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Phern Chern Tor,1 Nurmiati Amir,2 Johnson Fam,3 Roger Ho,3 Pichai Ittasakul,4 Margarita M Maramis,5 Benita Ponio,6 Dharmawan Ardi Purnama,7 Wanida Rattanasumawong,8 Elizabeth Rondain,9 Ahmad Hatim Bin Sulaiman,10 Kannokarn Wiroteurairuang,11 Kok Yoon Chee12 1Department of Mood and Anxiety, Institute of Mental Health, Singapore; 2Department of Psychiatry, Cipto Mangunkusumo Hospital, Jakarta Pusat, Indonesia; 3Department of Psychological Medicine, National University Hospital, Singapore; 4Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 5Department of Psychiatry, Dr. Soetomo General Academic Hospital-Faculty of Medicine, Airlangga University, Surabaya, Indonesia; 6Department of Psychiatry, Metro Psych Facility, Manila, Philippines; 7Dr Soeharto Heerdjan Jakarta Mental Hospital, Jakarta, Indonesia; 8Department of Psychiatry, Phramongkutklao Hospital, Bangkok, Thailand; 9Department of Psychiatry, Makati Medical Center, Makati City, Philippines; 10Department of Psychological Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 11Prasrimahabodhi Psychiatric Hospital, Ubon Ratchathani, Thailand; 12Department of Psychiatry, Hospital Kuala Lumpur, Kuala Lumpur, MalaysiaCorrespondence: Ahmad Hatim Bin Sulaiman, Department of Psychological Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia, Email hatim@um.edu.myIntroduction: Despite the abundance of literature on treatment-resistant depression (TRD), there is no universally accepted definition of TRD and available treatment pathways for the management of TRD vary across the Southeast Asia (SEA) region, highlighting the need for a uniform definition and treatment principles to optimize the management TRD in SEA.Methods: Following a thematic literature review and pre-meeting survey, a SEA expert panel comprising 13 psychiatrists with clinical experience in managing patients with TRD convened and utilized the RAND/UCLA Appropriateness Method to develop consensus-based recommendations on the appropriate definition of TRD and principles for its management.Results: The expert panel agreed that “pharmacotherapy-resistant depression” (PRD) is a more suitable term for TRD and defined it as “failure of two drug treatments of adequate doses, for 4– 8 weeks duration with adequate adherence, during a major depressive episode”. A stepwise treatment approach should be employed for the management of PRD – treatment strategies can include maximizing dose, switching to a different class, and augmenting or combining treatments. Non-pharmacological treatments, such as electroconvulsive therapy and repetitive transcranial magnetic stimulation, are also appropriate options for patients with PRD.Conclusion: These consensus recommendations on the operational definition of PRD and treatment principles for its management can be adapted to local contexts in the SEA countries but should not replace clinical judgement. Individual circumstances and benefit-risk balance should be carefully considered while determining the most appropriate treatment option for patients with PRD.Keywords: depression, pharmacotherapy, major depressive disorder, anti-depressive agents, depressive disorder – treatment resistant

The objective of the study is to determine the prevalence of substance abuse for alcohol, cannabis, opiates, stimulants, solvent and other substances among patients with schizophrenia in Hospital Bahagia Ulu Kinta (HBUK), Perak , Central Peninsular of Malaysia. This study also aims to determine the association of substance abuse with aggression, the demographic characteristics and total duration of hospitalization. Methods: This was a retrospective cross-sectional study whereby the first 194 subjects diagnosed to have schizophrenia based on International Classification of Disease, 10th edition (ICD-10) criteria were taken from data registry of patients admitted to HBUK from January until February 2004. The subjects’ medical files were examined for documentation of substances abuse, aggression and accumulative duration of hospitalization. Results: The results showed the prevalence of substances misuse among patients with schizophrenia in general (including alcohol) was 24.7%. Cannabis 16.7%, alcohol 13.4%, opiates(heroin) 6.7%, Amphetamine type stimulants (amphetamine, metamphetamine, ecstacy) 5.7%, and other substances (benzodiazepine, solvents) 1.5%. Conclusion: There is higher prevalence of substance misuse in patients with schizophrenia as compared to general population. Male patients with history of substance misuse are more likely to have aggression than female. This group needs special precaution and probably in need of specialist help.

We demonstrate a Sagnac-interferometer-based multiwavelength fiber laser with an intensity-dependent loss (IDL) mechanism in the L-band region using a semiconductor optical amplifier (SOA) as the gain medium. The IDL mechanism flattens and stabilizes the multiwavelength spectrum. We also investigate the effect of rotation angles of polarization controllers (PCs) at different polarization devices on multiwavelength performance. At best settings, 31 lasing lines within 3 dB uniformity were generated with an extinction ratio (ER) of 17 dB. Adjusting the half-wave plate of PC1 and PC2 from 0° to 90° shifted the multiwavelength output by 0.01 nm and 0.072 nm, respectively. PC2 adjustment also affects the multiwavelength flatness as compared to PC1. Furthermore, the number of lasing lines and the ER were directly influenced by the SOA current.

This post-hoc analysis evaluated the efficacy and safety of intranasal esketamine in the Asian subgroup from ASPIRE I. Patients with major depressive disorder and suicidal ideation with intent received intranasal esketamine (n = 26) or placebo (n = 27), plus standard of care for 25 days. The primary endpoint was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to Day 2. The MADRS score improved in favor of esketamine (least squares mean difference: -3.8). No unexpected safety concerns were noted. The Asian subgroup showed a similar efficacy and safety profile as the total ASPIRE I cohort., (© 2023 John Wiley & Sons Australia, Ltd.)

Background: Evaluate efficacy and safety of paliperidone palmitate 6-monthly (PP6M) for patients with schizophrenia in the Asian subgroup of a global, multicenter, noninferiority phase-3 study (NCT03345342)., Methods: Patients received paliperidone palmitate 1-monthly (PP1M, 100/150 mg eq.) or paliperidone palmitate 3-monthly (PP3M, 350/525 mg eq.) during the maintenance phase and entered a 12-month double-blind (DB) phase, wherein they were randomized (2:1) to PP6M (700/1000 mg. eq.) or PP3M (350/525 mg eq.). Subgroup analysis was performed for 90 (12.7%) patients from Asia region (India, Taiwan, Malaysia, Hong Kong, and Korea). Primary endpoint was time-to-relapse during DB phase (Kaplan-Meier estimates). Secondary endpoints were changes from baseline in Positive and Negative Syndrome Scale, Clinical Global Impression-Severity scale, Personal and Social Performance (PSP) scale score., Results: In Asian subgroup, 91.9% (82/90) of patients completed DB phase (PP6M: 54/62 [87%]; PP3M: 28/28 [100%]). Median time-to-relapse was "not-estimable" due to low relapse rates in both groups. Estimated difference (95% confidence interval [CI]) between relapse-free patients in PP6M and PP3M groups of Asian subgroup was -0.1% [-8.5%, 8.4%] (global study population: -2.9% [-6.8%, 1.1%]). Mean change from baseline in secondary efficacy parameters was comparable between both groups, similar to the global study population. The incidence of extrapyramidal symptoms was higher in the Asian subgroup than in the global study population., Conclusion: Consistent with the global study population, PP6M was noninferior to PP3M in preventing relapse in patients with schizophrenia from the Asia region. Findings suggest the possibility of switching from PP1M/PP3M to twice-yearly PP6M without loss of efficacy and with no unexpected safety concerns., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample., Methods: Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001., Results: The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger., Conclusion: UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition., (© 2023. The Author(s).)

This study aims to validate the Malay version of the Brief Resilience Scale (BRS-M) in order for the scale to be available among the Malay-speaking population. Two hundred and ninety-eight non-academic staff completed the Malay version of the Brief Resilience Scale (BRS-M), Malay Copenhagen Burnout Inventory (CBI-M), and Malay Depression, Anxiety, and Stress Scale (M-DASS-21). To explore the factor structure of BRS-M, exploratory factor analysis (EFA) with the first group of 149 participants was conducted using FACTOR (v.11) software. Confirmatory factor analysis (CFA) was conducted from the data of the second group of 149 participants using SEM_PLS software. The EFA revealed a two-factor model; Factor 1 ="Resilience" and Factor 2 = "Succumbing". The CFA indicated a sufficient internal consistency reliability (Cronbach's α = 0.806 and McDonald's omega, ω = 0.812) and a good fit with SRMR = 0.031. BRS-M, CBI-M, and M-DASS-21 displayed a satisfactory concurrent validity result. Household income and marital status had significant association with resilience level, with low household income (B40 group) being a predictor of lower resilience. The BRS-M demonstrated favourable psychometric properties in terms of reliability and validity to assess the level of resilience among non-academic staff in Malaysia.

The Juno Waves instrument measured plasma waves associated with Ganymede's magnetosphere during its flyby on 7 June, day 158, 2021. Three distinct regions were identified including a wake, and nightside and dayside regions in the magnetosphere distinguished by their electron densities and associated variability. The magnetosphere includes electron cyclotron harmonic emissions including a band at the upper hybrid frequency, as well as whistler-mode chorus and hiss. These waves likely interact with energetic electrons in Ganymede's magnetosphere by pitch angle scattering and/or accelerating the electrons. The wake is accentuated by low-frequency turbulence and electrostatic solitary waves. Radio emissions observed before and after the flyby likely have their source in Ganymede's magnetosphere., (© 2022. The Authors.)

The Juno spacecraft has been in orbit around Jupiter since 2016. Two flybys of Ganymede were executed in 2021, opportunities realized by evolution of Juno's polar orbit over the intervening 5 years. The geometry of the close flyby just prior to the 34th perijove pass by Jupiter brought the spacecraft inside Ganymede's unique magnetosphere. Juno's payload, designed to study Jupiter's magnetosphere, had ample dynamic range to study Ganymede's magnetosphere. The Juno radio system was used both for gravity measurements and for study of Ganymede's ionosphere. Remote sensing of Ganymede returned new results on geology, surface composition, and thermal properties of the surface and subsurface., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2022. The Authors.)

Objective: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth., Methods: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer., Results: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001)., Conclusion: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To evaluate the long-term efficacy and safety of three-monthly paliperidone palmitate (PP3M) in Asian patients with stable schizophrenia in a naturalistic setting., Methods: Asian patients recruited between May 2016 and March 2018 from the prospective, single-arm, non-randomized, open-label, multi-national REMISSIO study were analyzed. Patients received PP3M over 12 months following ≥ 4 months of treatment with one-monthly paliperidone palmitate. The primary efficacy endpoint was the proportion of patients who achieved symptomatic remission. Other endpoints were changes in Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) total scores, hospitalization rates, and safety., Results: A total of 71 patients (23.3%) were Asian (South Korea: 33, Malaysia: 21, Taiwan: 17); 95.8% of patients completed the study. At LOCF, 71% of Asian patients achieved symptomatic remission compared to the overall population (n = 172/303, 56.8%). Improvements in mean (standard deviation) PANSS and PSP total scores from baseline to LOCF in Asian patients and overall population were clinically significant. A lower proportion of Asian patients had ≥ 1 psychiatric hospitalization after PP3M treatment (n = 1/70, 1.4%) than during the 12 months before (n = 12/70, 17.1%); compared with patients in the overall population after (n = 8/303, 2.6%) and before PP3M treatment (n = 37/303, 12.2%). The overall incidence of treatment-emergent adverse events across Asian patients was 62.9% compared to 53.1% in the overall population. Safety findings were consistent with the known safety profile of PP3M., Conclusion: Our findings confirm existing evidence on the efficacy and tolerability of PP3M in Asian patients with stable schizophrenia over 12 months of treatment.

The Juno spacecraft's polar orbits have enabled direct sampling of Jupiter's low-altitude auroral field lines. While various data sets have identified unique features over Jupiter's main aurora, they are yet to be analyzed altogether to determine how they can be reconciled and fit into the bigger picture of Jupiter's auroral generation mechanisms. Jupiter's main aurora has been classified into distinct "zones", based on repeatable signatures found in energetic electron and proton spectra. We combine fields, particles, and plasma wave data sets to analyze Zone-I and Zone-II, which are suggested to carry upward and downward field-aligned currents, respectively. We find Zone-I to have well-defined boundaries across all data sets. H + and/or H 3 + cyclotron waves are commonly observed in Zone-I in the presence of energetic upward H + beams and downward energetic electron beams. Zone-II, on the other hand, does not have a clear poleward boundary with the polar cap, and its signatures are more sporadic. Large-amplitude solitary waves, which are reminiscent of those ubiquitous in Earth's downward current region, are a key feature of Zone-II. Alfvénic fluctuations are most prominent in the diffuse aurora and are repeatedly found to diminish in Zone-I and Zone-II, likely due to dissipation, at higher altitudes, to energize auroral electrons. Finally, we identify significant electron density depletions, by up to 2 orders of magnitude, in Zone-I, and discuss their important implications for the development of parallel potentials, Alfvénic dissipation, and radio wave generation., (© 2022. The Authors.)

There was a change in the pattern of substance usage among people who use substances during the COVID-19 pandemic period. This study aims to determine the effects of the COVID-19 pandemic on the pattern of substance usage among people who use drugs (PWUD) receiving treatment at the University Malaya Medical Centre (UMMC) as well as levels of anxiety and depression together with coping mechanisms and the factors affecting the pattern of substance use during COVID-19 pandemic period. A cross-sectional study was applied. The questionnaire used was the Mini-European Web Survey on Drugs (EWSD): COVID-19, Hospital Anxiety and Depression Scale (HADS), and Brief COPE Scale. In total, 130 PWUD were recruited. Of the participants, 36.2% of PWUD had not used/stopped the usage of illicit drugs/alcohol, 26.2% increased their usage, 20% decreased, and 14.6% used the same amount of illicit substances/alcohol during the COVID-19 pandemic period/restrictions. In addition, 28.5% of PWUD had an increased intention to seek professional support for drug counseling/treatment during the COVID-19 pandemic period. The prevalence anxiety and depression symptoms in PWUD according to HADS was 33% and 41.5%, respectively, with depression (p = 0.05) and isolation status (adjusted OR = 2.63, p < 0.05) being associated with an increase in alcohol/illicit substance use during the COVID-19 pandemic. PWUD who had increased their intention to seek professional support had significantly higher odds (adjusted OR = 4.42, p < 0.01) of reducing their alcohol/illicit substance use during the COVID-19 pandemic period. There were increased odds of maintaining alcohol/illicit substance usage among PWUD who practiced dysfunctional coping (adjusted OR = 3.87, p < 0.025) during the COVID-19 pandemic period. In conclusion, depression, isolation status, dysfunctional coping, and intention to seek professional support affected the pattern of alcohol/illicit substance use during the COVID-19 pandemic period. Strategies, substance rehabilitation/counseling, and proper mental health screening and the associated risk factors must be emphasized to prevent a further epidemic of substance use during the pandemic.

Objectives: This study aimed to develop and assess the effectiveness of an encounter decision aid for Malaysian patients with MDD to support treatment decision-making during the consultation., Methods: The decision aid prototype was developed following a literature review and six focus groups. Alpha testing assessed its comprehensibility, acceptability, usability and desirability through user-centered cognitive interviews. Beta-testing evaluated preliminary evidence on its efficacy using the SDM Scale and PDMS. Feasibility was assessed by timing the consultation., Results: The alpha testing demonstrated that the decision aid was patient-oriented, comprehensible, comprehensive, concise and objective with an appealing design. Beta-testing indicated that PtDA significantly increased patients satisfaction with SDM from patients' [83.32 (13.92) vs 85.76 (13.80); p < 0.05] and physicians' [81.07 (10.09) vs 86.36 (10.10); p < 0.05] perspectives and prepared the patients for decision making from the patients' [PDMS patients: 84.10 (12.69)] and physicians' [PDMS physicians: 83.78 (16.62)] perspectives as well. There was no change in the consultation time between the control and the intervention groups., Conclusions: We developed an antidepressant PtDA for Malaysian patients with MDD that increases patients' involvement in shared decision making and enhances their preparedness for decision making., Practice Implications: Using the PtDA can support collaborative decision-making in routine clinical practice without extending the consultation time., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Two distinct proton populations are observed over Jupiter's southern polar cap: a ∼1 keV core population and ∼1-300 keV dispersive conic population at 6-7 R J planetocentric distance. We find the 1 keV core protons are likely the seed population for the higher-energy dispersive conics, which are accelerated from a distance of ∼3-5 R J . Transient wave-particle heating in a "pressure-cooker" process is likely responsible for this proton acceleration. The plasma characteristics and composition during this period show Jupiter's polar-most field lines can be topologically closed, with conjugate magnetic footpoints connected to both hemispheres. Finally, these observations demonstrate energetic protons can be accelerated into Jupiter's magnetotail via wave-particle coupling., (© 2022. The Authors.)

The psychological distress reported among frontline healthcare workers (HCWs) is concerning. Little is known about the mental health of non-frontline, psychiatric HCWs, who play a central role in handling the mental health crisis during the COVID-19 pandemic. This study aimed to examine the prevalence of anxiety and depression among psychiatric HCWs and evaluate its association with socio-demographic, socio-economic, work-related factors and coping strategies. The authors proposed a cross-sectional study design using the Hospital Anxiety and Depressive Scale (HADS) and Brief-COPE scale. This study found that the prevalence of anxiety and depression were 22.0% and 16.8%, respectively. A multivariate analysis revealed that married psychiatric HCWs had a lower level of anxiety with OR = 0.31 (95% CI: 0.11-0.83). Psychiatric HCWs who were experiencing financial hardships, were unvaccinated and those who had a shorter duration of service in the psychiatric department had a higher level of depressive symptoms with OR = 0.31 (CI: 1.19-11.27), 3.21 (CI: 0.97-10.52), and 1.01 (CI: 1.00-1.02), respectively. For every increase of one unit of avoidant coping score among respondents, the odds of having anxiety and depression increased by 1.25 times (CI: 1.15-1.37) and 1.20 times (CI: 1.09-1.32), respectively, whereas for every increase of one unit of religious coping score among respondents, the odds of having anxiety reduced by 1.42 times (CI: 1.10-1.84). The authors highlight that psychosocial measures addressing the relatively high levels of anxiety and depression among psychiatric HCWs should be a key priority to ensure the sustainment of mental health services in the face of this prolonged pandemic.

Background: Psychiatric pharmaceutical care is the provision of pharmaceutical care services to patients with psychiatric related illnesses or disorders. Several studies have demonstrated the positive influence psychiatric pharmaceutical care on patients' clinical, humanistic and economic outcomes. This study aimed to examine the extent of psychiatric pharmaceutical care practice in a convenience sample of Malaysian government hospitals and the barriers to the provision of these services., Methods: An anonymous cross-sectional survey of registered pharmacists working at a convenience sample of government hospitals in Malaysia was undertaken from September 2019 to June 2020., Results: Pharmacists frequently ensured the appropriateness of the dose (55%), dosage form (47%) and dosing schedule (48%) of the dispensed medications. Most pharmacists infrequently worked with patients and healthcare professionals to develop a pharmacotherapeutic regimen and a corresponding monitoring plan (28%). There was no statistically significant difference in the provision of pharmaceutical care services with respect to gender, age, years of practice, and professional board certification. However, the services offered were influenced by the respondent's education and pharmacy setting. The obstacles perceived by pharmacists included lack of time (89%), shortage of pharmacy staff (87%), the patients' inability to comprehend medical information (85%), insufficient demand and acceptance by patients (82%), the lack of official policies and standardised practice protocols (78%), inaccessibility to the patients' medical records (77%) and the lack of structured communication channels between pharmacists and physicians (75%), the pharmacists lack of knowledge/skills and confidence (78%) and insufficient recognition from physicians to the pharmacists' skills (76%)., Conclusions: This is the first study to explore the extent and barriers of psychiatric pharmaceutical care in Malaysian hospitals; it highlighted the need for mobilising pharmacists to expand these services., (© 2022. The Author(s).)

Objective: To evaluate the long-term safety and efficacy of intranasal esketamine in patients with treatment-resistant depression from the Asian subgroup of the SUSTAIN-2 study., Methods: SUSTAIN-2 was a phase 3, open-label, single-arm, multicenter study comprising a 4-week screening, 4-week induction, 48-week optimization/maintenance, and 4-week follow-up (upon esketamine discontinuation) phase. Patients with treatment-resistant depression received esketamine plus an oral antidepressant during the treatment period., Results: The incidence of ≥ 1 serious treatment-emergent adverse event (TEAE) among the 78 subjects from the Asian subgroup (Taiwan: 33, Korea: 26, Malaysia: 19) was 11.5% (n = 9); with no fatal TEAE. 13 Asian patients (16.7%) discontinued esketamine due to TEAEs. The most common TEAEs were dizziness (37.2%), nausea (29.5%), dissociation (28.2%), and headache (21.8%). Most TEAEs were mild to moderate in severity, transient and resolved on the same day. Upon discontinuation of esketamine, no trend in withdrawal symptoms was observed to associate long-term use of esketamine with withdrawal syndrome. There were no reports of drug seeking, abuse, or overdose. Improvements in symptoms, functioning and quality of life, occurred during in the induction phase and were generally maintained through the optimization/maintenance phases of the study., Conclusion: The safety and efficacy of esketamine in the Asian subgroup was generally consistent with the total SUSTAIN-2 population. There was no new safety signal and no indication of a high potential for abuse with the long-term (up to one year) use of esketamine in the Asian subgroup. Most of the benefits of esketamine occurred early during the induction phase.

Diabetes is a category of metabolic illnesses defined by a persistently high blood sugar level. This complication is caused by either the pancreas failing to create enough insulin or the body's cells failing to respond correctly to the insulin produced. Diabetes, if left untreated, can lead to a slew of health issues. Diabetic ketoacidosis, hyperosmolar hyperglycemia, and mortality are all examples of acute complications. There are numerous serious long-term consequences, including chronic renal disease, foot ulcers, as well as nerve and eye damage. This study aimed to extract carbonic anhydrase (CA) from human red blood cells and estimate the activity and specific activity of the enzyme and some biochemical parameters, including total protein, albumin, globulin, free amino acids, free amino acids/total protein (TP), thiol, thiol/TP, as well as carbonyl and carbonyl/TP levels in patients with diabetes complications, compared to the healthy subjects; moreover, it was attempted to investigate the correlation among the aforementioned variables. This study included 60 blood samples obtained from patients with diabetes complications and 40 healthy individuals as control. The results revealed a significant ( P ≤0.05) decrease in the TP levels, while the CA activity and specific activity were significantly ( P ≤0.05) increased. Moreover, there was a non-significant ( P ≥0.05) increase in the free amino levels; however, a significant ( P ≤0.05) increase was observed in albumin, free amino/TP, thiol, thiol/TP, as well as carbonyl and carbonyl/TP levels. On the other hand, a significant ( P ≤0.05) decrease was found in the levels of globulin and albumin/globulin ratio (AGR) in the patients, compared to the healthy subjects. The results also indicated a significant ( P ≤0.05) difference in all cases of diabetes mellitus (DM) complications for the measured parameters, except for the TP in DM nephropathy, albumin in cardiovascular disease, free amino in neuropathy and cardiovascular disease, and free amino/TP in retinopathy that showed a clear non-significant ( P ≥0.05) difference in the patients' groups, compared to the healthy subjects. The results of correlation indicated a significant ( P ≤0.05) positive correlation among free amino/TP, free amino/carbonyl, globulin/TP, and AGR/albumin. However, a significant negative correlation was noted between globulin/albumin and AGR/globulin. The results revealed that the protein oxidation markers and CA as antioxidant markers may play a role in monitoring diabetes complications.

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries., Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun's electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries)., Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01., Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed., (© 2021. The Author(s).)

Jupiter's rapidly rotating, strong magnetic field provides a natural laboratory that is key to understanding the dynamics of high-energy plasmas. Spectacular auroral x-ray flares are diagnostic of the most energetic processes governing magnetospheres but seemingly unique to Jupiter. Since their discovery 40 years ago, the processes that produce Jupiter's x-ray flares have remained unknown. Here, we report simultaneous in situ satellite and space-based telescope observations that reveal the processes that produce Jupiter's x-ray flares, showing surprising similarities to terrestrial ion aurora. Planetary-scale electromagnetic waves are observed to modulate electromagnetic ion cyclotron waves, periodically causing heavy ions to precipitate and produce Jupiter's x-ray pulses. Our findings show that ion aurorae share common mechanisms across planetary systems, despite temporal, spatial, and energetic scales varying by orders of magnitude., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

Objective: At the dawn of the new decade of the 20th century, the world was taken aback by the scourge of the COVID-19 pandemic. The study aimed to study the nature of religious coping of frontline healthcare workers seen through the perspective of gender, socio-economic status, and occupation., Methods: An online-based study was carried out among frontline healthcare workers involved in the care of COVID-19 patients (n = 200). Sociodemographic data form and the Brief Religious Coping scale were used in this study., Results: There were more female healthcare workers (60.5%) and doctors (69.5% vs. 30.5%). Healthcare workers used more positive religious coping than negative religious coping (median score: 22 vs. 9). Positive religious coping was seen more in females (median score: 23 vs. 21, P = .015). Non-doctors applied positive coping more than doctors (median score: 26 vs. 21, P < .001). There were significant differences in positive religious coping scores across income groups, with the B40 group having the highest score (median score: 24). Post hoc pairwise comparison concluded that the B40 group had significantly higher positive religious coping scores than the M40 group., Conclusion: Positive coping was utilized more among female healthcare workers, nondoctors, and the lowest socio-economic group. As prior literature has shown that positive religious coping is desirable and has superior mental health outcomes, our findings show that more effort should be channeled into enhancing positive religious coping, particularly among male healthcare workers, doctors, and the middle and high socio-economic group., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare., (© Copyright 2021 authors.)

The mental wellbeing of doctors is becoming an increasing concern in the world today. In Malaysia, residency is a challenging period in a doctor's life, with many changes professionally and possibly in their personal lives as well. This study aims to determine the prevalence of depressive symptoms and the socio-demographic correlates among residents in a tertiary training hospital in Malaysia. It is a cross sectional study and all residents were approached to participate in the study. The instruments used were a socio-demographic questionnaire and the Patient Health Questionnaire 9 (PHQ-9). Chi-square test was used to explore the association between the socio-demographic correlates, and those that were found to have significant associations were further tested using multivariate logistic regression. The prevalence of depression among residents was 25.1 %. Longer working hours, missing meals, and working in Department of Surgery and Department of Anaesthesia was significantly positively associated while having protected study time, CME/lectures, leisure/hobbies and exercise were negatively associated with depression. The Department of Rehabilitation Medicine had a significantly negative association with depression. After logistic regression, longer working hours and a lack of protected study time was significantly associated with depression in the respective departments. In summary, the prevalence of depression among residents is high and is associated with longer working hours, missing meals and a lack of protected study time are significantly associated with depression. Remedial steps should be taken to improve the mental health among residents., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Anxiety and depression have been prevalent among Healthcare Workers (HCWs) amidst the COVID-19 pandemic. This study aims to evaluate the prevalence of anxiety and depression among HCWs amid the pandemic and their association with religious coping. A cross-sectional study design was applied. The scales utilized were Malay versions of the Brief Religious Coping Scale (Brief RCOPE M) and Hospital Anxiety and Depression Scale (HADS M). In total, 200 HCWs were recruited. HCWs scored higher in positive religious coping (mean: 21.33) than negative religious coping (mean: 10.52). The prevalence of anxiety and depression was 36.5% and 29.5%. Both positive and negative religious coping were significantly associated with anxiety ( p < 0.01) and depression ( p < 0.05, p < 0.01). Positive coping predicted reduction in anxiety (adjusted b = -0.15, p = 0.001) and log-transformed depression score (adjusted b = -0.019, p = 0.025). Negative coping predicted increment of anxiety (adjusted b = 0.289, p < 0.001) and log-transformed depression score (adjusted b = 0.052, p < 0.001). Positive religious coping is vital in reducing anxiety and depression among HCWs amid the pandemic. Strategies which increase positive religious coping and reduce negative religious coping must be emphasized to boost mental health among HCWs.

Clozapine remains as the gold standard for the management of treatment resistant schizophrenia. Nevertheless, mortality and morbidity associated with Clozapine is partly contributed by its adverse effect of constipation in view of its prominent anticholinergic properties. Despite the evidence that approximately 60% of patients on Clozapine will experience constipation, there is no proper guideline as to the best laxative in the treatment of Clozapine induced constipation. Hence this study was conducted to evaluate the efficacy and safety of Prucalopride and Lactulose in the treatment of Clozapine induced constipation. This was a four week, prospective, open-label head to head comparison study between Prucalopride and Lactulose in the treatment of Clozapine induced constipation. Male and female patients on Clozapine between the age of 18-60 with an established diagnosis of treatment resistant schizophrenia with ≤2 spontaneous complete bowel movement per week were recruited in this study. Eligible patients were assigned into two groups. Patients received Prucalopride 2 mg once daily or Lactulose 10 g once daily for four weeks. Efficacy was analyzed in 58 patients. The proportion of patient with ≥3 spontaneous complete bowel movement (SCBM) was higher in the Prucalopride 2 mg group, reaching significance at Week 4 with p -value of ( p = 0.029). The proportion of patient with ≥3 SCBM at Week 1 was 71.4% in the Prucalopride 2 mg group and 60% in the Lactulose 10 g group. The proportion of patient with ≥3 SCBM at Week 4 was 85.7% in the Prucalopride 2 mg group and the proportion remained at 60% in the Lactulose 10 g group. The improvement in the dissatisfaction and treatment satisfaction subscales of the patient assessment of constipation-quality of life (PAC-QOL) were higher in the Prucalopride 2 mg group compared to the Lactulose 10 g group. The common adverse events associated with Prucalopride 2 mg were abdominal pain and loose stools which was transient and subsided within a few days. Over four weeks, in this population of patients with Clozapine induced constipation, Prucalopride 2 mg significantly improved the bowel movement and it was safe.

Mental health disorders (MHDs) among refugees has been recognized as a major public health issue. However, to date, there is limited evidence on the prevalence of MHDs among Rohingya refugees in Malaysia. This study aimed to examine the prevalence and associated factors of major depressive disorder (MDD), generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD) among Rohingya refugees in Malaysia. A total of 220 refugees were randomly selected to participate in this cross-sectional study, conducted from June 2019 to November 2019. Perceived social support, religious orientation, food security, and sociodemographic characteristics were assessed as independent variables. The dependent variables assessed were MDD, GAD, and PTSD. The prevalence of GAD, PTSD, and MDD was reported at 92 (41.8%), 84 (38.2%), and 71 (32.3%). Several factors were significantly associated with MDD following multivariate analysis such as perceived low to moderate social support (AOR = 2.17; 95% CI 1.13, 4.19) and food insecurity (AOR = 2.77; 95% CI 1.19, 6.47). Exposure to violence (AOR = 38.46; 95% CI 16.27, 90.91) and food insecurity (AOR = 3.74; 95% CI 1.41, 9.91) were significantly associated with PTSD. Addressing these risk factors could be key in improving mental health outcomes among this vulnerable population.

The purpose of this article is to discuss the importance of addressing the psychological impact of coronavirus disease 2019 (COVID-19) on healthcare workers (HCWs) who are frontliners directly involved in mitigating the spread of the disease. This paper focuses on the utilization of a clinical practice protocol for identifying HCWs who are COVID-19-positive or under investigation and surveillance for suspected infection, in a tertiary, university teaching hospital of Malaysia. The protocol for Psychological First Aid (PFA), which is applied remotely via a mobile application and phone calls, outlines the work process in stages, with expected immediate, intermediate, and long-term goals within a "Specific, Measurable, Attainable, Relevant, and Realistic Timeframe" (SMART). This protocol is developed to provide a guideline for psychological crisis interventions that promote safety, calm, and hope in HCWs, allowing them to return to psychological functioning without being stigmatized. The unprecedented remote PFA protocol may serve as a platform for further research on the application of a goal-directed approach in a healthcare organization.

The pharmacy profession has undergone tremendous changes over the past few decades. Pharmacists' roles have expanded their boundaries to encompass more patient-centered services. However, the degree to which these roles are practised may vary. This scoping review is aimed at describing the extent and range of the professional pharmacy services offered in hospital pharmacies across different countries and the barriers underlying inappropriate or incomplete implementation of these services. Studies published in the English language between 2015 and 2019 were retrieved from the following databases: PubMed, CINAHL, Scopus, EBSCO Discovery Service, and Web of Science. A thematic analysis across the included studies produced two main themes. "Scope of practice" comprised three subthemes: pharmaceutical care practice, clinical pharmacy practice, and public health services and "Multiple levels of influence" comprised five subthemes: individual, interpersonal, institutional, community, and public policy-related factors. The hospital pharmacy services across countries ranged from traditional drug-centered pharmacy practice to a more progressive, clinically oriented practice. In some countries, there is an apparent inadequacy in the clinical pharmacy services provided compared to other clinical settings. Understanding the current pharmacy practice culture across different health care systems is an essential step towards improving the profession., Competing Interests: The authors declare no conflict of interest.

Objective: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD)., Methods: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years). Esketamine nasal spray (28-mg, 56-mg, or 84-mg) plus new OAD was administered twice a week in a 4-week induction (IND) phase and weekly or every-other-week for patients who were responders and entered a 48-week optimization/maintenance (OP/MAINT) phase., Results: Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry; 580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase. Common treatment-emergent adverse events (TEAEs) were dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%). Seventy-six patients (9.5%) discontinued esketamine due to TEAEs. Fifty-five patients (6.9%) experienced serious TEAEs. Most TEAEs occurred on dosing days, were mild or moderate in severity, and resolved on the same day. Two deaths were reported; neither was considered related to esketamine. Cognitive performance generally either improved or remained stable postbaseline. There was no case of interstitial cystitis or respiratory depression. Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose. Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12])., Conclusions: Long-term esketamine nasal spray plus new OAD therapy had a manageable safety profile, and improvements in depression appeared to be sustained in patients with TRD., Trial Registration: ClinicalTrials.gov identifier: NCT02497287., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

Background: Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia. This study determined the efficacy, safety and pharmacokinetics of a blonanserin transdermal patch in patients with acutely exacerbated schizophrenia., Methods: This double-blind, multicenter, phase 3 study consisted of a 1-week observation period during which patients were treated with two patches of placebo, followed by a 6-week double-blind period where patients were randomized (1:1:1) to receive once-daily blonanserin 40 mg, blonanserin 80 mg, or placebo patches. The primary endpoint was the change from baseline in the total Positive and Negative Symptom Scale (PANSS) score. Safety assessments included treatment-emergent adverse events (TEAEs)., Results: Between December 2014 and October 2018, patients were recruited and randomly assigned to blonanserin 40 mg (n = 196), blonanserin 80 mg (n = 194), or placebo (n = 190); of these, 77.2% completed the study. Compared with placebo, blonanserin significantly improved PANSS total scores at 6 weeks (least square mean [LSM] difference vs placebo: -5.6 with blonanserin 40 mg; 95% confidence interval [CI] -9.6, -1.6; adjusted p = 0.007, and - 10.4 with blonanserin 80 mg; 95% CI -14.4, -6.4; adjusted p < 0.001). Blonanserin was well tolerated; the most common TEAEs reported were application-site erythema and pruritus, akathisia, tremor, and insomnia., Conclusions: Blonanserin transdermal patch improved the symptoms of acute schizophrenia with acceptable tolerability., Competing Interests: Declaration of Competing Interest NI reports personal fees from Otsuka, Sumitomo Dainippon, Janssen, Eli Lilly, and Pfizer, grants from Otsuka, Daiichi-Sankyo, outside the submitted work. JI reports grants from Sumitomo Dainippon during the conduct of the study, personal fees from Meiji Seika Pharma, MSD, Astellas, Novartis, Pfizer, Otsuka, Eli Lilly, Takeda, and Eisai, outside the submitted work. WHK reports grants from Sumitomo Dainippon, during the conduct of the study. TH reports personal fees from Meiji Seika Pharma, MSD, Allergan, Eisai, Pfizer, Janssen, Lundbeck, Shionogi, Yoshitomi, Kyowa Hakko Kirin, Mochida, Otsuka, Sumitomo Dainippon, Mitsubishi Tanabe, Eli Lilly, and Takeda, outside the submitted work. CUC reports personal fees from Alkermes, Allergan, Angelini, Boehringer-Ingelheim, Gerson Lehrman Group, Indivior, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Neurocrine, Noven, Otsuka, Pfizer, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, Teva, Bristol-Myers Squibb, and UpToDate, grants from Janssen and Takeda, other from Boehringer-Ingelheim, Lundbeck, Rovi, Supernus, Teva, and LB Pharma, outside the submitted work. JMK reports personal fees from Alkermes, Sumitomo Dainippon, Eli Lilly, EnVivo Pharmaceuticals (Forum), Forest (Allergan), Genentech, H. Lundbeck, Intracellular Therapies, Janssen, Johnson and Johnson, LB Pharmaceuticals, Merck, Minerva, Neurocrine, Otsuka, Pierre Fabre, Reviva, Roche, Sunovion, Takeda and Teva, grants from Otsuka, Lundbeck and Janssen, participated in advisory boards for Alkermes, Sumitomo Dainippon, Intracellular Therapies, Lundbeck, Neurocrine, Otsuka, Pierre Fabre, Takeda and Teva, outside the submitted work. JMK is a shareholder in Vanguard Research Group and LB Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To examine subjective depressive symptoms associated with physical pain symptoms (PPSs) in Asian patients with major depressive disorder (MDD)., Design and Methods: Four PPSs, including headache, chest pain, low back pain, and muscle pain, and subjective depressive symptoms were assessed using the Symptom Checklist-90-Revised., Findings: Out of 528 participants, 390 (73.9%) had at least one PPS. After adjusting for sex, depression severity, disability, fatigue, physical health status, and mental health status, PPSs were found to be associated with crying easily, blaming oneself, feeling lonely, feeling blue, and worrying too much., Practical Implications: Almost three-quarters of Asian patients with MDD experience PPSs. PPSs are associated with some subjective feelings of depression., (© 2019 Wiley Periodicals, Inc.)

In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p < 0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: This study was conducted to assess the prevalence, pattern of smoking and sociodemographic factors among Kerinchi residents in Kuala Lumpur, as well as to identify the association between smoking, stress, anxiety and depression. Methods: This study was carried out at four community housing projects in the Lembah Pantai area in Kuala Lumpur. Data was collected between 3 February 2012, and 29 November 2012. Data collectors made house visits and used interviewer administered questionnaires containing questions on demographic data and smoking patterns. Depression anxiety stress scale (DASS) was used to assess psychological symptoms. Alcohol smoking and substance involvement screening tool (ASSIST) scale was used to assess nicotine use. Results: Data from 1989 individuals (833 households) showed the age of respondents ranged from 18 to 89 years and the mean age was 39.12 years. There were 316 smokers indicating the prevalence of smoking was 15.85%, with 35.5% among males and 1.8% among females. Further, 86.6% of smokers were Malay and 87% were Muslims. Divorce was associated with smoking. Unemployment and housewives were less associated with smoking. Depression and anxiety were significantly associated with smoking (OR = 1.347. 95% CI: 1.042-1.741) and (OR = 1.401. 95% CI: 1.095-1.793) respectively. Conclusion: Screening for depression and anxiety should be routinely performed in the primary care setting and in population-based health screening to intervene early in patients who smoke.

Medical students are vulnerable to depression and anxiety due to the nature of their academic life. This study aimed to determine the prevalence of depressive and anxiety symptoms among medical students and the association between religious coping, religiosity and socio-demographic factors with anxiety and depressive symptoms. A cross sectional design was used for this study. Scales used were the Malay version of the Duke Religious Index (DUREL-M), the Malay version of the Brief Religious Coping Scale (Brief RCOPE) and the Malay version Hospital and Anxiety Depression Scale (HADS-M). 622 students participated in this study. They scored moderately on the organized (mean: 3.51) and non-organized religious (mean: 3.85) subscales of the DUREL, but had high intrinsic religiosity (mean: 12.18). The prevalence of anxiety and depressive symptoms were 4.7% and 17.4% respectively, which is lower than local as well as international data. Islam, negative religious coping and the presence of depressive symptoms were significantly associated with anxiety symptoms. Only the presence of anxiety symptoms was significantly associated with depressive symptoms. Negative religious coping, rather than positive religious coping, has significant association with depressive and anxiety symptoms. Redirecting focus towards negative religious coping is imperative to boost mental health outcomes among medical students.

Background: The world population is aging and the number of older adults with bipolar disorder is increasing. Digital technologies are viewed as a framework to improve care of older adults with bipolar disorder. This analysis quantifies Internet use by older adults with bipolar disorder as part of a larger survey project about information seeking., Methods: A paper-based survey about information seeking by patients with bipolar disorder was developed and translated into 12 languages. The survey was anonymous and completed between March 2014 and January 2016 by 1222 patients in 17 countries. All patients were diagnosed by a psychiatrist. General estimating equations were used to account for correlated data., Results: Overall, 47% of older adults (age 60 years or older) used the Internet versus 87% of younger adults (less than 60 years). More education and having symptoms that interfered with regular activities increased the odds of using the Internet, while being age 60 years or older decreased the odds. Data from 187 older adults and 1021 younger adults were included in the analysis excluding missing values., Conclusions: Older adults with bipolar disorder use the Internet much less frequently than younger adults. Many older adults do not use the Internet, and technology tools are suitable for some but not all older adults. As more health services are only available online, and more digital tools are developed, there is concern about growing health disparities based on age. Mental health experts should participate in determining the appropriate role for digital tools for older adults with bipolar disorder.