Transitions in intrinsic capacity among community-dwelling older people and their associated factors: a multistate modelling analysis.

OBJECTIVES: Trajectory of intrinsic capacity (IC) can be non-linear and discontinuous, which traditional linear models may not be able to handle. This study thus aimed to model the trajectory of IC as transitions between different IC states and examine their associated factors. METHODS: Longitudinal data from a sample of community-dwelling older people aged 60 years or above (n = 1,588) was analysed. A set of 14 self-reported items representing different domains of IC were administered annually to measure IC at four time points. Based on the number of impaired IC domains (i.e., cognitive, locomotor, vitality, sensory, and psychological), participants at each time point were classified into one of three IC states, namely state 1 (0 impaired domain), state 2 (1-2 impaired domains), and state 3 (3-5 impaired domains). Multistate modelling was used to identify factors associated with the transitions from one state to another. RESULTS: The mean age of participants was 75.0 years, and 77.4% of them were female. At baseline, 12.4% were in state 1, 51.8% were in state 2, and 35.8% were in state 3. 62.8% of participants experienced at least one transition between states, among which 12% experienced a transition every year. The transitions occurred mostly between adjacent IC states and could take place back and forth. Age, sex, marital status, perceived financial adequacy, number of chronic diseases, and self-rated health were the factors associated with the transitions. CONCLUSION: Findings may serve as a valuable reference for guiding future policies to optimize IC and promote healthy ageing using a person-centred approach.

Developing a storybook package for bereaved siblings: a pilot study of the effectiveness for enhancing the perceived knowledge and confidence of health and social care professionals in Hong Kong.

A pilot randomized controlled trial was conducted to examine the effectiveness of a storybook package for enhancing the perceived knowledge and confidence of health and social care professionals in working with bereaved child siblings and their parents before and after the loss. Open-ended questions were asked to collect feedback, and thematic analyses were conducted to generate the themes. Quantitative findings provided preliminary but not strong evidence of its effectiveness, but qualitative findings showed that participants perceived their knowledge about supporting bereaved siblings and their parents was enhanced and considered the storybook package a useful tool for facilitating their practice. Participants also reflected on how real and specific the stories in the storybook should be. This study is the first step in developing an evidence-based practice tool for health and social care professionals. Future studies are required to further examine its effectiveness for practice.

Using cardiorespiratory fitness to operationalize vitality: a path analysis on the hierarchical structure of intrinsic capacity.

BACKGROUND: There is a lack of consensus about the operationalization of vitality, which is one of the intrinsic capacity (IC) domains. In particular, no study has investigated whether cardiorespiratory fitness (CRF) can be considered a vitality indicator. OBJECTIVE: To examine whether vitality is the upstream domain of IC, and establish the validity of CRF as a vitality indicator, using maximal oxygen consumption (VO2 max) as a representative. METHODS: 561 older adults from a longitudinal cohort study were included. Variables under consideration were VO2 max, other IC domains, instrumental activities of daily living (IADL), and handgrip strength, which was considered an already validated indicator of vitality. Using handgrip strength as the reference point, path analyses were performed to examine whether VO2 max followed a similar hierarchical structure in predicting change in IADL difficulty through other IC domains. RESULTS: The mean age of the participants was 75.5 years. The path model in which vitality was measured by VO2 max demonstrated adequate fit, which was similar to the model in which vitality was measured by handgrip strength. Regarding the path coefficients, the model using VO2 max demonstrated significant total and indirect effects. Notably, the indirect effect was due to the locomotor domain (standardized coefficient = -0.148, p < .001), but not the cognitive or psychological domain. CONCLUSION: Vitality is the upstream domain of IC. VO2 max can be considered an indicator to operationalize the vitality concept.

Translation, Cultural Adaptation, and Validation of the Cantonese Version of SarQoL in Hong Kong's Older Population: An Interviewer-Administered Questionnaire for Assessing Sarcopenia-Specific Quality of Life in Fieldwork Practice.

Objective: This study examined the psychometric properties of the Cantonese version of the SarQoL® questionnaire. Participants: A total of 118 (including 60 non-sarcopenic and 58 sarcopenic) community-dwelling older adults aged 65 years or above with Cantonese as their mother tongue. Methods: Translation and cultural adaptation of the SarQoL were conducted using a standardized protocol. To validate the Cantonese SarQoL, psychometric properties including discriminative power, reliability (including internal consistency and test-retest reliability), and construct validity (including convergent and divergent validity), as well as floor and ceiling effects, were assessed. Results: The translation of the questionnaire was completed without significant difficulties. Results indicated that the Cantonese SarQoL had (1) good discriminative power (sarcopenic participants had lower overall scores, mean = 66.1 vs 75.0, p < 0.001; the overall score was negatively predictive of the presence of sarcopenia, adjusted OR = 0.949, 95% CI = [0.912, 0.983]), (2) good internal consistency (Cronbach's alpha = 0.835; correlations between domain and overall scores ranged from 0.576 to 0.868), (3) excellent test-retest agreement (intraclass correlation coefficient = 0.801), (4) good construct validity (convergent: moderate to strong correlations were found between the overall score and almost all of the SF-36 and EQ-5D domains; divergent: weaker correlations were found between the overall score and SF-36 social functioning, ρ = -0.098, and EQ-5D self-care, ρ = -0.331), and (5) no floor or ceiling effect. Conclusion: The Cantonese SarQoL is valid and reliable, and thus can be used as an interviewer-administered questionnaire for assessing sarcopenia-specific quality of life in fieldwork practice.

Identifying the areas of low self-reported confidence of internal medicine residents in geriatrics: a descriptive study of findings from a structured geriatrics skills assessment survey.

BACKGROUND: Currently, no standardized methods exist to assess the geriatric skills and training needs of internal medicine trainees to enable them to become confident in caring for older patients. This study aimed to describe the self-reported confidence and training requirements in core geriatric skills amongst internal medicine residents in Toronto, Ontario using a standardized assessment tool. METHODS: This study used a novel self-rating instrument, known as the Geriatric Skills Assessment Tool (GSAT), among incoming and current internal medicine residents at the University of Toronto, to describe self-reported confidence in performing, teaching and interest in further training with regard to 15 core geriatric skills previously identified by the American Board of Internal Medicine. RESULTS: 190 (75.1%) out of 253 eligible incoming (Year 0) and current internal medicine residents (Years 1-3) completed the GSAT. Year 1-3 internal medicine residents who had completed a geriatric rotation reported being significantly more confident in performing 13/15 (P < 0.001 to P = 0.04) and in teaching 9/15 GSAT skills (P < 0.001 to P = 0.04). Overall, the residents surveyed identified their highest confidence in administering the Mini-Mental Status Examination and lowest confidence in assessing fall risk using a gait and balance tool, and in evaluating and managing chronic pain. CONCLUSION: A structured needs assessment like the GSAT can be valuable in identifying the geriatric training needs of internal medicine trainees based on their reported levels of self-confidence. Residents in internal medicine could further benefit from completing a mandatory geriatric rotation early in their training, since this may improve their overall confidence in providing care for the mostly older patients they will work with during their residency and beyond.

Intrinsic capacity and 10-year mortality: Findings from a cohort of older people.

BACKGROUND AND OBJECTIVES: Longitudinal data with regard to the association between intrinsic capacity (IC) and mortality is required for prevention efforts. We examined the association between IC and 10-year mortality among older people. RESEARCH DESIGN AND METHODS: We recruited a cohort of 2032 Chinese people aged 70 years and older, 1371 of them could be traced over follow-up, of which 1096 died within 10 years. Of those who were traceable, 846 were complete cases regarding the data for the exposure, outcome and covariates. Multiple imputation was used to handle missing data. Nine indicators were included to represent the construct of IC. All-cause mortality was collected from the Death Registry. Multivariable Cox proportional hazard regression model and Kaplan-Meier estimator were used to assess the association between IC and mortality. RESULTS: The mean age of the 2032 participants was 79.7 years and 51 % were female. Compared with those in the lowest (best) quartile of IC, those in the highest (worst) quartile were associated with 1.48-fold (95 % CI 1.21-1.82) higher risk of mortality, after adjustment for sociodemographic variables. When past medical illnesses were further adjusted, the hazard ratio was attenuated (1.41; 95 % CI 1.15-1.73). Kaplan-Meier estimator for survival probability similarly showed a graded mortality pattern. The association between IC and mortality remained similar when the analysis was confined to community-dwelling older people. DISCUSSION AND IMPLICATIONS: IC is associated with mortality in a dose-response fashion. Assessment of IC should be instituted in community and institutional settings to enable formulation of early interventions.

A US Time and Motion Pilot Study of Nebulized COPD Therapy in an Inpatient and a Long-Term Care Setting.

INTRODUCTION: There is a lack of quantitative data on healthcare professionals' (HCPs) time dedicated to nebulized chronic obstructive pulmonary disease (COPD) therapy in inpatient and long-term care (LTC) settings. Using time and motion methodology, we quantified HCP time and opportunity costs (time and materials) associated with nebulized COPD therapy in inpatient and LTC settings and estimated efficiencies of changing to once-daily therapy. METHODS: A case report form was built to reflect local nebulization workflow. Primary outcomes were mean active HCP time per predefined task and mean total active HCP time associated with short-acting beta agonist (SABA) and SABA/short-acting muscarinic antagonist (SAMA) combination nebulization processes. RESULTS: Twenty observations occurred within each setting. Inpatient observations included three SABA and 17 SABA/SAMA (from 18 different patients), and LTC observations included five SABA and 15 SABA/SAMA (from eight different patients). Mean total process time was 16.12 min in the inpatient setting (95% CI 14.48-17.76) and 21.0 min in the LTC setting (95% CI 18.8-23.2), with the actual nebulization comprising over 50% of process time for both. In LTC, CIs suggest a difference by cognitive impairment status: mean 24.1 min (95% CI 21.3-26.9) if cognitively impaired versus 19.0 min (95% CI 16.1-21.8) if not. In the inpatient setting, the estimated process time/admission was 7.8 h; a once-daily nebulized drug would require only 2.3 h. In LTC, the estimated process time was 32.1 h/month; a once-daily nebulized drug would require only 13.7 h/month. Estimated nebulization cost was $243/admission for current versus $72 for once-daily dosing in inpatient, and $1177/month versus $504 in LTC. CONCLUSIONS: The nebulization process for COPD patients in both inpatient and LTC settings consumes considerable HCP time. A switch from SABA or SABA/SAMA to a drug with a once-daily nebulization frequency could generate substantial time savings depending on the setting and site characteristics.

Randomized Controlled Trial on the Effects of a Combined Intervention of Computerized Cognitive Training Preceded by Physical Exercise for Improving Frailty Status and Cognitive Function in Older Adults.

(1) Objective: This study examined the effects of a combined intervention of Brainastic computerized cognitive training (CCT) preceded by physical exercise (PE) for improving frailty status and cognitive function in older adults. (2) Methods: Older adults aged 50 years or older attending elderly centers, without frailty/history of cognitive impairment, were randomly allocated into either a 12-week (i) multi-domain CCT + PE (n = 117), (ii) two-domain CCT + PE (n = 116) or (iii) video watching + PE (i.e., control, n = 114). Brainastic is an online application for cognitive training through video games. The multi-domain CCT targeted memory, attention, executive function, flexibility and visuospatial ability while the two-domain CCT targeted memory and attention. PE included both aerobic and resistance exercises. Outcomes were changes in frailty levels as measured with a simple frailty questionnaire (FRAIL), global cognition as measured with the Rapid Cognitive Screen (RCS), total learning and verbal memory abilities as measured with the Hong Kong List Learning Test (HKLLT), and executive functions as measured with the Frontal Assessment Battery (FAB) over 12 weeks. (3) Results: Participants in the intervention groups (multi-/two-domain CCT + PE) showed greater improvements in frailty status, total learning ability and verbal memory ability than control participants (all p < 0.05). The multi-domain CCT did not outperform the two-domain CCT in improving frailty status or cognitive function. The training effects were independent of the baseline cognition of the participants. (4) Conclusions: A combined intervention of multi-/two-domain CCT preceded by PE seemed to convey benefit over video watching preceded by PE in improving frailty status and cognitive function among older adults attending elderly centers.

Assessment of the validity and acceptability of the online FRAIL scale in identifying frailty among older people in community settings.

OBJECTIVES: To assess the validity and acceptability of the online FRAIL scale in identifying frailty in community settings. METHODS: Frailty was assessed using the online version of the FRAIL scale (a simple frailty questionnaire). Validity of the scale was examined in a sample of 1882 persons aged 60 years or older (inlcuding a pilot sample of 65 persons for assessing the face validity) recruited from 24 elderly centres in Hong Kong. Convergent validity was estimated using correlation coefficients between scores on the FRAIL, SARC-F (a simple questionnaire for assessing sarcopenia) and AMIC (Abbreviated Memory Inventory for the Chinese). Predictive validity was examined by logistic regression using IADL (Instrumental Activities of Daily Living) limitations and hospitalization as outcomes. Acceptability of the scale was assessed from the perspective of a sub-sample of 205 older persons and 33 centre staff. RESULTS: Following minor revisions, all participants were able to understand and answer the online FRAIL scale. The FRAIL scale correlated with SARC-F (r = 0.627, p < 0.001) and AMIC (r = 0.302, p < 0.001). Being pre-frail and frail were associated with incident IADL limitations (OR = 1.58, 95 %CI = 1.11-2.25 and OR = 3.01, 95 %CI = 1.87-4.84, respectively) and incident hospitalization (OR = 1.38, 95 %CI = 1.03-1.85 and OR = 2.79, 95 %CI = 1.89-4.12, respectively) at year 2, after controlling for age, sex, marital status, and educational level. 77.8 % of participants agreed that the scale would enable them to understand their health status. However, only 35.0 % accepted a digital approach for conducting health assessment or accessing assessment results. 90.9 % of centre staff agreed that the scale could be used to identify their members who are potential candidates for frailty intervention. CONCLUSIONS: The online FRAIL scale is valid for use in community elderly centres in identifying frailty. Further effort is required to improve the acceptability of the online FRAIL scale among older persons.

Hyperactivation of MAPK Signaling Is Deleterious to RAS/RAF-mutant Melanoma.

The most frequent genetic alterations in melanoma are gain-of-function (GOF) mutations in BRAF, which result in RAF-MEK-ERK signaling pathway addiction. Despite therapeutic success of RAF and MEK inhibitors in treating BRAFV600-mutant tumors, a major challenge is the inevitable emergence of drug resistance, which often involves reactivation of the MAPK pathway. Interestingly, resistant tumors are often sensitive to drug withdrawal, suggesting that hyperactivation of the MAPK pathway is not tolerated. To further characterize this phenomenon, isogenic models of inducible MAPK hyperactivation in BRAFV600E melanoma cells were generated by overexpression of ERK2. Using this model system, supraphysiologic levels of MAPK signaling led to cell death, which was reversed by MAPK inhibition. Furthermore, complete tumor regression was observed in an ERK2-overexpressing xenograft model. To identify mediators of MAPK hyperactivation-induced cell death, a large-scale pooled shRNA screen was conducted, which revealed that only shRNAs against BRAF and MAP2K1 rescued loss of cell viability. This suggested that no single downstream ERK2 effector was required, consistent with pleiotropic effects on multiple cellular stress pathways. Intriguingly, the detrimental effect of MAPK hyperactivation could be partially attributed to secreted factors, and more than 100 differentially secreted proteins were identified. The effect of ERK2 overexpression was highly context dependent, as RAS/RAF mutant but not RAS/RAF wild-type melanoma were sensitive to this perturbation. IMPLICATIONS: This vulnerability to MAPK hyperactivation raises the possibility of novel therapeutic approaches for RAS/RAF-mutant cancers.

Effective Antimicrobial Stewardship Strategies for Cost-effective Utilization of Telavancin for the Treatment of Patients With Hospital-acquired Bacterial Pneumonia Caused by Staphylococcus aureus.

PURPOSE: Clinicians and stewardship programs are challenged with positioning of novel, higher priced antibiotic agents for the treatment of clinical infections. We developed a decision-analytic model to describe costs, including drug, total treatment costs, and health care outcomes, associated with telavancin (TLV) compared with vancomycin (VAN) for patients with Staphylococcus aureus (SA) hospital-acquired bacterial pneumonia (HABP). METHODS: This decision-analytic model assessed the treatment of SA-HABP with TLV versus VAN. Data were obtained from the ATTAIN (Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia) clinical trials on the following: the probability of clinical cure; probability of nephrotoxicity; and prevalence of polymicrobial infection (30%), methicillin-resistant Staphylococcus aureus (MRSA) (68%), and SA with VAN MIC ≥1 µg/mL (85%). Data on length of stay for cure (10 days), failure (10 additional days), and nephrotoxicity (3.5 days) were based on literature. Cost per treated patient and incremental cost-effectiveness ratio (ICER) per additional cure were calculated for SA-HABP and for monomicrobial SA-HABP. One-way sensitivity analyses were performed. FINDINGS: Patients with SA-HABP were sub-grouped by methicillin susceptibility (n = 140, 32%) or resistance (n = 293, 68%), and occurrence of polymicrobial (n = 128, 30%) vs monomicrobial (n = 305, 70%) infections. Under the base case, hospital cost for patients with HABP treated with TLV was $42,564 and with VAN, it was $42,296. Telavancin was associated with higher drug ($2082) and nephrotoxicity ($467) costs and lower intensive care unit (-$1738) and ventilator (-$114) costs. ICER was $4156 per additional cure. ICER was sensitive to probabilities of cure, length of treatment in cures, intensive care unit cost, TLV cost, and additional length of stay due to failure. For monomicrobial SA-HABP, TLV was associated with a net cost savings of $907 per patient and yielded economic dominance. IMPLICATIONS: Our decision-analytic model suggests that TLV for monomicrobial SA-HABP is associated with higher drug acquisition costs but a favorable ICER relative to VAN, provided that effective antimicrobial stewardship limits therapy to 7 days. Sensitivity analyses suggest a potential economic benefit of TLV treatment with appropriate patient selection. Antimicrobial stewardship programs may be able to reduce total costs through judicious use of novel antimicrobial agents. ClinicalTrials.gov identifiers: NCT00107952 and NCT00124020.

Lifetime Prevalence and Correlates of Schizophrenia-Spectrum, Affective, and Other Non-affective Psychotic Disorders in the Chinese Adult Population.

Lifetime prevalence of psychotic disorders varies widely across studies. Epidemiological surveys have rarely examined prevalences of specific psychotic disorders other than schizophrenia, and the majority used a single-phase design without employing clinical reappraisal interview for diagnostic verification. The current study investigated lifetime prevalence, correlates and service utilization of schizophrenia-spectrum, affective, and other non-affective psychotic disorders in a representative sample of community-dwelling Chinese adult population aged 16-75 years (N = 5719) based on a territory-wide, population-based household survey for mental disorders in Hong Kong. The survey adopted a 2-phase design comprising first-phase psychosis screening and second-phase diagnostic verification incorporating clinical information from psychiatrist-administered semi-structured interview and medical record review to ascertain DSM-IV lifetime diagnosis for psychotic disorders. Data on sociodemographics, psychosocial characteristics and service utilization were collected. Our results showed that lifetime prevalence was 2.47% for psychotic disorder overall, 1.25% for schizophrenia, 0.15% for delusional disorder, 0.38% for psychotic disorder not otherwise specified, 0.31% for bipolar disorder with psychosis, and 0.33% for depressive disorder with psychosis. Schizophrenia-spectrum disorder was associated with family history of psychosis, cigarette smoking and variables indicating socioeconomic disadvantage. Victimization experiences were significantly related to affective psychoses and other non-affective psychoses. Around 80% of participants with any psychotic disorder sought some kind of professional help for mental health problems in the past year. Using comprehensive diagnostic assessment involving interview and record data, our results indicate that approximately 2.5% of Chinese adult population had lifetime psychotic disorder which represents a major public health concern.

Gestalt Intervention Groups for Anxious Parents in Hong Kong: A Quasi-Experimental Design.

This study examined the impact of gestalt intervention groups for anxious Chinese parents in Hong Kong. A non-randomized control group pre-test/post-test design was adopted. A total of 156 parents participated in the project. After 4 weeks of treatment, the intervention group participants had lower anxiety levels, less avoidance of inner experiences, and more kindness towards oneself and mindfulness when compared to control group participants. However, the dimension of self-judgment remained unchanged. The adaptation of gestalt intervention to suit the Chinese culture was discussed.

Physical Exercise Helped to Maintain and Restore Functioning in Chinese Older Adults With Mild Cognitive Impairment: A 5-Year Prospective Study of the Hong Kong Memory and Ageing Prospective Study (HK-MAPS).

OBJECTIVE: This study investigated the potential of physical exercise habit as a lifestyle modification against cognitive and functional decline at the community level. METHODS: A total of 454 community-dwelling Chinese older adults without dementia participated in the Hong Kong Memory and Ageing Prospective Study at baseline and follow-up at 5 years. Their cognitive and functional performances were assessed by the Cantonese version of the Mini-Mental State Examination (CMMSE) and the Chinese version of Disability Assessment in Dementia (DAD). Hierarchical multiple regression analyses were performed to examine whether physical exercise was a significant predictor of the follow-up CMMSE and DAD scores after controlling for the covariates. Subgroup analyses were performed with a group of 127 participants with mild cognitive impairment at baseline. RESULTS: Physical exercise habit was a significant predictor for both the follow-up CMMSE scores and DAD scores. Participants with exercise habits of 5 years or more showed better cognitive and functional performances at follow-up. Participants who picked up exercise habits only after the baseline assessment also demonstrated better functioning at follow-up. The same patterns were observed in the subgroup analyses with the mild cognitive impairment group. CONCLUSION: Results suggested that prolonged exercise habit is required for positive effects on cognition to emerge, but benefits on functioning can be observed when individuals take up an exercise habit later in life or even after the beginning of cognitive decline. These findings are encouraging in promoting an exercise habit among older adults living in the community.

A Retrospective Case-Series of Children With Bone and Joint Infection From Northern Australia.

Our clinical workload as infectious diseases pediatricians in northern Australia is dominated by complicated bone and joint infections in indigenous children. We reviewed the clinical presentation, microbiology, management, and outcomes of children presenting to Royal Darwin Hospital with bone and joint infections between 2010 and 2013, and aimed to compare severity and incidence with other populations worldwide.A retrospective audit was performed on children aged 0 to 18 years who were admitted to Royal Darwin Hospital between 1 January 2010 and 31 December 2013 with a bone and joint infection.Seventy-nine patients were identified, of whom 57 (72%) had osteomyelitis ± associated septic arthritis and 22 (28%) had septic arthritis alone. Sixty (76%) were indigenous Australians. The incidence rate of osteomyelitis for indigenous children was 82 per 100,000 children. Staphylococcus aureus was the confirmed pathogen in 43/79 (54%), of which 17/43 (40%) were methicillin resistant. Median length of stay was 17 days (interquartile range: 10-31 days) and median length of IV antibiotics was 15 days (interquartile range: 6-24 days). Fifty-six (71%) required at least 1 surgical procedure. Relapse within 12 months was documented in 12 (15%) patients.We report 3 key findings: osteomyelitis incidence in indigenous children of northern Australia is amongst the highest reported in the world; methicillin-resistant S aureus accounts for 36% of osteomyelitis with a positive microbiological diagnosis; and the severity of disease requires extended antibiotic therapy. Despite this, 15% of the cohort relapsed within 12 months and required readmission.

Rtt107 BRCT domains act as a targeting module in the DNA damage response.

Cells are constantly exposed to assaults that cause DNA damage, which must be detected and repaired to prevent genome instability. The DNA damage response is mediated by key kinases that activate various signaling pathways. In Saccharomyces cerevisiae, one of these kinases is Mec1, which phosphorylates numerous targets, including H2A and the DNA damage protein Rtt107. In addition to being phosphorylated, Rtt107 contains six BRCA1 C-terminal (BRCT) domains, which typically recognize phospho-peptides. Thus Rtt107 represented an opportunity to study complementary aspects of the phosphorylation cascades within one protein. Here we sought to describe the functional roles of the multiple BRCT domains in Rtt107. Rtt107 BRCT5/6 facilitated recruitment to sites of DNA lesions via its interaction with phosphorylated H2A. Rtt107 BRCT3/4 also contributed to Rtt107 recruitment, but BRCT3/4 was not sufficient for recruitment when BRCT5/6 was absent. Intriguingly, both mutations that affected Rtt107 recruitment also abrogated its phosphorylation. Pointing to its modular nature, replacing Rtt107 BRCT5/6 with the BRCT domains from the checkpoint protein Rad9 was able to sustain Rtt107 function. Although Rtt107 physically interacts with both the endonuclease Slx4 and the DNA replication and repair protein Dpb11, only Slx4 was dependent on Rtt107 for its recruitment to DNA lesions. Fusing Rtt107 BRCT5/6 to Slx4, which presumably allows artificial recruitment of Slx4 to DNA lesions, alleviated some phenotypes of rtt107Δ mutants, indicating the functional importance of Slx4 recruitment. Together this data revealed a key function of the Rtt107 BRCT domains for targeting of both itself and its interaction partners to DNA lesions.

Slow Stream Rehabilitation: A New Model of Post-Acute Care.

OBJECTIVES: To identify characteristics and outcomes of elderly patients admitted to a slow stream, low-intensity, and long-duration inpatient rehabilitation (SSR) program after an acute hospitalization because they were unable to tolerate traditional inpatient rehabilitation. DESIGN: Single group pre-post study with assessments conducted on admission and discharge. SETTING: Baycrest's 30-bed SSR Unit in Toronto, Ontario, Canada. PARTICIPANTS: A total of 104 patients older than 60 years admitted between September 2011 and December 2012. MEASUREMENTS: Admission assessments included demographic data, Functional Independence Measure (FIM), and ability to ambulate. Discharge outcomes included change in motor and total FIM scores from admission to discharge, discharge residential status, and length of stay. RESULTS: Mean age was 81.6 ± 8.4 years and 68.3% were women. Mean changes in motor and total FIM were 21.0 ± 12.2 (P < .001) and 22.6 ± 14.0 (P < .001), respectively. On admission, only 30.8% of patients were ambulatory even with mobility assistive devices, while on discharge, 68.3% of patients were ambulatory; 61.5% of patients returned to their preadmission living arrangement; 8.6% went from their own home to a retirement or relative's home. Only 16.3% were discharged to long-term nursing home care and 13.4% were transferred to an acute hospital. Mean length of SSR stay was 82.5 ± 26.4 days. CONCLUSION: SSR programs can benefit elderly patients at risk for institutionalization after acute hospitalization by improving their functioning and mobility, and allowing them to return to the community.

Combination of Vancomycin and ß-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial.

BACKGROUND: In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal ß-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. METHODS: In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. RESULTS: We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%-102%; P = .06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. CONCLUSIONS: Combining an antistaphylococcal ß-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au).

ZIKA VIRUS INFECTION IN AUSTRALIA FOLLOWING A MONKEY BITE IN INDONESIA.

A traveller returning to Australia developed Zika virus infection, with fever, rash and conjunctivitis, with onset five days after a monkey bite in Bali, Indonesia. Flavivirus RNA detected on PCR from a nasopharyngeal swab was sequenced and identified as Zika virus. Although mosquito-borne transmission is also possible, we propose the bite as a plausible route of transmission. The literature for non-vector transmissions of Zika virus and other flaviviruses is reviewed.

Physical activity and cognitive function of community Chinese elderly in Hong Kong (HK) and Guangzhou (GZ).

BACKGROUND: Some studies demonstrated that physical activity may have beneficial effect on cognitive function. The objective of the study was to estimate the association between physical activity and cognitive function in community-dwelling elderly Chinese in Hong Kong (HK) and Guangzhou (GZ). METHODS: In the neighborhood of HK and GZ, a convenience sample of 557 (260 in HK and 297 in GZ) older persons without dementia aged over 60 years (73.4 ± 6.5) was recruited. Physical activity was measured using a checklist. Information on physical activity participation, cognitive function, and other variables were collected. Multivariate linear regression analyses were performed to evaluate the association between physical activity and cognitive function. RESULTS: Total number of physical activities showed significant association with the delayed recall test (p 0.05) CONCLUSION: Physical activity may not be associated with better cognitive function among elderly Chinese independently of other factors.