Effectiveness of nirmatrelvir/ritonavir (Paxlovid®) in preventing hospitalisation and death among COVID-19 patients: a prospective cohort study.

INTRODUCTION: Previous trials and real-world studies have shown that nirmatrelvir/ritonavir (Paxlovid®) reduces hospitalisation and deaths in symptomatic, high-risk, nonsevere COVID-19 patients. However, there was a scarcity of data on its effectiveness in the local setting. This study aimed to determine the effectiveness of Paxlovid® in reducing hospitalisation and mortality among COVID-19 patients and to identify the types of adverse events that occur after taking Paxlovid®. MATERIALS AND METHODS: A two-arm prospective cohort study was conducted among adult patients with COVID-19 categories 2 and 3 treated with Paxlovid® and a matched control group. A standard risk-stratified scoring system was used to establish Paxlovid® eligibility. All patients who were prescribed Paxlovid® and took at least one dose of Paxlovid® were included in the study. The control patients were selected from a centralised COVID-19 patient registry and matched based on age, gender and COVID-19 stage severity. RESULTS: A total of 552 subjects were included in the study and evenly allocated to the treatment and control groups. There was no statistically significant difference in 28-day hospitalisation after diagnosis [Paxlovid®: 26 (9.4%), Control: 34 (12.3%), OR: 0.74; 95%CI, 0.43-1.27; p=0.274] or all-cause death [Paxlovid®: 2 (0.7%), Control: 3 (1.1%), OR 1.51; 95%CI, 0.25-9.09; p=0.999]. There was no significant reduction in hospitalisation duration, intensive care unit admission events or supplementary oxygen requirement in the treatment arm. Ethnicity, COVID-19 severity at diagnosis, comorbidities and vaccination status were predictors of hospitalisation events. CONCLUSION: In this two-arm study, Paxlovid® did not significantly lower the incidence of hospitalisation, all-cause death and the need for supplemental oxygen. Adverse effects were frequent but not severe. Paxlovid® efficacy varied across settings and populations, warranting further real-world investigations.

Adherence to tyrosine kinase inhibitors among adult chronic myeloid leukemia patients in a Malaysia hospital.

Background Tyrosine kinase inhibitors have been demonstrated to improve the survival of patients with chronic myeloid leukaemia. However, medication adherence is vital for patients on chronic treatment. Objective The objective of the current study was to evaluate response to treatment, adherence by patients to tyrosine kinase inhibitors and factors associated with adherence and response. Setting A haematology clinic in a regional referral hospital in Malaysia. Method Patients aged ≥ 13 years who had been on imatinib or nilotinib for ≥ 12 months were included in this cross-sectional study. An optimal response was defined as the achievement of major molecular response at 12 months of treatment. Patient medication adherence was determined using the average medication possession ratio based on the dispensing records. The patients were considered adherent if the medication possession ratio was > 90%. Multiple logistic regression was performed to evaluate the factors associated with adherence. The association of adherence with molecular response was analysed by univariate logistic regression. Main outcome measure The primary outcome measures were the proportion of patients who achieved optimal response and the medication possession ratio. Results A total of 151 patients were screened, and 71 patients were included. Twenty-eight patients (39%) achieved major molecular response at 12 months of treatment. The median time to achieve this was 15.5 months (an interquartile range of 15). The mean medication possession ratio for imatinib and nilotinib was 0.94 (± 0.14) and 0.96 (± 0.10), respectively, but this difference was without statistical significance (t  =  - 0.517, p  =  0.610). Nausea and vomiting (odds ratio [OR] of 0.25, 95% confidence interval [CI]: 0.07-0.83, p  =  0.023) and disease phase at diagnosis (OR of 0.20, 95% CI 0.04-1.06, p  =  0.059) were associated with patient adherence. An association was not found between patient adherence and molecular response (OR of 1.03, 95% CI 0.35-3.09, p  =  0.956). Conclusion The patients in this study demonstrated a relatively deep molecular response and optimal adherence. Nevertheless, one fourth of them were noncompliant with imatinib. Therefore, active interventions are warranted to prevent treatment-associated adverse events and improve adherence.

Bioequivalence and pharmacokinetic comparison of two fixed dose combination of Metformin/ Glibenclamide formulations in healthy subjects under fed condition.

AIM: This study is conducted to compare the pharmacokinetic profiles of two fixed dose combination of metformin/glibenclamide tablets (500mg/5 mg per tablet). MATERIALS AND METHODS: This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2- period crossover study with a washout period of 7 days. All 28 adult male subjects were required to fast for at least 10 hours prior to drug administration and they were given access to water ad libitum during this period. Thirty minutes prior to dosing, all subjects were served with a standardized high-fat and high-calorie breakfast with a total calorie of 1000 kcal which was in accordance to the EMA Guideline on the Investigation of Bioequivalence. Subsequently, subjects were administered either the test or reference preparation with 240mL of plain water in the first trial period. During the second trial period, they received the alternate preparation. Plasma levels of glibenclamide and metformin were analysed separately using two different high performance liquid chromatography methods. RESULTS: The 90% confidence interval (CI) for the ratio of the AUC0-t, AUC0-∞, and Cmax of the test preparation over those of the reference preparation were 0.9693-1.0739, 0.9598- 1.0561 and 0.9220 - 1.0642 respectively. Throughout the study period, no serious drug reaction was observed. However, a total of 26 adverse events (AE)/side effects were reported, including 24 that were definitely related to the study drugs, namely giddiness (n=17), while diarrheoa (n=3), headache (n=2) and excessive hunger (n=2) were less commonly reported by the subjects. CONCLUSION: It can be concluded that the test preparation is bioequivalent to the reference preparation.

Responses of photosynthesis and component processes to drought and temperature stress: are Mediterranean trees fit for climate change?

Global warming is raising concerns about the acclimatory capacity of trees and forests, especially in Mediterranean-type ecosystems. The sensitivity of photosynthesis to temperature is a key uncertainty for projecting the magnitude of terrestrial feedbacks on future climate change. While boreal, temperate and tropical species have been comparatively well investigated, our study provides the first comprehensive overview of the seasonal acclimatory responses of photosynthesis and its component processes to temperature in four Mediterranean climax species under natural conditions. We quantified seasonal changes in the responses of net photosynthesis (Anet), stomatal conductance (gs), mesophyllic conductance (gm) and electron-transport rate (Jcf), and investigated their sensitivity to drought and temperature stress in sunlit and shaded leaves of four Mediterranean tree species (Quercus ilex L., Pinus halepensis Mill., Arbutus unedo L. and Quercus pubescens Willd.). Sunlit leaves, but not shaded leaves, showed a pronounced seasonality in the temperature responses of Anet, gs, gm and Jcf. All four species and variables showed a remarkably dynamic and consistent acclimation of the thermal optimum (Topt), reaching peaks in summer ~29-32 °C. Changes in the shape of the response curves were, however, highly species-specific. Under severe drought, Topt of all variables were on average 22-29% lower. This was accompanied by narrower response curves above all in P. halepensis, reducing the optimal range for photosynthesis to the cooler morning or evening periods. Wider temperature-response curves and less strict stomatal control under severe drought were accompanied by wilting and drought-induced leaf shedding in Q. ilex and Q. pubescens and by additional branch dieback in A. unedo. Mild winter conditions led to a high Topt (~19.1-22.2 °C), benefitting the evergreen species, especially P. halepensis. Seasonal acclimation of Anet was explained better by gs and gm being less pronounced in Jcf. Drought was thus a key factor, in addition to growth temperature, to explain seasonal acclimation of photosynthesis. Severe drought periods may exceed more frequently the high acclimatory capacity of Mediterranean trees to high ambient temperatures, which could lead to reduced growth, increased leaf shedding and, for some species such as A. unedo, increased mortality risk.

Influence of bariatric surgery on weight reduction and control of chronic disease among obese patients in Malaysia.

INTRODUCTION: This study was designed to determine the influence of bariatric surgery on changes in the body mass index (BMI), and the control of diabetes, hypertension and dyslipidaemia among obese patients in Malaysia. MATERIALS AND METHODS: This was a retrospective cohort study undertaken at a public tertiary care centre in the state of Perak, Malaysia. Information of obese patients who underwent bariatric surgery was obtained from their medical records. The changes in the BMI, HbA1C, systolic and diastolic blood pressure (SBP and DBP), and lipid levels between three months before and after the surgery were assessed. RESULTS: The patients (n=106) were mostly Malay (66.0%), had at least one comorbidity (61.3%), and had a mean age of 40.38±11.75 years. Following surgery, the BMI of the patients was found to reduce by 9.78±5.82kg/m2. For the patients who had diabetes (n=24) and hypertension (n=47), their mean HbA1C, SBP and DBP were also shown to reduce significantly by 2.02±2.13%, 17.19±16.97mmHg, and 11.45±12.63mmHg, respectively. Meanwhile, the mean total cholesterol, triglyceride and low-density lipoprotein levels of those who had dyslipidaemia (n=21) were, respectively, lowered by 0.91±1.18mmol/L, 0.69±1.11mmol/L and 0.47±0.52mmol/L. CONCLUSION: The findings suggest that in addition to weight reduction, bariatric surgery is helpful in improving the diabetes, hypertension and dyslipidaemia control among obese patients. However, a large-scale trial with a control group is required to verify our findings.

An intervention based on the stages of change, health profiles and physical activity levels of overweight and obese adults in Sarawak, Malaysia - a feasibility study.

INTRODUCTION: Physical inactivity is the one of the leading causes of major non-communicable diseases in the world. The aim of this study is to assess the feasibility of an intervention program based on the stages of change, physical activity levels and health profiles of selected overweight and obese adults in Sarawak. METHODS: This intervention study was carried out using selected overweight and obese adults in Sarawak. A total of 75 participants were placed in the intervention group, and 80 respondents were placed in the control group participated. Respondent-determined weekly aerobic exercise sessions were conducted for six months. The Malay version of the long-form International Physical Activity Questionnaire (IPAQ) and Transtheoretical model of change (TTM) questionnaire were used, together with anthropometric measurements and the collection of venous fasting blood profiles. Data was entered and analyzed using SPSS Version 20. RESULTS: The intervention group had significant better stage transitions compared to the control group (p<0.01). They also had significantly lower total cholesterol, although both groups showed significant results (difference= 0.53, p<0.01; difference= 0.38, p=0.01). The respondent-determined intervention program was effective in improving stage transition; however, an intervention of longer duration could provide more conclusive health outcomes. CONCLUSION: Physical activity plays a role in assisting overweight and obese adults to be more active and healthier.

Hypertension and its association with Anthropometric indices among students in a public university.

INTRODUCTION: The present study aimed to determine the prevalence of hypertension and its association with nutritional status (body mass index, body fat percentage, and visceral fat) among students in a public university in Sarawak, Malaysia. METHODS: This was a cross-sectional study among undergraduate students aged 18 years old and above. Anthropometric measurements, such as weight, height, body composition, and blood pressure measurements, were collected. Hypertension was defined as equal or more than 140/90 mmHg. Statistical analyses were done using IBM SPSS version 20. RESULTS: A total of 354 respondents participated in the study. Mean age for the respondents was 21 years (SD 1.18 years). About 40% of the respondents were overweight or obese. Prevalence of hypertension was 8.2%. Mean systolic blood pressure was 119.1mmHg (SD14.36mmHg), and the mean diastolic blood pressure was 72.6mmHg (SD 9.73mmHg). There is a significant association between male gender (odds ratio =3.519, 95% CI is 1.886-6.566), body fat percentage (odds ratio = 1.944, 95% CI is 1.050-3.601), visceral fat (odds ratio = 2.830, 95% CI is 1.346-5.951), and family history of hypertension (odds ratio= 2.366, 95% CI is 1.334-4.194) and hypertension. CONCLUSION: The prevalence of hypertension was less than 10% and is associated with male gender, body composition, and family history of hypertension.

Utilization of Western medicine and traditional Chinese medicine among patients with Alzheimer's disease in Taiwan: a nationwide population-based study.

BACKGROUND AND PURPOSE: Large-scale studies of utilization of medical services among patients with Alzheimer's disease (AD) are lacking. We aimed to investigate the usage of Western medicine and traditional Chinese medicine (TCM) among these patients in Taiwan. METHODS: We analyzed one million samples from the National Health Insurance Research Database in Taiwan. Patients (n = 1814) newly diagnosed with AD in 2001-2010 were divided into TCM users (n = 528) and non-TCM users (n = 1286). RESULTS: Compared with non-TCM users, TCM users were younger, had a higher female:male ratio and higher utilization rate of Western medicine. The median interval between diagnosis and the first TCM consultation was 7.92 months. Donepezil and rivastigmine were commonly prescribed medications. Chinese herbal medicine was the most popular treatment among TCM users. CONCLUSIONS: This study revealed the specific usage patterns of TCM and non-TCM medical services among patients with AD. The information could be used for improving the healthcare of patients with AD.

Antibiotic treatment of zebrafish mycobacteriosis: tolerance and efficacy of treatments with tigecycline and clarithromycin.

Zebrafish (Danio rerio) are a popular model organism used in a growing number of research fields. Maintaining healthy, disease-free laboratory fish is important for the integrity of many of these studies. Mycobacteriosis is a chronic bacterial infection caused by several Mycobacterium spp. and is the second most common disease found in laboratory zebrafish. Current mycobacteriosis control measures recommend the removal of infected fish and in severe outbreaks, depopulation. These measures can be effective, but less disruptive measures should be assessed for controlling mycobacteriosis, particularly when valuable and rare lines of fish are affected. Here, the in vivo efficacy of two drug candidates, tigecycline (1 µg g-1 ) and clarithromycin (4 µg g-1 ), was tested in adult zebrafish experimentally infected with Mycobacterium chelonae. We assessed both short (14 day)- and long-term (30 day) treatments and evaluated fecundity and pathological endpoints. Fecundity and histology results show that zebrafish tolerated antibiotics. Antibiotic treatments did not significantly impact the prevalence of acid-fast granulomas; however, the severity of infections (acid-fast granuloma intensity) was significantly decreased following treatments.

Dental Prophylaxis and Osteoradionecrosis: A Population-Based Study.

The aim of this study was to investigate the association of different dental prophylactic modalities and osteoradionecrosis (ORN) and determine the risk of ORN under different timing periods of scaling, with the use chlorhexidine mouth rinse after surgery and with different strategies of fluoride gel application in head and neck cancer (HNC) participants. A cohort of 18,231 HNC participants, including 941 ORN patients and 17,290 matched control cases, were enrolled from a Longitudinal Health Insurance Database for Catastrophic Illness Patients (LHID-CIP) in Taiwan. Based on different dental prophylactic modalities before radiotherapy, including chlorhexidine mouth rinse, scaling, and fluoride gel, all HNC subjects were stratified into different groups. The Cox proportional hazard regression was used to compare ORN incidences under different dental prophylactic modalities. The results revealed that scaling and chlorhexidine mouth rinse were significantly related to ORN risk ( P = 0.004 and P < 0.0001). Chlorhexidine mouth rinse was highly correlated to ORN occurrence (hazard ratio [HR], 1.83-2.66), as exposure increased the risk by 2.43-fold among oral cancer patients, regardless of whether they had received major oral surgery or not. Oral cancer patients receiving scaling within 2 wk before radiotherapy increased their incidence of ORN by 1.28-fold compared with patients who had not undergone scaling within 6 mo. There is no significance of fluoride application for dental prophylaxis in increasing ORN occurrence. In conclusion, dental prophylaxis before radiotherapy is strongly correlated to ORN in HNC patients. Chlorhexidine exposure and dental scaling within 2 wk before radiotherapy is significantly related to ORN risk, especially in oral cancer patients. The use of 1.1% NaF topical application did not significantly increase the risk of ORN in HNC patients. An optimal dental prophylaxis protocol to reduce ORN should concern cancer location, cautious prescription of chlorhexidine mouth rinse, and proper timing of scaling.

Simulation of synaptic short-term plasticity using Ba(CF3SO3)2-doped polyethylene oxide electrolyte film.

The simulation of synaptic plasticity using new materials is critical in the study of brain-inspired computing. Devices composed of Ba(CF3SO3)2-doped polyethylene oxide (PEO) electrolyte film were fabricated and with pulse responses found to resemble the synaptic short-term plasticity (STP) of both short-term depression (STD) and short-term facilitation (STF) synapses. The values of the charge and discharge peaks of the pulse responses did not vary with input number when the pulse frequency was sufficiently low(~1 Hz). However, when the frequency was increased, the charge and discharge peaks decreased and increased, respectively, in gradual trends and approached stable values with respect to the input number. These stable values varied with the input frequency, which resulted in the depressed and potentiated weight modifications of the charge and discharge peaks, respectively. These electrical properties simulated the high and low band-pass filtering effects of STD and STF, respectively. The simulations were consistent with biological results and the corresponding biological parameters were successfully extracted. The study verified the feasibility of using organic electrolytes to mimic STP.

Seasonal variability of foliar photosynthetic and morphological traits and drought impacts in a Mediterranean mixed forest.

The Mediterranean region is a hot spot of climate change vulnerable to increased droughts and heat waves. Scaling carbon fluxes from leaf to landscape levels is particularly challenging under drought conditions. We aimed to improve the mechanistic understanding of the seasonal acclimation of photosynthesis and morphology in sunlit and shaded leaves of four Mediterranean trees (Quercus ilex L., Pinus halepensis Mill., Arbutus unedo L. and Quercus pubescens Willd.) under natural conditions. Vc,max and Jmax were not constant, and mesophyll conductance was not infinite, as assumed in most terrestrial biosphere models, but varied significantly between seasons, tree species and leaf position. Favourable conditions in winter led to photosynthetic recovery and growth in the evergreens. Under moderate drought, adjustments in the photo/biochemistry and stomatal/mesophyllic diffusion behaviour effectively protected the photosynthetic machineries. Severe drought, however, induced early leaf senescence mostly in A. unedo and Q. pubescens, and significantly increased leaf mass per area in Q. ilex and P. halepensis. Shaded leaves had lower photosynthetic potentials but cushioned negative effects during stress periods. Species-specificity, seasonal variations and leaf position are key factors to explain vegetation responses to abiotic stress and hold great potential to reduce uncertainties in terrestrial biosphere models especially under drought conditions.

Angiotensin II receptor blocker prevents upper gastrointestinal bleeding in hypertensive patients with chronic kidney disease not on dialysis.

AIMS: Investigate if angiotensin II receptor blocker (ARB) decreases risk of upper gastrointestinal bleeding (UGIB) in hypertensive patients with chronic kidney disease (CKD) not on dialysis. METHODS: All hypertensive patients with CKD not on dialysis in outpatient department of China Medical University Hospital from 2003 to May 2013 were enrolled. The risk of UGIB was analysed using Cox proportional hazard regression. RESULTS: A total of 2744 hypertensive CKD patients including 1515 male and 1229 female, aged 64.9 ± 13.8 years old in a median of 1.9 (0.9-3.9) years were analysed. The incidence of UGIB was 4.5 per 100 patient-years. ARB was associated with a decreased risk of UGIB (p < 0.001) with an adjusted hazard ratio (HR) of 0.533 [95% confidence interval (CI) 0.404-0.703]. A history of UGIB, Helicobacter pylori infection, diabetes, lower estimated glomerular filtration rate, elevated blood urea nitrogen and decreased serum albumin were independently associated with an increased risk of UGIB. CONCLUSIONS: Angiotensin II receptor blocker is associated with a decreased risk of UGIB in hypertensive CKD patients not on dialysis, independent of their renal function, history of gastrointestinal bleeding and nutrition status.

Subdural hematoma in diabetic patients.

BACKGROUND AND PURPOSE: Subdural hematoma (SDH) is associated with a high mortality rate. However, the risk of SDH in diabetic patients has not been well studied. The aim of the study was to examine the risk of SDH in incident diabetic patients. METHODS: From a universal insurance claims database of Taiwan, a cohort of 28,045 incident diabetic patients from 2000 to 2005 and a control cohort of 56,090 subjects without diabetes were identified. The incidence and hazard ratio of SDH were measured by the end of 2010. RESULTS: The mean follow-up years were 7.24 years in the diabetes cohort and 7.44 years in the non-diabetes cohort. The incidence of SDH was 1.57-fold higher in the diabetes cohort than in the non-diabetes cohort (2.04 vs. 1.30 per 1000 person-years), with an adjusted hazard ratio of 1.63 [95% confidence interval (CI) 1.43-1.85]. The stratified data showed that adjusted hazard ratios were 1.51 (95% CI 1.28-1.77) for traumatic SDH and 1.89 (95% CI 1.52-2.36) for non-traumatic SDH. The 30-day mortality rate for those who developed SDH in the diabetes cohort was 8.94%. CONCLUSIONS: This study demonstrates that incident diabetic patients are at higher risk of SDH than individuals without diabetes. Proper intervention for diabetic patients is necessary for preventing the devastating disorder.

Subdural hematoma in patients with end-stage renal disease receiving hemodialysis.

BACKGROUND AND PURPOSE: Hemodialysis (HD) may increase the risk of acute subdural hematoma (SDH) with high fatality, but the extent of this disease in non-western populations is unclear. The incidence of and fatality from SDH in patients with end-stage renal disease (ESRD) on HD were examined for an Asian population. METHODS: A cohort of 4709 newly diagnosed ESRD patients on HD from 1998 to 2010 and a control cohort of 18 663 subjects without any kidney disease were identified from a universal insurance claims database in Taiwan. The incidence and hazard of SDH for the two cohorts and 30-day mortality from SDH were measured by the end of 2010. RESULTS: The incidence of SDH was 4.47-fold higher in the HD cohort than in the control cohort (56.3 vs. 12.6 per 10 000 person-years) with an adjusted hazard ratio (HR) of 3.81 (95% CI 2.77-5.25). HD patients with SDH had a high odds of 30-day mortality with an adjusted odds ratio of 6.34 (95% CI 2.37-16.9). CONCLUSIONS: ESRD patients with HD were demonstrated to be at high risk of subsequent SDH and to have a high mortality risk from SDH. Proper care for HD patients is necessary to prevent the devastating disorder.

Historical connectivity, contemporary isolation and local adaptation in a widespread but discontinuously distributed species endemic to Taiwan, Rhododendron oldhamii (Ericaceae).

Elucidation of the evolutionary processes that constrain or facilitate adaptive divergence is a central goal in evolutionary biology, especially in non-model organisms. We tested whether changes in dynamics of gene flow (historical vs contemporary) caused population isolation and examined local adaptation in response to environmental selective forces in fragmented Rhododendron oldhamii populations. Variation in 26 expressed sequence tag-simple sequence repeat loci from 18 populations in Taiwan was investigated by examining patterns of genetic diversity, inbreeding, geographic structure, recent bottlenecks, and historical and contemporary gene flow. Selection associated with environmental variables was also examined. Bayesian clustering analysis revealed four regional population groups of north, central, south and southeast with significant genetic differentiation. Historical bottlenecks beginning 9168-13,092 years ago and ending 1584-3504 years ago were revealed by estimates using approximate Bayesian computation for all four regional samples analyzed. Recent migration within and across geographic regions was limited. However, major dispersal sources were found within geographic regions. Altitudinal clines of allelic frequencies of environmentally associated positively selected outliers were found, indicating adaptive divergence. Our results point to a transition from historical population connectivity toward contemporary population isolation and divergence on a regional scale. Spatial and temporal dispersal differences may have resulted in regional population divergence and local adaptation associated with environmental variables, which may have played roles as selective forces at a regional scale.

Aliskiren attenuates proteinuria in mice with lupus nephritis by a blood pressure-independent mechanism.

This study revealed that low-dose aliskiren treatment could attenuate proteinuria by interrupting the renin-angiotensin system in mice with lupus nephritis, and the beneficial effect was beyond blood pressure control. An in and ex vivo fluorescence imaging (using a non-invasion in vivo imaging system) showed intense labeling of renin in the kidneys of female MRL/lpr mice. In the study, Alzet mini-osmotic pumps were implanted into 6-week-old female MRL/lpr mice. Pumps were filled with either phosphate-buffered saline or a solution of aliskiren dissolved in phosphate-buffered saline (20 mg/kg/day) and replaced at 28-day intervals. Mice were sacrificed at four and eight weeks. To label cells for DNA synthesis, bromodeoxyuridine (BrdU) (50 mg/kg) was injected intraperitoneally an hour prior to sacrifice. The level of renin inhibition was adequate, as aliskiren-treated mice demonstrated higher renal renin mRNA expression than controls (p < 0.05). Although there were no significant differences in the systolic blood pressure (control versus aliskiren-treated: 127.20 ± 4.44 mmHg versus 103.80 ± 7.40 mmHg, p > 0.05) and heart rate (control versus aliskiren-treated: 680.50 ± 11.71 versus 647.80 ± 13.90, p > 0.05) of both groups after eight weeks, there was significant reduction of inflammatory cytokines (transforming growth factor-beta1, regulated on activation normal T cell expressed, monocyte chemoattractant protein-1 and osteopontin, p < 0.05), reduction of innate immunity (toll-like receptor 7, p < 0.05), as well as a reduction of glomerular proliferation and inflammation (BrdU-, CD45-, CD3- and F4/80-positive glomerular cells, p < 0.01) after aliskiren infusion, which might translate into an improvement in proteinuria (control versus aliskiren-treated: 493.7 versus 843.7 mg/g, p < 0.01) or weight gain (control versus aliskiren-treated: 5.65 ± 1.61 versus 8.67 ± 0.97%, p < 0.05).

Childhood obesity, self-esteem and health-related quality of life among urban primary schools children in Kuching, Sarawak, Malaysia.

INTRODUCTION: There is limited data on childhood obesity and its impact on children from diverse cultural backgrounds. This study is aimed at determining the association between obesity, self-esteem and health-related quality of life (HRQOL) among Malaysian urban primary school children of different ethnicity. METHODS: A cross-sectional study was conducted involving 311 children aged 11-13 years from primary schools in Kuching, Sarawak. Self-esteem and health-related quality of life (HRQOL) were measured using the Lawrence Self-esteem Questionnaire (LAWSEQ) questionnaire and the Paediatric Quality of Life Inventory (PedsQL), respectively. Body weight and height were taken and body mass index for age calculated. RESULTS: The prevalence of overweight and obesity among the children were 18.2% and 15.2% respectively. Parent-proxy and child self-reported PedsQL scores were higher for normal weight children compared to thin and obese children, but lower than overweight children. At the subscale level, only parent-proxy PedsQL scores in psychosocial health and emotional component were significantly different between overweight and obese children (p=0.019, p=0.02). The Self-esteem score was significantly correlated with parent and child PedsQL scores. Although obesity was associated with lower HRQOL among children, both parent and child PedsQL scores among the overweight group were higher than that for the normal weight group. Overweight and obesity did affect quality of life and self-esteem of children in this study, particularly in the areas of psychosocial and emotional health. CONCLUSION: Policy makers and programme managers should take into consideration the impact of obesity on children and parents in designing intervention programmes.

Gene polymorphisms of adiponectin and leptin receptor are associated with early onset of type 2 diabetes mellitus in the Taiwanese population.

OBJECTIVE: Adipocytokine genes encoding adiponectin (ADIPOQ) and the leptin receptor (LEPR) affect glucose and fatty acid metabolism. The purpose of this study was to examine the association between early-onset type 2 diabetes mellitus (T2DM) and variability within these two genes in the Han Chinese population of Taiwan. SUBJECTS: A cross-sectional study of 999 patients from the Han Chinese population of Taiwan with early-onset T2DM (n=264; age at diagnosis, 20 to <45 years) and late-onset T2DM (n=735; age at diagnosis, ~45 years) was performed. Blood samples from T2DM patients were taken for DNA extraction, and levels of serological markers were measured at enrollment. Seven single-nucleotide polymorphisms (SNPs) were selected for genotyping (three SNPs in AIDPOQ and four SNPs in LEPR) by polymerase chain reaction in each patient. RESULTS: Polymorphisms at the position rs10937273 in ADIPOQ and at the positions rs1892534 and rs2211651 in LEPR were statistically associated with early-onset T2DM (P=0.0246, 0.0014 and 0.0012, respectively). C-reactive protein levels were significantly different among the early-onset T2DM patients with different genotypes at the SNPs rs1892534 and rs2211651 in LEPR (P=0.003 and P=0.004, respectively). In addition, fasting glucose levels were also significantly different among different genotypes at the SNP rs1892534 in LEPR (P=0.038). CONCLUSION: We conclude that the polymorphisms in the adipocytokine genes ADIPOQ and LEPR are significantly associated with the age at diagnosis of T2DM in the Han Chinese population of Taiwan.

Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes.

AIMS: Most treatments for type 2 diabetes fail over time, necessitating combination therapy. We investigated the safety, tolerability and efficacy of liraglutide monotherapy compared with glimepiride monotherapy over 2 years. METHODS: Participants were randomized to receive once-daily liraglutide 1.2 mg, liraglutide 1.8 mg or glimepiride 8 mg. Participants completing the 1-year randomized, double-blind, double-dummy period could continue open-label treatment for an additional year. Safety data were evaluated for the full population exposed to treatment, and efficacy data were evaluated for the full intention-to-treat (ITT) and 2-year completer populations. Outcome measures included change in glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and frequency of nausea and hypoglycaemia. RESULTS: For patients completing 2 years of therapy, HbA1c reductions were -0.6% with glimepiride versus -0.9% with liraglutide 1.2 mg (difference: -0.37, 95% CI: -0.71 to -0.02; p = 0.0376) and -1.1% with liraglutide 1.8 mg (difference: -0.55, 95% CI: -0.88 to -0.21; p = 0.0016). In the ITT population, HbA1c reductions were -0.3% with glimepiride versus -0.6% with liraglutide 1.2 mg (difference: -0.31, 95% CI: -0.54 to -0.08; p = 0.0076) and -0.9% with liraglutide 1.8 mg (difference: -0.60, 95% CI: -0.83 to -0.38; p < 0.0001). For both ITT and completer populations, liraglutide was more effective in reducing HbA1c, FPG and weight. Over 2 years, rates of minor hypoglycaemia [self-treated plasma glucose <3.1 mmol/l (<56 mg/dl)] were significantly lower with liraglutide 1.2 mg and 1.8 mg compared with glimepiride (p < 0.0001). CONCLUSION: Liraglutide monotherapy for 2 years provides significant and sustained improvements in glycaemic control and body weight compared with glimepiride monotherapy, at a lower risk of hypoglycaemia.