Bacterial infections in patients with COVID-19: the impact of procalcitonin testing on antibiotics prescription in the real world.

BACKGROUND: Bacterial infections are not prevalent among patients hospitalized with COVID-19, while unnecessary prescription of antibiotics was commonly observed. This study aimed to determine the impact of procalcitonin testing on antibiotics prescription in the real-world setting. METHODS: We performed a territory-wide retrospective cohort study involving all laboratory-confirmed patients hospitalized in public hospitals in Hong Kong in 2020 with COVID-19. We determined the prevalence of bacterial co-infections (documented infections within 72 h of admission) and secondary bacterial infections (infections after 72 h of admission) and antibiotics consumption, and the correlation between procalcitonin testing and antibiotics prescription. RESULTS: The cohort included 8666 patients, with mean age 45.3 ± 19.9 years, 48.5% male, and comorbidities in 26.9%. Among 2688 patients with bacterial cultures performed, 147 (5.5%) had bacterial co-infections, and 222 (8.3%) had secondary bacterial infections. Antibiotics were prescribed for 2773 (32.0%) patients during the hospital admission. Procalcitonin tests were performed for 2543 (29.3%) patients. More patients with procalcitonin testing received antibiotics (65.9% vs. 17.9%, p < 0.001). Procalcitonin testing was associated with 5-fold increased risk of antibiotics prescription after adjusting for confounding variables. At hospital level, procalcitonin testing correlated with antibiotics prescription. Patients with procalcitonin level < 0.5 ng/mL had a lower probability of antibiotics initiation and shorter duration of antibiotics therapy. CONCLUSIONS: Procalcitonin testing was not associated with lower prescription of antibiotics. Patients with low procalcitonin level had lower antibiotics exposure, supporting the use of procalcitonin to exclude bacterial infections aiding early stopping of antibiotics among patients hospitalized with COVID-19.

Safety Profile and Clinical and Virological Outcomes of Nirmatrelvir-Ritonavir Treatment in Patients With Advanced Chronic Kidney Disease and Coronavirus Disease 2019.

BACKGROUND: Nirmatrelvir-ritonavir is currently not recommended in patients with an estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2. METHODS: To determine the safety profile and clinical and virological outcomes of nirmatrelvir-ritonavir use at a modified dosage in adults with chronic kidney disease (CKD), a prospective, single-arm, interventional trial recruited patients with eGFR <30 mL/minute/1.73 m2 and on dialysis. Primary outcomes included safety profile, adverse/serious adverse events, and events leading to drug discontinuation. Disease symptoms, virological outcomes by serial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral polymerase chain reaction (PCR) tests, rapid antigen tests, and virological and symptomatic rebound were also recorded. RESULTS: Fifty-nine (69.4%) of the 85 participants had stage 5 CKD and were on dialysis. Eighty (94.1%) completed the full treatment course; 9.4% and 5.9% had adverse and serious adverse events, and these were comparable between those with eGFR < or >30 mL/minute/1.73 m2. The viral load significantly decreased on days 5, 15, and 30 (P < .001 for all), and the reduction was consistent in the subgroup with eGFR <30 mL/minute/1.73 m2. Ten patients had virological rebound, which was transient and asymptomatic. CONCLUSIONS: Among patients with CKD, a modified dose of nirmatrelvir-ritonavir is a well-tolerated therapy in mild COVID-19 as it can effectively suppress the SARS-CoV-2 viral load with a favorable safety profile. Virological and symptomatic rebound, although transient with low infectivity, may occur after treatment. Nirmatrelvir-ritonavir should be considered for use in patients with CKD, including stage 5 CKD on dialysis. Clinical Trials Registration. Clinical Trials.gov; identifier: NCT05624840.

Erythrocytosis and thrombotic events in kidney transplant recipients prescribed a sodium glucose cotransport-2 inhibitor.

INTRODUCTION: The safety and efficacy of sodium glucose cotransport-2 inhibitors (SGLT2i) in kidney transplant recipients remains uncertain. Transplant recipients may be at risk of thrombosis because of post-transplant erythrocytosis and SGLT2i are associated with an increase in hematocrit. METHODS: We determined SGLT2i use, the change in hematocrit and incidence of thrombotic events in kidney transplant recipients in 1700 prevalent patients in our center. RESULTS: Among the 42 patients treated with SGLT2i, the mean pre-transplant hematocrit was 31%, and none of the patients had a hematocrit ≥50%. The mean percent change in hematocrit measured at an average of 53 days after initiation of an SGLT2i was 11% and four patients (10%) had a hematocrit ≥ 50%. The mean hematocrit measured 3 months after treatment was 42% and two patients (5%) had a hematocrit ≥50%. One patient had a cerebellar stroke 14 months post-SGLT2i initiation when the hemoglobin was 173 grams/liter, and the hematocrit was 52%. CONCLUSIONS: All patients had a sustained increase in hematocrit 3 months after SGLT2i treatment. Hematocrit ≥50% occurred in 10%, and one patient had a thrombotic event that may or may not have been related to an increase in hematocrit. Clinicians may consider monitoring for erythrocytosis after starting and SGLT2i in kidney transplant recipients.

Patient-reported outcome measures for life participation in peritoneal dialysis: a systematic review.

BACKGROUND: Patients receiving peritoneal dialysis (PD) endure an ongoing regimen of daily fluid exchanges and are at risk of potentially life-threatening complications and debilitating symptoms that can limit their ability to participate in life activities. The aim of the study was to identify the characteristics, content and psychometric properties of measures for life participation used in research in PD. METHODS: We searched MEDLINE, Embase, PsychInfo, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Central Register of Controlled Trials from inception to May 2020 for all studies that reported life participation in patients on PD. The characteristics, dimensions of life participation and psychometric properties of these measures were extracted and analyzed. RESULTS: Of the 301 studies included, 17 (6%) were randomized studies and 284 (94%) were nonrandomized studies. Forty-two different measures were used to assess life participation. Of these, 23 (55%) were used in only one study. Fifteen (36%) measures were specifically designed to assess life participation, while 27 (64%) measures assessed broader constructs, such as quality of life, but included questions on life participation. The 36-Item Short Form Health Survey and Kidney Disease Quality of Life Short Form were the most frequently used measures [122 (41%) and 86 (29%) studies, respectively]. Eight (19%) measures had validation data to support their use in patients on PD. CONCLUSIONS: The many measures currently used to assess life participation in patients receiving PD vary in their characteristics, content and validation. Further work to pilot and validate potential measures is required to establish a core patient-reported outcome measure to assess life participation in patients receiving PD.

Direct Oral Anticoagulant Use in Chronic Kidney Disease and Dialysis Patients With Venous Thromboembolism: A Systematic Review of Thrombosis and Bleeding Outcomes.

OBJECTIVE: To evaluate how treatment with DOACs for VTE affects thrombosis and bleeding outcomes compared to warfarin in CKD and dialysis patients. DATA SOURCES: A literature search was conducted for studies evaluating VTE and bleeding outcomes with DOAC use in CKD and dialysis patients. Searches conducted through EMBASE, MEDLINE/PubMed, Scopus, and Cochrane Central Register of Controlled Trials, from inception to September 22, 2020. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials, cohort studies, and case series with ≥10 patients included. DATA SYNTHESIS: From 7286 studies, nine studies met inclusion criteria. There was no significant difference between DOACs (dabigatran, rivaroxaban, apixaban) and warfarin for reducing recurrent VTE and bleeding events in moderate CKD patients. The risk of overall major bleeding increased when the degree of kidney impairment increased. There was no significant difference between apixaban and warfarin for VTE outcomes in dialysis patients. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: There continues to be a controversial debate whether it may be more beneficial to use DOACs versus warfarin in CKD/dialysis patients with venous thromboembolism (VTE). The risk vs benefit of using DOACs in the CKD/ESKD population should continue to be evaluated for each individual patient. CONCLUSION: Apixaban may be used cautiously as an alternative in acute VTE treatment in severe CKD patients. Insufficient evidence is available to suggest the use of dabigatran and rivaroxaban in this patient population. The benefit of using DOACs in this population for VTE treatment should be weighed against the potential bleeding risk in patients with CKD.

Trauma team activation criteria and outcomes of geriatric trauma: 10 year single centre cohort study.

BACKGROUND: With the aging population, the number of older patients with multiple injuries is increasing. The aim of this study was to understand the patterns and outcomes of older patients admitted to a major trauma centre in Hong Kong from 2006 to 2015, and investigate the performance of the trauma team activation (TTA) criteria for these elderly patients. METHODS: This was a retrospective cohort study from a university hospital major trauma centre in Hong Kong from 2006 to 2015. Patients aged 55 or above who entered the trauma registry were included. Patients were divided into those aged 55-70, and above 70. To test the performance of the TTA criteria, we defined injured patients with severe outcomes as those having any of the following: death within 30 days; the need for surgery; or the need for intensive care unit (ICU) care. RESULTS: 2218 patients were included over the 10 year period. The 30-day mortality was 7.5% for aged 55-70 and 17.7% for those aged above 70. The sensitivity of TTA criteria for identifying severe outcomes for those aged 55 or above was 35.6%, with 91.6% specificity. The under-triage rate was 59% for age 55-70, and 69.1% for those aged above 70. CONCLUSION: There is a need to consider alternative TTA criteria for our geriatric trauma population, and to more clearly define the process and standards of care in Hong Kong.

Older Adults, Falls, and Skin Integrity.

GENERAL PURPOSE: To provide an overview of the assessment and management of risk factors for falls in older adults. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant should be better able to:1. Outline the components of an evidence-based falls assessment and identify risk factors for falls.2. Specify strategies to reduce falls in older adults, especially as related to maintaining skin integrity. ABSTRACT: Older adult patients may present to skin and wound care clinicians with skin injuries as a result of falls. In addition, chronic wounds associated with the patient's conditions may also increase his/her falls risk. Hence, appropriate assessment and management of the risk of falls in older adult patients are key elements of patient-centered care.

High Viral Load and Respiratory Failure in Adults Hospitalized for Respiratory Syncytial Virus Infections.

A prospective study among adults hospitalized for polymerase chain reaction-confirmed respiratory syncytial virus infections (n = 123) showed frequent occurrence of lower respiratory-tract complications causing respiratory insufficiency (52.8%), requirement for assisted ventilation (16.3%), and intensive care unit admission/death (12.2%). High viral RNA concentration was detected at time of hospitalization, including in patients who presented later than 2 days of illness (day 1-2, 7.29 ± 1.47; day 3-4, 7.28 ± 1.41; day 5-8, 6.66 ± 1.87 log10 copies/mL). RNA concentration was independently associated with risk of complications and respiratory insufficiency (adjusted odds ratio 1.40 per log10 copies/mL increase, 95% confidence interval, 1.03-1.90; P = .034). Our data indicate the need and provide a basis for clinical research on antiviral therapy in this population.

Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients.

We aimed to study factors influencing outcomes of adults hospitalised for seasonal and pandemic influenza.  Individual-patient data from three Asian cohorts (Hong Kong, Singapore and Beijing; N=2649) were analysed. Adults hospitalised for laboratory-confirmed influenza (prospectively diagnosed) during 2008-2011 were studied. The primary outcome measure was 30-day survival. Multivariate Cox regression models (time-fixed and time-dependent) were used. Patients had high morbidity (respiratory/nonrespiratory complications in 68.4%, respiratory failure in 48.6%, pneumonia in 40.8% and bacterial superinfections in 10.8%) and mortality (5.9% at 30 days and 6.9% at 60 days). 75.2% received neuraminidase inhibitors (NAI) (73.8% received oseltamivir and 1.4% received peramivir/zanamivir; 44.5% of patients received NAI ≤2 days and 65.5% ≤5 days after onset of illness); 23.1% received systemic corticosteroids. There were fewer deaths among NAI-treated patients (5.3% versus 7.6%; p=0.032). NAI treatment was independently associated with survival (adjusted hazard ratio (HR) 0.28, 95% CI 0.19-0.43), adjusted for treatment-propensity score and patient characteristics. Superinfections increased (adjusted HR 2.18, 95% CI 1.52-3.11) and chronic statin use decreased (adjusted HR 0.44, 95% CI 0.23-0.84) death risks. Best survival was shown when treatment started within ≤2 days (adjusted HR 0.20, 95% CI 0.12-0.32), but there was benefit with treatment within 3-5 days (adjusted HR 0.35, 95% CI 0.21-0.58). Time-dependent analysis showed consistent results of NAI treatment (adjusted HR 0.39, 95% CI 0.27-0.57). Corticosteroids increased superinfection (9.7% versus 2.7%) and deaths when controlled for indications (adjusted HR 1.73, 95% CI 1.14-2.62). Early NAI treatment was associated with shorter length of stay in a subanalysis. NAI treatment may improve survival of hospitalised influenza patients; benefit is greatest from, but not limited to, treatment started within 2 days of illness. Superinfections and corticosteroids increase mortality. Antiviral and non-antiviral management strategies should be considered.

Current morphologic criteria perform poorly in identifying hereditary leiomyomatosis and renal cell carcinoma syndrome-associated uterine leiomyomas.

The contemporary oncologic pathology report conveys diagnostic, prognostic, predictive, and hereditary predisposition information. Each component may be premised on a morphologic feature or a biomarker. Clinical validity and reproducibility are paramount as is standardization of reporting and clinical response to ensure individualization of patient care. Regarding hereditary predisposition, morphology-based genetic referral systems in some instances have eclipsed genealogy-based systems, for example, cell type in ovarian cancer and BRCA screening. In other instances such as Lynch syndrome, morphology-based schemas supplement clinical schemas and there is an emerging standard of care for reflex biomarker testing. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome predisposes patients to uterine and cutaneous leiomyomas (LMs) and renal cell carcinomas (RCCs). Several authors have emphasized the role pathologists may play in identifying this syndrome by recognizing the morphologic characteristics of syndromic uterine LMs and RCCs. Recently immunohistochemical overexpression of S-(2-succinyl) cysteine (2SC) has been demonstrated as a robust biomarker of mutation status in tumors from HLRCC patients. In this blinded control-cohort study we demonstrate that the proposed morphologic criteria used to identify uterine LMs in HLRCC syndrome are largely irreproducible among pathologists and lack sufficient robustness to serve as a trigger to triage cases for 2SC immunohistochemistry or patients for further family/personal history inquiry. Although refinement of morphologic criteria can be considered, in view of the availability of a clinically robust biomarker, consideration should be given to reflex testing of uterine LMs with an appropriate age cut off or in the setting of a suspicious family history.

Use of sodium-glucose co-transporter 2 inhibitors in solid organ transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus: A systematic review.

INTRODUCTION: Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitors have demonstrated kidney, cardiovascular and mortality benefits in the general population; however, the evidence is limited in solid organ transplant recipients. The aim of this systematic review was to evaluate the current efficacy and safety data of SGLT2 inhibitors in adult kidney, heart, lung, and liver transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus. METHOD: We searched MEDLINE, MEDLINE Epub, CENTRAL, CDSR, EMBASE, CINAHL, and sources of unpublished literature. All primary interventional and observational studies on SGLT2 inhibitors in transplant recipients were included. Clinical outcomes included mortality, cardiovascular and kidney events, and adverse events such as graft rejection. Surrogate markers including hemoglobin A1c (HbA1c) and weight reduction were also evaluated. RESULTS: Of the 17 studies that were included in this systematic review, there were 15 studies on kidney transplant recipients (n = 2417 patients) and two studies on heart transplant recipients (n = 122 patients). There was only one randomized controlled trial which evaluated 49 kidney transplant patients over 24 weeks. Overall, studies were heterogeneous in study design, sample size, duration of diabetes, time to SGLT2 inhibitor initiation post-transplantation (ranging from 0.88 to 11 years post kidney transplant; five to 5.7 years post heart transplant) and follow-up (ranging from 0.4 to 5.25 years in kidney transplant patients; 0.75 to one year in heart transplant patients). Only one retrospective study evaluated mortality as a part of a composite outcome in kidney transplant patients; however, study limitations restrict generalizability of results. Overall, studies could not confirm clinical cardiovascular and kidney benefits in the transplant population. Findings suggested that SGLT2 inhibitors may improve glycemic control; however, they are associated with urinary tract infection. Diabetic ketoacidosis and acute kidney injury also occurred in these studies, with precipitating factors such as infection and acute heart failure exacerbation. CONCLUSIONS: While SGLT2 inhibitors are promising agents with expanding indications in the non-transplant population, these agents may not be suitable for all solid organ transplant recipients, and close monitoring (e.g. for urinary tract infections) and patient education (e.g. sick day management) are essential if these agents are initiated. Evidence is based on short-term findings and suggests an association with hemoglobin A1c reduction and increased adverse events. Further long-term randomized controlled trials are needed to evaluate the effect of SGLT2 inhibitors on clinically important outcomes, including mortality reduction, in solid organ transplant recipients.

Incidence of hepatocellular carcinoma and mortality in chronic viral hepatitis in an Asian population with and without HIV infection.

BACKGROUND: It is uncertain whether people with HIV infection have a higher incidence of hepatocellular carcinoma (HCC) than the general population. AIMS: To compare the incidence of HCC between people infected with HBV and/or HCV with and without HIV METHODS: We performed a retrospective population-based cohort study, involving people with HBV and/or HCV infection from 2001 to 2018. The primary endpoint was incidence of HCC; secondary endpoint was all-cause mortality. We performed Cox proportional hazard regression models to estimate the hazard ratios (HR) of HIV for the primary and secondary endpoints. RESULTS: We identified 1374 people infected with HIV and 39,908 people without HIV with HBV and/or HCV infection. Among those with HIV, 654 (47.6%) had HBV, 649 (47.2%) HCV and 71 (5.2%) HBV-HCV-co-infection; they were younger, and had a higher prevalence of HCV and a lower prevalence of cirrhosis. The incidence rate estimates of HCC were, respectively, 1.5 (95% CI: 0.8-2.5) and 7.6 (95% CI 7.3-8.0) per 1000 person-years for those with and without HIV infection. Using multivariate Cox proportional hazard regression models, among people with HBV, HIV was associated with lower risk of HCC (adjusted HR: 0.376, 95% CI: 0.201-0.704, p = 0.01) and death (adjusted HR: 0.692, 95% CI: 0.552-0.867, p = 0.007). Risks of HCC were similar for HCV and HBV-HCV co-infection for people with and without HIV. CONCLUSIONS: Among individuals with HBV infection, the Incidence of HCC was lower in those with HIV. For HCV infection, incidence of HCC was similar between those with and without HIV.

An automatic MEG low-frequency source imaging approach for detecting injuries in mild and moderate TBI patients with blast and non-blast causes.

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. Injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1-4 Hz) that can be measured and localized by magnetoencephalography (MEG). We developed a new automated MEG low-frequency source imaging method and applied this method in 45 mild TBI (23 from combat-related blasts, and 22 from non-blast causes) and 10 moderate TBI patients (non-blast causes). Seventeen of the patients with mild TBI from blasts had tertiary injuries resulting from the blast. The results show our method detected abnormalities at the rates of 87% for the mild TBI group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities were 96% and 77% for the blast and non-blast TBI groups, respectively. The spatial characteristics of abnormal slow-wave generation measured by Z scores in the mild blast TBI group significantly correlated with those in non-blast mild TBI group. Among 96 cortical regions, the likelihood of abnormal slow-wave generation was less in the mild TBI patients with blast than in the mild non-blast TBI patients, suggesting possible protective effects due to the military helmet and armor. Finally, the number of cortical regions that generated abnormal slow-waves correlated significantly with the total post-concussive symptom scores in TBI patients. This study provides a foundation for using MEG low-frequency source imaging to support the clinical diagnosis of TBI.

Early data from the first population-wide breast cancer-specific registry in Hong Kong.

BACKGROUND: Current measures for breast cancer prevention and options for treatment adopted in Hong Kong are mainly based on research data and clinical evidence from overseas. It is essential to establish a cancer-specific registry to monitor the status of breast cancer in Hong Kong. OBJECTIVES: We summarized the current status of breast cancer in Hong Kong based on the data collected from Hong Kong Breast Cancer Registry (HKBCR). METHODS: Prevalent and newly diagnosed breast cancers (including in situ and invasive breast cancers) were registered in the HKBCR. Information on patient demographics, risk factors, medical information, and survival were analyzed and reported in this study. RESULTS: Data of 2,330 breast cancer patients were analyzed. We observed an earlier median age at diagnosis in Hong Kong than those reported in other countries. Distribution of cancer stage was: stage 0 (11.4%), stage I (31.4%), stage II (41%), stage III (12.5%), stage IV (0.8%), and unclassified (2.9%). The percentages of patients who received surgery, chemotherapy, radiation therapy, and endocrine therapy were 98.7, 67.9, 64.8, and 64.1%, respectively. At a median follow-up of 1.2 years, locoregional recurrence was recorded at 2%, distant recurrence at 2.8%, and breast-cancer-related mortality at 0.3%. CONCLUSIONS: The HKBCR serves as a surveillance program to monitor disease and treatment patterns. It is pivotal to support research for more effective breast cancer prevention and treatment strategies in Hong Kong.

Histo-blood group antigens and rotavirus vaccine virus shedding in Australian infants.

Rotavirus vaccine performance varies between high and low income countries. One possible explanation is inherited histo-blood group antigens (HBGAs) the expression of which differs between populations. HBGAs are polymorphic glycans on mucosal surfaces. Their presence indicates the secretor phenotype, while their absence identifies a non-secretor status. HBGAs can act as rotavirus receptors and might influence live-attenuated rotavirus vaccine virus replication and shedding. Studies in low and middle income countries of the human rotavirus vaccine Rotarix (RV1), suggest HBGA secretor phenotype is important for vaccine immunogenicity. We investigated in a high income country the association between HBGA phenotype (secretor and Lewis) and the bovine-human reassortment vaccine RotaTeq (RV5) vaccine shedding in the stools of infants following each vaccine dose. Eighty-two infants from an Australian birth cohort provided saliva and weekly stool samples after RV5 vaccination doses. Lewis and secretor HBGA phenotyping was identified from saliva samples and confirmed by genotyping. Vaccine virus strains were detected by real-time polymerase chain reaction assays. No significant association between secretor status and vaccine virus shedding was identified. The proportion of infants who shed rotavirus following the first RV5 dose for secretor and non-secretor infants was 57/64 (89%) and 17/18 (94%), respectively, decreasing to 24/64 (33%) and 9/18 (50%) after the second dose and 26/64 (42%) and 8/18 (44%) following the third vaccine dose, respectively. Similarly, no significant differences were observed in vaccine virus shedding by Lewis, or combined Lewis and secretor status, after each vaccine dose. We found HBGAs were not associated with RV5 vaccine virus shedding in Australian infants.

Seven-year excess mortality, functional outcome and health status after trauma in Hong Kong.

PURPOSE: The purpose was to investigate long-term health impacts of trauma and the aim was to describe the functional outcome and health status up to 7 years after trauma. METHODS: We conducted a prospective, multi-centre cohort study of adult trauma patients admitted to three regional trauma centres with moderate or major trauma (ISS ≥ 9) in Hong Kong (HK). Patients were followed up at regular time points (1, 6 months and 1, 2, 3, 4, 5, 6, and 7 years) by telephone using extended Glasgow Outcome Scale (GOSE) and the Short-Form 36 (SF36). Observed annual mortality rate was compared with the expected mortality rate estimated using the HK population cohort. Linear mixed model (LMM) analyses examined the changes in SF36 with subgroups of age ≥ 65 years, ISS > 15, and GOSE ≥ 5 over time. RESULTS: At 7 years, 115 patients had died and 48% (138/285) of the survivors responded. The annual mortality rate (AMR) of the trauma cohort was consistently higher than the expected mortality rate from the general population. Forty-one percent of respondents had upper good recovery (GOSE = 8) at 7 years. Seven-year mean PCS and MCS were 45.06 and 52.06, respectively. LMM showed PCS improved over time in patients aged < 65 years and with baseline GOSE ≥ 5, and the MCS improved over time with baseline GOSE ≥ 5. Higher mortality rate, limited functional recovery and worse physical health status persisted up to 7 years post-injury. CONCLUSION: Long-term mortality and morbidity should be monitored for Asian trauma centre patients to understand the impact of trauma beyond hospital discharge.

Older adults and ulcers: chronic wounds in the geriatric population.

PURPOSE: To provide the wound care practitioner with information about how chronic wound healing differs in the older adult population. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to: 1. Compare chronic wound healing processes and outcomes in older adults with those in younger persons. 2. Explain the relationships between wound healing, comorbidities, and adverse drug events. 3. Apply known relationships among wound healing, comorbid medical conditions, and functional decline to care of the older adult.

Social Decision Making in Autistic Adolescents: The Role of Theory of Mind, Executive Functioning and Emotion Regulation.

Social decision making is often challenging for autistic individuals. Twenty autistic adolescents made decisions in the socially interactive context of a one-shot ultimatum game, and performance was compared to a large matched typical reference sample. Theory of mind, executive functioning and emotion regulation were measured via direct assessments, self- and parent report. Relative to the reference sample, autistic adolescents proposed fewer fair offers, and this was associated with poorer theory of mind. Autistic adolescents responded similarly to the reference sample when making decisions about offers proposed to them, however they did not appear to down regulate their negative emotion in response to unfair treatment in the same way. Atypical processes may underpin even apparently typical decisions made by autistic adolescents.

Dissociable effects of subthalamic nucleus deep brain stimulation surgery and acute stimulation on verbal fluency in Parkinson's disease.

OBJECT: Verbal fluency (VF) is the cognitive test which shows the most consistent and persistent post-operative decline after subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD). However, the reasons are not completely understood, and the debate has focused on two hypotheses: a surgical effect or an acute STN-DBS effect. METHODS: We recruited 3 PD samples: (1) a group assessed before and after STN-DBS surgery (2) a group assessed On vs. Off STN-DBS and (3) an unoperated PD control group. All groups performed letter, category and switching category VF tasks. The total number of correct words generated were noted and measures of clustering and switching were also obtained. RESULTS: We found a significant effect of STN-DBS surgery on all VF tasks which was associated with a post-operative decline in the total number of words generated, and a reduction of phonemic switching during the letter and category VF tasks, and a reduction of semantic clustering for category VF. By contrast to the effects of surgery, acute On vs. Off stimulation did not influence the number of words generated on any of the VF tasks. Acute stimulation only produced two effects on the category VF task: increased semantic cluster size and decreased number of semantic switches when STN-DBS was switched On. CONCLUSIONS: This study differentiates between the effects of STN-DBS surgery and acute stimulation on VF performance. Our findings indicate that the STN-DBS effect on VF are a surgical and not an acute STN stimulation effect.

Induction of human arylamine N-acetyltransferase type I by androgens in human prostate cancer cells.

Human arylamine N-acetyltransferases (NAT) bioactivate arylamine and heterocyclic amine carcinogens present in red meat and tobacco products. As a result, factors that regulate expression of NATs have the potential to modulate cancer risk in individuals exposed to these classes of carcinogens. Because epidemiologic studies have implicated well-done meat consumption as a risk factor for prostate cancer, we have investigated the effects of androgens on the expression of arylamine N-acetyltransferase type I (NAT1). We show that NAT1 activity is induced by R1881 in androgen receptor (AR)-positive prostate lines 22Rv1 and LNCaP, but not in the AR-negative PC-3, HK-293, or HeLa cells. The effect of R1881 was dose dependent, with an EC(50) for R1881 of 1.6 nmol/L. Androgen up-regulation of NAT1 was prevented by the AR antagonist flutamide. Real-time PCR showed a significant increase in NAT1 mRNA levels for R1881-treated cells (6.60 +/- 0.80) compared with vehicle-treated controls (1.53 +/- 0.17), which was not due to a change in mRNA stability. The increase in NAT1 mRNA was attenuated by concurrent cycloheximide treatment, suggesting that the effect of R1881 may not be by direct transcriptional activation of NAT1. The dominant NAT1 transcript present following androgen treatment was type IIA, indicating transcriptional activation from the major NAT1 promoter P1. A series of luciferase reporter deletions mapped the androgen responsive motifs to a 157-bp region of P1 located 745 bases upstream of the first exon. These results show that human NAT1 is induced by androgens, which may have implications for cancer risk in individuals.