Search

BackgroundThe most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.MethodsFace-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents.Results3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness.ConclusionADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.

The non-invasive treatment of glioblastoma (GBM) is of great significance and can greatly reduce the complications of craniotomy. Sonodynamic therapy (SDT) is an emerging tumor therapeutic strategy that overcomes some fatal flaws of photodynamic therapy (PDT). Different from PDT, SDT has deep tissue penetration and can be applied in the non-invasive treatment of deep-seated tumors. However, effective sonosensitizers that can be used for SDT of GBM are still very rare. Herein, we have prepared a suitable assembly based on a hypocrellin derivative (CTHB) with good biocompatibility. Excitedly, the hypocrellin-based assembly (CTHB NPs) can effectively produce reactive oxygen species under ultrasound stimulation. The inherent fluorescence and photoacoustic imaging characteristics of the CTHB NPs are conducive to the precise positioning of the tumors. It has been proved both in subcutaneous and in intracranial tumor models that CTHB NPs can be used as an effective sonosensitizer to inhibit tumor growth under ultrasound irradiation. This hypocrellin-based assembly has a good clinical prospect in the non-invasive treatment of GBM.

Introduction: The rising prevalence of multiple chronic diseases is an important public health issue as it is associated with increased healthcare utilisation. This paper aimed to explore the annual per capita healthcare cost in primary care for patients with multiple chronic diseases (multimorbidity). Methods: This was a retrospective cohort study conducted in a cluster of public primary care clinics in Singapore. De-identified data from electronic medical records were extracted from July 2015 to June 2017. Only patients with at least 1 chronic disease were included in the study. Basic demographic data and healthcare cost were extracted. A list of 20 chronic diseases was considered for multimorbidity. Results: There were 254,377 patients in our study population, of whom 52.8% were female. The prevalence of multimorbidity was 62.4%. The median annual healthcare cost per capita for patients with multimorbidity was about twice the amount compared to those without multimorbidity (SGD683 versus SGD344). The greatest percentage increment in cost was when the number of chronic diseases increased from 2 to 3 (43.0%). Conclusion: Multimorbidity is associated with higher healthcare cost in primary care. Since evidence for the optimal management of multimorbidity is still elusive, prevention or delay in the onset of multimorbidity in the general population is paramount. Keywords: Chronic disease, healthcare cost, multimorbidity, primary care

INTRODUCTION Patients with chronic diseases face difficulties when navigating the healthcare system. Using the Healthcare System Hassles Questionnaire (HSHQ) developed by Parchman et al, this study aimed to explore the degree of hassles faced by patients in primary care in Singapore and identify the characteristics associated with greater hassles. METHODS A cross-sectional study was conducted on patients with chronic diseases at Hougang Polyclinic, Singapore, using the interviewer-administered HSHQ. The mean HSHQ score was compared with that reported by Parchman et al. The associations between the number of chronic diseases, demographic variables and healthcare hassles were assessed using multivariate linear logistic regression analysis. RESULTS In total, 217 outpatients aged 21 years and above were enrolled. Their overall mean HSHQ score (4.77 ± 6.18) was significantly lower than that of patients in the study by Parchman et al (15.94 ± 14.23, p < 0.001). Patients with five or more chronic diseases scored 3.38 (95% confidence interval [CI] 0.11–6.65, p = 0.043) points higher than those with one chronic disease did. With each increasing year of age, the mean HSHQ score decreased by 0.17 (95% CI −0.26 to −0.08, p = 0.001) points. Patients with polytechnic/diploma/university education and higher scored 2.65 (95% CI 0.19–5.11, p = 0.035) points higher than those with primary education and lower did. CONCLUSION Patients in our population reported less hassles than those in the study by Parchman et al did. Increasing age and lower education level were associated with less hassles. Further analysis of the types of chronic diseases may yield new information about the association of healthcare hassles with the number and types of chronic diseases.

BACKGROUND: Although randomized trials show that specific phobia treatments can be effective, it is unclear whether patients experience treatment as helpful in clinical practice. We investigated this issue by assessing perceived treatment helpfulness for specific phobia in a cross-national epidemiological survey.METHODS: Cross-sectional population-based WHO World Mental Health (WMH) surveys in 24 countries (n=112,507) assessed lifetime specific phobia. Respondents who met lifetime criteria were asked whether they ever received treatment they considered helpful and the number of professionals seen up to the time of receiving helpful treatment. Discrete-event survival analysis was used to calculate conditional-cumulative probabilities of obtaining helpful treatment across number of professionals seen and of persisting in help-seeking after prior unhelpful treatment.RESULTS: 23.0% of respondents reported receiving helpful treatment from the first professional seen, whereas cumulative probability of receiving helpful treatment was 85.7% after seeing up to 9 professionals. However, only 14.7% of patients persisted in seeing up to 9 professionals, resulting in the proportion of patients ever receiving helpful treatment (47.5%) being much lower than it could have been with persistence in help-seeking. Few predictors were found either of perceived helpfulness or of persistence in help-seeking after earlier unhelpful treatments.LIMITATIONS: Retrospective recall and lack of information about either types of treatments received or objective symptomatic improvements limit results.CONCLUSIONS: Despite these limitations, results suggest that helpfulness of specific phobia treatment could be increased, perhaps substantially, by increasing patient persistence in help-seeking after earlier unhelpful treatments. Improved understanding is needed of barriers to help-seeking persistence.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Several treatment options are available for managing HCC patients, classified roughly as local, local-regional, and systemic therapies. The high post-monotherapy recurrence rate of HCC urges the need for the use of combined modalities to increase tumor control and patient survival. Different international guidelines offer treatment recommendations based on different points of view and classification systems. Radiotherapy (RT) is a well-known local-regional treatment modality for managing many types of cancers, including HCC. However, only some of these treatment guidelines include RT, and the role of combined modalities is rarely mentioned. Hence, the present study reviewed clinical evidence for the use of different combined modalities in managing HCC, focusing on modern RT's role. Modern RT has an increased utility in managing HCC patients, mainly due to two driving forces. First, technological advancement (e.g., stereotactic body radiotherapy and advanced proton-beam therapy) enables precise delivery of radiation to increase tumor control and reduce side effects in the surrounding normal tissue. Second, the boom in developing target therapies and checkpoint-blockade immunotherapy prolongs overall survival in HCC patients, re-emphasizing the importance of local tumor control. Remarkably, RT combines with systemic therapies to generate the systemic therapy augmented by radiotherapy effect, a benefit now being actively investigated.

Objectives: Recently, Stereotactic Body Radiotherapy (SBRT) has been suggested for managing hepatocellular carcinoma (HCC) curatively. Thus, we conducted this clinical study to evaluate retrospectively the effect of individualized audio-visual (AV) coaching, respiratory modulated SBRT. Materials and Methods: Between 2014 and 2018, 29 patients with inoperable Barcelona Clinic Liver Cancer (BCLC) stage 0-B HCC received AV coaching, respiratory-modulated SBRT. We constructed a task-oriented multidisciplinary team to establish a standard operation process of respiratory modulation procedures and developed our AV coaching devices. In the training period, a goodness-of-fit test was applied individually. SBRT was delivered with a total dose of 40–54 Gy in 5–6 fractions individually. Freedom from local progression (FFLP) and overall survival (OS) were estimated using SPSS (version 17, SPSS Inc., Chicago, IL, USA) life tables. Results: The patient characteristics were as follows: 32.7 ± 16 mm in maximum tumor diameter (range 11–94); BCLC stage 0: 3.4%, BCLC A: 48.3%, BCLC B: 48.3%; Child-Pugh classification A: 86.2%, Child-Pugh classification B: 13.8%, and a median of 2 prior liver-directed treatments (range 0–7). One-, 2-, and 3-year rates of FFLP of SBRT were 96.6%, 96.6%, and 96.6%, respectively. One-, 2-, and 3-year rates of OS were 81.5%, 72.4%, and 67.2%, respectively. No adverse event (AE) occurred in 41.4% of patients, 48.3% developed grade (G) 1–2 AE, 10.3% had G3 AE and none had G4-5 AE. Conclusion: Respiration-modulated SBRT is a promising noninvasive treatment option for patients with inoperable and localized HCC. Our data show that SBRT provides comparable tumor control to historical curative options like surgery and radiofrequency ablation of localized tumors. Thus, we are conducting a further prospective clinical trial with the intent to demarcate the clinical effectiveness of SBRT in a larger population of patients with HCC.

Immunosuppressed tumor microenvironment (TME) is a major cause of the low response rate in solid tumor patients during PD-1/PD-L1 checkpoint blockade therapy. In this study, a series of small molecule nanomedicines with a 100% drug loading rate were prepared via the nanoprecipitation method. They were used in synergistic chemo-immunotherapy for 4T1 tumors. Among four PD-L1 small-molecule nanoinhibitors, BMS-1 NP with the best anti-tumor performance was selected to replace the therapeutic PD-L1 antibody. The core-shell small-molecule nanomedicine DTX@VTX NP (DTX: Docetaxel and VTX: VTX-2337 or Motolimod) was used to reverse immunosuppressed TME through the depletion of myeloid-derived suppressor cells (MDSCs) and the polarization of macrophages from an M2-like phenotype to M1-like phenotype. Thus, the frequency of cytotoxic CD8+ T cells was significantly increased, resulting in an effective attack on cancer cells. Combining BMS-1 NPs with DTX@VTX NPs, synergistic chemo-immunotherapy of 4T1 tumors was performed, and the results indicate that the inhibition rates of primary and rechallenge tumors achieved 90.5% and 94.3%, respectively. These results indicate that DTX@VTX NPs can synergize PD-L1 nanoinhibitor BMS-1 NPs to reshape the immunosuppressive tumor microenvironment for enhancing the anti-tumor effect of chemo-immunotherapy for breast.

Although piperine-an extract from pepper-has a mild chemotherapeutic effect, its poor water solubility has limited its applications for cancer therapy. With self-assembling of piperine into nanoparticles along with PEG (Pip NPs), both the water dispersibility and the chemotherapeutic efficacy can be substantially enhanced. It is further shown that the NPs can generate reactive oxygen species (ROS) with or without additional white light irradiation. Interestingly, the Pip NP induced cell death can be suppressed by ferroptosis inhibitors such as liproxstatin-1 and deferoxamine. Lipid ROS production is also observed in Pip NP treated cells. In addition to their cancer cell killing ability, the Pip NPs also show strong green fluorescence. These multiple functions make the Pip NPs a promising and low-cost nanotheranostic agent with herbal origin.

A huge challenge exists in the diagnosis and treatment of malignant glioblastoma (GBM) due to the presence of the blood-brain barrier (BBB). Herein, a multifunctional phototheranostic agent is designed on the basis of an octadecane-modified temozolomide (

BACKGROUND The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is indicated for adults who have a high risk of pneumonia; however, its effectiveness in patients with prostate cancer who are at a risk of pneumonia because of age and cancer treatments, including androgen-deprivation therapy, is unknown. METHODS Between 2000 and 2010, 38,735 patients with prostate cancer were diagnosed in Taiwan. After exclusions and exact matching for age, previous pneumonia, and influenza vaccination, 2188 vaccinated patients and 2188 unvaccinated patients were recruited. The incidence density of all-cause bacterial pneumonia hospitalizations was analyzed. RESULTS Over 7 years of follow-up, patients who received the PPSV23 had a significantly lower incidence density, with 142.8 per 1000 person-years versus 162.0 per 1000 person-years for unvaccinated patients. More patients in the vaccinated cohort were never hospitalized for pneumonia compared with those in the unvaccinated cohort (64.2% vs 62.2%, respectively). After adjusting for the Charlson comorbidity index, cancer treatment modalities, and socioeconomic levels, the risk of pneumonia-related hospitalization in the PPSV23 vaccination cohort was 0.48 times lower than that in the unvaccinated cohort (adjusted incidence rate ratio, 0.48; P = .046). For patients who received the influenza vaccination, subgroup analysis demonstrated that PPSV23 vaccination significantly decreased the risk (adjusted incidence rate ratio, 0.45; P < .001). Compared with unvaccinated controls, PPSV23-vaccinated patients had a lower cumulative incidence for the first occurrence of pneumonia-related hospitalization (34.49% vs 36.36%; P = .178) and higher overall survival (47.5% and 42.3%, respectively; P < .001). CONCLUSIONS Vaccination of elderly patients who have prostate cancer with the relatively common and inexpensive PPSV23 can decrease the risk of pneumonia and prolong survival.

Hypocrellin B (HB) derived from naturally produced hypocrellins has attracted considerable attention in photodynamic therapy (PDT) because of its excellent photosensitive properties. However, the weak absorption within a "phototherapy window" (600-900 nm) and poor water solubility of HB have limited its clinical application. In this study, two HB derivatives (i. e., HE and HF) were designed and synthesized for the first time by introducing two different substituent groups into the HB structure. The obtained derivatives showed a broad absorption band covering the near-infrared (NIR) region, NIR emission (peaked at 805 nm), and singlet oxygen quantum yields of 0.27/0.31. HE-PEG-NPs were also prepared using 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000) to achieve excellent dispersion in water and further explored their practical applications. HE-PEG-NPs not only retained their 1 O2 -generating ability, but also exhibited a photothermal conversion efficiency of 25.9%. In vitro and in vivo therapeutic results revealed that the synergetic effect of HE-PEG-NPs on PDT and photothermal therapy (PTT) could achieve a good performance. Therefore, HE-PEG-NPs could be regarded as a promising phototheranostic agent.

Cancer is the second leading cause of death globally, responsible for an estimated 9.6 million deaths in 2018, and this burden continues to increase. Therefore, there is a clear and urgent need for novel drugs with increased efficacy for the treatment of different cancers. Previous research has demonstrated that brevilin A (BA) exerts anticancer activity in various cancers, including human multiple myeloma, breast cancer, lung cancer, and colon carcinoma, suggesting the anticancer potential present in the chemical scaffold of BA. Here, we designed and synthesized a small library of 12 novel BA derivatives and evaluated the biological anticancer effects of the compounds in various cancer cell lines. The results of this structure–activity relationship study demonstrated that BA derivatives BA-9 and BA-10 possessed significantly improved anticancer activity toward lung, colon, and breast cancer cell lines. BA-9 and BA-10 could more effectively reduce cancer cell viability and induce DNA damage, cell-cycle arrest, and apoptosis when compared with BA. Our findings represent a significant step forward in the development of novel anticancer entities.

Organic nanoparticles with intriguing features have attracted widespread attention for various biomedical applications, such as disease diagnosis, drug delivery, bioimaging, and cancer therapy. The...

Traditional photosensitizers (PSs) show reduced singlet oxygen (1 O2 ) production and quenched fluorescence upon aggregation in aqueous media, which greatly affect their efficiency in photodynamic therapy (PDT). Meanwhile, non-targeting PSs generally yield low efficiency in antibacterial performance due to their short lifetimes and small effective working radii. Herein, a water-dispersible membrane anchor (TBD-anchor) PS with aggregation-induced emission is designed and synthesized to generate 1 O2 on the bacterial membrane. TBD-anchor showed efficient antibacterial performance towards both Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). Over 99.8 % killing efficiency was obtained for methicillin-resistant S. aureus (MRSA) when they were exposed to 0.8 μm of TBD-anchor at a low white light dose (25 mW cm-2 ) for 10 minutes. TBD-anchor thus shows great promise as an effective antimicrobial agent to combat the menace of multidrug-resistant bacteria.

BackgroundThe prevalence of multimorbidity varies widely due to the lack of consensus in defining multimorbidity. This study aimed to measure the prevalence of multimorbidity in a primary care setting using two definitions of multimorbidity with two different lists of chronic conditions.MethodsWe conducted a cross-sectional study of 787,446 patients, aged 0 to 99 years, who consulted a family physician between July 2015 to June 2016. Multimorbidity was defined as ‘two or more’ (MM2+) or ‘three or more’ (MM3+) chronic conditions using the Fortin list and Chronic Disease Management Program (CDMP) list of chronic conditions. Crude and standardised prevalence rates were reported, and the corresponding age, sex or ethnic-stratified standardised prevalence rates were adjusted to the local population census.ResultsThe number of patients with multimorbidity increased with age. Age-sex-ethnicity standardised prevalence rates of multimorbidity using MM2+ and MM3+ for Fortin list (25.9, 17.2%) were higher than those for CDMP list (22.0%; 12.4%). Sex-stratified, age-ethnicity standardised prevalence rates for MM2+ and MM3+ were consistently higher in males compared to females for both lists. Chinese and Indians have the highest standardised prevalence rates among the four ethnicities using MM2+ and MM3+ respectively.ConclusionsMM3+ was better at identifying a smaller number of patients with multimorbidity requiring higher needs compared to MM2+. Using the Fortin list seemed more appropriate than the CDMP list because the chronic conditions in Fortin’s list were more commonly seen in primary care. A consistent definition of multimorbidity will help researchers and clinicians to understand the epidemiology of multimorbidity better.

We report the first demonstration using a stable π-radical as a versatile photosensitizer for hypoxia-overcoming photodynamic therapy. After self-assembling the radical molecules into radical nanoparticles (NPs), the NPs show good water dispersibility, good biocompatibility, broad near-infrared (NIR) absorption and emission at ∼800 nm. Significantly, the radical NPs remain stable in various biological mediums, after 100 days exposure to the ambient environment, and even after long-term laser irradiation, which is superior to many reported radical-based materials. More importantly, upon 635 nm laser irradiation, sufficient superoxide radical (O2−˙) generation and in vitro cytotoxicity were observed addressing the most important hurdle for successful PDT in the oxygen-deficient tumor microenvironment. In addition, the radical NPs are also demonstrated to have effective in vivo PDT efficacy, and excellent biosafety.

Background: Chronic conditions are a leading cause of death and disability worldwide and respective data on dietary patterns remain scant. The present study aimed to investigate dietary patterns and identify sociodemographic factors associated with Dietary Approach to Stop Hypertension (DASH) scores within a multi-ethnic population with various chronic conditions. Method: The present study utilised data from the Knowledge, Attitudes, and Practices on diabetes study in Singapore – a nationwide survey conducted to track the knowledge, attitudes, and practices pertaining to diabetes. The study analysed data collected from a sample of 2,895 Singapore residents, with information from the sociodemographic section, DASH diet screener, and the modified version of the World Mental Health Composite International Diagnostic Interview (CIDI) version 3.0 checklist of chronic medical conditions.Results: Respondents with no chronic condition had a mean DASH score of 18.5 (±4.6), those with one chronic condition had a mean DASH score of 19.2 (±4.8), and those with two or more chronic conditions had a mean DASH score of 19.8 (±5.2). Overall, the older age groups [35– 49 years (B = 1.78, 95% CI: 1.23 – 2.33, p p p p p Conclusion: Overall, respondents with two or more chronic conditions reported better quality of diet while the sociodemographic factors of age, gender and ethnicity demonstrated a consistent pattern in correlating with diet quality, consistent with the extant literature. Results provide further insights for policymakers to refine ongoing efforts in relation to healthy dietary practices for Singapore.

Funding Information: The World Health Organization World Mental Health (WMH) Survey Initiative is supported by the United States National Institute of Mental Health (NIMH; R01 MH070884), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the United States Public Health Service (R13-MH066849, R01-MH069864 and R01 DA016558), the Fogarty International Center (FIRCA R03-TW006481), the Pan American Health Organization, Eli Lilly and Company, Ortho-McNeil Pharmaceutical Inc., GlaxoSmithKline, and Bristol-Myers Squibb. We thank the staff of the WMH Data Collection and Data Analysis Coordination Centres for assistance with instrumentation, fieldwork and consultation on data analysis. None of the funders had any role in the design, analysis, interpretation of results or preparation of this paper. The views and opinions expressed in this report are those of the authors and should not be construed to represent the views of the World Health Organization, other sponsoring organisations, agencies or governments. The 2007 Australian National Survey of Mental Health and Wellbeing is funded by the Australian Government Department of Health and Ageing. The Argentina survey – Estudio Argentino de Epidemiología en Salud Mental (EASM) – was supported by a grant from the Argentinian Ministry of Health (Ministerio de Salud de la Nación) – (Grant Number 2002–17270/13−5). The São Paulo Megacity Mental Health Survey is supported by the State of São Paulo Research Foundation (FAPESP) Thematic Project Grant 03/00204-3. The Bulgarian Epidemiological Study of common mental disorders, EPIBUL, is supported by the Ministry of Health and the National Center for Public Health Protection. The Colombian National Study of Mental Health (NSMH) is supported by the Ministry of Social Protection. The Mental Health Study Medellín – Colombia was carried out and supported jointly by the Center for Excellence on Research in Mental Health (CES University) and the Secretary of Health of Medellín. The ESEMeD project is funded by the European Commission (Contracts QLG5-1999-01042; SANCO 2004123, and EAHC 20081308), the Piedmont Region (Italy), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnología, Spain (SAF 2000-158-CE), Generalitat de Catalunya (2017 SGR 452; 2014 SGR 748), Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS RD06/0011 REM-TAP), and other local agencies and by an unrestricted educational grant from GlaxoSmithKline. Implementation of the Iraq Mental Health Survey (IMHS) and data entry were carried out by the staff of the Iraqi MOH and MOP with direct support from the Iraqi IMHS team with funding from both the Japanese and European Funds through United Nations Development Group Iraq Trust Fund (UNDG ITF). The Israel National Health Survey is funded by the Ministry of Health with support from the Israel National Institute for Health Policy and Health Services Research and the National Insurance Institute of Israel. The World Mental Health Japan (WMHJ) Survey is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013, H25-SEISHIN-IPPAN-006) from the Japan Ministry of Health, Labour and Welfare. The Lebanese Evaluation of the Burden of Ailments and Needs of the Nation (L.E.B.A.N.O.N.) is supported by the Lebanese Ministry of Public Health, the WHO (Lebanon), National Institute of Health/Fogarty International Center (R03 TW006481-01), anonymous private donations to IDRAAC, Lebanon, and unrestricted grants from, Algorithm, AstraZeneca, Benta, Bella Pharma, Eli Lilly, Glaxo Smith Kline, Lundbeck, Novartis, OmniPharma, Pfizer, Phenicia, Servier, UPO. The Mexican National Comorbidity Survey (MNCS) is supported by The National Institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544- H), with supplemental support from the Pan American Health Organization (PAHO). Te Rau Hinengaro: The New Zealand Mental Health Survey (NZMHS) is supported by the New Zealand Ministry of Health, Alcohol Advisory Council and the Health Research Council. The Nigerian Survey of Mental Health and Wellbeing (NSMHW) is supported by the WHO (Geneva), the WHO (Nigeria) and the Federal Ministry of Health, Abuja, Nigeria. The Northern Ireland Study of Mental Health was funded by the Health & Social Care Research & Development Division of the Public Health Agency. The Peruvian World Mental Health Study was funded by the National Institute of Health of the Ministry of Health of Peru. The Polish project Epidemiology of Mental Health and Access to Care –EZOP Project (PL 0256) was carried out by the Institute of Psychiatry and Neurology in Warsaw in consortium with the Department of Psychiatry – Medical University in Wroclaw and National Institute of Public Health-National Institute of Hygiene in Warsaw and in partnership with Psykiatrist Institut Vinderen–Universitet, Oslo. The project was funded by the European Economic Area Financial Mechanism and the Norwegian Financial Mechanism. EZOP project was co-financed by the Polish Ministry of Health. The Portuguese Mental Health Study was carried out by the Department of Mental Health, Faculty of Medical Sciences, NOVA University of Lisbon, with the collaboration of the Portuguese Catholic University, and was funded by Champalimaud Foundation, Gulbenkian Foundation, Foundation for Science and Technology (FCT) and Ministry of Health. The Romania WMH study projects ‘Policies in Mental Health Area’ and ‘National Study regarding Mental Health and Services Use’ were carried out by the National School of Public Health & Health Services Management (former National Institute for Research & Development in Health), with technical support of Metro Media Transilvania, the National Institute of Statistics-National Centre for Training in Statistics, SC Cheyenne Services SRL, Statistics Netherlands and were funded by the Ministry of Public Health (former Ministry of Health) with supplemental support of Eli Lilly Romania SRL. The South Africa Stress and Health Study (SASH) is supported by the US National Institute of Mental Health (R01-MH059575) and the National Institute of Drug Abuse with supplemental funding from the South African Department of Health and the University of Michigan. The Shenzhen Mental Health Survey is supported by the Shenzhen Bureau of Health and the Shenzhen Bureau of Science, Technology, and Information. The Psychiatric Enquiry to General Population in Southeast Spain – Murcia (PEGASUS-Murcia) Project has been financed by the Regional Health Authorities of Murcia (Servicio Murciano de Salud and Consejería de Sanidad y Política Social) and Fundación para la Formación e Investigación Sanitarias (FFIS) of Murcia. The Ukraine Comorbid Mental Disorders during Periods of Social Disruption (CMDPSD) study is funded by the US National Institute of Mental Health (RO1-MH61905). The US National Comorbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the National Institute of Drug Abuse (NIDA), the Substance Abuse and Mental Health Services Administration (SAMHSA), the Robert Wood Johnson Foundation (RWJF; Grant 044708), and the John W. Alden Trust. Dr Dan J. Stein is supported by the Medical Research Council of South Africa (MRC). A complete list of all within-country and cross-national WMH publications can be found at http://www.hcp.med.harvard.edu/wmh/ . Publisher Copyright: Copyright © The Author(s), 2021. Published by Cambridge University Press. Abstract Aims Major depressive disorder (MDD) is characterised by a recurrent course and high comorbidity rates. A lifespan perspective may therefore provide important information regarding health outcomes. The aim of the present study is to examine mental disorders that preceded 12-month MDD diagnosis and the impact of these disorders on depression outcomes. Methods Data came from 29 cross-sectional community epidemiological surveys of adults in 27 countries (n = 80 190). The Composite International Diagnostic Interview (CIDI) was used to assess 12-month MDD and lifetime DSM-IV disorders with onset prior to the respondent's age at interview. Disorders were grouped into depressive distress disorders, non-depressive distress disorders, fear disorders and externalising disorders. Depression outcomes included 12-month suicidality, days out of role and impairment in role functioning. Results Among respondents with 12-month MDD, 94.9% (s.e. = 0.4) had at least one prior disorder (including previous MDD), and 64.6% (s.e. = 0.9) had at least one prior, non-MDD disorder. Previous non-depressive distress, fear and externalising disorders, but not depressive distress disorders, predicted higher impairment (OR = 1.4-1.6) and suicidality (OR = 1.5-2.5), after adjustment for sociodemographic variables. Further adjustment for MDD characteristics weakened, but did not eliminate, these associations. Associations were largely driven by current comorbidities, but both remitted and current externalising disorders predicted suicidality among respondents with 12-month MDD. Conclusions These results illustrate the importance of careful psychiatric history taking regarding current anxiety disorders and lifetime externalising disorders in individuals with MDD. publishersversion published

ObjectiveThe study aimed to examine the prevalence and sociodemographic correlates of physical activity and sedentary behaviour in the general population of the multi-ethnic nation of Singapore as part of the Knowledge, Practice and Attitudes towards Diabetes study, a cross-sectional and population-based survey. It also examined the relationship between physical activity, sedentary behaviour, and health-related quality of life (HRQoL).MethodsPhysical activity and sedentary behaviour were assessed via the Global Physical Activity Questionnaire (GPAQ), while physical and mental HRQoL was assessed via the Short Form Health Survey (SF-12v2). Survey weights were employed to account for complex survey design. Multivariable logistic regression models were utilized to examine sociodemographic correlates of physical activity (insufficient vs. sufficient physical activity) and sedentary behaviour (ResultsTwo thousand eight hundred sixty seven participants recruited from February 2019 to March 2020 (prior to COVID-19 lockdown and related restrictions in Singapore) were included in the analyses. 83.3% of respondents had sufficient physical activity. Age (65 years and above) and income (SGD 2000 to 3999) were associated with a higher likelihood of insufficient physical activity. In contrast, those of Malay ethnicity and having one chronic physical condition were associated with a lower likelihood of insufficient physical activity. 47.7% reported that they had sedentary behaviour of ≥7 h/day. Older age and a primary school education were related to a lower likelihood of sedentary behaviour, while being single, having higher income, obesity, and multimorbidity were associated with higher sedentary behaviour. Insufficient physical activity was significantly associated with lower physical HRQoL but was not significantly associated with mental HRQoL. Sedentary behaviour was not significantly associated with mental or physical HRQoL.ConclusionAbout 17% of the population did not meet the minimum requirements for physical activity, while around half of the population spent a considerable time being sedentary. As insufficient physical activity was associated with poorer physical HRQoL, policymakers should promote moderate physical activity and encouraging the breaking up of prolonged sedentary periods within the middle- and high-income groups, especially at the workplace. Increased leisure-time exercise should be encouraged for those in the lower- income group.

Early diagnosis and effective treatment of hepatocellular carcinoma (HCC) is quite critical for improving patients’ prognosis. The combination of second near-infrared window photoacoustic imaging (NIR-II PAI) and T2-magnetic resonance imaging (T2-MRI) is promising for achieving omnibearing information on HCC diagnosis due to the complementary advantages of outstanding optical contrast, high temporospatial resolution and soft-tissue resolution. Thus, the rational design of a multifunctional targeted nanoplatform with outstanding performance in dual-modal NIR-II PAI/T2-MRI is particularly valuable for precise diagnosis and imaging-guided non-invasive photothermal therapy (PTT) of early-stage HCC. Herein, a versatile targeted organic–inorganic hybrid nanoprobe was synthesized as a HCC-specific contrast agent for sensitive and efficient theranostics. The developed multifunctional targeted nanoprobe yielded superior HCC specificity, reliable stability and biocompatibility, high imaging contrast in both NIR-II PAI and T2-MRI, and an excellent photothermal conversion efficiency (74.6%). Furthermore, the theranostic efficiency of the targeted nanoprobe was systematically investigated using the orthotopic early HCC-bearing mice model. The NIR-II PAI exhibited sensitive detection of ultra-small HCCs (diameter less than 1.8 mm) and long-term real-time monitoring of the tumor and nanoprobe targeting process in deep tissues. The T2-MRI demonstrated clear imaging contrast and a spatial relationship between micro-HCC and adjacent structures for a comprehensive description of the tumor. Moreover, when using the targeted nanoprobe, the non-invasively targeted PTT of orthotopic early HCC was carried out under reliable dual-modal imaging guidance with remarkable anti-tumor efficiency and biosafety. This study provides an insight for constructing a multifunctional targeted nanoplatform for precise and comprehensive theranostics of early-stage HCC, which would greatly benefit the patients in the era of precision medicine.

Introduction Singapore is facing an ageing population and the care needs of the population will increase in tandem. A segment of this population would be living with multimorbidity and frailty. Frailty is defined as an age-related state characterised by reduced strength and physiologic malfunctioning. Multimorbidity refers to the coexistence of multiple chronic conditions in an individual. Older adults are more likely to have frailty and multimorbidity, and this would increase the burden of their caregiver. Our study aimed to determine the prevalence of caregiver burden for primary family caregivers of frail older adults with multimorbidity. We also investigated the factors that were associated with primary family caregiver burden. Methods This was an interviewer-administered, cross-sectional study of primary family caregivers of frail older patients with multimorbidity that was conducted in two National Healthcare Group polyclinics. Convenience sampling was used. The 12-item Zarit Burden Index (ZBI) was used to assess primary family caregiver burden. The scores of the ZBI range from 0 to 48, with a score of 10 or above indicating that the primary family caregiver perceives burden. Descriptive statistics were used to provide information regarding the caregivers and the care recipients. Multivariable logistic regression was used to investigate the factors affecting primary family caregiver burden. Results One hundred eighty-eight family caregivers were interviewed and 71.8% of them perceived burden on the ZBI. 59.6% were caregivers to their parents and 18.1% of them had multimorbidity. Almost two-thirds of the caregivers interviewed were female. After adjusting for other factors via multivariable analysis, the ethnicity of the caregiver and the increase in time spent caregiving per week were the two factors positively associated with family caregiver burden. A Chinese primary family caregiver had almost three times the odds of perceiving burden when compared to a non-Chinese primary family caregiver. Conclusion Caregiver burden was high amongst primary family caregivers of frail older adults with multimorbidity. Being a Chinese primary family caregiver compared to non-Chinese ethnic groups as well as being a primary family caregiver who spent increased time caregiving per week were the two factors positively associated with family caregiver burden. Further exploratory, qualitative studies can be done to find out the reasons to Chinese primary family caregivers being more burdened compared to the non-Chinese primary family caregivers. In addition, the specific factors related to increased time caregiving per week and family caregiver burden can also be studied.

Background—One year has passed since the first COVID-19 case in Singapore. This scoping review commemorates Singaporean researchers that have expanded the knowledge on this novel virus. We aim to provide an overview of healthcare-related articles published in peer-reviewed journals, authored by the Singapore research community about COVID-19 during the first year of the pandemic. Methods—This was reported using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) protocol. It included healthcare-related articles about COVID-19 published between 23 January 2020 and 22 January 2021 with a Singapore-affiliated author. MEDLINE, Embase, Scopus, Web of Science, CINAHL, PsycINFO, Google Scholar, and local journals were searched. The articles were screened independently by two reviewers. Results—The review included 504 articles. Most of the articles narrated the changes to hospital practice (210), while articles on COVID-19 pathology (94) formed most of the non-narrative papers. Publications on public health (61) and the indirect impacts to clinical outcomes (45) were other major themes explored by the research community. The remaining articles detailed the psychological impact of the pandemic (35), adaptations of medical education (30), and narratives of events (14). Conclusion—Amidst a resurgence of community cases involving variant COVID-19 strains, the resources from the research community will provide valuable guidance to navigate these uncertain times.

AIM: We examined prevalence and factors associated with receiving perceived helpful alcohol use disorder (AUD) treatment, and persistence in help-seeking after earlier unhelpful treatment.METHODS: Data came from 27 community epidemiologic surveys of adults in 24 countries using the World Health Organization World Mental Health surveys (n = 93,843). Participants with a lifetime history of treated AUD were asked if they ever received helpful AUD treatment, and how many professionals they had talked to up to and including the first time they received helpful treatment (or how many ever, if they had not received helpful treatment).RESULTS: 11.8% of respondents with lifetime AUD reported ever obtaining treatment (n = 9378); of these, 44% reported that treatment was helpful. The probability of obtaining helpful treatment from the first professional seen was 21.8%; the conditional probability of subsequent professionals being helpful after earlier unhelpful treatment tended to decrease as more professionals were seen. The cumulative probability of receiving helpful treatment at least once increased from 21.8% after the first professional to 79.7% after the seventh professional seen, following earlier unhelpful treatment. However, the cumulative probability of persisting with up to seven professionals in the face of prior treatments being unhelpful was only 13.2%.CONCLUSION: Fewer than half of people with AUDs who sought treatment found treatment helpful; the most important factor was persistence in seeking further treatment if a previous professional had not helped. Future research should examine how to increase the likelihood that AUD treatment is found to be helpful on any given contact.

ObjectivesThere are multiple instruments for measuring multimorbidity. The main objective of this systematic review was to provide a list of instruments that are suitable for use in studies aiming to measure the association of a specific outcome with different levels of multimorbidity as the main independent variable in community-dwelling individuals. The secondary objective was to provide details of the requirements, strengths and limitations of these instruments, and the chosen outcomes.MethodsWe conducted the review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO registration number: CRD42018105297). We searched MEDLINE, Embase and CINAHL electronic databases published in English and manually searched the Journal of Comorbidity between 1 January 2010 and 23 October 2020 inclusive. Studies also had to select adult patients from primary care or general population and had at least one specified outcome variable. Two authors screened the titles, abstracts and full texts independently. Disagreements were resolved with a third author. The modified Newcastle-Ottawa Scale was used for quality assessment.ResultsNinety-six studies were identified, with 69 of them rated to have a low risk of bias. In total, 33 unique instruments were described. Disease Count and weighted indices like Charlson Comorbidity Index were commonly used. Other approaches included pharmaceutical-based instruments. Disease Count was the common instrument used for measuring all three essential core outcomes of multimorbidity research: mortality, mental health and quality of life. There was a rise in the development of novel weighted indices by using prognostic models. The data obtained for measuring multimorbidity were from sources including medical records, patient self-reports and large administrative databases.ConclusionsWe listed the details of 33 instruments for measuring the level of multimorbidity as a resource for investigators interested in the measurement of multimorbidity for its association with or prediction of a specific outcome.

A bromine-substituted thermally activated delayed fluorescent (TADF) molecule AQCzBr2 is designed with both small singlet-triplet splitting (ΔEST) and increased spin-orbit coupling (SOC) to boost intersystem crossing (ISC) for singlet oxygen generation. AQCzBr2 nanoparticles (NPs) demonstrate high productivity of singlet oxygen generation (ΦΔ = 0.91) which allows highly efficient photodynamic therapy toward cancer cells.

Hydrophobic photosensitizers greatly affect cell permeability and enrichment in tumors, but they cannot be used directly for clinical applications because they always aggregate in water, preventing their circulation in the blood and accumulation in tumor cells. As a result, amphiphilic photosensitizers are highly desirable. Although nanomaterial-based photosensitizers can solve water solubility, they have the disadvantages of complicated operation, poor reproducibility, low drug loading, and poor stability. In this work, an efficient synthesis strategy is proposed that converts small molecules into nanoparticles in 100 % aqueous solution by molecular assembly without the addition of any foreign species. Three photosensitizers with triphenylphosphine units and ethylene glycol chains of different lengths, TPP-PPh3 , TPP-PPh3 -2PEG and TPP-PPh3 -4PEG, were synthesized to improve amphiphilicity. Of the three photosensitizers, TPP-PPh3 -4PEG is the most efficient (singlet oxygen yield: 0.89) for tumor photodynamic therapy not only because of its definite constituent, but also because its amphiphilic structure allows it to self-assemble in water.

Background Mental health symptoms can be subtle, resulting in delaying treatment. A prompt identification of mental signs and symptoms is important for preventing mental disorders in the public. This study examined whether local public have adequate knowledge to identify mental health symptoms and the need to get timely professional help. Methods The population-based telephone surveys were conducted in 2015 and 2018. It involved a random sample of 4033 respondents aged 12–75 years. Mental health knowledge and help seeking attitude were assessed using six vignettes depicting subtle and obvious symptoms of anxiety disorders, mixed anxiety and depressive disorders, and dementia. Logistic regression models were performed to examine association between mental health knowledge and help-seeking attitude. Results Individuals with poor knowledge in subtle symptoms were more likely to be males (t = − 5.0, p Conclusions Poorly identified subtle mental health symptoms is a major barrier to early professional help in highly educated working males. Future research should explore specific interventions to increase knowledge and professional help seeking in this group.

BACKGROUND: Illicit drug use and associated disease burden are estimated to have increased over the past few decades, but large gaps remain in our knowledge of the extent of use of these drugs, and especially the extent of problem or dependent use, hampering confident cross-national comparisons. The World Mental Health (WMH) Surveys Initiative involves a standardised method for assessing mental and substance use disorders via structured diagnostic interviews in representative community samples of adults. We conducted cross-national comparisons of the prevalence and correlates of drug use disorders (DUDs) in countries of varied economic, social and cultural nature.METHODS AND FINDINGS: DSM-IV DUDs were assessed in 27 WMH surveys in 25 countries. Across surveys, the prevalence of lifetime DUD was 3.5%, 0.7% in the past year. Lifetime DUD prevalence increased with country income: 0.9% in low/lower-middle income countries, 2.5% in upper-middle income countries, 4.8% in high-income countries. Significant differences in 12-month prevalence of DUDs were found across country in income groups in the entire cohort, but not when limited to users. DUDs were more common among men than women and younger than older respondents. Among those with a DUD and at least one other mental disorder, onset of the DUD was usually preceded by the 'other' mental disorder.CONCLUSIONS: Substantial cross-national differences in DUD prevalence were found, reflecting myriad social, environmental, legal and other influences. Nonetheless, patterns of course and correlates of DUDs were strikingly consistent. These findings provide foundational data on country-level comparisons of DUDs.

Importance: Limited empirical research has examined the extent to which cohort-level prevalence of substance use is associated with the onset of drug use and transitioning into greater involvement with drug use. Objective: To use cross-national data to examine time-space variation in cohort-level drug use to assess its associations with onset and transitions across stages of drug use, abuse, dependence, and remission. Design, setting, and participants: The World Health Organization World Mental Health Surveys carried out cross-sectional general population surveys in 25 countries using a consistent research protocol and assessment instrument. Adults from representative household samples were interviewed face-to-face in the community in relation to drug use disorders. The surveys were conducted between 2001 and 2015. Data analysis was performed from July 2017 to July 2018. Main outcomes and measures: Data on timing of onset of lifetime drug use, DSM-IV drug use disorders, and remission from these disorders was assessed using the Composite International Diagnostic Interview. Associations of cohort-level alcohol prevalence and drug use prevalence were examined as factors associated with these transitions. Results: Among the 90 027 respondents (48.1% [SE, 0.2%] men; mean [SE] age, 42.1 [0.1] years), 1 in 4 (24.8% [SE, 0.2%]) reported either illicit drug use or extramedical use of prescription drugs at some point in their lifetime, but with substantial time-space variation in this prevalence. Among users, 9.1% (SE, 0.2%) met lifetime criteria for abuse, and 5.0% (SE, 0.2%) met criteria for dependence. Individuals who used 2 or more drugs had an increased risk of both abuse (odds ratio, 5.17 [95% CI, 4.66-5.73]; P < .001) and dependence (odds ratio, 5.99 [95% CI, 5.02-7.16]; P < .001) and reduced probability of remission from abuse (odds ratio, 0.86 [95% CI, 0.76-0.98]; P = .02). Birth cohort prevalence of drug use was also significantly associated with both initiation and illicit drug use transitions; for example, after controlling for individuals' experience of substance use and demographics, for each additional 10% of an individual's cohort using alcohol, a person's odds of initiating drug use increased by 28% (odds ratio, 1.28 [95% CI, 1.26-1.31]). Each 10% increase in a cohort's use of drug increased individual risk by 12% (1.12 [95% CI, 1.11-1.14]). Conclusions and relevance: Birth cohort substance use is associated with drug use involvement beyond the outcomes of individual histories of alcohol and other drug use. This has important implications for understanding pathways into and out of problematic drug use. The World Health Organization World Mental Health (WMH) Survey Initiative is supported by the United States National Institute of Mental Health (NIMH; R01 MH070884), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the United States Public Health Service (R13-MH066849, R01-MH069864, and R01 DA016558), the Fogarty International Center (FIRCA R03-TW006481), the Pan American Health Organization, Eli Lilly and Company, Ortho-McNeil Pharmaceutical Inc., GlaxoSmithKline, and Bristol-Myers Squibb. This work was supported by an Australian National Health and Medical Research Council (NHMRC) project grant (no. 1081984). Dr Degenhardt is supported by a NHMRC Senior Principal Research Fellowship (no. 1135991) and NIDA NIH grant R01 DA044170–02. We thank the staff of the WMH Data Collection and Data Analysis Coordination Centres for assistance with instrumentation, fieldwork, and consultation on data analysis. None of the funders had any role in the design, analysis, interpretation of results, or preparation of this paper. The views and opinions expressed in this report are those of the authors and should not be construed to represent the views of the World Health Organization, other sponsoring organizations, agencies, or governments. The 2007 Australian National Survey of Mental Health and Wellbeing is funded by the Australian Government Department of Health and Ageing. The Argentina survey -- Estudio Argentino de Epidemiología en Salud Mental (EASM) -- was supported by a grant from the Argentinian Ministry of Health (Ministerio de Salud de la Nación). The São Paulo Megacity Mental Health Survey is supported by the State of São Paulo Research Foundation (FAPESP) Thematic Project Grant 03/00204–3. The Bulgarian Epidemiological Study of common mental disorders EPIBUL is supported by the Ministry of Health and the National Center for Public Health Protection. The Chinese World Mental Health Survey Initiative is supported by the Pfizer Foundation. The Colombian National Study of Mental Health (NSMH) is supported by the Ministry of Social Protection. The Mental Health Study Medellín – Colombia was carried out and supported jointly by the Center for Excellence on Research in Mental Health (CES University) and the Secretary of Health of Medellín. The ESEMeD project is funded by the European Commission (Contracts QLG5–1999-01042; SANCO 2004123, and EAHC 20081308), (the Piedmont Region (Italy)), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnología, Spain (SAF 2000–158-CE), Departament de Salut, Generalitat de Catalunya, Spain, DIUE de la Generalitat de Catalunya (2017 SGR 452; 2014 SGR 748), Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS Degenhardt et al. Page 12 JAMA Psychiatry. Author manuscript; available in PMC 2019 August 05. Author Manuscript Author Manuscript Author Manuscript Author Manuscript RD06/0011 REM-TAP), and other local agencies and by an unrestricted educational grant from GlaxoSmithKline. Implementation of the Iraq Mental Health Survey (IMHS) and data entry were carried out by the staff of the Iraqi MOH and MOP with direct support from the Iraqi IMHS team with funding from both the Japanese and European Funds through United Nations Development Group Iraq Trust Fund (UNDG ITF). The Israel National Health Health Services Research and the National Insurance Institute of Israel. The World Mental Health Japan (WMHJ) Survey is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13- SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013, H25-SEISHIN-IPPAN-006) from the Japan Ministry of Health, Labour and Welfare. The Lebanese Evaluation of the Burden of Ailments and Needs Of the Nation (L.E.B.A.N.O.N.) is supported by the Lebanese Ministry of Public Health, the WHO (Lebanon), National Institute of Health / Fogarty International Center (R03 TW006481–01), anonymous private donations to IDRAAC, Lebanon, and unrestricted grants from, Algorithm, AstraZeneca, Benta, Bella Pharma, Eli Lilly, Glaxo Smith Kline, Lundbeck, Novartis, OmniPharma, Pfizer, Phenicia, Servier, UPO. The Mexican National Comorbidity Survey (MNCS) is supported by The National Institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544- H), with supplemental support from the Pan American Health Organization (PAHO). Te Rau Hinengaro: The New Zealand Mental Health Survey (NZMHS) is supported by the New Zealand Ministry of Health, Alcohol Advisory Council, and the Health Research Council. The Nigerian Survey of Mental Health and Wellbeing (NSMHW) is supported by the WHO (Geneva), the WHO (Nigeria), and the Federal Ministry of Health, Abuja, Nigeria. The Northern Ireland Study of Mental Health was funded by the Health & Social Care Research & Development Division of the Public Health Agency. The Peruvian World Mental Health Study was funded by the National Institute of Health of the Ministry of Health of Peru. The Polish project Epidemiology of Mental Health and Access to Care –EZOP Project (PL 0256) was supported by Iceland, Liechtenstein and Norway through funding from the EEA Financial Mechanism and the Norwegian Financial Mechanism. EZOP project was co-financed by the Polish Ministry of Health. The South Africa Stress and Health Study (SASH) is supported by the US National Institute of Mental Health (R01-MH059575) and National Institute of Drug Abuse with supplemental funding from the South African Department of Health and the University of Michigan. The Psychiatric Enquiry to General Population in Southeast Spain – Murcia (PEGASUSMurcia) Project has been financed by the Regional Health Authorities of Murcia (Servicio Murciano de Salud and Consejería de Sanidad y Política Social) and Fundación para la Formación e Investigación Sanitarias (FFIS) of Murcia. The Ukraine Comorbid Mental Disorders during Periods of Social Disruption (CMDPSD) study is funded by the US National Institute of Mental Health (RO1-MH61905). The US National Comorbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the National Institute of Drug Abuse (NIDA), the Substance Abuse and Mental Health Services Administration (SAMHSA), the Robert Wood Johnson Foundation (RWJF; Grant 044708), and the John W. Alden Trust. Dr Andrade is supported by the Brazilian Council for Scientific and Technological Development (CNPq Grant # 307784/2016–9). Dr Stein is supported by the Medical Research Council of South Africa (MRC). In the past three years, Dr Degenhardt has received investigator-initiated untied educational grants for studies of opioid medications in Australia from Indivior, Mundipharma and Seqirus. Dr Kessler received support for his epidemiological studies from Sanofi Aventis; was a consultant for Johnson & Johnson Wellness and Prevention, Sage Pharmaceuticals, Shire, Takeda; served on an advisory board for the Johnson & Johnson Services Inc. Lake Nona Life Project; and being a co-owner of DataStat, Inc., a market research firm that carries out healthcare research. Dr Demyttenaere has served on advisory boards for Boehringer Ingelheim, Eli Lilly, Lundbeck, Johnson&Johnson, Livanova, Servier, and has research grants from Eli Lilly, foundation ‘ga voor geluk’, Fonds voor Wetenschappelijk Onderzoek Vlaanderen. Dr Stein has received research grants and/or consultancy honoraria from AMBRF, Biocodex, Cipla, Lundbeck, National Responsible Gambling Foundation, Novartis, Servier, and Sun. The views expressed in this report are those of the authors and should not be construed to represent the views or policies of the WHO, other sponsoring organisations, agencies, or governments, and do not necessarily represent the views, official policy, or position of the US. Department of Health and Human Services or any of its affiliated institutions or agencies. Dr Glantz’s role on this study is through his involvement as a Science Officer on U01- MH60220. He had no involvement in the other cited grants.

OBJECTIVE To examine the prevalence and comorbidity of gastro-oesophageal reflux disease (GORD) with generalised anxiety disorder (GAD) and major depressive episodes (MDE) in a general population using DSM-IV, and to evaluate the associations between these conditions and healthcare utilisation. METHODS A random population-based telephone survey was conducted to record frequency of GORD symptoms, symptoms of GAD and MDE based on DSM-IV, and healthcare utilisation. RESULTS Of 2011 respondents, 4.2% had weekly GORD and 13.9% had monthly GORD, whereas 3.8% reported GAD and 12.4% reported MDE. Those with monthly GORD had higher risk of GAD (p = 0.01) and MDE (p < 0.001). GORD symptom frequency was independently correlated with MDE and GAD in a dose-response manner. The number of psychiatric diagnoses was independently correlated with GORD. GORD symptom frequency, GAD, and MDE were correlated with consultation frequency. GORD symptom frequency was corelated with high investigation expenditure. CONCLUSION GORD had a strong dose-response relationship with GAD and MDE in a Hong Kong population. Excessive healthcare utilisation should alert clinicians to the risk of psychiatric comorbidity.

Background and aim Comorbid generalized anxiety disorder and irritable bowel syndrome are common and therapeutically challenging. We aimed to assess the effectiveness of electroacupuncture in relieving anxiety and bowel symptoms in Chinese adults with this form of comorbidity. Methods In a single-blind randomized sham-controlled trial, subjects with comorbid generalized anxiety disorder and irritable bowel syndrome were randomly assigned to receive 10 weekly sessions of electroacupuncture or sham electroacupuncture. Patients were assessed at baseline, immediately after intervention and at 6-week follow-up. Primary outcome was anxiety (7-item Patient Health Questionnaire section for anxiety). Secondary outcomes included bowel symptoms (bowel symptoms questionnaire), depressive symptoms (9-item Patient Health Questionnaire), somatic symptoms (15-item Patient Health Questionnaire), and health-related quality of life (EuroQol-5 Dimensions). Results Eighty subjects, 40 in each arm, were randomized. All but two in the sham group completed 10 weekly sessions. There was no significant difference in the proportion of patients experiencing significant (≥ 50%) reduction of anxiety symptoms between the two groups immediately after intervention (32.4% vs 21.6%, P = 0.06) and at 6-week follow-up (25.7% in electroacupuncture vs 27% in sham, P = 0.65). Anxiety, depressive symptom, and bowel symptom severity did not differ significantly between electroacupuncture and sham groups. Conclusions Findings failed to support the effectiveness of electroacupuncture for comorbid generalized anxiety disorder and irritable bowel syndrome. Further studies are needed to identify effective acupuncture treatment protocols for such comorbidity.

Nanomaterial-mediated phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is an effective anticancer intervention that relies on light activation of photoactive nanomaterials localized in tumors. Recently, combinational PDT/PTT offered a practical pathway to relieve resistance of monotherapy, surmount undesirable side effects and provide a synergistic effect to enhance phototherapeutic efficiency. Herein, we report a facile strategy to integrate protoporphyrin IX (PpIX) into nanoscale metal-organic frameworks (NMOFs) and control their photoactive properties for combinational cancer PDT and PTT. With optimized PpIX conjugation, the as-fabricated nanoparticles (nPCU NPs) exhibit (1) improved dispersibility and particle stability, (2) simultaneous generation of reactive oxygen species and heat effectively through activation by a single-wavelength laser of 635 nm, and (3) maintenance of porosity for further application as drug delivery vehicles. Moreover, in vitro investigation of nPCU NPs demonstrates effective cellular uptake, successful endosomal escape and enhanced phototherapeutic efficacy under both normoxic and hypoxic conditions. Therefore, this study developed a novel type of phototherapeutic nanoplatform with optimal properties for applicable cancer phototherapy.

Background Stroke is one of the top contributors to burden of disability-adjusted life-years worldwide. Family physicians have key role in optimising secondary prevention following stroke by managing clinical risk factors and promoting overall control in accordance with clinical practice guidelines. Methods Our objectives were: (i) to examine level of overall risk factor control together with control of singular risk factors one-year after an index-stroke event in individuals attending primary care facility and (ii) to describe factors associated with satisfactory risk factors control in individuals following stroke. Study Design: Retrospective cohort study. We conducted a study looking retrospectively at records from our electronic chronic disease database. Our study included individuals following stroke who visited primary care setting in Singapore between January 2012 to December 2016. Results There were 24,240 individuals in our study. Overall control was better in individuals without diabetes following stroke (49.2%) as compared to those with diabetes (28.1%). Among individuals without diabetes following stroke, factors significantly associated with overall control were sex (male) [OR (reference: female): 1.23, 95% CI: 1.10, 1.39], ethnicity (Malay) [OR (reference: Chinese): 0.72, 95% CI: 0.58, 0.90], BMI (high risk) [OR (reference: low risk): 0.72, 95% CI: 0.62, 0.84) and atrial fibrillation [OR: 1.47, 95% CI: 1.21, 1.78]. Among individuals with diabetes following stroke, factors significantly associated with overall control were sex (male) [OR (reference: female): 1.28, 95% CI: 1.12, 1.46], ethnicity (Malay) [OR (reference: Chinese): 0.81, 95% CI: 0.65, 0.99], ethnicity (Indian) [OR (reference: Chinese): 0.70, 95% CI: 0.55, 0.88], BMI (high risk) [OR (reference: low risk): 0.71, 95% CI: 0.59, 0.84), BMI (moderate risk) [OR (reference: low risk): 0.84, 95% CI: 0.72, 0.98), atrial fibrillation [OR: 1.24; 95% CI: 1.02, 1.51], chronic kidney disease [OR: 0.63, 95% CI: 0.54, 0.72] and smoking status [OR: 0.68, 95% CI: 0.54, 0.88]. Conclusion We reported sub-optimal level of overall control. Among individuals following stroke, those with diabetes had higher proportion of sub-optimal control as compared to those without diabetes. Irrespective of diabetic status, being female, having high BMI, and of Malay ethnicity as compared to Chinese ethnicity were associated with poorer overall risk factor control.

Background: The study examined the association between sedentary behavior and self-rated health-related quality of life (HRQoL) in a sample of patients with multimorbidity in Singapore recruited from a primary care clinic. Methods: Sedentary behavior and physical activity were assessed with the International Physical Activity Questionnaire short form (IPAQ-SF). HRQoL was assessed with EuroQol-5 Dimension (EQ-5D) utility index, visual analogue scale (EQ-VAS) and its 5 subscales (Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression). Depression was assessed via Patient Health Questionnaire (PHQ-9). Logistic and linear regression analyses adjusting for the effect of physical activity, depression, and sociodemographic variables (i.e., age, gender, ethnicity, education) were conducted. Results: 932 patients participated in the study (mean age:64.5±8.5 years, range: 35-80) and 55% were men. Results indicated that women were less likely to have sedentary behavior (≥7 hrs/day) than men. Results indicated sedentary behavior was associated with lower EQ-5D index scores, but not EQ-VAS scores. Participants who were sedentary for ≥7 hrs/day were more likely to endorse having problems with mobility, self-care, and usual activities, but not with pain/discomfort, nor anxiety/depression. Conclusion: Sedentary behavior was associated with poorer HRQoL. There is a need for interventions and health promotions to reduce sedentary behavior in patients with multimorbidity.

Photodynamic therapy (PDT) is extensively explored for anticancer and antibacterial applications. It typically relies on oxygen-dependent generation of reactive oxygen species (ROS) to realize its killing effect. This type of therapy modality shows compromised therapeutic results for treating hypoxic tumors or bacteria-infected wounds. Recently, alkyl radicals attracted much attention as they can be generated from some azo-based initiators only under mild heat stimulus without oxygen participation. Many nanocarriers or hydrogel systems have been developed to load and deliver these radical initiators to lesion sites for theranostics. These systems show good anticancer or antimicrobial effect in hypoxic environment and some of them possess specific imaging abilities providing precise guidance for treatment. This review summarizes the developed materials that aim at treating hypoxic cancer and bacteria-infected wound by using this kind of oxygen-irrelevant alkyl radicals. Based on the carrier components, these agents are divided into three groups: inorganic, organic, as well as inorganic and organic hybrid carrier-based therapeutic systems. The construction of these agents and their specific advantages in biomedical field are highlighted. Finally, the existing problems and future promising development directions are discussed.

SARM1 regulates axonal degeneration through its NAD-metabolizing activity and is a drug target for neurodegenerative disorders. We designed and synthesized fluorescent conjugates of styryl derivative with pyridine to serve as substrates of SARM1, which exhibited large red-shifts after conversion. With the conjugates, SARM1 activation was visualized in live cells following elevation of endogenous NMN or treatment with a cell-permeant NMN-analog. In neurons, imaging documented SARM1 activation preceded vincristine-induced axonal degeneration by hours. Library screening identified a derivative of nisoldipine as a covalent inhibitor of SARM1 that reacted with Cys311 in its Armadillo-domain and blocked its NMN-activation, protecting axons from degeneration. CryoEM showed that SARM1 was locked into an inactive conformation by the inhibitor, uncovering an unsuspected neuroprotective mechanism of dihydropyridines.

BackgroundThe prevalence of diabetes is on the rise in developed countries. Yet discrepancies exist in reports regarding the level of knowledge of diabetes. This study evaluates the recognition of diabetes among residents in the Singapore population. Sociodemographic characteristics associated with the ability to correctly recognise diabetes were also examined.MethodsThis was a nationwide cross-sectional vignette-based study. Data were collected from 2895 residents aged 18 years and above through face-to-face interviews, of which 436 are persons with diabetes. Descriptive statistics, chi-square tests, and binary logistic regression were used in the analyses.ResultsIn total, 82.7% (2418/2895) of respondents recognised diabetes correctly. In adjusted models, correct recognition was significantly higher among respondents aged 35-49 years (OR, 1.85; 95% CI, 1.15 to 2.98; P= 0.01), 50-64 years (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.19 to 3.56; P= 0.01), ethnic Malays (OR, 1.39; 95% CI, 1.02 to 1.89; P= 0.04) (vs. Chinese) and persons with diagnosed diabetes (OR, 2.64; 95% CI, 1.38 to 5.08; P < 0.01). Being male (OR, 0.64; 95% CI, 0.46 to 0.90; P < 0.01), ethnic Others (OR, 0.59; 95% CI, 0.37 to 0.93; P < 0.01), and being unemployed (OR, 0.48; 95% CI, 0.25 to 0.92; P= 0.03), were significantly associated with poor recognition of diabetes.ConclusionOverall public recognition of diabetes is high, but the significant gaps in knowledge in certain demographic groups are of concern. Public health interventions aimed at preventing and controlling diabetes should continue to target all members of the population with accurate and appropriate information. Ongoing efforts of diabetes awareness and educational programs need to be improved, particularly for young adults, males, and the unemployed.

Background: Multimorbidity presents a key challenge to healthcare systems globally. However, heterogeneity in the definition of multimorbidity and design of epidemiological studies results in difficulty in comparing multimorbidity studies. This scoping review aimed to describe multimorbidity prevalence in studies using large datasets and report the differences in multimorbidity definition and study design. Methods: We conducted a systematic search of MEDLINE, EMBASE, and CINAHL databases to identify large epidemiological studies on multimorbidity. We used the Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews (PRISMA-ScR) protocol for reporting the results. Results: Twenty articles were identified. We found two key definitions of multimorbidity: at least two (MM2+) or at least three (MM3+) chronic conditions. The prevalence of multimorbidity MM2+ ranged from 15.3% to 93.1%, and 11.8% to 89.7% in MM3+. The number of chronic conditions used by the articles ranged from 15 to 147, which were organized into 21 body system categories. There were seventeen cross-sectional studies and three retrospective cohort studies, and four diagnosis coding systems were used. Conclusions: We found a wide range in reported prevalence, definition, and conduct of multimorbidity studies. Obtaining consensus in these areas will facilitate better understanding of the magnitude and epidemiology of multimorbidity.

Photodynamic therapy (PDT) synergized photothermal therapy (PTT) shows superior clinical application prospects than single PDT or PTT. On the other hand, multimodal imaging can delineate comprehensive information about the lesion site and thus help to improve therapy accuracy. However, integrating all these functions into one single molecule is challenging, let alone balancing and maximizing the efficacy of each function. Herein, a near-infrared (NIR) small molecule (ETTC) with an "acceptor-donor-acceptor" structure was designed and synthesized by coupling rigity and flexibility to simultaneously achieve NIR-II fluorescence imaging (NIR-II FLI), photoacoustic imaging, PTT and PDT. The efficacy of each functionality was well balanced and optimized (NIR-II quantum yield: 3.0%; reactive oxygen species generation: 3.2-fold higher than ICG; photothermal conversion efficiency: 52.8%), which may be attributed to the coupling of the rigid and flexible structures in ETTC to tactically manipulate the energy dissipation paths (non-radiative against radiative decay). As a proof-of-concept, under the effective guidance of local-tumor imaging by PA and whole-body imaging by NIR-II FL, complete tumor eradication was achieved via PDT and PTT combinational therapy. This work provides a novel perspective into conceiving and developing single molecule for efficient versatile biomedical applications.

ObjectiveTo measure the psychological well-being of healthcare workers (HCWs) during this COVID-19 pandemic and examine the experiences of the subgroup of participants who were also HCWs during the 2003 SARS epidemic.DesignAnonymous online survey adapted from a similar study conducted during the SARS epidemic, disseminated from July 2020 to August 2020.SettingNine healthcare institutions across Singapore ranging from primary care, community care, tertiary care and specialised referral centres.ParticipantsEmployees working in the participating healthcare institutions.ResultsOf 3828 survey returns, 3616 had at least one completed item on the questionnaire. Majority were female (74.7%), nurses (51.7%), foreign-born (53.2%) and not working in the tertiary care setting (52.1%). The median score on the Impact of Events Scale (IES) was 15 (IQR 23) and 28.2% of the sample scored in the moderate/severe range. 22.7% of the participants were also HCWs during SARS and more than half of them felt safer and better equipped in the current pandemic. 25.2% of SARS HCWs and 25.9% of non-SARS HCWs had moderate/severe IES scores (p=0.904). After adjusting for age, marital status, parity and length of work experience, racial minority groups and living apart from family were independent predictors of high IES regardless of prior SARS epidemic experience. Daily exposure to confirmed or suspect COVID-19 cases increased the odds of high IES for non-SARS HCWs only.Conclusions and relevanceOverall, while 28% of HCWs in our study suffered from significant trauma-related psychological symptoms regardless of prior experience with the SARS epidemic, those with prior experience reported feeling safer and better equipped, finding the workload easier to manage, as well as having more confidence in their healthcare leaders. We recommend for more trauma-informed support strategies for our HCWs especially those from racial minority groups, who are foreign-born and isolated from their families.