DESIGN: A post hoc subgroup analysis of the effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicenter, pragmatic, registry-based randomized trial.
SETTING: Eighty-five adult ICUs across 16 countries.
PATIENTS: Patients with obesity defined as a body mass index (BMI) greater than or equal to 30 kg/m 2 ( n = 425).
INTERVENTIONS: In the primary study, patients were randomized into a high-dose (≥ 2.2 g/kg/d) or usual-dose protein group (≤ 1.2 g/kg/d).
MEASUREMENTS AND MAIN RESULTS: Protein intake was monitored for up to 28 days, and outcomes (time to discharge alive [TTDA], 60-d mortality, days of mechanical ventilation [MV], hospital, and ICU length of stay [LOS]) were recorded until 60 days post-randomization. Of the 1301 patients in the primary study, 425 had a BMI greater than or equal to 30 kg/m 2 . After adjusting for sites and covariates, we observed a nonsignificant slower rate of TTDA with higher protein that ruled out a clinically important benefit (hazard ratio, 0.78; 95% CI, 0.58-1.05; p = 0.10). We found no evidence of difference in TTDA between protein groups when subgroups with different classes of obesity or patients with and without various nutritional and frailty risk variables were examined, even after the removal of patients with baseline acute kidney injury. Overall, 60-day mortality rates were 31.5% and 28.2% in the high protein and usual protein groups, respectively (risk difference, 3.3%; 95% CI, -5.4 to 12.1; p = 0.46). Duration of MV and LOS in hospital and ICU were not significantly different between groups.
CONCLUSIONS: In critically ill patients with obesity, higher protein doses did not improve clinical outcomes, including those with higher nutritional and frailty risk.
METHODS: PubMed, Cochrane CENTRAL, and EMBASE were searched for randomized trials comparing pharmacologic or surgical obesity interventions to usual care, placebo, or no treatment in adults with OSA. The association between percentage weight loss and AHI change between randomization and last follow-up was evaluated using meta-regression.
PROSPERO: CRD42022378853.
RESULTS: Ten eligible trials (n = 854 patients) were included. Four (n = 211) assessed bariatric surgery, and 6 (n = 643) assessed pharmacologic interventions over a median follow-up of 13 months (interquartile range 6-26 months). The linear best estimate of the change in AHI is 0.45 events per hour (95% Confidence Interval 0.18 to 0.73 events per hour) for every 1% body weight lost.
CONCLUSIONS: Weight loss caused by medication or surgery caused a proportionate improvement of the AHI. Providers could consider extrapolating from this relationship when advising patients of the expected effects of other pharmacologic or surgical interventions without direct evidence in OSA.
METHODS: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution.
RESULTS: This study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non-GFR clearance not associated with normal GFR. All three drugs had GFR clearance estimated as a drug-specific percentage of normal GFR (gentamicin 39%, amikacin 90% and vancomycin 57%). The total clearance (sum of GFR and non-GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% confidence interval [CI] 5.50-5.69) (gentamicin), 7.77 L/h (95% CI 7.26-8.19) (amikacin) and 4.70 L/h (95% CI 4.61-4.80) (vancomycin).
CONCLUSIONS: GFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention.
METHODS: In this cross-sectional study, 300 young adult women from Romania with mean age of 22.19 years (SD = 2.07) and who possessed an Instagram account were asked to complete an online survey consisting of measures of dysmorphic concerns, Instagram addiction, and appearance-based rejection sensitivity.
RESULTS: Correlational analyses revealed that all three variables were positively and moderately inter-correlated. Mediation analysis supported the hypothesis that appearance-based rejection sensitivity mediates the relationship between Instagram addiction and dysmorphic concerns.
CONCLUSIONS: Implications of this study are discussed in terms of the urgency of prevention and intervention strategies, especially given the link between dysmorphic concerns and more extreme manifestations of severity, such as body dysmorphic disorder.
OBJECTIVE: To describe the demographic characteristics, treatment duration, and survival of patients with GIST in LMICs treated with imatinib and sunitinib through The Max Foundation programs.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective database cohort analysis included patients in 2 access programs administered by The Max Foundation: the Glivec International Patient Assistance Program (GIPAP), from January 1, 2001, to December 31, 2016, and the Max Access Solutions (MAS) program, January 1, 2017, to October 12, 2020. Sixty-six countries in which The Max Foundation facilitates access to imatinib and sunitinib were included. Participants consisted of patients with approved indications for imatinib, including adjuvant therapy in high-risk GIST by pathologic evaluation of resected tumor or biopsy-proven unresectable or metastatic GIST. All patients were reported to have tumors positive for CD117(c-kit) by treating physicians. A total of 9866 patients received treatment for metastatic and/or unresectable disease; 2100 received adjuvant imatinib; 49 received imatinib from another source and were only included in the sunitinib analysis; and 53 received both imatinib and sunitinib through The Max Foundation programs. Data were analyzed from October 13, 2020, to January 30, 2024.
MAIN OUTCOMES AND MEASURES: Demographic and clinical information was reported by treating physicians. Kaplan-Meier analysis was used to estimate time to treatment discontinuation (TTD) and overall survival (OS). An imputation-based informed censoring model estimated events for patients lost to follow-up after treatment with adjuvant imatinib. Patients who were lost to follow-up with metastatic or unresectable disease were presumed deceased.
RESULTS: A total of 12 015 unique patients were included in the analysis (6890 male [57.6%]; median age, 54 [range, 0-100] years). Of these, 2100 patients were treated with imatinib in the adjuvant setting (median age, 54 [range 8-88] years) and 9866 were treated with imatinib for metastatic or unresectable disease (median age, 55 [range, 0-100] years). Male patients comprised 5867 of 9866 patients (59.5%) with metastatic or unresectable disease and 1023 of 2100 patients (48.7%) receiving adjuvant therapy. The median OS with imatinib for unresectable or metastatic disease was 5.8 (95% CI, 5.6-6.1) years, and the median TTD was 4.2 (95% CI, 4.1-4.4) years. The median OS with sunitinib for patients with metastatic or unresectable GIST was 2.0 (95% CI, 1.5-2.5) years; the median TTD was 1.5 (95% CI, 1.0-2.1) years. The 10-year OS rate in the adjuvant setting was 73.8% (95% CI, 67.2%-81.1%).
CONCLUSIONS AND RELEVANCE: In this cohort study of patients with GIST who were predominantly from LMICs and received orally administered therapy through the GIPAP or MAS programs, outcomes were similar to those observed in high-resource countries. These findings underscore the feasibility and relevance of administering oral anticancer therapy to a molecularly defined population in LMICs, addressing a critical gap in cancer care.
METHODS: This was a cross-sectional, single-centre study conducted via questionnaire. Patients aged 18 years old and above, who were diagnosed with non-curable pulmonary hypertension were recruited and given the assessment tool - perceptions of palliative care instrument electronically. The severity of pulmonary hypertension was measured using WHO class, N-terminal pro B-type natriuretic peptide and the 6-minute walking test distance.
RESULTS: A total of 84 patients [mean age: 35 ±11 years, female: 83.3%, median N-terminal pro B-type natriuretic peptide: 491 pg/ml (interquartile range: 155,1317.8), median 6-minute walking test distance: 420m (interquartile range: 368.5, 480m)] completed the questionnaires. Patients with a higher WHO functional class and negative feelings (r = 0.333, p = 0.004), and cognitive reaction to palliative care: hopeless (r = 0.340, p = 0.003), supported (r = 0.258, p = 0.028), disrupted (r = 0.262, p = 0.025), and perception of burden (r = 0.239, p = 0.041) are more receptive to palliative care. WHO class, N-terminal pro B-type natriuretic peptide, and 6-minute walking test distance were not associated with higher readiness for palliative care. In logistic regression analyses, patients with positive feelings (β = 2.240, p = < 0.05), and practical needs (β = 1.346, p = < 0.05), were more receptive to palliative care.
CONCLUSIONS: Disease severity did not directly influence patients' readiness for palliative care. Patients with a positive outlook were more receptive to palliative care.
METHODS: Data came from the 2020 ITC Malaysia Survey, a web-based survey of a nationally representative sample of adults who smoked (n=1047) aged 18 and older. They were asked on ever heard of, ever used, and currently using HTPs, and their reasons for using HTPs.
RESULTS: Overall, 25.4% (n= 324; 95% CI:22.3%-28.7%) of Malaysians who smoked reported ever used HTPs with 6.7% (n=85; 95% CI:22.3%-28.7%) were using them daily and 8.1% (n=110; 95% CI:6.4% -10.2%) were using HTPs non-daily. Most of them (57.2%) who dual use were of aged 25-39 and 97.3% were males. Among those who smoked daily, almost half (49.3%) were also using HTP daily. Among those who used HTPs daily and non-daily, curiosity (84.2%, 95% CI:78.4%-90.0%), taste (83.2%, 95% CI:77.3%-89.1%), and appealing technology (78.5%, 95% CI:71.3%-85.6%) were the most reported reasons. Among those who used HTPs daily, curiosity was the top reason (87.9%, 95% CI:78.9%-93.4%), while among non-daily, taste good was the top reason (81.9%, 95% CI:71.9%-88.8%).
CONCLUSIONS: The very high use of HTPs among Malaysians who smoked requires continued public health surveillance that can inform the regulation of these novel tobacco products.
METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included.
RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results.
DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.
METHODS: In this longitudinal study, we randomly selected community members aged between 18 and 70 years who resided in Segamat district of Johor state, Malaysia. Over 21 days, we conducted three home visits to each participant. During each visit, participants completed a questionnaire consisting of Likert scale, multiple choice, and free text questions and we collected quantitative and qualitative data. These inquiries assessed the participants' perception of heat as health threat, whether or not they took heat preventive measures, and the specific protective measures they routinely employed. Descriptive data analyses were conducted and patterns of protective measures were investigated.
FINDINGS: Between March 29 and July 31, 2023, 120 participants (72 women and 48 men) completed 360 questionnaires over three home visits. Initially, 58% participants recognised heat hazards to daily activities, decreasing to 42% and 35% by visits 2 and 3. Participants took preventive measures throughout the day, which was consistently high between 1200 h and 1400 h, with 77% of participants taking preventive measures on visit 1, 82% on visit 2, and 82% on visit 3. Use of preventive measures was also high between 1400 h and 1730 h, with 77% using preventive measure on visit 1, 81% on visit 2, and 79% on visit 3. The most common protective measures were fans (used by 68-88% of participants), drinking more water (70-78% of participants), and resting (44-72% of participants). The least common were relocating to cooler places, removing clothes, and using wet towels (0-2·5%). Despite high temperatures, perceptions of heat risks decreased over time. Participants took basic protections, especially at midday, but improved literacy and affordable cooling options are needed to protect vulnerable rural populations.
INTERPRETATION: Our findings underline the need to improve heat literacy and adaptation as only half of the population assessed perceived heat as a potential health hazard and practised limited heat protective measures. Addressing climate change and health necessitates fundamental behavioural changes on the part of individuals and communities, to protect them against the adverse effects of heat.
FUNDING: Monash University Malaysia and Heidelberg Institute of Global Health, Heidelberg University.
METHODS: Patients with AF were enrolled in the Cryo Global Registry (NCT02752737) from May 2016 to Sept 2021 at 128 sites in 37 countries and treated with cryoballoon ablation according to local clinical practice. Baseline patient and procedural characteristics were summarized for 8 regions (Central Asia & Russia, East Asia, Europe, Middle East, North America, South Africa, South America, and Southeast Asia). Serious procedure-related adverse events (SAEs) were evaluated in a subset of patients with ≥ 7 days of follow-up.
RESULTS: A total of 3,680 patients undergoing initial PVI for AF were included. Cryoballoon ablation was commonly performed in patients with paroxysmal AF. Mean age ranged from 47 ± 12 years in the Middle East to 64 ± 11 years in East Asia. Mean procedure time was ≤ 95 min in all regions. Average freeze duration ranged from 153 ± 41 s in Southeast Asia to 230 ± 29 s in Central Asia & Russia. Acute procedural success was ≥ 94.7% in all geographies. In 3,126 subjects with ≥ 7 days of follow-up, 122 procedure-related SAEs were reported in 111 patients (3.6%) and remained low in all regions. One procedure-related death was reported during data collection.
CONCLUSIONS: Despite regional variations in patient selection and procedural characteristics, PVI using cryoballoon ablation was performed with high acute success and short procedural times around the world.
CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02752737.
METHODS: From 2010 to 2014, men with HIV (N = 212) and opioid dependence before incarceration were enrolled in MMT within 6 months of release from Malaysia's largest prison and followed for 12-months post-release. As a prospective trial, allocation to MMT was at random and later by preference design (predictive nonetheless). MMT dosing was individually targeted to minimally achieve 80 mg/day. Time-to-event analyses were conducted to model linkage to MMT after release.
FINDINGS: Of the 212 participants allocated to MMT, 98 (46 %) were prescribed higher dosages (≥80 mg/day) before release. Linkage to MMT after release occurred in 77 (36 %) participants and significantly higher for those prescribed higher dosages (46% vs 28 %; p = 0.011). Factors associated with higher MMT dosages were being married, on antiretroviral therapy, longer incarceration periods, having higher levels of depression, and methadone preference compared to randomization. After controlling for other variables, being prescribed higher methadone dosage (aHR: 2.53, 95 %CI: 1.42-4.49) was the only independent predictor of linkage to methadone after release.
INTERPRETATION: Higher doses of methadone prescribed before release increased the likelihood of linkage to MMT after release. Methadone dosing should be introduced into international guidelines for treatment of opioid use disorder in prisons and further post-release benefits should be explored.
FUNDING: National Institute of Drug Abuse (NIDA).
METHODS: A cross-sectional study was carried out in Malaysia to assess the knowledge, perception and attitudes of the women in Malaysia. The study was conducted using an online questionnaire, and samples were obtained using convenience sampling. The questionnaire was distributed trilingual in English, Bahasa Malaysia and Chinese. The data was collected with content validated questionnaire. Data was analyzed with descriptive statistics and General Linear Model analysis in SPSS (Version 27).
RESULTS: A total of 201 respondents' data were analyzed. From our study we were able to summarize that the women in Malaysia have a suboptimal knowledge towards personalized risk-stratified breast cancer screening as only 48.9% aware of the term for personalized risk-stratified breast cancer screening. Meanwhile, the majority of the respondents (96.7%) showed positive attitudes towards the importance of risk assessment and screening. Experience of participating in health education programmes about breast cancer and personalized risk-stratified screening was found to be significantly associated with knowledge, attitude and perception towards personalized risk-stratified breast cancer screening.
CONCLUSION: General population's awareness of individualized risk-stratified breast cancer screening was insufficient despite their favourable attitude towards the disease. A multimodal strategy may be used to improve women's knowledge, attitude, and perception of individualized risk-stratified breast cancer screening.
METHODS: The study population included all women diagnosed with uterine cancer in Sarawak, Malaysia between January 1996 and December 2015. Data on demographic and clinical characteristics were obtained from the Sarawak Cancer Registry. The crude incidence rate, age-standardized incidence rate (ASR), and incidence risk ratios (IRR) were calculated. Joinpoint regression analyses were performed to assess trends in incidence rates.
RESULTS: A total of 811 women were diagnosed with primary uterine cancer during the study period. The overall crude incidence rate for uterine cancer in Sarawak for the period 1996-2015 was 3.7 per 100,000. The ASR was 4.4 per 100,000 with a 95% CI (4.1-4.8). The ASR in 2011-2015 is 1.6 times higher than the ASR of uterine cancer in 1996-2000. Higher incidence rates were observed in women aged 40-59 years and those aged 60 years and above. Chinese women had the highest ASR, followed by Malay and Iban women. Joinpoint regression analyses showed a significant increase in cases of uterine cancer among all ethnic groups and age groups.
CONCLUSION: The incidence of primary uterine cancer in Sarawak, Malaysia, has increased over the past 20 years, with higher incidence rates observed in older age groups and among Chinese women. The findings suggest the need for continued efforts to improve the prevention, early detection, and treatment of uterine cancer in Sarawak.
CASE REPORT: A 35-year-old lady, post-radioactive iodine therapy for Graves' disease remained euthyroid for a year on oral LT4. Two years later, she was clinically and biochemically hypothyroid despite claiming LT4 compliance. As all laboratory investigations were within the reference range, pseudomalabsorption was suspected and a LT4 absorption test was done. During the test, her free thyroxine increased significantly at 4 hours, reaching a peak of more than 50% from baseline while TSH decreased appropriately from 0 minute to 360 minutes. This was followed by normalisation of TSH with LT4 treatment under direct observation.
DISCUSSION: The LT4 absorption test is a prompt and economical means to rule out true malabsorption, decrease unwarranted subspecialty referrals and validate the weight-adjusted LT4 dose reduction.