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OBJECTIVE: To characterise lifestyle patterns (comprising dietary and movement behaviour aspects) of children in Singapore and examine the correlates of these patterns. DESIGN: An observational study approach was used. Children recorded their diet and activities over two weekdays and two weekend days on a validated web-based assessment, My E-Diary for Activities and Lifestyle (MEDAL). Lifestyle patterns were derived using principal component analysis, and the correlations of these with multiple known determinants organised by distal, intermediate, and proximal levels of influence were studied. SETTING: Children of the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. PARTICIPANTS: Ten-year-old children (n = 397). RESULTS: Three lifestyle patterns, "high snacks and processed food", "balanced" and "mixed", were identified. We focused on the more health-promoting "balanced" pattern, characterised by lower screen-viewing and higher consumption of fruits, vegetables, wholegrains, and dairy. Among the distal factors, girls were more adherent to the "balanced" pattern compared to boys, and children of parents with lower education levels were less adherent to this pattern. Among intermediate factors, children of mothers with higher diet quality were more adherent to the "balanced" pattern. Among the proximal factors, engagement in active transport, leisure sports, and educational activities outside of school were positively associated with the "balanced" pattern, whereas screen-viewing while travelling was negatively associated with this pattern. Having siblings, pet ownership, mother's physical activity, parenting style, parental bonding, child's outdoor time, and breakfast consumption were not associated with children's lifestyle patterns. CONCLUSIONS: These findings provide direction for future interventions by identifying vulnerable groups and contexts that should be prioritised.
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Estilo de Vida , Humanos , Singapura , Masculino , Feminino , Criança , Dieta/estatística & dados numéricos , Exercício FísicoRESUMO
BACKGROUND: Dependency on screen viewing (SV) has reached unprecedented levels, and mental health issues are becoming a major public health concern. However, the associations between SV, including variations in purposes, devices, and timing, and mental health remain unclear. This study aims to provide insights into these associations among university students. METHODS: This analysis used baseline data from a longitudinal cohort study among first-year university students matriculating in the 2021-2022 academic year. Self-reported data on sociodemographics, health behaviors and mental health outcomes alongside anthropometric measurements were collected. Unadjusted and adjusted logistic regression analyses were conducted. RESULTS: The average age of the 997 valid students was 20.2 years, with 59.6% being female and 41.4% male. Students spent 14.3 h daily on SV, with females reporting higher SV than males. Daily SV was predominant for study purposes (7.6 h/day). Computer usage was the highest (7.0 h/day), while TV usage was the lowest (1.7 h/day). Poor mental wellbeing was reported by 33.6% of students, while 13.9% experienced psychological distress. Compared to students with low total SV, those with high levels were more likely to have poor mental wellbeing [OR (95% CI): 1.40 (0.99, 1.98)] and psychological distress [1.56 (1.00, 2.44)]. High levels of recreational and study related SV were significantly associated with poor mental wellbeing [1.81 (1.27, 2.56)] and psychological distress [1.75 (1.11, 2.83)], respectively. Those with high levels of computer time were more likely to have poor mental wellbeing [1.44 (1.01, 2.06)], and high weekend day SV was associated with greater odds of psychological distress [2.16 (1.17, 4.06)]. CONCLUSIONS: SV among university students was high, as was the high prevalence of poor mental wellbeing and psychological distress. Greater SV was associated with poor mental wellbeing and psychological distress. Differences according to purpose of SV were noted. Although recreational SV was associated with poor mental wellbeing, study related SV was associated with psychological distress. Variations across different devices and timing were also noted. This highlights the need for further longitudinal research to understand the impact of SV on mental health and to guide interventions for promoting mental health of university students globally.
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Saúde Mental , Angústia Psicológica , Tempo de Tela , Estudantes , Humanos , Feminino , Masculino , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Universidades , Estudos Transversais , Adulto Jovem , Saúde Mental/estatística & dados numéricos , Estudos Longitudinais , Adolescente , Televisão/estatística & dados numéricosRESUMO
Preclinical and limited epidemiological studies suggest that oxidative stress may be implicated in geriatric depression. Our study investigated the association between midlife dietary total antioxidant capacity (TAC) and depressive symptoms in late life among 13,712 participants in a population-based cohort of Chinese in Singapore. At baseline (1993-1998), intake of antioxidants from diet and supplements at a mean age of 52.4 years was estimated using a validated food frequency questionnaire to derive two dietary TAC indices from vitamins C and E, carotenoids and flavonoids: the Comprehensive Dietary Antioxidant Index (CDAI) and Vitamin C Equivalent Antioxidant Capacity (VCEAC). At follow-up 3 (2014-2016), when participants were at a mean age of 72.5 years, depressive symptoms were assessed using the Geriatric Depression Scale, and depression, defined as having ≥5 symptoms, was presented in 3173 (23.1%) participants. Both CDAI and VCEAC indices were inversely associated with odds of depressive symptoms in a stepwise manner: the OR (95% CI) comparing the extreme quartiles was 0.73 (0.64-0.83; Ptrend < 0.01) for the CDAI and 0.77 (0.68-0.87; Ptrend < 0.01) for the VCEAC. Specifically, higher intakes of vitamin C, carotenoids, and flavonoids were associated with a lower likelihood of depressive symptoms. Our findings support the recommendation of an antioxidant-rich diet for the prevention of depression.
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INTRODUCTION: Diabetes and hypertension are prevalent and costly to the health system. We have developed a mobile app (EMPOWER app) which enables remote monitoring and education through personalised nudges. We aim to study the effectiveness of a multi-component intervention comprising the EMPOWER mobile app with health coaching and shared decision-making for diabetes and hypertension. METHODS: We will conduct a two-arm, open-label, pragmatic randomised controlled trial (RCT). Participants with comorbid diabetes and hypertension enrolled from public primary care clinics will be randomised to either intervention or control in a 1:1 ratio. The intervention group participants will have access to health coaching with shared decision-making interventions in addition to the EMPOWER app and their usual primary care. The control group participants will continue to receive usual primary care and will neither receive the EMPOWER app nor health coaching and shared decision-making interventions. Our primary outcome is change in HbA1c level over 9 months. Secondary outcomes include change in systolic blood pressure, quality of life, patient activation, medication adherence, physical activity level, diet, and healthcare cost (direct and indirect) over 9 months. DISCUSSION: Our trial will provide key insights into clinical- and cost-effectiveness of a multi-component intervention comprising EMPOWER mobile app, health coaching and shared decision-making in diabetes and hypertension management. This trial will also offer evidence on cost-effective and sustainable methods for promoting behavioural changes among patients with comorbid diabetes and hypertension. TRIAL REGISTRATION: This study was registered on clintrials.gov on August 3, 2022, with the trial registration number: NCT05486390.
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Diabetes Mellitus , Hipertensão , Tutoria , Aplicativos Móveis , Humanos , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/terapia , Poder Psicológico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
This study aim to investigate if remote intensive coaching for the first 6 months post-AMI will improve adherence to the twice-a-day antiplatelet medication, ticagrelor. Between July 8, 2015, to March 29, 2019, AMI patients were randomly assigned to remote intensive management (RIM) or standard care (SC). RIM participants underwent 6 months of weekly then two-weekly consultations to review medication side effects and medication adherence coaching by a centralized nurse practitioner team, whereas SC participants received usual cardiologist face-to-face consultations. Adherence to ticagrelor were determined using pill counting and serial platelet reactivity measurements for 12 months. A total of 149 (49.5%) of participants were randomized to RIM and 152 (50.5%) to SC. Adherence to ticagrelor was similar between RIM and SC group at 1 month (94.4 ± 0.7% vs. 93.6±14.7%, p = 0.537), 6 months (91.0±14.6% vs. 90.6±14.8%, p = 0.832) and 12 months (87.4±17.0% vs. 89.8±12.5%, p = 0.688). There was also no significant difference in platelet reactivity between the RIM and SC groups at 1 month (251AU*min [212-328] vs. 267AU*min [208-351], p = 0.399), 6 months (239AU*min [165-308] vs. 235AU*min [171-346], p = 0.610) and 12 months (249AU*min [177-432] vs. 259AU*min [182-360], p = 0.678). Sensitivity analysis did not demonstrate any association of ticagrelor adherence with bleeding events and major adverse cardiovascular events. RIM, comprising 6 months of intensive coaching by nurse practitioners, did not improve adherence to the twice-a-day medication ticagrelor compared with SC among patients with AMI. A gradual decline in ticagrelor adherence over 12 months was observed despite 6 months of intensive coaching.
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Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Ticagrelor/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/induzido quimicamente , Inibidores da Agregação Plaquetária/uso terapêutico , Plaquetas , Hemorragia/induzido quimicamente , Resultado do TratamentoRESUMO
INTRODUCTION: Malignant peripheral nerve sheath tumors (MPNSTs) are malignancies that demonstrate nerve sheath differentiation in the peripheral nervous system. They can occur sporadically or be associated with neurofibromatosis type 1 (NF1), an autosomal dominant neurocutaneous disorder, with up to 13% of patients developing MPNSTs in their lifetimes. Previous studies have suggested conflicting findings regarding the prognosis of NF1 for patients with MPNSTs. The elucidation of NF1 as an independent prognostic factor on mortality has implications for clinical management. We aim to investigate the role of NF1 status as an independent prognostic factor of overall survival (OS) and disease-specific survival (DSS) in MPNSTs. METHODS: An electronic literature search of PubMed and MEDLINE was performed on studies reporting OS or DSS outcomes of MPNSTs with and without NF1. A grey literature search by reviewing bibliographies of included studies and review articles was performed to find pertinent studies. Data was extracted and assessed in accordance with the PRISMA guidelines. A meta-analysis was performed to calculate hazard ratios (HRs) using a random-effects model. The primary and secondary outcomes were all-cause and disease-specific mortality, respectively, with NF1 as an independent prognostic factor of interest. RESULTS: A total of 59 retrospective studies involving 3602 patients fulfilled the inclusion criteria for OS analysis, and 23 studies involving 704 MPNST patients were included to evaluate DSS outcomes. There was a significant increase in the hazard of all-cause mortality (HR 1.63, 95% CI 1.45 to 1.84) and disease-specific mortality (HR 1.52, 95% CI 1.24 to 1.88) among NF1 as compared to sporadic cases. Subgroup analyses and meta-regression showed that this result was consistent regardless of the quality of the study and year of publication. CONCLUSION: NF1 is associated with a substantially higher risk of all-cause and disease-specific mortality. This finding suggests that closer surveillance is required for NF1 patients at risk of developing MPNSTs.
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Neurofibromatose 1 , Neurofibrossarcoma , Humanos , Neurofibromatose 1/complicações , Estudos RetrospectivosRESUMO
BACKGROUND: Selecting the smaller kidney for donation has been advocated if there is a size difference of > 10% between the 2 kidneys but has never been prospectively evaluated. With increase in donor nephrectomies, it is important to evaluate this to minimize loss of renal function to donors. METHODS: 75 consecutive donor nephrectomy patients were included in our longitudinal study. The Split Renal Volume (SRV) of bilateral kidneys were measured using contrasted computer tomography scans and patients segregated into 2 groups depending on donated kidney having more (Group 1) or less than (Group 2) 52.5% of SRV. RESULTS: Patients in Group 1 (n = 19) and 2 (n = 56) were of similar age (43.8 vs. 48.3), BMI (22.4 vs. 25.2), sex (57.9 vs. 55.4% women), respectively. Although total kidney volumes were similar in both groups, Group 1 had significantly smaller right kidney volumes (120.4 ± 24.9 vs. 142.7 ± 28.4 mls, p = 0.003). EGFR pre-operatively (116.3 ± 20.8 vs. 106.3 ± 23.8 mL/min/1.73 m2) and at 6-months (65.7 ± 13.3 vs. 66.9 ± 15.5 mL/min/1.73 m2) were not different between groups. However, patients in Group 1 had significantly greater absolute (50.6 ± 14.9 vs. 39.5 ± 14.7 mL/min/1.73 m2) and relative decline (43.0 ± 8.6 vs. 36.3 ± 10.6%) in eGFR at 6 months (p = 0.06, 0.009). CONCLUSION: With a SRV difference of 5% between the 2 sides, removal of the larger kidney for living kidney donation resulted in greater early decline of renal function than kidney donors whose larger or equivalent kidney is preserved.
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Transplante de Rim , Humanos , Feminino , Masculino , Transplante de Rim/métodos , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Doadores Vivos , Estudos Longitudinais , Estudos Retrospectivos , Rim/diagnóstico por imagem , Taxa de Filtração Glomerular , Tomografia Computadorizada por Raios X/métodosRESUMO
Background: Good physical and mental health are essential for healthy ageing. Holistic mobile health (mHealth) interventions-including at least three components: physical activity, diet, and mental health-could support both physical and mental health and be scaled to the population level. This review aims to describe the characteristics of holistic mHealth interventions and their effects on related behavioural and health outcomes among adults from the general population. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, Scopus, China National Knowledge Infrastructure, and Google Scholar (first 200 records). The initial search covered January 1, 2011, to April 13, 2022, and an updated search extended from April 13, 2022 to August 30, 2023. Randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) were included if they (i) were delivered via mHealth technologies, (ii) included content on physical activity, diet, and mental health, and (iii) targeted adults (≥18 years old) from the general population or those at risk of non-communicable diseases (NCDs) or mental disorders. Studies were excluded if they targeted pregnant women (due to distinct physiological responses), individuals with pre-existing NCDs or mental disorders (to emphasise prevention), or primarily utilised web, email, or structured phone support (to focus on mobile technologies without exclusive human support). Data (summary data from published reports) extraction and risk-of-bias assessment were completed by two reviewers using a standard template and Cochrane risk-of-bias tools, respectively. Narrative syntheses were conducted for all studies, and random-effects models were used in the meta-analyses to estimate the pooled effect of interventions for outcomes with comparable data in the RCTs. The study was registered in PROSPERO, CRD42022315166. Findings: After screening 5488 identified records, 34 studies (25 RCTs and 9 pre-post NRSIs) reported in 43 articles with 5691 participants (mean age 39 years, SD 12.5) were included. Most (91.2%, n = 31/34) were conducted in high-income countries. The median intervention duration was 3 months, and only 23.5% (n = 8/34) of studies reported follow-up data. Mobile applications, short-message services, and mobile device-compatible websites were the most common mHealth delivery modes; 47.1% (n = 16/34) studies used multiple mHealth delivery modes. Of 15 studies reporting on weight change, 9 showed significant reductions (6 targeted on individuals with overweight or obesity), and in 10 studies reporting perceived stress levels, 4 found significant reductions (all targeted on general adults). In the meta-analysis, holistic mHealth interventions were associated with significant weight loss (9 RCTs; mean difference -1.70 kg, 95% CI -2.45 to -0.95; I2 = 89.00%) and a significant reduction in perceived stress levels (6 RCTs; standardised mean difference [SMD] -0.32; 95% CI -0.52 to -0.12; I2 = 14.52%). There were no significant intervention effects on self-reported moderate-to-vigorous physical activity (5 RCTs; SMD 0.21; 95%CI -0.25 to 0.67; I2 = 74.28%) or diet quality scores (5 RCTs; SMD 0.21; 95%CI -0.47 to 0.65; I2 = 62.27%). All NRSIs were labelled as having a serious risk of bias overall; 56% (n = 14/25) of RCTs were classified as having some concerns, and the others as having a high risk of bias. Interpretation: Findings from identified studies suggest that holistic mHealth interventions may aid reductions in weight and in perceived stress levels, with small to medium effect sizes. The observed effects on diet quality scores and self-reported moderate-to-vigorous physical activity were less clear and require more research. High-quality RCTs with longer follow-up durations are needed to provide more robust evidence. To promote population health, future research should focus on vulnerable populations and those in middle- and low-income countries. Optimal combinations of delivery modes and components to improve efficacy and sustain long-term effects should also be explored. Funding: National Research Foundation, Prime Minister's Office, Singapore, under its Campus for Research Excellence and Technological Enterprise (CREATE) Programme and Physical Activity and Nutrition Determinants in Asia (PANDA) Research Programme.
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Diabetes mellitus (DM) is the third most common chronic condition associated with frequent hospital readmissions. Predictors of the number of readmissions within 1 year among patients with DM are less often studied compared with those of 30-day readmission. This study aims to identify predictors of number of readmissions within 1 year amongst adult patients with DM and compare different count regression models with respect to model fit. Data from 2008 to 2015 were extracted from the electronic medical records of the National University Hospital, Singapore. Inpatients aged ≥ 18 years at the time of index admission with a hospital stay > 24 h and survived until discharge were included. The zero-inflated negative binomial (ZINB) model was fitted and compared with three other count models (Poisson, zero-inflated Poisson and negative binomial) in terms of predicted probabilities, misclassification proportions and model fit. Adjusted for other variables in the model, the expected number of readmissions was 1.42 (95% confidence interval [CI] 1.07 to 1.90) for peripheral vascular disease, 1.60 (95% CI 1.34 to 1.92) for renal disease and 2.37 (95% CI 1.67 to 3.35) for Singapore residency. Number of emergency visits, number of drugs and age were other significant predictors, with length of stay fitted as a zero-inflated component. Model comparisons suggested that ZINB provides better prediction than the other three count models. The ZINB model identified five patient characteristics and two comorbidities associated with number of readmissions. It outperformed other count regression models but should be validated before clinical adoption.
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Diabetes Mellitus , Readmissão do Paciente , Adulto , Humanos , Hospitalização , Tempo de Internação , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Modelos Estatísticos , Convulsões , Fatores de Risco , Estudos RetrospectivosRESUMO
Epidermal growth factor receptor (EGFR) T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second generation (1G/2G) EGFR tyrosine kinase inhibitors (TKIs) and are sensitive to Osimertinib. Tissue sampling is the gold-standard modality of T790M testing, but it is invasive. We evaluated the efficacy of Osimertinib in patients with EGFR mutant NSCLC and T790M in circulating tumour DNA (ctDNA). PLASMA is a prospective, open-label, multicentre single-arm Phase II study. Patients with advanced NSCLC harbouring sensitizing EGFR and T790M mutations in plasma at progression from ≥one 1G/2G TKI were treated with 80 mg of Osimertinib daily until progression. The primary endpoint was the objective response rate (ORR); the secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and toxicities. Plasma next-generation sequencing was performed to determine Osimertinib resistance mechanisms and assess serial ctDNA. A total of 110 patients from eight centres in five countries were enrolled from 2017 to 2019. The median follow-up duration was 2.64 (IQR 2.44-3.12) years. The ORR was 50.9% (95% CI 41.2-60.6) and the DCR was 84.5% (95% CI 76.4-90.7). Median PFS was 7.4 (95% CI 6.0-9.3) months; median OS was 1.63 (95% CI 1.35-2.16) years. Of all of the patients, 76% had treatment-related adverse events (TRAEs), most commonly paronychia (22.7%); 11% experienced ≥ Grade 3 TRAEs. The ctDNA baseline load and dynamics were prognostic. Osimertinib is active in NSCLC harbouring sensitizing EGFR and T790M mutations in ctDNA testing post 1G/2G TKIs.
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Introduction: Vitamin K deficiency among patients on hemodialysis (HD) affects the function of matrix GLA protein (MGP), a potent vitamin K-dependent inhibitor of vascular calcification (VC). Methods: We conducted a single-center randomized controlled trial (RCT) on maintenance HD patients to examine if vitamin K2 supplementation can reduce progression of coronary artery calcification (CAC) over an 18-month study period. Patients were randomized to vitamin K2 group receiving menaquinone-7360 µg 3 times/wk or control group. The primary outcome was CAC scores at the end of the study period. The secondary outcomes were aortic valve calcification (AVC), carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx), dephosphorylated undercarboxylated MGP (dp-ucMGP) levels, major adverse cardiac events (MACE), and vascular access events. Results: Of the 178 patients randomized, follow-up was completed for 138 patients. The CAC scores between the 2 groups were not statistically different at the end of 18 months (relative mean difference [RMD] 0.85, 95% CI 0.55-1.31). The secondary outcomes did not differ significantly in AVC (RMD 0.82, 95% CI 0.34-1.98), cfPWV (absolute mean difference [AMD] 0.55, 95% CI -0.50 to 1.60), and AIx (AMD 0.13, 95% CI -3.55 to 3.80). Supplementation with vitamin K2 did reduce dp-ucMGP levels (AMD -86, 95% CI -854 to -117). The composite outcome of MACE and mortality was not statistically different between the 2 groups (Hazard ratio = 0.98, 95% CI 0.50-1.94). Conclusion: Our study did not demonstrate a beneficial effect of vitamin K2 in reducing progression of VC in this population at the studied dose and duration.
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BACKGROUND: Fluoropyrimidines are commonly used in the treatment of metastatic breast cancer (MBC), and trifluridine/tipiracil (FTD/TPI) has shown activity in patients with colorectal and gastric cancers despite prior exposure to fluoropyrimidines. We investigate the role of FTD/TPI in patients with MBC with or without prior fluoropyridines in a single-arm phase II study. METHODS: Patients with MBC were enroled first into a run-in dose confirmation phase, followed by two parallel cohorts including patients with (Cohort A) and without (Cohort B) prior exposure to fluoropyrimidines, where they were treated with FTD/TPI. Primary objectives for each cohort included determination of progression-free survival (PFS), and secondary objectives included determination of objective response rates (ORR), safety, and tolerability. RESULTS: Seventy-four patients (42 Cohort A, 32 Cohort B) were enroled, all of whom were evaluable for toxicity and survival, with 72 evaluable for response. Median PFS was 5.7 months (95% confidence interval 3.8-8.3) and 9.4 months (95% CI 5.5-14.0) respectively in Cohorts A and B. Responses were observed regardless of prior exposure to fluoropyrimidines, with ORR of 19.5% (95% CI 8.8-34.9) and 16.1% (95% CI 5.5-33.7) in Cohorts A and B, and 6-month clinical benefit rates of 56.1% (95% CI 39.7-71.5) and 61.3% (95% CI 42.2-78.2) respectively. The safety profile was consistent with known toxicities of FTD/TPI, including neutropenia, fatigue, nausea, and anorexia, mitigated with dose modifications. CONCLUSION: FTD/TPI showed promising antitumour activity with manageable toxicity and is a clinically valid option in patients with MBC.
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PURPOSE: To assess the effect of aromatherapy with lavender oil alone, and in combination with music, on pain and anxiety during extracorporeal shockwave lithotripsy for kidney stones. METHODS: This was a single-centre prospective, randomised controlled trial. The subjects were block randomised into 3 study groups, Group 1: Control; Group 2: Aromatherapy only; Group 3: Aromatherapy and music. All subjects were given patient-controlled intravenous alfentanil as standard analgesia. The primary outcome measures were pain and anxiety scores using visual analogue scale (VAS) and State-Trait Anxiety Inventory. RESULTS: Ninety patients were recruited and randomised prospectively into Group 1 (n = 30), Group 2 (n = 30), and Group 3 (n = 30). For pain outcome, both Group 2 and Group 3 showed a trend towards lower mean VAS pain scores of 2.73 in both groups compared to the control with a mean VAS score of 3.50, but it was not statistically significant (p = 0.272). There was no significant difference in anxiety scores between groups post-treatment. CONCLUSIONS: Our study was unable to show a significant improvement in pain relief and anxiety when aromatherapy with lavender oil was added to standard analgesia alone during shockwave lithotripsy. There was also no difference when aromatherapy was combined with music.
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Analgesia , Aromaterapia , Litotripsia , Musicoterapia , Música , Humanos , Manejo da Dor , Estudos Prospectivos , Dor/etiologia , Dor/prevenção & controle , Ansiedade/etiologia , Ansiedade/terapia , Litotripsia/efeitos adversosRESUMO
PURPOSE OF REVIEW: The development of potent novel agents has improved outcomes for patients with multiple myeloma (MM). Heterogeneity of response to therapy, an expanding arsenal of treatment options, and cost are however major challenges for physicians making treatment decisions. Response-adapted therapy is hence an attractive strategy for sequencing of therapy in MM. Despite its successful application in other haematologic malignancies, response-adapted therapy is yet to become a standard of care for MM. We provide our perspective on response-adapted therapeutic strategies evaluated thus far and how they may be implemented and improved on in treatment algorithms of the future. RECENT FINDINGS: While older studies suggested that early response based on International Myeloma Working Group response criteria could impact long-term outcomes, recent data have contradicted these findings. The advent of minimal residual disease (MRD) as a powerful prognostic factor in MM has raised the promise of MRD-adapted treatment strategies. The development of more sensitive techniques for paraprotein quantification as well as imaging modalities to detect extramedullary disease is likely to change response assessment in MM. These techniques combined with MRD assessment may provide sensitive and holistic response assessments which could be evaluated in clinical trials. Response-adapted treatment algorithms have the potential to allow an individualised treatment strategy, maximising efficacy, while minimising toxicities and cost. Standardisation of MRD methodology, incorporation of imaging into response assessment, and the optimal management of MRD positive patients are key questions to be addressed in future trials.
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Neoplasias Hematológicas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/tratamento farmacológico , Intervalo Livre de Doença , Neoplasia Residual/diagnósticoRESUMO
Background: Sedentary behaviour increases the risks of non-communicable diseases. The objective of this trial was to evaluate the effect of the Physical Activity at Work multicomponent intervention to reduce sedentary behaviour in Thai office workers. Methods: Offices under the Ministry of Public Health Thailand, were randomly allocated to the intervention and control group in a 1:1 ratio, stratified by office size. The intervention included individual (pedometer and lottery-based financial incentives), social (group movement breaks), environmental (posters), and organisational (leader encouragement) components. At baseline and 6-month follow-up, participants wore ActiGraphTM on the waist for ten days. The primary outcome was the between-group difference in sedentary time at 6-month, analysed using a linear mixed-effects model. Other outcomes were physical activity, biomarkers, productivity, and musculoskeletal health. Trial registration: The PAW study was registered at the Thai Clinical Trials Registry (ID TCTR20200604007) on 02 June 2020. Findings: 282 office workers were recruited and randomly allocated to the control group (142 participants, nine offices) and the intervention group (140 participants, nine offices). The mean age was 38.6 years (SD = 10.4), and 81% were women. There was no evidence of intervention effects on sedentary time during waking hours (-26.8; 95% CI = -69.2 to 15.7 min), physical activity levels, or biomarkers between groups at 6-month. In the adjusted analysis, increases in time spent in moderate-to-vigorous physical activity (5.45; 95% CI = -0.15 to 11.1 min) and step count (718; 95% CI = -45 to 1481 steps) during waking hours were observed, although there was no evidence of a difference between groups. Interpretation: The intervention did not significantly reduce sedentary time in Thai office workers. Suboptimal intervention uptake due to Covid-19 pandemic restrictions and loss of statistical power associated with recruitment constraints may explain this result. Further investigations are needed to evaluate the processes of the trial. Funding: The Thai Health Promotion Foundation and the International Decision Support Initiative (iDSI).
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BACKGROUND: Patient selection is key in Phase I studies, and prognosis can be difficult to estimate in heavily pre-treated patients. Previous prognostic models like the Royal Marsden Hospital (RMH) score or using the neutrophil-lymphocyte ratio (NLR) have not been validated in current novel therapies nor in the Asian Phase I population. METHODS: We conducted a retrospective review of 414 patients with solid tumours participating in Phase I studies at our centre between October 2013 and December 2020. RESULTS: The RMH model showed poorer prognosis with increasing scores [RMH score 1, HR 1.28 (95% CI: 0.96-1.70); RMH score 2, HR 2.27 (95% CI: 1.62-3.17); RMH score 3, HR 4.14 (95% CI: 2.62-6.53)]. NLR did not improve the AUC of the model. Poorer ECOG status (ECOG 1 vs. 0: HR = 1.59 (95% CI = 1.24-2.04), P < 0.001) and primary tumour site (GI vs. breast cancer: HR = 3.06, 95% CI = 2.16-4.35, P < 0.001) were prognostic. CONCLUSIONS: We developed a NCIS prognostic score with excellent prognostic ability for both short-term and longer-term survival (iAUC: 0.71 [95% CI 0.65-0.76]), and validated the RMH model in the largest Asian study to date.
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Neoplasias da Mama , Humanos , Feminino , Prognóstico , Resultado do Tratamento , Neoplasias da Mama/terapia , Linfócitos , Seleção de Pacientes , Estudos Retrospectivos , NeutrófilosRESUMO
OBJECTIVE: The primary objective is to develop a prediction model of 30-day hospital readmission among adults with diabetes mellitus (DM) whose index admission was DM-related. The secondary aims are to internally and externally validate the prediction model and compare its performance with 2 existing models. RESEARCH DESIGN AND SETTING: Data of inpatients agedâ ≥â 18 years from 2008 to 2015 were extracted from the electronic medical record system of the National University Hospital, Singapore. Unplanned readmission within 30 days was calculated from the discharge date of the index hospitalization. Multivariable logistic regression and 10-fold cross-validation were performed. For external validation, simulations based on prevalence of 30-day readmission, and the regression coefficients provided by referenced papers were conducted. RESULTS: Eleven percent of 2355 patients reported 30-day readmission. The prediction model included 4 predictors: length of stay, ischemic heart disease, peripheral vascular disease, and number of drugs. C-statistics for the prediction model and 10-fold cross-validation were 0.68 (95% CI 0.66, 0.70) and 0.67 (95% CI 0.63 to 0.70), respectively. Those for the 3 simulated external validation data sets ranged from 0.64 to 0.68. CONCLUSION: The prediction model performs well with good internal and external validity for identifying patients with DM at risk of unplanned 30-day readmission.
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Diabetes Mellitus , Readmissão do Paciente , Adulto , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Hospitalização , Hospitais , Humanos , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Existing modes of collecting self-reported 24-hour movement information from children, including digital assessments, have not been demonstrated to be of acceptable validity when compared to objective measurements. My E-Diary for Activities and Lifestyle (MEDAL) is an interactive web-based diary developed to collect time-use information from children aged 10 years and older. OBJECTIVE: This study evaluated the validity of MEDAL for assessing children's movement behaviors by comparing self-reported and accelerometer-measured time spent in movement behavior among children in Singapore aged 10-11 years. METHODS: Funding for this study was obtained in October 2017, and data were collected between April and August 2020. Participants recorded their daily activities using MEDAL over 2 specified weekdays and 2 weekend days and wore an Actigraph accelerometer on their nondominant wrist throughout the study to objectively assess movement behaviors. Spearman correlation coefficient and intraclass correlation coefficient (ICC) were used to compare the accelerometer measurements and self-reports for each movement behavior. Bland-Altman plots were generated to investigate trends of bias in the self-reports. RESULTS: Among the participants aged 10-11 years (29/49, 59% boys), we observed that children reported lower light physical activity (LPA) and higher moderate-to-vigorous physical activity (MVPA), inactivity, and night sleep than that measured by the accelerometer. There was a moderate-to-strong correlation between self-reported and accelerometer-measured MVPA (r=0.37; 95% CI 0.20-0.54), inactivity (r=0.36; 95% CI 0.18-0.54), and night sleep (r=0.58; 95% CI 0.43-0.74); the correlation for LPA was poor (r=0.19; 95% CI 0.02-0.36). Agreement was poor for all behaviors (MVPA: ICC=0.24, 95% CI 0.07-0.40; LPA: ICC=0.19, 95% CI 0.01-0.36; inactivity: ICC=0.29, 95% CI 0.11-0.44; night sleep: ICC=0.45, 95% CI 0.29-0.58). There was stronger correlation and agreement on weekdays for inactivity and night sleep; conversely, there was stronger correlation and agreement for MVPA and LPA on weekend days. Finally, based on Bland-Altman plots, we observed that with increasing MVPA, children tended to report higher MVPA than that measured by the accelerometer. There were no clear trends for the other behaviors. CONCLUSIONS: MEDAL may be used to assess the movement behaviors of children. Based on self-reports, the children are able to estimate their time spent in MVPA, inactivity, and night sleep although actual time spent in these behaviors may differ from accelerometer-derived estimates; self-reported LPA warrant cautious interpretation. Observable differences in reporting accuracy exist between weekdays and weekend days.
RESUMO
BACKGROUND: Gay, bisexual, and other men who have sex with men (GBMSM) are at disproportionately higher risk of acquiring HIV and other sexually transmitted infections (STI). While HIV/STI testing rates among GBMSM are increasing worldwide, they remain suboptimal in a variety of settings. While many studies have attempted to evaluate the efficacy of a variety of community-based campaigns, including peer and reminder-based interventions on HIV/STI testing, however few have attempted to do so for a web drama series. OBJECTIVE: This study evaluates the effectiveness of a popular web drama video series developed by a community-based organization in Singapore for GBMSM on HIV and other STI testing behaviors. METHODS: The study is a pragmatic, randomized controlled trial to evaluate a popular web drama video series developed by a community-based organization in Singapore for GBMSM. A total of 300 HIV-negative, GBMSM men in Singapore aged 18 to 29 years old were recruited and block-randomized into the intervention (n=150) and control arms (n=150). Primary outcomes included changes in self-reported intention to test for, actual testing for, and regularity of testing for HIV, syphilis, chlamydia or gonorrhea, while secondary outcomes include changes in a variety of other knowledge-based and psychosocial measures at the end of the study period. RESULTS: Overall, 83.3% (125/150) of participants in the intervention arm completed the proof of completion survey, compared to 88.7% (133/150) in the control arm. We found improvements in self-reporting as a regular (at least yearly) tester for HIV (15.9% difference, 95% CI, 3.2% to 28.6%; P=.02), as well as chlamydia or gonorrhea (15.5% difference, 95% CI, 4.2% to 26.9%; P=.009), indicating that the intervention had positively impacted these outcomes compared to the control condition. We also found improvements in participants' intentions to test for HIV (16.6% difference, 95% CI, 4.3% to 28.9%; P=.009), syphilis (14.8% difference, 95% CI, 3.2% to 26.4%; P=.01), as well as chlamydia or gonorrhea (15.4% difference, 95% CI, 4.2% to 26.6%; P=.008), in the next 3 months, indicating that the intervention was effective in positively impacting intention for HIV and other STI testing among participants. CONCLUSIONS: There are clear benefits for promoting intentions to test regularly and prospectively on a broad scale through this intervention. This intervention also has potential to reach GBMSM who may not have access to conventional HIV and other STI prevention messaging, which have typically been implemented at sex-on-premises venues, bars, clubs, and in sexual health settings frequented by GBMSM. When coupled with community or population-wide structural interventions, the overall impact on testing will likely be significant. TRIAL REGISTRATION: ClinicalTrials.gov NCT04021953; https://clinicaltrials.gov/ct2/show/NCT04021953. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-033855.
Assuntos
Gonorreia , Infecções por HIV , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Sífilis , Adolescente , Adulto , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , Homossexualidade Masculina/psicologia , Humanos , Masculino , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/prevenção & controle , Singapura , Sífilis/diagnóstico , Sífilis/prevenção & controle , Adulto JovemRESUMO
Neurosurgeons today are inundated with rapidly amassing neurosurgical research publications. Systematic reviews and meta-analyses have consequently surged in popularity because, when executed properly, they constitute a high level of evidence and may save busy neurosurgeons many hours of combing and reviewing the literature for relevant articles. Meta-analysis refers to the quantitative (and discretionary) component of systematic reviews. It involves applying statistical techniques to combine effect sizes from multiple studies, which might offer more actionable insights than a systematic review without meta-analysis. Well-executed meta-analyses may prove instructive for clinical practice, but poorly conducted ones sow confusion and have the potential to cause harm. Unfortunately, recent audits have found the conduct and reporting of meta-analyses in neurosurgery (but also other surgical disciplines) to be relatively lackluster in methodologic rigor and compliance to established guidelines. Some of these deficiencies can be easily remedied through better awareness and adherence to prescribed standards-which will be reviewed in this article-but others stem from inherent problems with the source data (e.g., poor reporting of original research) as well as unique constraints faced by surgery as a field (e.g., lack of equipoise for randomized trials, or existence of learning curves for novel surgical procedures, which can lead to temporal heterogeneity), which may require unconventional tools (e.g., cumulative meta-analysis) to address. Therefore, it is also our goal to take stock of the unique issues encountered by surgeons who do meta-analysis and to highlight various techniques-some of which less well-known-to address such challenges.