasma levels of 25-hydoxyvitamin D (25-OHD), PTH and cardiac biomarkers including high sensitive C-reactive protein (hs-CRP), high sensitive troponin I (hs-TNI) and brain natriuretic peptide (BNP) were measured. RESULTS: Despite similar systolic and diastolic LV function, patients with severe psoriasis had impaired LV global longitudinal (-18.1 ± 2.6 vs.-19.6 ± 2.9%, P < 0.01) and circumferential strain (-18.7 ± 3.6 vs. -20.8 ± 4.3%, P < 0.01) compared with controls. Patients with severe psoriasis also had a significantly higher PTH (49.9 ± 18.0 vs. 40.5 ± 15.4 pmol/mL, P < 0.01) and hs-CRP (5.7 ± 6.9 vs. 1.9 ± 2.5 pg/mL, P < 0.01), but similar levels of 25-OHD, hs-TNI and BNP (all P > 0.05) compared with controls. Importantly, PTH level was negatively correlated with LV global longitudinal strain (R = -0.30, P < 0.01); and higher PTH level was independently associated with impaired global LV longitudinal strain (R = -0.33, P = 0.04), independent of cardiovascular risk factors, vit-D status and serum biomarkers. CONCLUSIONS: Severe psoriasis patients had an elevated PTH level and suffered from subclinical LV systolic dysfunction as detected by impaired global LV longitudinal strain. Importantly, a higher PTH level was independently associated with impaired global LV longitudinal strain.

Primitive neuroectodermal adrenal gland tumour.

Ewing's sarcoma, also called primitive neuroectodermal tumour of the adrenal gland, is extremely rare. Only a few cases have been reported in the literature. We report on a woman with adult-onset primitive neuroectodermal tumour of the adrenal gland presenting with progressive flank pain. Computed tomography confirmed an adrenal tumour with invasion of the left diaphragm and kidney. Radical surgery was performed and the pain completely resolved; histology confirmed the presence of primitive neuroectodermal tumour, for which she was given chemotherapy. The clinical presentation of this condition is non-specific, and a definitive diagnosis is based on a combination of histology, as well as immunohistochemical and cytogenic analysis. According to the literature, these tumours demonstrate rapid growth and aggressive behaviour but there are no well-established guidelines or treatment strategies. Nevertheless, surgery remains the mainstay of local disease control; curative surgery can be performed in most patients. Adjuvant chemoirradiation has been advocated yet no consensus is available. The prognosis of patients with primitive neuroectodermal tumours remains poor.

Alzheimer's Disease Biomarker Decision-Making among Patients with Mild Cognitive Impairment and Their Care Partners.

BACKGROUND: Alzheimer's disease (AD) biomarker tests can be ordered as part of the diagnostic workup of patients with mild cognitive impairment (MCI). Little is known about how patients with MCI and their care partners decide whether to pursue testing. OBJECTIVE: To examine factors that influence AD biomarker testing decisions among patients with MCI and their care partners. DESIGN: We performed structured research interviews with patients with MCI and their study partners to assess the importance of eight factors in the decision whether to undergo AD biomarker testing (6-point Likert scale; 1-extremely unimportant to 6-extremely important): cost, fear of testing procedures, learning if AD is the cause of cognitive problems, concern about health insurance, instructing future planning, informing treatment decisions, family members' opinions, and doctor recommendation. SETTING: Two researchers administered interviews with participants in-person (i.e., participant home, research center) or remotely (i.e., telephone, video-conference). PARTICIPANTS: We completed interviews with 65 patients with a diagnosis of MCI and 57 study partners, referred by dementia specialist clinicians from the University of California, Irvine health system. MEASUREMENTS: We used generalized estimating equations (GEE) to examine the mean importance of each factor among patients and study partners, and the mean difference in importance of each factor within dyads. RESULTS: One third of participants reported the patient had previously undergone AD biomarker testing. Fifty-five percent of patients and 65% of study partners who reported no previous testing indicated a desire for the patient to be tested. GEE analyses found that patients and study partners rated the following factors with highest importance: informing treatment decisions (mean score 5.29, 95% CI: 5.06, 5.52 for patients; mean score 5.56, 95% CI: 5.41, 5.72 for partners); doctor recommendation (4.94, 95% CI: 4.73, 5.15 for patients; 5.16, 95% CI: 4.97, 5.34 for partners); and instructing future planning (4.88, 95% CI: 4.59, 5.16 for patients; 5.11, 95% CI: 4.86, 5.35 for partners). High dyadic agreement was observed for all factors except fear of testing, which patients rated with lower importance than their study partners. CONCLUSIONS: Biomarker testing for AD in patients with MCI is a rapidly evolving practice and limited data exist on patient perspectives. In this study, most patients and their care partners were interested in testing to help inform treatment decisions and to plan for the future. Participants placed high importance on clinician recommendations for biomarker testing, highlighting the need for clear communication and education on the options, limitations, risks, and benefits of testing.

Contribution of FcRn binding to intestinal uptake of IgG in suckling rat pups and human FcRn-transgenic mice.

Immunoglobulin G (IgG) is transcytosed across intestinal epithelial cells of suckling mammals by the neonatal Fc receptor (FcRn); however, the contribution of FcRn vs. FcRn-independent uptake to serum IgG levels had not been determined in either rat pups or human (h)FcRn-expressing mice (Tg276 and Tg32). In isoflurane-anesthetized rodents, serum levels were determined after regional intestinal delivery of human monoclonal antibodies (hIgG) with either wild-type (WT) Fc sequences or variants engineered for different FcRn binding affinities. Detection of full-length hIgG was by immunoassay; intestinal hFcRn and hIgG localization was by immunocytochemistry. High (µg/ml) serum levels of hIgG were detected after proximal intestinal delivery (0.1-10 mg/kg) in 2-wk-old rats. Human FcRn was visualized in epithelial cells of Tg276 mice, but low serum hIgG levels (<10 ng/ml) were obtained. In rat pups, intraintestinal hIgG1 WT administration resulted in dose-related and saturable uptake, whereas uptake of a low FcRn-binding affinity variant was nonsaturable. There were no differences in hIgG levels from systemic and hepatic portal vein serum samples, and intense hIgG immunostaining was noted in villi enterocytes and within lymphatic lacteal-like vessels. This study demonstrated that FcRn-mediated uptake in rat pups accounted for ~80% of serum hIgG levels and that IgG enters the circulation via the lymph and not the hepatic portal vein. The remaining uptake though the immature intestine is nonreceptor mediated. Intestinal epithelial cell hFcRn expression occurred in Tg276 mice, but receptor-mediated transport of IgG was not observed. The suckling rat pup intestine is a mechanistic model of FcRn-IgG-mediated transcytosis.

Prevalence and extent of subclinical atherosclerosis in patients with psoriasis.

OBJECTIVE: Patients with psoriasis are prone to premature atherosclerosis and increased risk of cardiovascular disease events. However, the prevalence and extent of atherosclerosis in patients with psoriasis are unknown. DESIGN: A cross-sectional study. SETTING AND SUBJECTS: The prevalence and extent of coronary and carotid atherosclerosis were compared in 70 patients with psoriasis (46 ± 9 years, 71% male) without known cardiovascular disease or joint involvement and 51 age- and gender-matched healthy control subjects (45 ± 7 years, 71% male). Systemic inflammation was assessed by the level of high-sensitivity C-reactive protein (hs-CRP). Coronary atherosclerosis was determined by the coronary calcification score (CCS) measured by multi-detector computed tomography. Carotid atherosclerosis was assessed by high-resolution ultrasound-derived carotid intima-media thickness (cIMT). RESULTS: Patients with psoriasis had a higher prevalence of coronary atherosclerosis (CCS > 0; 28.6% vs. 3.9%, P < 0.01), and a higher degree of coronary atherosclerosis estimated by the mean CCS (67.4 ± 349.2 vs. 0.5 ± 3.0, P < 0.05) compared with controls. Similarly, cIMT was significantly greater in patients with psoriasis than in control subjects (0.73 ± 0.11 mm vs. 0.67 ± 0.08 mm, P < 0.01). Multiple logistic regression revealed that psoriasis [odd ratio (OR): 10.54, 95% confidence interval (CI) 1.89-58.67, P < 0.01] and serum total cholesterol level (OR 2.10, 95% CI 1.01-4.37) were associated with the presence of coronary atherosclerosis (CCS > 0). By contrast, only age was independently associated with increased cIMT. Amongst participants with no traditional cardiovascular disease risk factors, hs-CRP level was higher in patients with psoriasis than in controls. CONCLUSION: The present results demonstrate early-onset, diffuse arterial atherosclerosis in coronary and carotid arteries in patients with psoriasis, but not in age- and gender-matched control subjects. Low-grade inflammation could explain the presence of premature atherosclerosis in patients with psoriasis.

Increased dietary fruit intake was associated with lower burden of carotid atherosclerosis in Chinese patients with Type 2 diabetes mellitus.

BACKGROUND: Previous studies demonstrated that high fruit consumption was associated with a lower risk of cardiovascular events in patients with Type 2 diabetes mellitus. However, the relationship between fruit intake and carotid atherosclerosis in these patients is unknown. We studied the relationship between dietary fruit intake and carotid intima-media thickness in patients with Type 2 diabetes. METHODS: A total of 255 Chinese patients with Type 2 diabetes were recruited. Dietary fruit intake was assessed by a validated food-frequency questionnaire, and carotid intima-media thickness was measured by high-resolution ultrasonography. RESULTS: Among patients with three different tertiles of fruit intake (14.5 ± 8.6 vs. 41.5 ± 7.1 vs. 92.6 ± 39.7 g/day), there was no difference in their clinical characteristics (all P > 0.05). Patients with the highest tertile of fruit intake had a significantly higher BMI and diastolic blood pressure than those with the lowest tertile intake. Furthermore, serum high-sensitivity C-reactive protein, 8-isoprostane and superoxide dismutase were similar among the three tertiles of patients (all P > 0.05). However, patients with the highest tertile of fruit intake had lower carotid intima-media thickness (0.97 ± 0.02 vs. 1.08 ± 0.03 mm, P = 0.046) and prevalence of carotid plaque (11.76 vs. 1.18%, P = 0.022) than those with the lowest tertile of fruit intake. Multivariate regression analysis revealed the highest tertile of fruit intake (ß = -0.086, P = 0.049) was independently associated with carotid intima-media thickness. CONCLUSIONS: Our results demonstrated that, in Chinese patients with Type 2 diabetes, higher dietary fruit intake was associated with a lower burden of carotid atherosclerosis as reflected by lower carotid intima-media thickness and prevalence of carotid plaque.

Reliability and validity of the overactive bladder symptom score in Hong Kong Chinese.

OBJECTIVE: To validate the Hong Kong Chinese translation of the Overactive Bladder Symptom Score questionnaire (OABSS-HKC). DESIGN: Cross-sectional study. SETTING: Five urology clinics of different regional hospitals in Hong Kong. PARTICIPANTS: The Overactive Bladder Symptom Score questionnaire was translated and culturally adapted for Hong Kong Chinese, according to the Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes Measures. Chinese-speaking patients with overactive bladder symptoms were recruited from five urology clinics. The patients completed the OABSS-HKC, a 3-day micturition diary, International Prostate Symptom Scores, and the Patient Perception of Bladder Condition questionnaires (visit 1), and again after a 2-week interval (visit 2). Test-retest reliability was evaluated by the intraclass correlation coefficient and weighted Kappa coefficient. The relationship between OABSS-HKC total scores and items in the comparison measures was evaluated using Spearman's correlation coefficients. RESULTS: The OABSS-HKC was successfully translated and culturally adapted. Fifty-one patients completed the validation study. A high level of reliability was observed between the OABSS-HKC total score answered at visit 1 and 2 for all subjects (intraclass correlation coefficient, 0.82) and among the four items answered (weighted Kappa coefficients, 0.57-0.75). The OABSS-HKC total score correlated significantly with numbers of micturitions, incontinence and urgency episodes recorded in the 3-day micturition diary, as well as the total International Prostate Symptom Scores and the Patient Perception of Bladder Condition score. However, the OABSS-HKC total score was not significantly associated with nocturia episodes, total voided volume, or number of pads used. CONCLUSIONS: The OABSS-HKC total scores are reliable and moderately valid for the quantitative evaluation of overactive bladder symptoms in Hong Kong Chinese-speaking adults.

Continuous home cage monitoring of activity and sleep in mice during repeated paroxetine treatment and discontinuation.

RATIONALE: Non-invasive home cage monitoring is emerging as a valuable tool to assess the effects of experimental interventions on mouse behaviour. A field in which these techniques may prove useful is the study of repeated selective serotonin reuptake inhibitor (SSRI) treatment and discontinuation. SSRI discontinuation syndrome is an under-researched condition that includes the emergence of sleep disturbances following treatment cessation. OBJECTIVES: We used passive infrared (PIR) monitoring to investigate changes in activity, sleep, and circadian rhythms during repeated treatment with the SSRI paroxetine and its discontinuation in mice. METHODS: Male mice received paroxetine (10 mg/kg/day, s.c.) for 12 days, then were swapped to saline injections for a 13 day discontinuation period and compared to mice that received saline injections throughout. Mice were continuously tracked using the Continuous Open Mouse Phenotyping of Activity and Sleep Status (COMPASS) system. RESULTS: Repeated paroxetine treatment reduced activity and increased behaviourally-defined sleep in the dark phase. These effects recovered to saline-control levels within 24 h of paroxetine cessation, yet there was also evidence of a lengthening of sleep bouts in the dark phase for up to a week following discontinuation. CONCLUSIONS: This study provides the first example of how continuous non-invasive home cage monitoring can be used to detect objective behavioural changes in activity and sleep during and after drug treatment in mice. These data suggest that effects of paroxetine administration reversed soon after its discontinuation but identified an emergent change in sleep bout duration, which could be used as a biomarker in future preclinical studies to prevent or minimise SSRI discontinuation symptoms.

Effect of fixed-dose combined isosorbide dinitrate/hydralazine in elderly patients in the African-American heart failure trial.

BACKGROUND: Fixed-dose combined isosorbide dinitrate/hydralazine (FDC I/H) significantly improved outcomes in patients with advanced heart failure (HF) receiving background neurohormonal therapy in the African-American Heart Failure Trial (A-HeFT). In this analysis, we investigated treatment effects by age <65 or ≥65 years. METHODS AND RESULTS: Time-to-event curves were produced by the Kaplan-Meier method. Hazard ratios were calculated with the Cox proportional hazards model. Baseline characteristics showed that patients ≥65 years old had less hypertensive and more ischemic HF, better quality of life (QoL) scores, higher plasma B-type natriuretic peptide and creatinine levels, and received less background neurohormonal therapy. Kaplan-Meier curves showed that FDC I/H improved mortality and event-free survival in elderly patients. The hazard ratios for mortality, first heart failure hospitalization, and event-free survival (both unadjusted and adjusted for baseline differences), were similar quantitatively and in direction of effect in both age groups. CONCLUSIONS: In A-HeFT, FDC I/H improved outcomes in HF patients aged <65 or ≥65 years, despite significant baseline differences between these age groups. Patients aged ≥65 years, a group at greater mortality risk, had the greatest survival benefit from FDC I/H.

Clinical experience using a novel wound management system for venous leg ulcers.

Recent preliminary studies have shown Sepaderm® to be well tolerated and useful for the treatment of chronic, lower-extremity ulcerations, burn wounds, surgical excisions, chronic abdominal ulcers of hematoma origin, and chronic pressure ulcers. To confirm these initial findings, 18 cases of venous leg ulcers were treated with Sepaderm in conjunction with compression bandages. Patients had a mean age of 54.9 ± 13.5 years, and 78.9% were men. Six of the patients had previous standard treatments and 12 patients had Sepaderm as their initial treatment. Treatment duration with Sepaderm ranged from 6 to 90 days with a mean of 44.3 ± 25 days. The system was changed every 3 to 8 days depending on the amount of exudate. All the wounds responded positively with either partial or complete closure during treatment. Importantly, no patient experienced pain during the treatment. These findings suggest that Sepaderm may be effective for the treatment of venous leg ulcers.

Rodent models in translational circadian photobiology.

Over the last decades remarkable advances have been made in the understanding of the photobiology of circadian rhythms. The identification of a third photoreceptive system in the mammalian eye, in addition to the rods and cones that mediate vision, has transformed our appreciation of the role of light in regulating physiology and behavior. These photosensitive retinal ganglion cells (pRGCs) express the blue-light sensitive photopigment melanopsin and project to the suprachiasmatic nuclei (SCN)-the master circadian pacemaker-as well as many other brain regions. Much of our understanding of the fundamental mechanisms of the pRGCs, and the processes that they regulate, comes from mouse and other rodent models. Here we describe the contribution of rodent models to circadian photobiology, including both their strengths and limitations. In addition, we discuss how an appreciation of both rodent and human data is important for translational circadian photobiology. Such an approach enables a bi-directional flow of information whereby an understanding of basic mechanisms derived from mice can be integrated with studies from humans. Progress in this field is being driven forward at several levels of analysis, not least by the use of personalized light measurements and photoreceptor specific stimuli in human studies, and by studying the impact of environmental, rather than laboratory, lighting on different rodent models.