DESIGN: Population-based cross-sectional study.
SETTING: South East Asia Community Observatory HDSS site in Malaysia.
PARTICIPANTS: Of 45 246 participants recruited from 13 431 households, 18 101 eligible adults aged 18-97 years (mean age 47 years, 55.6% female) were included.
MAIN OUTCOME MEASURES: The main outcome was prevalence of multimorbidity. Multimorbidity was defined as the coexistence of two or more chronic conditions per individual. A total of 13 chronic diseases were selected and were further classified into 11 medical conditions to account for multimorbidity. The conditions were heart disease, stroke, diabetes mellitus, hypertension, chronic kidney disease, musculoskeletal disorder, obesity, asthma, vision problem, hearing problem and physical mobility problem. Risk factors for multimorbidity were also analysed.
RESULTS: Of the study cohort, 28.5% people lived with multimorbidity. The individual prevalence of the chronic conditions ranged from 1.0% to 24.7%, with musculoskeletal disorder (24.7%), obesity (20.7%) and hypertension (18.4%) as the most prevalent chronic conditions. The number of chronic conditions increased linearly with age (p<0.001). In the logistic regression model, multimorbidity is associated with female sex (adjusted OR 1.28, 95% CI 1.17 to 1.40, p<0.001), education levels (primary education compared with no education: adjusted OR 0.63, 95% CI 0.53 to 0.74; secondary education: adjusted OR 0.60, 95% CI 0.51 to 0.70; tertiary education: adjusted OR 0.65, 95% CI 0.54 to 0.80; p<0.001) and employment status (working adults compared with retirees: adjusted OR 0.70, 95% CI 0.60 to 0.82, p<0.001), in addition to age (adjusted OR 1.05, 95% CI 1.05 to 1.05, p<0.001).
CONCLUSIONS: The current single-disease services in primary and secondary care should be accompanied by strategies to address complexities associated with multimorbidity, taking into account the factors associated with multimorbidity identified. Future research is needed to identify the most commonly occurring clusters of chronic diseases and their risk factors to develop more efficient and effective multimorbidity prevention and treatment strategies.
METHODS: Data collection was done retrospectively from five centers and included general patients' information, and clinical and laboratory variables. Inclusion criteria were untransplanted patients who are either dead or alive with a follow-up period ≥6 months after diagnosis.
RESULTS: Two hundred and thirty-six CID patients were reported by participating centers, of whom 111 were included in the study with a cumulative follow-up period of 278.6 years. Seventy-two patients died with the median age of death of 10.5 months. 35.1% of the patients succumbed within 6 months after the diagnosis. Having a history of Candida infections, sepsis or hepatomegaly was associated with an increased risk of early death. None of the other general or clinical variables was associated with such risk. Bivariate analysis of lymphocyte subsets showed that patients with the following counts: CD3+
OBJECTIVE: Camptothecin (CPT) is one of the most promising anticancer drugs but it produces various side effects because of its non-selectivity towards cancer cells. To overcome these adverse effects, we synthesized biotin conjugate of camptothecin, which was linked via a self-immolative disulfide linker (CPT-SS-Biotin).
METHODS: Biotin conjugated camptothecin linked through a disulfide bond was synthesized following schemes, and the structural characterization was carried out. The stability and drug release studies were performed in the presence of glutathione (GSH) while in vitro studies were performed on 4T1 tumor cell lines. In vivo pharmacological investigation was done using an antitumor Wistar rat model.
RESULTS: The stability and drug release studies were performed in the presence of glutathione (GSH), and CPT-SSBiotin was found to be physiologically stable moiety and can only be cleaved in the presence of GSH to release free CPT. The CPT-SS-Biotin showed higher toxicity in the biotin-overexpressing 4T1 tumor cell line with a lower IC50 value (8.44 μM) compared to camptothecin alone (IC50 > 30 μM). CPT-SS-Biotin also showed 10.6% higher cellular uptake by cells in comparison to free camptothecin. The CPT-SS-Biotin was delivered to cells by binding to the biotin receptors on the cell surface, followed by energy-dependent endocytosis and internalization to cause cellular toxicity.
CONCLUSION: In-vivo tumor suppression studies and in vitro cell line studies along with serological parameters and histopathological studies showed that conjugate produced a high therapeutic effect and remarkably reduced toxic effects in comparison to free CPT. The results suggested that biotinylation of camptothecin via disulfide linker can be a safe and efficacious method in cancer therapeutics.
METHODS: Intermolecular synthons, hydrogen bonding, crystal morphology and surface chemistry are modelled using empirical force fields with the data integrated into the analysis of lattice deformation as computed using a statistical approach.
RESULTS: The approach developed comprises three main components. Firstly, the identification of the likely direction of deformation based on lattice unit cell geometry; secondly, the identification of likely lattice planes for deformation through the calculation of the strength and stereochemistry of interplanar intermolecular interactions, surface plane rugosity and surface energy; thirdly, identification of potential crystal planes for cleavage fracture by assessing intermolecular bonding anisotropy. Pentaerythritol is predicted to fracture by brittle cleavage on the {001} lattice planes by strong in-plane hydrogen-bond interactions in the <110>, whereas pentaerythritol tetranitrate is predicted to deform by plastic deformation through the slip system {110} , with both predictions being in excellent agreement with known experimental data.
CONCLUSION: A crystallographic framework and associated workflow for predicting the mechanical deformation of molecular crystals is developed through quantitative assessment of lattice energetics, crystal surface chemistry and crystal defects. The potential for the de novo prediction of the mechanical deformation of pharmaceutical materials using this approach is highlighted for its potential importance in the design of formulated drug products process as needed for manufacture by direct compression.
OBJECTIVES: The current systematic review aims to synthesize existing feasibility studies on LRI among persons with cancer.
METHODS: A literature search was conducted from the databases PubMed, ScienceDirect, PsychArticles, Scopus, Psychology and Behavioral Science Collection, Cochrane, EBSCO, and other methods. Eligible articles were selected based on the predetermined inclusion criteria and data extraction revolved around the study design, intervention procedure, and feasibility and psychological outcome measures.
RESULTS: The search yielded 8,627 articles, to which respondents simultaneously receiving other forms of psychological interventions were excluded. Eight were selected for evaluation. Four were integrated interventions while the remaining were conducted with the standard intervention. The sample size range from 5 to 90 persons with cancer. All reviewed articles reported optimum feasibility, as presented by recruitment capability, participant retention rate, acceptability and satisfaction, intervention implementation, and evaluation of intervention outcome measures. However, a majority of psychological outcome measures indicated no statistical significance.
CONCLUSION: LRI is feasible to be implemented among persons with cancer, given the high acceptability and availability of resources for its implementation. The present review highlighted the preliminary knowledge on the feasibility of the intervention.
METHODS: We did an individual participant data meta-analysis comparing balloon catheters and vaginal prostaglandins for cervical ripening before labour induction. We systematically identified published and unpublished randomised controlled trials that completed data collection between March 19, 2019, and May 1, 2021, by searching the Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and PubMed. Further trials done before March 19, 2019, were identified through a recent Cochrane review. Data relating to the combined use of the two methods were not included, only data from women with a viable, singleton pregnancy were analysed, and no exclusion was made based on parity or membrane status. We contacted authors of individuals trials and participant-level data were harmonised and recoded according to predefined definitions of variables. Risk of bias was assessed with the ROB2 tool. The primary outcomes were caesarean delivery, indication for caesarean delivery, a composite adverse perinatal outcome, and a composite adverse maternal outcome. We followed the intention-to-treat principle for the main analysis. The primary meta-analysis used two-stage random-effects models and the sensitivity analysis used one-stage mixed models. All models were adjusted for maternal age and parity. This meta-analysis is registered with PROSPERO (CRD42020179924).
FINDINGS: Individual participant data were available from 12 studies with a total of 5460 participants. Balloon catheters, compared with vaginal prostaglandins, did not lead to a significantly different rate of caesarean delivery (12 trials, 5414 women; crude incidence 27·0%; adjusted OR [aOR] 1·09, 95% CI 0·95-1·24; I2=0%), caesarean delivery for failure to progress (11 trials, 4601 women; aOR 1·20, 95% CI 0·91-1·58; I2=39%), or caesarean delivery for fetal distress (10 trials, 4441 women; aOR 0·86, 95% CI 0·71-1·04; I2=0%). The composite adverse perinatal outcome was lower in women who were allocated to balloon catheters than in those allocated to vaginal prostaglandins (ten trials, 4452 neonates, crude incidence 13·6%; aOR 0·80, 95% CI 0·70-0·92; I2=0%). There was no significant difference in the composite adverse maternal outcome (ten trials, 4326 women, crude incidence 22·7%; aOR 1·02, 95% CI 0·89-1·18; I2=0%).
INTERPRETATION: In induction of labour, balloon catheters and vaginal prostaglandins have comparable caesarean delivery rates and maternal safety profiles, but balloon catheters lead to fewer adverse perinatal events.
FUNDING: Australian National Health and Medical Research Council and Monash Health Emerging Researcher Fellowship.