METHODS: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged ≥18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540.
FINDINGS: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 26·1 months (95% CI 22·1-31·8; 149 [52%] of 284 died) versus 13·3 months (10·5-16·2; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 0·57, 95% CI 0·46-0·71; p<0·0001), median progression-free survival was 8·1 months (95% CI 6·2-8·8; 214 events occurred) in the cemiplimab group versus 5·3 months (4·3-6·1; 236 events occurred) in the chemotherapy group (HR 0·51, 95% CI 0·42-0·62; p<0·0001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 6·6 months (6·1-9·3) and overall survival of 15·1 months (11·3-18·7). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signals INTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer.
FUNDING: Regeneron Pharmaceuticals and Sanofi.
METHODS/DESIGN: This study is a two-arm parallel group randomized controlled trial (RCT) in which adolescents are randomly assigned (after baseline assessment) to one of two group interventions (PEERS® vs. active control condition). In total, 150 adolescents are to be included, with multi-informant involvement of their parents and teachers. The ACCEPT study uses an active control condition (puberty psychoeducation group training, focussing on social-emotional development) and explores possible moderators and mediators in improving social skills. The primary outcome measure is the Contextual Assessment of Social Skills (CASS). The CASS assesses social skills performance in a face to face social interaction with an unfamiliar, typically developing peer, making this a valuable instrument to assess the social conversational skills targeted in PEERS®. In addition, to obtain a complete picture of social skills, self-, parent- and teacher-reported social skills are assessed using the Social Skills improvement System (SSiS-RS) and Social Responsiveness Scale (SRS-2). Secondary outcome measures (i.e. explorative mediators) include social knowledge, social cognition, social anxiety, social contacts and feelings of parenting competency of caregivers. Moreover, demographic and diagnostic measures are assessed as potential moderators of treatment effectiveness. Assessments of adolescents, parents, and teachers take place at baseline (week 0), intermediate (week 7), post intervention (week 14), and at follow-up (week 28).
CONCLUSION: This is the first RCT on the effectiveness of the PEERS® parent-assisted curriculum which includes an active control condition. The outcome of social skills is assessed using observational assessments and multi-informant questionnaires. Additionally, factors related to social learning are assessed at several time points, which will enable us to explore potential mediators and moderators of treatment effect.
TRAIL REGISTRATION: Dutch trail register NTR6255 (NL6117). Registered February 8th, 2017 - retrospectively registered.
METHODS: VKA control was assessed retrospectively by time-in-the-therapeutic range (TTR) (Rosendaal method) and percentage INR-in-range (PINRR) in 991 White, Afro-Caribbean and South-Asian AF patients [overall mean (SD) age 71.6 (9.4) years; 55% male; mean (SD) CHA2DS2-VASc score 3.4 (1.6)] over a median (IQR) follow-up of 5.2 (3.2-7.0) years.
RESULTS: Compared to Whites, mean (SD) TTR and PINRR were significantly lower in South-Asians [TTR 67.9% vs. 60.5%; PINRR 58.8% vs. 51.6%, respectively] and Afro-Caribbeans [TTR 67.9% vs. 61.3%; PINRR 58.8% vs. 53.1%, respectively], despite similar INR monitoring intensity. Logistic regression revealed non-white ethnicity [OR 2.62; 95% Confidence Interval [CI] (1.67-4.10) and OR 3.47 (1.44-8.34)] and anaemia [OR 1.65 (1.00-2.70) and OR 6.27 (1.89-20.94)] as independent predictors of both TTR and PINRR follow-up, 329 (33.2%) patients experienced ≥1 major adverse clinical event. Cardiovascular hospitalisation was significantly higher among South-Asians (32.3%) compared to the Whites and Afro-Caribbeans (21.3% vs 25.6% respectively).
CONCLUSIONS: Ethnic disparities in quality of anticoagulation control are evident, with South-Asians and Afro-Caribbeans having poorer control compared to Whites, despite similar intensity INR monitoring. Non-white ethnicity remained the strongest independent predictor of poor TTR and PINRR. Interventions to improve anticoagulation control need to be implemented, particularly targeting ethnic minority patients.
MATERIALS AND METHODS: A total of 898 students from 21 schools across comprehensive- and partial-SFL states were recruited. SHS exposures and respiratory symptoms were assessed via questionnaire. Prenatal and postnatal SHS exposure information was obtained from parental-completed questionnaire.
RESULTS: The prevalence of respiratory symptoms was: 11.9% ever wheeze, 5.6% current wheeze, 22.3% exercise-induced wheeze, 12.4% nocturnal cough, and 13.1% self-reported asthma. SHS exposure was most frequently reported in restaurants. Hierarchical logistic regression indicates living in a comprehensive-SFL state was not associated with a lower risk of reporting asthma symptoms. SHS exposure in public transport was linked to increased risk for wheeze (Adjusted Odds Ratio (AOR) 16.6; 95%confidence interval (CI), 2.69-101.7) and current wheezing (AOR 24.6; 95%CI, 3.53-171.8).
CONCLUSIONS: Adolescents continue to be exposed to SHS in a range of public venues in both comprehensive- and partial-SFL states. Respiratory symptoms are common among those reporting SHS exposure on public transportation. Non-compliance with SFL appears to be frequent in many venues across Malaysia and enforcement should be given priority in order to reduce exposure.
METHODS: A cross-sectional study was conducted involving 22 cases of glioma diagnosed intraoperatively from January 2013 until August 2019 in Hospital Universiti Sains Malaysia. The selected tissues were processed for cytology smear and frozen section. The remaining tissues were proceeded for paraffin section. The diagnosis was categorized as either low-grade or high-grade glioma based on cellularity, nuclear pleomorphism, mitotic count, microvascular proliferation and necrosis. The sensitivity and specificity of frozen section and cytology smears were determined based on paraffin section being as the gold standard. The accuracy of both techniques was compared using statistical analysis.
RESULTS: The overall sensitivity and specificity of cytology smear were 100% and 76.9%, respectively. Meanwhile, the sensitivity and specificity of frozen section were 100% and 84.6%. There was no significant difference in diagnostic accuracy between cytology smear and frozen section in glioma (p>0.05).
CONCLUSION: Cytology smears provides an alternative method for frozen section due to good cellularity and morphology on smear. Cytology smear is rapid, inexpensive, small amount of tissue requirement and less technical demand. This finding may benefit to the hospital or treatment centres where frozen section facility is unavailable.
DESIGN AND SETTINGS: This is a retrospective study of all patients who had undergone coronary angioplasty from 2007 to 2009 in 11 hospitals across Malaysia.
METHODS: Data were obtained from the NCVD-PCI Registry, 2007 to 2009. Patients were categorized into 2 groups-young and old, where young was defined as less than 45 years for men and less than 55 years for women and old was defined as more than or equals to 45 years for men and more than or equals to 55 years for women. Patients' baseline characteristics, risk factor profile, extent of coronary disease and outcome on dis.charge, and 30-day and 1-year follow-up were compared between the 2 groups.
RESULTS: We analyzed 10268 patients, and the prevalence of young CAD was 16% (1595 patients). There was a significantly low prevalence of Chinese patients compared to other major ethnic groups. Active smoking (30.2% vs 17.7%) and obesity (20.9% vs 17.3%) were the 2 risk factors more associated with young CAD. There is a preponderance toward single vessel disease in the young CAD group, and they had a favorable clinical outcome in terms of all-cause mortality at discharge (RR 0.49 [CI 0.26-0.94]) and 1-year follow-up (RR 0.47 [CI 0.19-1.15]).
CONCLUSION: We observed distinctive features of young CAD that would serve as a framework in the primary and secondary prevention of the early onset CAD.
DESIGN: This study was designed as a retrospective cohort study.
SETTING AND PARTICIPANTS: In this study, we analysed the prescription databases of tertiary hospitals in Malaysia. This study included patients aged ≥18 years with at least one opioid prescription (buprenorphine, morphine, oxycodone, fentanyl, dihydrocodeine or tramadol) between 1 January 2011 and 31 December 2016. These patients had no opioid prescriptions in the 365 days prior, and were followed up for 365 days after the initial opioid prescription.
MAIN OUTCOME MEASURES: The main outcome measures were the number of short-term (<90 days) and long-term opioid users (≥90 days), initial opioid prescription period and daily dose.
RESULTS: There were 33 752 opioid-naïve patients who received opioid prescriptions (n=43 432 prescriptions) during the study period. Of these, 29 824 (88.36%) were short-term opioid users and 3928 (11.64%) were long-term opioid users. The majority of these short-term (99.09%) and long-term users (96.18%) received an initial daily opioid dose of <50 mg/day with a short-acting opioid formulation. Short-term opioid users were predominantly prescribed opioids for 3-7 days (59.06%) by the emergency department (ED, 60.56%), while long-term opioid users were primarily prescribed opioids for ≥7 days (91.85%) by non-ED hospital departments (91.8%). The adjusted model showed that the following were associated with long-term opioid use: increasing opioid daily doses, prescription period ≥7 days and long-acting opioids initiated by non-EDs.
CONCLUSIONS: The majority of opioid-naïve patients in tertiary hospital settings in Malaysia were prescribed opioids for short-term use. The progression to long-term use among opioid-naïve patients was attributed to the prescription of higher opioid doses for a longer duration as well as long-acting opioids initiated by non-ED hospital departments.
METHODS: The authors describe a modified second toe transfer that addresses cosmesis in six patients. These include (1) harvesting a flap from the adjacent side of the great toe and insetting it into the volar aspect of the second toe to give more bulk, (2) making skin excisions on each side of the tip to reduce the bulbous appearance, and (3) excising the eponychium to produce apparent lengthening of the nail.
RESULTS: The mean follow-up period was 18 months (range, 6 to 36 months). The procedure resulted in good function and improved cosmesis in all six cases. Part of the great toe flap was lost in one case. The mean two-point discrimination in the transferred toes was 10.1 mm, with protective sensation present in the flaps. The range of motion of the transferred toe was 14 to 38 degrees at the metatarsophalangeal joint, 16 to 55 degrees at the proximal interphalangeal joints, and 20 to 36 degrees in the distal interphalangeal joints. All patients except one were happy with the appearance of the transferred toe.
CONCLUSION: This novel approach will allow patients to take advantage of the lower morbidity to the donor site afforded by second toe-to-thumb transfer and provide the patients with a more aesthetic appearance of the new thumb.
METHODS: This was a cross-sectional study that included 47 patients with post-traumatic osteomyelitis of the lower limb. Functional outcome was assessed using the Lower Extremity Functional Score (LEFS), and quality of life was assessed using the validated Malay version of Short Form-36 version 2.
RESULTS: Mean follow-up time was 4.6 (range 2.3-9.5) years. Median age was 44 years. Osteomyelitis was located in the tibia for 26 patients and in the femur for 21 patients. Osteomyelitis was consequent to internal infection in 38 patients and due to infected open fractures in nine patients. 42 (89.4%) patients had fracture union and control of infection. Bone defect was found to be a significant contributing factor for treatment failure (p = 0.008). The median LEFS for the success group was 65 when compared to 49 for the failure group. Although the success group showed better scores with regard to quality of life, the difference between the two groups was not statistically significant.
CONCLUSION: The success rate for post-traumatic osteomyelitis of the lower limb was high. The presence of a bone defect was associated with treatment failure. Successfully treated patients had significantly better functional outcomes than failed ones.