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Abstract This study aimed to determine the degree of family relations and associated socio-demographics characteristics, clinical/physical and mental disorders in type 2 diabetes mellitus in a Kenyan diabetes clinic. This study was part of a large multicentre study whose protocol and results had been published. It took place at the outpatient diabetes clinic at a County Teaching and Referral Hospital in South East Kenya involving 182 participants. We used a socio-demographic questionnaire, the Hamilton Depression (HAM-D) and PHQ-9 rating scales for depression, the MINI International Neuropsychiatric Interview (MINI; V5 or V6) for DSM-5 diagnoses, the WHO-5 Well-being scale and Problem Areas in Diabetes Scale (PAID). We extracted from the notes all physical conditions. We enquired about similar conditions in 1st and 2nd degree relatives. Descriptive, Chi-square test, Fisher’s exact test, one way ANOVA, and Multinomial logistic regression analysis were conducted to test achievements of our specific aims. Of the 182 patients who participated in the study, 45.1% (82/182) reported a family history of diabetes. Conditions significantly (p

Objectives Workplace stigmatisation and discrimination are significant barriers to accessing employment opportunities, reintegration and promotion in the workforce for people with mental illnesses in comparison to other disabilities. This paper presents qualitative evidence of anticipated and experienced workplace stigma and discrimination among individuals with major depressive disorder (MDD) in 35 countries, and how these experiences differ across countries based on their Human Development Index (HDI) level.Design Mixed-method cross-sectional survey.Participants, setting and measures The qualitative data were gathered as part of the combined European Union Anti-Stigma Programme European Network and global International Study of Discrimination and Stigma Outcomes for Depression studies examining stigma and discrimination among individuals with MDD across 35 countries. Anticipated and experienced stigma and discrimination were assessed using the Discrimination and Stigma Scale version 12 (DISC-12). This study used responses to the open-ended DISC-12 questions related to employment. Data were analysed using the framework analysis method.Results The framework analysis of qualitative data of 141 participants identified 6 key ‘frames’ exploring (1) participants reported experiences of workplace stigma and discrimination; (2) impact of experienced workplace stigma and discrimination; (3) anticipated workplace stigma and discrimination; (4) ways of coping; (5) positive work experiences and (6) contextualisation of workplace stigma and discrimination. In general, participants from very high HDI countries reported higher levels of anticipated and experienced discrimination than other HDI groups (eg, less understanding and support, being more avoided/shunned, stopping themselves from looking for work because of expectation and fear of discrimination). Furthermore, participants from medium/low HDI countries were more likely to report positive workplace experiences.Conclusions This study makes a significant contribution towards workplace stigma and discrimination among individuals with MDD, still an under-researched mental health diagnosis. These findings illuminate important relationships that may exist between countries/contexts and stigma and discrimination, identifying that individuals from very high HDI countries were more likely to report anticipated and experienced workplace discrimination.

In an era marked by ubiquitous reliance on mobile applications for nearly every need, the opacity of apps’ behavior poses significant threats to their users’ privacy. Although major data protection regulations require apps to disclose their data practices transparently, previous studies have pointed out difficulties in doing so. To further delve into this issue, this article describes an automated method to capture data-sharing practices in Android apps and assess their proper disclosure according to the EU General Data Protection Regulation. We applied the method to 9,000 random Android apps, unveiling an uncomfortable reality: over 80% of Android applications that transfer personal data off device potentially fail to meet GDPR transparency requirements. We further investigate the role of third-party libraries, shedding light on the source of this problem and pointing towards measures to address it.

Abstract Background For better disease management and improved prognosis, early identification of co-morbid depression in diabetic patients is warranted. the WHO-5 well-being index (WHO-5) has been used to screen for depression in diabetic patients, and its Chinese version (WHO-5-C) has been validated. However, its psychometric properties remain to be further validated in the type 2 diabetes patient population. The aim of our study was to examine the reliability and validity of the WHO-5-C in patients with type 2 diabetes mellitus. Methods The cross-sectional study was conducted on 200 patients from July 2014 to March 2015. All patients should complete the WHO-5-C, the Patient Health Questionnaire-9 (PHQ-9), the 20-item Problem Areas in Diabetes Scale (PAID-20), the Mini International Neuropsychiatric Interview (M.I.N.I), and Hamilton Rating Scale for Depression (HAM-D). Internal consistency of WHO-5 was revealed by Cronbach’s alpha, and constructive validity by confirmatory factor analysis (CFA). Relationship with PHQ-9, HAM-D, and PAID-20 was examined for concurrent validity, and ROC analysis was performed for criterion validity. Results The WHO-5-C presented satisfactory reliability (Cronbach’s alpha = 0.88). CFA confirmed the unidimensional factor structure of WHO-5-C. The WHO-5-C had significant negative correlation with HAM-D (r = -0.610), PHQ-9 (r = -0.694) and PAID-20 (r = -0.466), confirming good concurrent validity. Using M.I.N.I as the gold standard, the cut-off value of WHO-5-C was 42, with a sensitivity of 0.83 and specificity of 0.75. Conclusion The WHO-5-C holds satisfactory reliability and validity that is suitable for depression screening in type 2 diabetes patients as a short and convenient instrument.

IntroductionPrevious research has revealed a bidirectional relationship between type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD). A very limited proportion of patients with T2DM comorbid MDD received adequate psychiatric intervention. This study investigated the help-seeking behaviors of patients with T2DM comorbid with MDD during one-year follow-up.MethodsAt a medical center in China, a cohort of outpatients with T2DM were assessed and diagnosed for comorbid depression at baseline and after one year. The Mini International Neuropsychiatric Interview was used to diagnose MDD, while The Patient Health Questionnaire-9 (PHQ-9) and The Hamilton Depression Scale 17-item (HAMD-17) were used for depression assessment. Mental health help-seeking behaviors of patients during follow-up period were also evaluated.ResultsOut of the 203 patients with T2DM at baseline, 114 (56.2%) completed the follow-up. The prevalence of MDD in participants with T2DM was 12.8% at baseline and 22.8% at follow-up. Patients who completed the follow-up had a lower baseline PHQ-9 score (test statistic -2.068, p=0.039), HAMD-17 score (test statistic -2.285, p=0.022) than those who did not complete the follow-up. A total of 26 patients had comorbid MDD during the follow-up period, among which 8 patients (30.8%) voluntarily visited psychiatric clinics, while others did not seek assistance. The level of HbA1c at follow-up was higher in patients who sought help than in those who did not (8.1 ± 1.8% vs. 7.0 ± 0.7%), although the difference was not statistically significant.ConclusionVoluntary psychiatric help-seeking for Chinese patients with comorbid T2DM and MDD is uncommon. It is crucial to increase awareness of depression among patients and healthcare professionals alike.

Background Protecting all human rights of people with mental health conditions is globally important. However, to facilitate practical implementation of rights, it is often necessary to decide which of these rights should be given priority, especially when they conflict with each other. Aims The aim of the Priorities of Human Rights and Mental Health (PHRAME) project is to develop a replicable approach to establish a proposed set of high-priority human rights of people with mental health conditions, to facilitate practical decision-making and implementation of such rights. Method A two-stage Delphi-style study with stakeholders was conducted to generate a list of key rights of people with mental health conditions, and rank priorities among these rights in terms of feasibility, urgency and overall importance. Results The stakeholders in this study consistently ranked three rights as top priorities: (a) the right to freedom from torture, cruel inhuman treatment and punishment; (b) the right to health and access to services/treatment; and (c) the right to protection and safety in emergency situations. Conclusions Insights from PHRAME can support decision-making about the priority to be given to human rights, to guide practical action. This approach can also be used to assess how human rights are prioritised in different settings and by different stakeholders. This study identifies the clear need for a central voice for people with lived experience in research and implementation of decisions about the priority of human rights, ensuring that action respects the opinion of people whose rights are directly affected.

Abstract This study aimed to analyze treatment guidelines of 12 SEE countries to identify non-pharmacological interventions recommended for schizophrenia, explore the evidence base supporting recommendations, and assess the implementation of recommended interventions. Desk and content analysis were employed to analyze the guidelines. Experts were surveyed across the 12 countries to assess availability of non-pharmacological treatments in leading mental health institutions, staff training, and inclusion in the official service price list. Most SEE countries have published treatment guidelines for schizophrenia focused on pharmacotherapy. Nine countries—Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Greece, Moldova, Montenegro, North Macedonia, and Serbia—included non-pharmacological interventions. The remaining three countries—Kosovo (UN Resolution), Romania, and Slovenia—have not published such treatment guidelines, however they are on offer in leading institutions. The median number of recommended interventions was seven (range 5–11). Family therapy and psychoeducation were recommended in most treatment guidelines. The majority of recommended interventions have a negative or mixed randomized controlled trial evidence base. A small proportion of leading mental health institutions includes these interventions in their official service price list. The interventions recommended in the treatment guidelines seem to be rarely implemented within mental health services in the SEE countries.

Background: Olanzapine is used to treat schizophrenia and bipolar disorder in women of childbearing age. Continuation of psychotropic medications throughout pregnancy and lactation is often required as cessation could be dangerous for both mother and child. However, there is a lack of information on the transfer of these drugs into the developing brain. Methods: Sprague Dawley rats at three developmental ages: embryonic day E19, postnatal day P4 and non-pregnant adult females were administered unlabelled or radiolabelled (3H) olanzapine (0.15 mg/kg) either as monotherapy or in combination with each of seven other common medications. Similar injections were administered to pregnant E19 females to investigate placental transfer. Olanzapine in plasma, cerebrospinal fluid (CSF) and brain was measured by liquid scintillation counting after a single dose (acute) or following 5 days of treatment (prolonged). Results: Olanzapine entry into brain and CSF was not age-dependent. Prolonged olanzapine treatment reduced placental transfer from 53% to 46% (p

Abstract Background Patients suffering from severe mental disorders, including schizophrenia, major depression and bipolar disorders, have a reduced life expectancy compared to the general population of up to 10–25 years. This mortality gap requires urgent actions from a public health perspective in order to be reduced. Main text Factors associated with the high mortality rates in patients with severe mental disorders can be grouped into four groups: those related to the patients, to psychiatrists, to other non-psychiatrist medical doctors and to the healthcare system. Each of these factors should become the target of specific and dedicated interventions, in order to reduce the morbidity and mortality rate in patients with severe mental disorders. All these elements contribute to the neglect of physical comorbidity in patients with severe mental. In particular, the long-standing separation of psychiatry from other branches of medicine and the lack of specific training on this issue further contribute to the poor attention dedicated to management of physical comorbidities. Recently, several professional associations have invited national bodies regulating education of healthcare professionals to include the management of physical health of people with severe mental disorders in undergraduate and postgraduate educational programs. Conclusions The premature mortality in patients with severe mental disorders is a complex phenomenon resulting by the interaction of several protective and risk factors. Therefore, a multilevel approach is needed, in which the different stakeholders involved in health care provision establish workforces for the long-term management of physical and mental health conditions.

Abstract Background Pathways to care studies are feasible and tested means of finding the actual routes taken by patients before reaching proper care. In view of the predominance of nonprofessional service providers and the lack of previous large studies on pathways in Nepal, this multicenter study is needed. The aim of the study was to trace the various pathways and carers involved in mental health care; assess clinical variables such as the duration of untreated illness, clinical presentation and treatment; and compare geographically and culturally diverse landscapes. Methods This was a cross-sectional, convenience sampling study performed at 14 centers where new cases were being taken. The World Health Organization Study of the Pathways-to-Care Schedule was applied. The Nepali version of the encounter form was used. The data were collected between 17 September and 16 October 2020 and were analyzed using the Statistical Package for the Social Sciences (SPSS). Additionally, perspectives from local investigators were collected and discussed. Results Most of the first carers were native/religious faith healers (28.2%), followed by psychiatrists (26%). The median duration for the first psychiatric consultation was 3 weeks. The duration of untreated illness was 30.72 ± 80.34 (median: 4) weeks, and the time taken for this journey was 94.99 ± 274.58 (median: 30) min. The longest delay from the onset of illness to psychiatric care was for epilepsy {90.0 ± 199.0 (median: 25.5)} weeks, followed by neurotic illness {22.89 ± 73.45 (median: 2)} and psychotic illness {10.54 ± 18.28 (median: 2)} weeks. Overall, most patients with severe mental illnesses (SMIs) had their first contact with faithhealers (49%), then met with medical doctors (13%) or psychiatrists (28%). Marked differences in clinical presentation surfaced when hilly centers were compared with the Terai belt. Conclusions Faith healers, general practitioners and hospital doctors are major carers, and the means of educating them for proper referral can be considered. The investigators see several hindrances and opportunities in the studied pathways. The employment of more mental health professionals and better mental health advocacy, public awareness programs and school education are suggested strategies to improve proper mental health care.

Background: Olanzapine is used to treat schizophrenia and bipolar disorder in women of childbearing age. Continuation of psychotropic medications throughout pregnancy and lactation is often required as cessation could be dangerous for both mother and child. However, there is a lack of information on the transfer of these drugs into the developing brain. Methods: Sprague Dawley rats at three developmental ages: embryonic day E19, postnatal day P4 and non-pregnant adult females were administered unlabelled or radiolabelled (3H) olanzapine (0.15 mg/kg) either as monotherapy or in combination with each of seven other common medications. Similar injections were administered to pregnant E19 females to investigate placental transfer. Olanzapine in plasma, cerebrospinal fluid (CSF) and brain was measured by liquid scintillation counting after a single dose (acute) or following 5 days of treatment (prolonged). Results: Olanzapine entry into brain and CSF was not age-dependent. Prolonged olanzapine treatment reduced placental transfer from 53% to 46% (p

Background: The COVID-19 pandemic has forced people to change their lifestyles, especially with respect to restrictions on going out. Forced quarantine (i.e., lockdown) and self-restraint behavior (SRB), including self-quarantine, are suggested to induce potential negative impacts on public mental health. SRB seems to be related to governmental policies, each individual’s social background and mental condition; however, no empirical studies have been conducted. Methods: 1053 participants (mainly office workers) from epidemic areas and non-epidemic areas in Japan voluntarily conducted an online survey in June 2020. We assessed COVID-19-related aspects such as the degree of SRB, motivation for SRB, stigma, anxiety and depressive feelings due to COVID-19 by original questionnaires) and general mental health status (social anxiety by MINI-SPIN, depressive tendency by PHQ-9, depression-related personality traits by TACS-22 and resilience by TRS). Results: Regional comparison showed significant differences in SRB and social anxiety. People in epidemic areas tend to refrain from going out. Conversely, people in non-epidemic areas tend to shun the public eye. Regardless of epidemic status, proactive SRB was associated with higher motivation for SRB, higher social anxiety, higher depressive tendency, stronger COVID-19-related psychological factors and lower resilience. Moreover, people with proactive SRB in non-epidemic areas had the highest depressive tendency. Discussion: The present cross-sectional survey among office workers in Japan showed that people with proactive SRB have stronger COVID-19-related anxiety and depressive feelings, regardless of where they live. Our key finding is that people with proactive SRB in non-epidemic areas have the highest depressive tendency. Based on the present finding, we herein propose the following hypothesis: Higher levels of depressive tendency may enhance proactive SRB, which may be partly associated with higher levels of stigma, anxiety and depressive feelings related to COVID-19. Limitations: The general tendencies to avoid danger and stigma were not evaluated. Conclusions: Depressive tendency is suggested to be associated with proactive SRB against COVID-19. Intervention for depressive tendency in non-clinical settings (e.g., workplaces) may help citizens understand the infectious situation appropriately and to behave effectively during the pandemic. Further investigations should be conducted to clarify the present findings.

Since the Second World War mental health programmes and psychiatry have made significant advances. Countries, as well as the United Nations, have recognized the magnitude and severity of mental health problems, and numerous national programmes have been launched to deal with them. Technology relating to the treatment of mental disorders has advanced and significant progress has been made in terms of knowledge regarding the functioning of the brain. The awareness of the need to protect the human rights of those with mental illness has increased. National and regional programmes against stigma and the consequent discrimination of those with mental illness, have been launched in many countries. Associations bringing together those who have experienced mental illness and their relatives, have come into existence in many countries. While these are great steps forward, more work is necessary to complete these advances. In low- and middle-income countries, the vast majority of people with mental disorders do not receive adequate treatment. Even in highly industrialized countries, a third of people with severe forms of mental illness are not receiving the appropriate therapy. Laws concerning mental health are outdated in many countries. The protection of the human rights of the mentally ill is incomplete and imperfect. The emphasis on economic gain and the digitalization of medicine in recent years has not helped. On occasions, this has even slowed down the development of mental health services, and the provision of mental healthcare. Thus, psychiatry must still deal with the challenges of the past century, while facing new demands and tasks. Among the new tasks for psychiatry are undoubtedly reforms which will allow (i) the provision of appropriate care of people with comorbid mental and physical disorders, (ii) the application of interventions leading to the primary prevention of mental and neurological disorders, and (iii) a radical reform of the education of psychiatrists and other mental health workers, dealing with mental illness. Collaboration with other stakeholders in the field of mental health and medicine, will be of crucial importance in relation to all these tasks.

Abstract Although the association between antipsychotic use and corrected QT interval (QTc) prolongation has been repeatedly confirmed, the relationship has been rarely studied in a practical setting. Using data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP‐AP) survey, our study aimed to investigate the prevalence and clinical correlates of QTc prolongation in 2553 Asian patients with schizophrenia. After adjusting for the potential effect of confounding factors, the baseline and clinical characteristics of the schizophrenia patients with and without QTc prolongation were compared using analyses of covariance and binary logistic analyses. In addition, a binary logistic analysis model with a forward selection method was used to identify the distinctive clinical correlates of QTc prolongation. QTc prolongation was noted in 1.1% of Asian patients with schizophrenia. Schizophrenia patients were characterized by lower proportions of disorganized speech and negative symptoms; higher use of amisulpride and clozapine; and higher proportions of rigidity, hypercholesterolemia, and sedation than those without QTc prolongation. Finally, a binary logistic mode showed that amisulpride, clozapine, rigidity, and hypercholesterolemia might be the distinctive clinical correlates of QTc prolongation in Asian patients with schizophrenia. These findings indicate the clinical implications that the uses of amisulpride and clozapine and the occurrences of rigidity and hypercholesterolemia may be potential risk factors for QTc prolongation of schizophrenia patients.

The number of tourist arrivals is one of the main points in assessing the success of the tourism sector. Because of that, the seasonal pattern of tourist arrivals is an important thing that must be observed in making policies in the field of tourism marketing. Therefore, identifying seasonal patterns will influence the strategy of allocating available resources, especially in markets that have great potential in producing quality tourists like Australia. By using the calculation of Seasonality Ratio, Seasonality Indicator, Gini Coefficients, and Seasonality Index, this study compares the seasonal patterns of Australian tourists arriving in Indonesia with other competing countries, namely Singapore and Thailand. This research has succeeded in identifying that the Seasonality Ratio and Seasonality Indicator values show the pattern of Australian tourists arrives in Indonesia has more fluctuations every month. Despite this, the seasonal level of Australian tourists to Indonesia is low the same as the two other countries. This is seen from the results of the Gini Coefficient calculation in the three countries are below 0.5, or the difference in tourist arrivals per month is not significant. The Seasonality Index indicator shows that January, April, and December are the peak season periods for Australian tourists arriving Singapore and Thailand. However, this is different in Indonesia which is in the off-season phase. Thus, Indonesia has opportunities to optimize Australian tourist arrives in the off-season with the right marketing policies.

Organoid technology has enabled the generation of several breast cancer organoids. Here, the authors combine propagation of normal human mammary tissues with mass cytometry to evaluate the ability of organoid culture technologies to preserve stem cells and differentiated cell types.

Background There are limited data on the role of body image in patients with type 2 diabetes. The purpose of this study was to compare body self-esteem in this group with norms for the general Polish population and to investigate the relationship between body self-esteem and the psychological and clinical characteristics of the course of diabetes. Methods A group of 100 consecutive adult patients with type 2 diabetes (49 women and 51 men) aged 35 to 66 years were assessed using the Body Esteem Scale (BES), World Health Organization-Five Well-Being Index (WHO-5), Problem Areas in Diabetes Scale (PAID), and Hamilton Rating Scale for Depression (HAM-D). Results In comparison to norms for the general population, women with type 2 diabetes had lower body self-esteem only in the dimension of Physical Condition (M = 30.71; SD = 7.11 versus M = 32.96; SD = 5.69; P = 0.003), whereas men in the dimensions of Physical Condition (M = 42.43; SD = 9.43 versus M = 48.30; SD = 8.42; P Conclusions Persons with diabetes seem to have lower body self-esteem than the general population, which is significantly associated with clinical and psychological characteristics of the diabetes course. The observed differences and relationships are gender-specific.

Objective: Using data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), our study aimed to establish the remission and severity ranges (mild, moderate, and severe) of schizophrenia on the Brief Psychiatric Rating Scale-6 (BPRS-6). Methods: A total of 1,438 patients with schizophrenia from India, Indonesia, Japan, Malaysia, and Taiwan were enrolled in the study. Using the receiver operating characteristic (ROC) curve analyses, the optimal cut-off scores for the remission and severity ranges on the BPRS-6 were established. Results: The scalability of the BPRS-6 was considered to have an acceptable “unidimensionality” (coefficient of scalability = 0.43). The cut-off scores for the remission of schizophrenia and mild, moderate, and severe schizophrenia can be optimally defined as the BPRS-6 total score of 20, respectively. Conclusion: The BPRS-6 can be a promising, brief, and unidimensional rating scale to supplement the measurement-based care of schizophrenia.

OBJECTIVE: We aimed to present the scalability and cut-off score for the presence of aggression on the Brief Psychiatric Rating Scale-Excited Component (BPRS-EC) in schizophrenia patients. METHODS: From the Research on Asian Psychotropic Prescription Patterns for Antipsychotics, 1,438 Asian patients with schizophrenia were recruited in present study. The Mokken analysis was used to evaluate scalability of the BPRS-EC. The receiver operating characteristic (ROC) curve was used to establish the optimal cut-off score for the presence of aggression on the BPRS-6 in schizophrenia patients. RESULTS: The Mokken model presented that the scalability of the BPRS-EC was considered to have a strong “unidimensionality” (coefficient of scalability = 0.57). The ROC curve showed that, with the cut-off score of 5, the total score on the BPRS-EC distinguished the absence and presence of aggression in schizophrenia patients. CONCLUSION: The BPRS-EC can be used as a supplementary scale for evaluating aggression in patients with schizophrenia.

Background: Although disorganized speech is seen as one of the nuclear features of schizophrenia, there have been few reports of disorganized speech-associated psychotropic drug-prescribing patterns in large samples of schizophrenia patients. Objective: We aimed to examine the prevalence of disorganized speech and its correlates in terms of psychotropic drug prescribing, using the data from the Research on Asian Psychotropic Patterns for Antipsychotics (REAP-AP) study. Method: A total of 3744 patients with the ICD-10 diagnosis of schizophrenia were enrolled from 71 survey centers in 15 Asian countries/areas. An essential criterion of disorganized speech was that it was “severe enough to impair substantially effective communication” as defined in the DSM-5. A binary logistic model was fitted to identify the psychotropic drug-prescribing correlates of disorganized speech. Results: After adjusting for the potential effects of confounding variables, the binary logistic regression model showed that the presence of disorganized speech was directly associated with adjunctive use of mood stabilizers (P

Abstract Objective To provide an estimate of the effect of interventions on comorbid depressive disorder (MDD) or subthreshold depression in type 1 and type 2 diabetes. Methods Systematic review and meta‐analysis. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomized controlled trials evaluating the outcome of depression treatments in diabetes and comorbid MDD or subthreshold symptoms published before August 2019 compared to care as usual (CAU), placebo, waiting list (WL), or active comparator treatment as in a comparative effectiveness trial (CET). Primary outcomes were depressive symptom severity and glycemic control. Cohen's d is reported. Results Forty‐three randomized controlled trials (RCTs) were selected, and 32 RCTs comprising 3,543 patients were included in the meta‐analysis. Our meta‐analysis showed that, compared to CAU, placebo or WL, all interventions showed a significant effect on combined outcome 0,485 (95% CI 0.360; 0.609). All interventions showed a significant effect on depression. Pharmacological treatment, group therapy, psychotherapy, and collaborative care had a significant effect on glycemic control. High baseline depression score was associated with a greater reduction in HbA1c and depressive outcome. High baseline HbA1c was associated with a greater reduction in HbA1c. Conclusion All treatments are effective for comorbid depression in type 1 diabetes and type 2 diabetes. Over the last decade, new interventions with large effect sizes have been introduced, such as group‐based therapy, online treatment, and exercise. Although all interventions were effective for depression, not all treatments were effective for glycemic control. Effective interventions in comorbid depressive disorder may not be as effective in comorbid subthreshold depression. Baseline depression and HbA1c scores modify the treatment effect. Based on the findings, we provide guidance for treatment depending on patient profile and desired outcome, and discuss possible avenues for further research.

Background: Human milk contains both arachidonic acid (ARA) and docosahexaenoic acid (DHA). Supplementation of infant formula with ARA and DHA results in fatty acid (FA) profiles, neurodevelopmental outcomes, and immune responses in formula-fed infants that are more like those observed in breastfed infants. Consequently, ARA and DHA have been historically added together to infant formula. This study investigated the impact of ARA or DHA supplementation alone or in combination on tissue FA incorporation, immune responses, and neurodevelopment in the young pig.Methods: Male pigs (N = 48 total) received one of four dietary treatments from postnatal day (PND) 2–30. Treatments targeted the following ARA/DHA levels (% of total FA): CON (0.00/0.00), ARA (0.80/0.00), DHA (0.00/0.80), and ARA+DHA (0.80/0.80). Plasma, red blood cells (RBC), and prefrontal cortex (PFC) were collected for FA analysis. Blood was collected for T cell immunophenotyping and to quantify a panel of immune outcomes. Myelin thickness in the corpus callosum was measured by transmission electron microscopy and pig movement was measured by actigraphy.Results: There were no differences in formula intake or growth between dietary groups. DHA supplementation increased brain DHA, but decreased ARA, compared with all other groups. ARA supplementation increased brain ARA compared with all other groups but did not affect brain DHA. Combined supplementation increased brain DHA levels but did not affect brain ARA levels compared with the control. Pigs fed ARA or ARA+DHA exhibited more activity than those fed CON or DHA. Diet-dependent differences in activity suggested pigs fed ARA had the lowest percent time asleep, while those fed DHA had the highest. No differences were observed for immune or myelination outcomes.Conclusion: Supplementation with ARA and DHA did not differentially affect immune responses, but ARA levels in RBC and PFC were reduced when DHA was provided without ARA. Supplementation of either ARA or DHA alone induced differences in time spent asleep, and ARA inclusion increased general activity. Therefore, the current data support the combined supplementation with both ARA and DHA in infant formula and raise questions regarding the safety and nutritional suitability of ARA or DHA supplementation individually.

Aim: Diabetic peripheral neuropathy (DPN) is a common, severe microvascular complication of diabetes. Our study was to assess prevalence and risk factors for DPN in subjects with type 2 diabetes from 14 different countries.Methods: A total of 2,733 subjects with type 2 diabetes aged 18–65 years (45.3% men, mean duration of diabetes = 8.8 years) were included to perform this International Prevalence and Treatment of Diabetes and Depression (INTERPRET-DD) study in 14 countries. After a structured questionnaire was used in face-to-face interviews to collect sociodemographic characteristics and medical records of the participating subjects, laboratory tests were carried out for clinical measurement. Depressive symptoms were diagnosed and measured using the Patient Health Questionnaire-9. The potential risk factors for DPN were determined by multilevel mixed-effects logistic regression, accounting for clustering of participants within the country. Robustness of the estimates was assessed by sensitivity analysis.Results: The overall prevalence of DPN across different countries was 26.71%, whereas country-specific prevalences showed considerable variation. Multivariate analysis revealed that duration of diabetes (OR: 1.08 per 1-year increase, 95% CI: 1.06–1.09), poor glycemic control (OR: 1.11 per 1% increase in HbA1c, 95% CI: 1.05–1.18), and history of hypertension (OR: 1.58, 95% CI: 1.18–2.12), cardiovascular disease (OR: 2.07, 95% CI: 1.55–2.78) and depressive symptoms (OR: 1.92, 95% CI: 1.43–2.58) were independently and positively associated with the risk of DPN. Sensitivity analyses including or excluding patients from countries with extreme low or high prevalence of DPN yielded similar estimates in terms of trend and magnitude.Conclusions: This international study illustrates that more than a quarter of individuals with type 2 diabetes developed DPN. The prevalence was positively associated with the duration of diabetes, poor glycemic control, and history of hypertension, cardiovascular disease and depressive symptoms.

Myelodysplastic syndromes and acute myeloid leukemia with TP53 mutations are characterized by frequent relapses, poor or short responses, and poor survival with the currently available therapies including chemotherapy and 5-azacitidine (AZA). PRIMA-1Met(APR-246,APR) is a methylated derivative of PRIMA-1, which induces apoptosis in human tumor cells through restoration of the transcriptional transactivation function of mutant p53. Here we show that low doses of APR on its own or in combination with AZA reactivate the p53 pathway and induce an apoptosis program. Functionally, we demonstrate that APR exerts these activities on its own and that it synergizes with AZA in TP53-mutated myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) cell lines and in TP53-mutated primary cells from MDS/AML patients. Low doses of APR on its own or in combination with AZA also show significant efficacy in vivo. Lastly, using transcriptomic analysis, we found that the APR + AZA synergy was mediated by downregulation of the FLT3 pathway in drug-treated cells. Activation of the FLT3 pathway by FLT3 ligand reversed the inhibition of cell proliferation by APR + AZA. These data suggest that TP53-mutated MDS/AML may be better targeted by the addition of APR-246 to conventional treatments.

AimsThis study evaluated the psychometric characteristics of the Polish version of the PHQ-9 in detecting major depression (MDD) and 'MDD and/or dysthymia' in people with and without type 2 diabetes.MethodsParticipants were randomly selected from a diabetes outpatient facility (N = 216) and from among patients admitted to a medical center and psychiatric hospital (N = 99). The participants completed the PHQ-9. The Hamilton Depression Rating Scale and the Mini International Neuropsychiatric Interview were used to identify the presence of psychiatric symptoms. The optimal cut-offs for PHQ-9 in people with and without type 2 diabetes were investigated based on two methods: 1) Youden's index which identifies cut-off points useful in scientific research; 2) a second method of two-stage screening for depressive disorders to provide guidance for clinical practice.ResultsThe Polish version of the PHQ-9 is a reliable and valid screening tool for depression in people with and without type 2 diabetes. An optimal cut-off of ≥ 7 was indicated by Youden's index and ≥ 5 by the two-stage method for screening for MDD and 'MDD and/or dysthymia' in the group with type 2 diabetes. A cut-off of ≥ 11 was optimal for screening for both MDD and 'MDD and/or dysthymia' among people without diabetes (Youden's index). The two-stage approach suggested a ≥ 10 score for screening for MDD and ≥ 9 for screening for 'MDD and/or dysthymia' in people without diabetes.ConclusionsA lower cut-off score of the PHQ-9 is recommended for people with type 2 diabetes as compared to the general population.

Fabry disease (FD) is an X-linked disorder with α-galactosidase A deficiency. Males (>30 years) and females (>40 years) often present with cardiac manifestations, predominantly left ventricular hypertrophy (LVH). The aim of this study was to evaluate electrocardiographic (ECG) characteristics within FD patients to identify gender related differences, and to additionally explore the association of ECG parameters with structural and functional alterations on transthoracic echocardiography (TTE). Retrospective cross-sectional analysis of 45 FD patients with contemporaneous ECG and TTE was performed and compared to age and gender matched healthy controls. FD patients demonstrated alterations in several ECG parameters particularly in males, including prolonged P-wave duration (91 vs. 81 ms, p = 0.022), prolonged QRS duration (96 vs. 84 ms, p < 0.001), increased R-wave amplitude in lead I (8.1 vs. 5.7 mV, p = 0.047), increased Sokolow–Lyon index (25 vs. 19 mV, p = 0.002) and were more likely to meet LVH criteria (31% vs. 7%, p = 0.006). FD patients with impaired basal longitudinal strain (LS) on TTE were more likely to meet LVH criteria (41% vs. 0%, p = 0.018). Those with more advanced FD (increased LV wall thickness on TTE) were more likely to meet LVH criteria but additionally demonstrated prolonged ventricular depolarization (QRS duration 101 vs. 88 ms, p = 0.044). Therefore, alterations on ECG demonstrating delayed atrial activation, delayed ventricular depolarization and evidence of LVH were more often seen in male FD patients. Impaired basal LS, a TTE marker of early cardiac involvement, correlated with ECG abnormalities. Increased LV wall thickness on TTE, a marker of more advanced FD, was associated with more severe ECG abnormalities.

BackgroundPopulation-based examination of comorbidity is an emerging field of study.AimsThe purpose of the present population level study is to expand our understanding of how cancer and mental illness are temporally associated.MethodA sample of 83 648 056 physician billing records for 664 838 (56% female) unique individuals over the age of 18 was stratified on ages 19–49 years and 50+ years, with temporal order of mental disorder and cancer forming the basis of comparison.ResultsMental disorders preceded cancers for both genders within each age strata. The full range of cancers and mental disorders preceding or following each pivot ICD class are described in terms of frequency of diagnosis and duration in days, with specific examples illustrated.ConclusionsThe temporal comorbidity between specific cancers and mental disorders may be useful in screening or clinical planning and may represent indicators of disease mechanism that warrant further screening or investigation.Declaration of interestNone.

Our study aimed to assess the psychometric validity of the conceptual disorganization item and other items of the Brief Psychiatric Rating Scale (BPRS) for detecting disorganized speech in patients with schizophrenia. We included 357 schizophrenia patients with disorganized speech and 1082 without disorganized speech from the survey centers in India, Indonesia, Japan, Malaysia, and Taiwan, using the data from the Research on Asian Psychotropic Patterns for Antipsychotics (REAP-AP) study. After adjusting the effects of confounding variables, a binary logistic regression model was fitted to identify BPRS items independently associated with disorganized speech. Receiver operating characteristic (ROC) curves were used to identify optimum cut-off scores and their sensitivities and specificities for detecting disorganized speech. After adjusting the effects of confounding variables, the fitted binary logistic regression model indicated that conceptual disorganization (P

Abstract Background Clinical and social services both are important for dementia care. The International Dementia Alliance (IDEAL) Schedule for the Assessment and Staging of Care was developed to guide clinical and social care for dementia. Our study aimed to assess the validity and reliability of the IDEAL schedule in China. Methods Two hundred eighty-two dementia patients and their caregivers were recruited from 15 hospitals in China. Each patient-caregiver dyad was assessed with the IDEAL schedule by a rater and an observer simultaneously. The Clinical Dementia Rating (CDR), Mini-Mental Status Examination (MMSE), and Caregiver Burden Inventory (CBI) were assessed for criterion validity. IDEAL repeated assessment was conducted 7-10 days after the initial interview for 62 dyads. Results Two hundred seventy-seven patient-caregiver dyads completed the IDEAL assessment. Inter-rater reliability for the total score of the IDEAL schedule was 0.93 (95%CI = 0.92-0.95). The inter-class coefficient for the total score of IDEAL was 0.95 for the interviewers and 0.93 for the silent raters. The IDEAL total score correlated with the global CDR score (ρ = 0.72, p

Abstract There is considerable debate about whether the partition volumes of the mammalian brain (e.g. cerebrum, cerebellum) evolve according to functional selection, or whether developmental constraints of conserved neurogenetic scheduling cause predictable partition scaling with brain size. Here we provide the first investigation of developmental constraints on partition volume growth, derived from contrast-enhanced micro-computed tomography of hydrogel-stabilized brains from three marsupial species. ANCOVAs of partition vs. brain volume scaling, as well as growth curve comparisons, do not support several hypotheses consistent with developmental constraints: brain partition growth significantly differs between species, or between developing vs. adult marsupials. Partition growth appears independent of adult brain volume, with no discernable growth spurts/lags relatable to internal structural change. Rather, adult proportion differences appear to arise through growth rate/duration heterochrony. Substantial phylogenetic signal in adult brain partitions scaling with brain volume also counters expectations of development-mediated partition scaling conservatism. However, the scaling of olfactory bulb growth is markedly irregular, consistent with suggestions that it is less constrained. The very regular partition growth curves suggest intraspecific developmental rigidity. We speculate that a rigid, possibly neuromer-model-like early molecular program might be responsible both for regular growth curves within species and impressions of a link between neurogenesis and partition evolution.

A 61-year-old Caucasian male with severe plaque psoriasis without joint involvement was initiated on adalimumab therapy. Shortly thereafter he presented to the emergency room with acute loss of vision in the right eye. A comprehensive systemic workup was instituted which included magnetic resonance imaging (MRI) with and without gadolinium of the brain and orbits. MRI revealed findings that were consistent with CNS demyelination and retrobulbar optic neuritis. Immediate cessation of adalimumab was instituted without any other systemic therapy. Complete return of vision occurred within 6 weeks. No additional psoriatic or neurologic treatment was instituted, and the patient has remained stable now for 14 months.

Abstract Background The aim of the study is to carry out a cost-effectiveness analysis of three different interventions to promote the uptake of screening for cervical cancer in general practice in the county of Valles Occidental, Barcelona, Spain. Methods Women aged from 30 to 70 years (n = 15,965) were asked to attend a general practice to be screened. They were randomly allocated to one of four groups: no intervention group (NIG); one group where women received an invitation letter to participate in the screening (IG1); one group where women received an invitation letter and informative leaflet (IG2); and one group where women received an invitation letter, an informative leaflet and a phone call reminder (IG3). Clinical effectiveness was measured as the percentage increase in screening coverage. A cost-effectiveness analysis was performed from the perspective of the public health system with a time horizon of three to five years – the duration of the randomised controlled clinical trial. In addition, a deterministic sensitivity analysis was performed. Results are presented according to different age groups. Results The incremental cost-effectiveness ratio (ICER) for the most cost-effective intervention, IG1, compared with opportunistic screening was € 2.78 per 1% increase in the screening coverage. The age interval with the worst results in terms of efficiency was women aged

Background Anxiety disorder, one of the highly disabling, prevalent and common mental disorders, is known to be more prevalent in persons with type 2 diabetes mellitus (T2DM) than the general population, and the comorbid presence of anxiety disorders is known to have an impact on the diabetes outcome and the quality of life. However, the information on the type of anxiety disorder and its prevalence in persons with T2DM is limited.Aims To assess the prevalence and correlates of anxiety disorder in people with type 2 diabetes in different countries.Methods People aged 18–65 years with diabetes and treated in outpatient settings were recruited in 15 countries and underwent a psychiatric interview with the Mini-International Neuropsychiatric Interview. Demographic and medical record data were collected.Results A total of 3170 people with type 2 diabetes (56.2% women; with mean (SD) duration of diabetes 10.01 (7.0) years) participated. The overall prevalence of anxiety disorders in type 2 diabetic persons was 18%; however, 2.8% of the study population had more than one type of anxiety disorder. The most prevalent anxiety disorders were generalised anxiety disorder (8.1%) and panic disorder (5.1%). Female gender, presence of diabetic complications, longer duration of diabetes and poorer glycaemic control (HbA1c levels) were significantly associated with comorbid anxiety disorder. A higher prevalence of anxiety disorders was observed in Ukraine, Saudi Arabia and Argentina with a lower prevalence in Bangladesh and India.Conclusions Our international study shows that people with type 2 diabetes have a high prevalence of anxiety disorders, especially women, those with diabetic complications, those with a longer duration of diabetes and poorer glycaemic control. Early identification and appropriate timely care of psychiatric problems of people with type 2 diabetes is warranted.

Background: A major concern for clinicians in prescribing medications to pregnant women and neonates is the possibility that drugs might have damaging effects, particularly on long-term brain development. Current understanding of drug permeability at placental and blood-brain barriers during development is poor. In adults, ABC transporters limit many drugs from entering the brain; however, little is known about their function during development. Methods: The transfer of clinically relevant doses of paracetamol (acetaminophen), digoxin and cimetidine into the brain and cerebrospinal fluid (CSF) was estimated using radiolabelled drugs in Sprague Dawley rats at three developmental stages: E19, P4 and adult. Drugs were applied intraperitoneally either acutely or following chronic exposure (for five days). Entry into brain, CSF and transfer across the placenta was measured and compared to three markers (L-glucose, sucrose, glycerol) that cross barriers by “passive diffusion”. The expression of ABC transporters in the brain, choroid plexus and placenta was estimated using RT-qPCR. Results: All three drugs entered the developing brain and CSF in higher amounts than the adult brain and CSF. Comparisons with “passive” permeability markers suggested that this might be due to age-related differences in the functional capacity of ABC-efflux mechanisms. In adult animals, chronic treatment reduced digoxin (12% to 5%, p

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Breastfeeding is universally recommended as the optimal choice of infant feeding and consequently human milk has been extensively investigated to unravel its unique nutrient profile. The human milk lipid composition is unique and supplies specifically long-chain polyunsaturated fatty acids (LC-PUFAs), in particular, arachidonic acid (ARA, 20:4n−6) and docosahexaenoic acid (DHA, 22:6n−3). Arachidonic acid (ARA) is the most predominant long-chain polyunsaturated fatty acid in human milk, albeit at low concentrations as compared to other fatty acids. It occurs predominantly in the triglyceride form and to a lesser extent as milk fat globule membrane phospholipids. Human milk ARA levels are modulated by dietary intake as demonstrated by animal and human studies and consequently vary dependent on dietary habits among mothers and regions across the globe. ARA serves as a precursor to eicosanoids and endocannabinoids that also occur in human milk. A review of scientific and clinical studies reveals that ARA plays an important role in physiological development and its related functions during early life nutrition. Therefore, ARA is an important nutrient during infancy and childhood and, as such, appropriate attention is required regarding its nutritional status and presence in the infant diet. Data are emerging indicating considerable genetic variation in encoding for desaturases and other essential fatty acid metabolic enzymes that may influence the ARA level as well as other LC-PUFAs. Human milk from well-nourished mothers has adequate levels of both ARA and DHA to support nutritional and developmental needs of infants. In case breastfeeding is not possible and infant formula is being fed, experts recommend that both ARA and DHA are added at levels present in human milk.