Search the source libraries

حَدَّثَنَا أَحْمَدُ بْنُ مَنِيعٍ، حَدَّثَنَا إِسْحَاقُ بْنُ يُوسُفَ الأَزْرَقُ، حَدَّثَنَا دَاوُدُ بْنُ أَبِي هِنْدٍ، عَنِ الشَّعْبِيِّ، عَنْ مَسْرُوقٍ، قَالَ كُنْتُ مُتَّكِئًا عِنْدَ عَائِشَةَ فَقَالَتْ يَا أَبَا عَائِشَةَ ثَلاَثٌ مَنْ تَكَلَّمَ بِوَاحِدَةٍ مِنْهُنَّ فَقَدْ أَعْظَمَ عَلَى اللَّهِ الْفِرْيَةَ مَنْ زَعَمَ أَنَّ مُحَمَّدًا رَأَى رَبَّهُ فَقَدْ أَعْظَمَ الْفِرْيَةَ عَلَى اللَّهِ وَاللَّهُ يَقُولُ ‏:‏ ‏(‏ لَا تُدْرِكُهُ الأَبْصَارُ وَهُوَ يُدْرِكُ الأَبْصَارَ وَهُوَ اللَّطِيفُ الْخَبِيرُ ‏)‏ ، ‏(‏ مَا كَانَ لِبَشَرٍ أَنْ يُكَلِّمَهُ اللَّهُ إِلاَّ وَحْيًا أَوْ مِنْ وَرَاءِ حِجَابٍ ‏)‏ وَكُنْتُ مُتَّكِئًا فَجَلَسْتُ فَقُلْتُ يَا أُمَّ الْمُؤْمِنِينَ أَنْظِرِينِي وَلاَ تُعْجِلِينِي أَلَيْسَ يَقُولُ اللَّهُ ‏:‏ ‏(‏ وَلَقَدْ رَآهُ نَزْلَةً أُخْرَى ‏)‏، ‏(‏ وَلََقَدْ رَآهُ بِالأُفُقِ الْمُبِينِ ‏)‏ قَالَتْ أَنَا وَاللَّهِ أَوَّلُ مَنْ سَأَلَ عَنْ هَذَا رَسُولَ اللَّهِ صلى الله عليه وسلم قَالَ ‏"‏ إِنَّمَا ذَاكَ جِبْرِيلُ مَا رَأَيْتُهُ فِي الصُّورَةِ الَّتِي خُلِقَ فِيهَا غَيْرَ هَاتَيْنِ الْمَرَّتَيْنِ رَأَيْتُهُ مُنْهَبِطًا مِنَ السَّمَاءِ سَادًّا عِظَمُ خَلْقِهِ مَا بَيْنَ السَّمَاءِ وَالأَرْضِ ‏"‏ ‏.‏ وَمَنْ زَعَمَ أَنَّ مُحَمَّدًا كَتَمَ شَيْئًا مِمَّا أَنْزَلَ اللَّهُ عَلَيْهِ فَقَدْ أَعْظَمَ الْفِرْيَةَ عَلَى اللَّهِ يَقُولُ اللَّهُ ‏:‏ ‏(‏ يَا أَيُّهَا الرَّسُولُ بَلِّغْ مَا أُنْزِلَ إِلَيْكَ مِنْ رَبِّكَ ‏)‏ وَمَنْ زَعَمَ أَنَّهُ يَعْلَمُ مَا فِي غَدٍ فَقَدْ أَعْظَمَ الْفِرْيَةَ عَلَى اللَّهِ وَاللَّهُ يَقُولُ ‏:‏ ‏(‏قُلْ لاَ يَعْلَمُ مَنْ فِي السَّمَوَاتِ وَالأَرْضِ الْغَيْبَ إِلاَّ اللَّهُ ‏)‏ ‏.‏ قَالَ أَبُو عِيسَى هَذَا حَدِيثٌ حَسَنٌ صَحِيحٌ وَمَسْرُوقُ بْنُ الأَجْدَعِ يُكْنَى أَبَا عَائِشَةَ وَهُوَ مَسْرُوقُ بْنُ عَبْدِ الرَّحْمَنِ وَهَكَذَا كَانَ اسْمُهُ فِي الدِّيوَانِ ‏.‏

Narrated Masruq:"I was reclining in the presence of 'Aishah when she said: 'O Abu 'Aishah! There are three things, whoever speaks of one of them, then he has uttered one of the worst lies against Allah. Whoever claims that Muhammad saw his Lord. Then he has uttered one the worst lies against Allah, Allah says: No vision can grasp Him, but His grasp is over all vision, and He is the Most Subtle, Well-Acquainted with all things (6:103). It is not for any human being that Allah should speak to him unless (it be) by revelation or from behind a veil (42:51).' I was reclining so I sat up an said: 'O Mother of the Believers! Take your time with me and do not be hasty with me! Did Allah Most High not say: And indeed he saw him at a second descent (53:13). (And) 'And indeed he saw him in the clear horizon (81:23).' She said 'By Allah! I was the first who asked the Messenger of Allah (ﷺ) about this. He said: "That was only Jibril. I did not see him in the appearance he was created in except for these two times. I saw him descending from the heavens, and due to his tremendous size he filled what was between the heavens and the earth." "And whoever claimed that Muhammad hid anything that Allah revealed to him, then he uttered one of the worst lies against Allah. Allah says: O Messenger! Proclaim what has been sent down to you from your Lord (5:67)." "And whoever claimed that he (ﷺ) knew what would be tomorrow, then he has uttered one of the worst lies against Allah. Allah says: Say: 'None in the heavens and in the earth knows the unseen but Allah (27:)

full record with gradings →

حَدَّثَنِي زُهَيْرُ بْنُ حَرْبٍ، حَدَّثَنَا إِسْمَاعِيلُ بْنُ إِبْرَاهِيمَ، عَنْ دَاوُدَ، عَنِ الشَّعْبِيِّ، عَنْ مَسْرُوقٍ، قَالَ كُنْتُ مُتَّكِئًا عِنْدَ عَائِشَةَ فَقَالَتْ يَا أَبَا عَائِشَةَ ثَلاَثٌ مَنْ تَكَلَّمَ بِوَاحِدَةٍ مِنْهُنَّ فَقَدْ أَعْظَمَ عَلَى اللَّهِ الْفِرْيَةَ ‏.‏ قُلْتُ مَا هُنَّ قَالَتْ مَنْ زَعَمَ أَنَّ مُحَمَّدًا صلى الله عليه وسلم رَأَى رَبَّهُ فَقَدْ أَعْظَمَ عَلَى اللَّهِ الْفِرْيَةَ ‏.‏ قَالَ وَكُنْتُ مُتَّكِئًا فَجَلَسْتُ فَقُلْتُ يَا أُمَّ الْمُؤْمِنِينَ أَنْظِرِينِي وَلاَ تَعْجَلِينِي أَلَمْ يَقُلِ اللَّهُ عَزَّ وَجَلَّ ‏{‏ وَلَقَدْ رَآهُ بِالأُفُقِ الْمُبِينِ‏}‏ ‏{‏ وَلَقَدْ رَآهُ نَزْلَةً أُخْرَى‏}‏ ‏.‏ فَقَالَتْ أَنَا أَوَّلُ هَذِهِ الأُمَّةِ سَأَلَ عَنْ ذَلِكَ رَسُولَ اللَّهِ صلى الله عليه وسلم فَقَالَ ‏"‏ إِنَّمَا هُوَ جِبْرِيلُ لَمْ أَرَهُ عَلَى صُورَتِهِ الَّتِي خُلِقَ عَلَيْهَا غَيْرَ هَاتَيْنِ الْمَرَّتَيْنِ رَأَيْتُهُ مُنْهَبِطًا مِنَ السَّمَاءِ سَادًّا عِظَمُ خَلْقِهِ مَا بَيْنَ السَّمَاءِ إِلَى الأَرْضِ ‏"‏ ‏.‏ فَقَالَتْ أَوَلَمْ تَسْمَعْ أَنَّ اللَّهَ يَقُولُ ‏{‏ لاَ تُدْرِكُهُ الأَبْصَارُ وَهُوَ يُدْرِكُ الأَبْصَارَ وَهُوَ اللَّطِيفُ الْخَبِيرُ‏}‏ أَوَلَمْ تَسْمَعْ أَنَّ اللَّهَ يَقُولُ ‏{‏ وَمَا كَانَ لِبَشَرٍ أَنْ يُكَلِّمَهُ اللَّهُ إِلاَّ وَحْيًا أَوْ مِنْ وَرَاءِ حِجَابٍ أَوْ يُرْسِلَ رَسُولاً فَيُوحِيَ بِإِذْنِهِ مَا يَشَاءُ إِنَّهُ عَلِيٌّ حَكِيمٌ‏}‏ قَالَتْ وَمَنْ زَعَمَ أَنَّ رَسُولَ اللَّهِ صلى الله عليه وسلم كَتَمَ شَيْئًا مِنْ كِتَابِ اللَّهِ فَقَدْ أَعْظَمَ عَلَى اللَّهِ الْفِرْيَةَ وَاللَّهُ يَقُولُ ‏{‏ يَا أَيُّهَا الرَّسُولُ بَلِّغْ مَا أُنْزِلَ إِلَيْكَ مِنْ رَبِّكَ وَإِنْ لَمْ تَفْعَلْ فَمَا بَلَّغْتَ رِسَالَتَهُ‏}‏ ‏.‏ قَالَتْ وَمَنْ زَعَمَ أَنَّهُ يُخْبِرُ بِمَا يَكُونُ فِي غَدٍ فَقَدْ أَعْظَمَ عَلَى اللَّهِ الْفِرْيَةَ وَاللَّهُ يَقُولُ ‏{‏ قُلْ لاَ يَعْلَمُ مَنْ فِي السَّمَوَاتِ وَالأَرْضِ الْغَيْبَ إِلاَّ اللَّهُ‏}‏ ‏.‏

It is narrated on the authority of Masruq that he said:I was resting at (the house of) 'A'isha that she said: O Abu 'A'isha (kunya of Masruq), there are three things, and he who affirmed even one of them fabricated the greatest lie against Allah. I asked that they were. She said: He who presumed that Muhammad (ﷺ) saw his Lord (with his ocular vision) fabricated the greatest lie against Allah. I was reclining but then sat up and said: Mother of the Faithful, wait a bit and do not be in a haste. Has not Allah (Mighty and Majestic) said:" And truly he saw him on the clear horizon" (Al-Qur'an, Surat at-Takwir, 81:23) and" he saw Him in another descent" (Al-Qur'an, Surat Najm 53:13)? She said: I am the first of this Ummah who asked the Messenger of Allah (ﷺ) about it, and he said: Verily he is Gabriel. I have never seen him in his original form in which he was created except on those two occasions (to which these verses refer); I saw him descending from the heaven and filling (the space) from the sky to the earth with the greatness of his bodily structure. She said: Have you not heard Allah saying: "Eyes comprehend Him not, but He comprehends (all) vision. and He is Subtle, and All-Aware" (Al-Qur'an, Surat al-An`am 6:103)? (She, i.e. 'A'isha, further said): Have you not heard that, verily, Allah says: "And it is not for any human being that Allah should speak to him except by revelation or from behind a partition or that He sends a messenger to reveal, by His permission, what He wills. Indeed, He is Most High and Wise." (Al-Qur'an, Surat ash-Shura, 42:51) She said: He who presumes that the Messenger of Allah (ﷺ) concealed anything from the Book of Allah fabricates the greatest lie against Allah. Allah says: "O Messenger, announce that which has been revealed to you from your Lord, and if you do not, then you have not conveyed His message. And Allah will protect you from the people. Indeed, Allah does not guide the disbelieving people." (Al-Qur'an, Surat al-Ma'idah, 5:67). She said: He who presumes that he would inform about what was going to happen tomorrow fabricates the greatest lie against Allah. And Allah says "Say, 'None in the heavens and earth knows the unseen except Allah , and they do not perceive when they will be resurrected.'" (Al-Qur'an, Surat an-Naml, 27:)

full record with gradings →

Tenofovir-diphosphate in peripheral blood mononuclear cells during low, medium and high adherence to emtricitabine/ tenofovir alafenamide vs. emtricitabine/ tenofovir disoproxil fumarate.

Objective: Tenofovir alafenamide (TAF) preferentially loads peripheral blood mononuclear cells (PBMCs), resulting in higher PBMC tenofovir-diphosphate (TFV-DP) vs. tenofovir disoproxil fumarate (TDF). No studies have yet compared TFV-DP in PBMC from lower than daily dosing between prodrugs, which has potential implications for event-driven preexposure prophylaxis and pharmacologic forgiveness. Design: Two separate randomized, directly observed therapy (DOT) crossover studies (DOT-DBS and TAF-DBS) were conducted to mimic low, medium and high adherence. Methods: HIV-negative adults were randomized to two 12-week DOT regimens of 33, 67 or 100% of daily dosing with emtricitabine (F)/TAF 200 mg/25 mg (TAF-DBS) or F/TDF 200 mg/300 mg (DOT-DBS), separated by a 12-week washout. PBMC steady-state concentrations (Css) of TFV-DP and FTC-TP were estimated using nonlinear mixed models and compared between F/TAF and F/TDF. Results: Thirty-five participants contributed to 33% (n = 23), 67% (n = 23) and 100% (n = 23) of daily F/TAF regimens. Forty-four contributed to 33% (n = 15), 67% (n = 16) and 100% (n = 32) of daily F/TDF regimens. PBMC TFV-DP Css were 7.3 [95% confidence interval (95% CI): 6.4-8.2], 7.1 (5.9-8.2) and 6.7- (4.4-8.9) fold higher (P < 0.0001) following F/TAF vs. F/TDF; 593 vs. 81.7, 407 vs. 57.4, and 215 vs. 32.3 fmol/106 cells, respectively. TFV-DP was 2.6 (2.1-3.1) fold higher with 33% F/TAF vs. 100% F/TDF. Estimated half-lives (95% CI) of TFV-DP in PBMC were 2.9 (1.5-5.5) days for F/TAF and 2.1 (1.5-2.9) days for F/TDF. FTC-TP was similar in both studies (P = 0.119). Conclusion: F/TAF produced 6.7 to 7.3-fold higher TFV-DP in PBMC vs. F/TDF across adherence levels, supporting increased potency and pharmacologic forgiveness with F/TAF in the PBMC compartment.

AIDS (London, England) · randomised controlled trial · 27 citationsread the source →

Suicide prevention strategies revisited: 10-year systematic review.

Background: Many countries are developing suicide prevention strategies for which up-to-date, high-quality evidence is required. We present updated evidence for the effectiveness of suicide prevention interventions since 2005. Methods: We searched PubMed and the Cochrane Library using multiple terms related to suicide prevention for studies published between Jan 1, 2005, and Dec 31, 2014. We assessed seven interventions: public and physician education, media strategies, screening, restricting access to suicide means, treatments, and internet or hotline support. Data were extracted on primary outcomes of interest, namely suicidal behaviour (suicide, attempt, or ideation), and intermediate or secondary outcomes (treatment-seeking, identification of at-risk individuals, antidepressant prescription or use rates, or referrals). 18 suicide prevention experts from 13 European countries reviewed all articles and rated the strength of evidence using the Oxford criteria. Because the heterogeneity of populations and methodology did not permit formal meta-analysis, we present a narrative analysis. Findings: We identified 1797 studies, including 23 systematic reviews, 12 meta-analyses, 40 randomised controlled trials (RCTs), 67 cohort trials, and 22 ecological or population-based investigations. Evidence for restricting access to lethal means in prevention of suicide has strengthened since 2005, especially with regard to control of analgesics (overall decrease of 43% since 2005) and hot-spots for suicide by jumping (reduction of 86% since 2005, 79% to 91%). School-based awareness programmes have been shown to reduce suicide attempts (odds ratio [OR] 0·45, 95% CI 0·24-0·85; p=0·014) and suicidal ideation (0·5, 0·27-0·92; p=0·025). The anti-suicidal effects of clozapine and lithium have been substantiated, but might be less specific than previously thought. Effective pharmacological and psychological treatments of depression are important in prevention. Insufficient evidence exists to assess the possible benefits for suicide prevention of screening in primary care, in general public education and media guidelines. Other approaches that need further investigation include gatekeeper training, education of physicians, and internet and helpline support. The paucity of RCTs is a major limitation in the evaluation of preventive interventions. Interpretation: In the quest for effective suicide prevention initiatives, no single strategy clearly stands above the others. Combinations of evidence-based strategies at the individual level and the population level should be assessed with robust research designs. Funding: The Expert Platform on Mental Health, Focus on Depression, and the European College of Neuropsychopharmacology.

The lancet. Psychiatry · systematic review · 1070 citationsread the source →

Status and drivers of maternal, newborn, child and adolescent health in the Islamic world: a comparative analysis.

Background: The Millennium Development Goal (MDG) period saw dramatic gains in health goals MDG 4 and MDG 5 for improving child and maternal health. However, many Muslim countries in the south Asian, Middle Eastern, and African regions lagged behind. In this study, we aimed to evaluate the status of, progress in, and key determinants of reproductive, maternal, newborn, child, and adolescent health in Muslim majority countries (MMCs). The specific objectives were to understand the current status and progress in reproductive, maternal, newborn, child, and adolescent health in MMCs, and the determinants of child survival among the least developed countries among the MMCs; to explore differences in outcomes and the key contextual determinants of health between MMCs and non-MMCs; and to understand the health service coverage and contextual determinants that differ between best and poor or moderate performing MMCs. Methods: In this country-level ecological study, we examined data from between 1990 and 2015 from multiple publicly available data repositories. We examined 47 MMCs, of which 26 were among the 75 high-burden Countdown to 2015 countries. These 26 MMCs were compared with 48 non-Muslim Countdown countries. We also examined characteristics of the eight best performing MMCs that had accelerated improvement in child survival (ie, that reached their MDG 4 targets). We estimated adolescent, maternal, under-5, and newborn mortality, and stillbirths, and the causes of death, essential interventions coverage, and contextual determinants for all MMCs and comparative groups using standardised methods. We also did a hierarchical multivariable analysis of determinants of under-5 mortality and newborn mortality in low-income and middle-income MMCs. Findings: Despite notable reductions between 1990 and 2015, MMCs compared with a global esimate of all countries including MMCs had higher mortality rates, and MMCs relative to non-MMCs within Countdown countries also performed worse. Coverage of essential interventions across the continuum of care was on average lower among MMCs, especially for indicators of reproductive health, prenatal care, delivery, and labour, and childhood vaccines. Outcomes within MMCs for mortality and many reproductive, maternal, newborn, child, and adolescent health indicators varied considerably. Structural and contextual factors, especially state governance, conflict, and women and girl's empowerment indicators, were significantly worse in MMCs compared with non-MMCs within the high-burden Countdown countries, and were shown to be strongly associated with child and newborn mortality within low-income and middle-income MMCs. In adjusted hierarchical models, among other factors, under-5 mortality in MMCs increased with more refugees originating from a country (β=23·67, p=0·0116), and decreased with better political stability or absence of terrorism (β=-0·99, p=0·0285), greater political rights or government effectiveness (β=-1·17, p<0·0001), improvements in log gross national income per capita (β=-4·44, p<0·0001), higher total adult literacy (β=-1·69, p<0·0001), higher female adult literacy (β=-0·97, p<0·0001), and greater female to male enrolment in secondary school (β=-16·1, p<0·0001). The best performing MMCs were Azerbaijan, Bangladesh, Egypt, Indonesia, Kyrgyzstan, Morocco, Niger, and Senegal, which had higher coverage of family planning interventions and newborn or child vaccinations, and excelled in many of the above contextual determinants when compared with moderate or poorly performing MMCs. Interpretation: The status and progress in reproductive, maternal, newborn, child, and adolescent health is heterogeneous among MMCs, with little indication that religion and its practice affects outcomes systemically. Some Islamic countries such as Niger and Bangladesh have made great progress, despite poverty. Key findings from this study have policy and programmatic implications that could be prioritised by national heads of state and policy makers, development partners, funders, and the Organization of the Islamic Cooperation to scale up and improve these health outcomes in Muslim countries in the post-2015 era. Funding: US Fund for UNICEF under the Countdown to 2015 for Maternal, Newborn, and Child Survival, the Centre for Global Child Health, Hospital for Sick Children, and the Aga Khan University.

Lancet (London, England) · 25 citationsread the source →

The prevalence of exposure to potentially morally injurious events among physicians during the COVID-19 pandemic.

Background: Given the profound psychological distress caused by the Covid-19 pandemic, healthcare workers are at high risk of being exposed to potentially morally injurious events (PMIEs). Objective: We aimed to explore the prevalence and associated factors with PMIEs in a sample of Romanian physicians, of which almost half worked in Covid-19 treatment medical units. Method: We ran a web-based survey in April 2020, three weeks after the general lockdown to contain the novel coronavirus. Participants (N = 114, aged 23 to 67, M = 38.85, SD = 9.82, 74.6% females) answered the PMIE scale items, in addition to questions related to the physical and emotional self-impact related questions, and demographical and work-related variables (i.e. age, gender, medical experience, and speciality). Results: Results suggested that almost 50% of the participants reported high levels of PMIE exposure. No significant associations were found between PMIE exposure, and the type of medical unit physicians worked in (Covid-19 or non-Covid-19), nor their specialization and medical experience. Demographic variables (i.e. age and gender) and experience did not predict PMIE exposure. However, we found significant associations between PMIE and the physicians' physical and emotional self-reported impact. Conclusions: Healthcare systems, governments, and societies worldwide need to recognize that physicians are prone to PMIE exposure and related adverse psychological outcomes due to their daily activity in containing the pandemic. Public policies need to actively offer and promote psychological support, to protect and help physicians from the adverse mental health outcomes following the pandemic.

European journal of psychotraumatology · 33 citationsread the source →

Defining the determinants of vaccine uptake and undervaccination in migrant populations in Europe to improve routine and COVID-19 vaccine uptake: a systematic review.

Understanding why some migrants in Europe are at risk of underimmunisation and show lower vaccination uptake for routine and COVID-19 vaccines is critical if we are to address vaccination inequities and meet the goals of WHO's new Immunisation Agenda 2030. We did a systematic review (PROSPERO: CRD42020219214) exploring barriers and facilitators of vaccine uptake (categorised using the 5As taxonomy: access, awareness, affordability, acceptance, activation) and sociodemographic determinants of undervaccination among migrants in the EU and European Economic Area, the UK, and Switzerland. We searched MEDLINE, CINAHL, and PsycINFO from 2000 to 2021 for primary research, with no restrictions on language. 5259 data sources were screened, with 67 studies included from 16 countries, representing 366 529 migrants. We identified multiple access barriers-including language, literacy, and communication barriers, practical and legal barriers to accessing and delivering vaccination services, and service barriers such as lack of specific guidelines and knowledge of health-care professionals-for key vaccines including measles-mumps-rubella, diphtheria-pertussis-tetanus, human papillomavirus, influenza, polio, and COVID-19 vaccines. Acceptance barriers were mostly reported in eastern European and Muslim migrants for human papillomavirus, measles, and influenza vaccines. We identified 23 significant determinants of undervaccination in migrants (p<0·05), including African origin, recent migration, and being a refugee or asylum seeker. We did not identify a strong overall association with gender or age. Tailored vaccination messaging, community outreach, and behavioural nudges facilitated uptake. Migrants' barriers to accessing health care are already well documented, and this Review confirms their role in limiting vaccine uptake. These findings hold immediate relevance to strengthening vaccination programmes in high-income countries, including for COVID-19, and suggest that tailored, culturally sensitive, and evidence-informed strategies, unambiguous public health messaging, and health system strengthening are needed to address access and acceptance barriers to vaccination in migrants and create opportunities and pathways for offering catch-up vaccinations to migrants.

The Lancet. Infectious diseases · systematic review · 165 citationsread the source →

Promoting school climate and health outcomes with the SEHER multi-component secondary school intervention in Bihar, India: a cluster-randomised controlled trial.

Background: School environments affect health and academic outcomes. With increasing secondary school retention in low-income and middle-income countries, promoting quality school social environments could offer a scalable opportunity to improve adolescent health and wellbeing. Methods: We did a cluster-randomised trial to assess the effectiveness of a multi-component whole-school health promotion intervention (SEHER) with integrated economic and process evaluations in grade 9 students (aged 13-14 years) at government-run secondary schools in the Nalanda district of Bihar state, India. Schools were randomly assigned (1:1:1) to three groups: the SEHER intervention delivered by a lay counsellor (the SEHER Mitra [SM] group), the SEHER intervention delivered by a teacher (teacher as SEHER Mitra [TSM] group), and a control group in which only the standard government-run classroom-based life-skills Adolescence Education Program was implemented. The primary outcome was school climate measured with the Beyond Blue School Climate Questionnaire (BBSCQ). Students were assessed at the start of the academic year (June, 2015) and again 8 months later at the end of the academic year (March, 2016) via self-completed questionnaires. This study is registered with ClinicalTrials.gov, number NCT02484014. Findings: Of the 112 eligible schools in the Nalanda district, 75 were randomly selected to participate in the trial. We randomly assigned 25 schools to each of the three groups. One school subsequently dropped out of the TSM group, leaving 24 schools in this group. The baseline survey included a total of 13 035 participants, and the endpoint survey included 14 414 participants. Participants in the SM-delivered intervention schools had substantially higher school climate scores at endpoint survey than those in the control group (BBSCQ baseline-adjusted mean difference [aMD] 7·57 [95% CI 6·11-9·03]; effect size 1·88 [95% CI 1·44-2·32], p<0·0001) and the TSM-delivered intervention (aMD 7·57 [95% CI 6·06-9·08]; effect size 1·88 [95% CI 1·43-2·34], p<0·0001). There was no effect of the TSM-delivered intervention compared with control (aMD -0·009 [95% CI -1·53 to 1·51], effect size 0·00 [95% CI -0·45 to 0·44], p=0·99). Compared with the control group, participants in the SM-delivered intervention schools had moderate to large improvements in the secondary outcomes of depression (aMD -1·23 [95% CI -1·89 to -0·57]), bullying (aMD -0·91 [95% CI -1·15 to -0·66]), violence victimisation (odds ratio [OR] 0·62 [95% CI 0·46-0·84]), violence perpetration (OR 0·68 [95% CI 0·48-0·96]), attitude towards gender equity (aMD 0·41 [95% CI 0·21-0·61]), and knowledge of reproductive and sexual health (aMD 0·29 [95% CI 0·06-0·53]). Similar results for these secondary outcomes were noted for the comparison between SM-delivered intervention schools and TSM-delivered intervention schools (depression: aMD -1·23 [95% CI -1·91 to -0·55]; bullying: aMD -0·83 [95% CI -1·08 to -0·57]; violence victimisation: OR 0·49 [95% CI 0·35-0·67]; violence perpetration: OR 0·49 [95% CI 0·34-0·71]; attitude towards gender equity: aMD 0·23 [95% CI 0·02-0·44]; and knowledge of reproductive and sexual health: aMD 0·22 [95% CI -0·02 to 0·47]). However, no effects on these secondary outcomes were observed for the TSM-delivered intervention schools compared with the control group (depression: aMD -0·03 [95% CI -0·70 to 0·65]; bullying: aMD -0·08 [95% CI -0·34 to 0·18]; violence victimisation: OR 1·27 [95% CI 0·93-1·73]; violence perpetration: OR 1·37 [95% CI 0·95-1·95]; attitude towards gender equity: aMD 0·17 [95% CI -0·09 to 0·38]; and knowledge of reproductive and sexual health: aMD 0·06 [95% CI -0·18 to 0·32]). Interpretation: The multi-component whole-school SEHER health promotion intervention had substantial beneficial effects on school climate and health-related outcomes when delivered by lay counsellors, but no effects when delivered by teachers. Future research should focus on the evaluation of the scaling up of the SEHER intervention in diverse contexts and delivery agents. Funding: John D. and Catherine T. MacArthur Foundation, USA and the United Nations Population Fund India Office.

Lancet (London, England) · randomised controlled trial · 121 citationsread the source →

Evaluation of Drinking Risk Levels as Outcomes in Alcohol Pharmacotherapy Trials: A Secondary Analysis of 3 Randomized Clinical Trials.

Importance: The US Food and Drug Administration recognizes total abstinence and no heavy drinking days as outcomes for pivotal pharmacotherapy trials for alcohol use disorder (AUD). Many patients have difficulty achieving these outcomes, which can discourage seeking treatment and has slowed the development of medications that affect alcohol use. Objective: To compare 2 drinking-reduction outcomes with total abstinence and no heavy drinking outcomes. Design, setting, and participants: Data were obtained from 3 multisite, randomized, placebo-controlled clinical trials of medications for treating alcohol dependence (naltrexone, varenicline, and topiramate) in adults with DSM-IV-categorized alcohol dependence. Main outcomes and measures: Within each trial, the percentage of participants in active and placebo conditions who met responder definitions of abstinence, no heavy drinking days, a WHO 1-level reduction, and a WHO 2-level reduction was computed by month with corresponding effect sizes (Cohen h). Results: Across the 3 trials (N = 1169; mean [SD] age, 45 [10] years; 824 [70.5%] men), the percentage of participants classified as responders during the last 4 weeks of treatment was lowest for abstinence (naltrexone, 34.7% [100 of 288]; varenicline, 7.3% [7 of 96]; topiramate, 11.7% [21 of 179]) followed by no heavy drinking days (naltrexone, 51.0% [147 of 288]; varenicline, 24.0% [23 of 96]; topiramate, 20.7% [37 of 179]), WHO 2-level reduction (naltrexone, 75.0% [216 of 288]; varenicline, 55.2% [53 of 96]; topiramate, 44.7% [80 of 179]), and WHO 1-level reduction (naltrexone, 83.3% [240 of 288]; varenicline, 69.8 [67 of 96]; topiramate, 54.7% [98 of 179]) outcomes. Standardized treatment effects observed for the WHO 2-level reduction outcomes (naltrexone, Cohen h = 0.214 [95% CI, 0.053 -0.375]; varenicline, 0.273 [95% CI, -0.006 to 0.553]; topiramate, 0.230 [95% CI, 0.024-0.435]) and WHO 1-level reduction (naltrexone, Cohen h = 0.116 [95% CI, -0.046 to 0.277]; varenicline, 0.338 [95% CI, 0.058-0.617]; topiramate, 0.014 [95% CI, -0.192 to 0.219]) were comparable with those obtained using abstinence (naltrexone, Cohen h = 0.142 [95% CI, -0.020 to 0.303]; varenicline, 0.146 [95% CI, -0.133 to 0.426]; topiramate, 0.369 [95% CI, 0.163-0.574]) and no heavy drinking days (naltrexone, Cohen h = 0.140 [95% CI, -0.021 to 0.302]; varenicline, 0.232 [95% CI, -0.048 to 0.511]; topiramate, 0.207 [95% CI, 0.002-0.413]). Conclusions and relevance: WHO drinking risk level reductions appear to be worthwhile indicators of treatment outcome in AUD pharmacotherapy trials. These outcomes may align with drinking reduction goals of many patients and capture clinically meaningful improvements experienced by more patients than either abstinence or no heavy drinking days. Trial registration: ClinicalTrials.gov identifiers: NCT00006206; NCT01146613; NCT00210925.

JAMA psychiatry · randomised controlled trial · 98 citationsread the source →

Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trial

BACKGROUND: Individuals with a history of recurrent depression have a high risk of repeated depressive relapse or recurrence. Maintenance antidepressants for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to medication. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce risk of relapse or recurrence compared with usual care, but has not yet been compared with maintenance antidepressant treatment in a definitive trial. We aimed to see whether MBCT with support to taper or discontinue antidepressant treatment (MBCT-TS) was superior to maintenance antidepressants for prevention of depressive relapse or recurrence over 24 months. METHODS: In this single-blind, parallel, group randomised controlled trial (PREVENT), we recruited adult patients with three or more previous major depressive episodes and on a therapeutic dose of maintenance antidepressants, from primary care general practices in urban and rural settings in the UK. Participants were randomly assigned to either MBCT-TS or maintenance antidepressants (in a 1:1 ratio) with a computer-generated random number sequence with stratification by centre and symptomatic status. Participants were aware of treatment allocation and research assessors were masked to treatment allocation. The primary outcome was time to relapse or recurrence of depression, with patients followed up at five separate intervals during the 24-month study period. The primary analysis was based on the principle of intention to treat. The trial is registered with Current Controlled Trials, ISRCTN26666654. FINDINGS: Between March 23, 2010, and Oct 21, 2011, we assessed 2188 participants for eligibility and recruited 424 patients from 95 general practices. 212 patients were randomly assigned to MBCT-TS and 212 to maintenance antidepressants. The time to relapse or recurrence of depression did not differ between MBCT-TS and maintenance antidepressants over 24 months (hazard ratio 0·89, 95% CI 0·67-1·18; p=0·43), nor did the number of serious adverse events. Five adverse events were reported, including two deaths, in each of the MBCT-TS and maintenance antidepressants groups. No adverse events were attributable to the interventions or the trial. INTERPRETATION: We found no evidence that MBCT-TS is superior to maintenance antidepressant treatment for the prevention of depressive relapse in individuals at risk for depressive relapse or recurrence. Both treatments were associated with enduring positive outcomes in terms of relapse or recurrence, residual depressive symptoms, and quality of life. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula.

The Lancet · randomised controlled trial · 531 citationsread the source →

Asymmetry between salivary cortisol and alpha-amylase reactivity to stress: relation to aggressive behavior in adolescents.

This study used a multiple physiological systems measurement approach to test the hypothesis that asymmetry between the major components of the psychobiology of stress is associated with atypical behavior in youth [Bauer, A.M., Quas, J.A., Boyce, W.T., 2002. Associations between physiological reactivity and children's behavior: advantages of a multisystem approach. J. Dev. Behav. Pediatr. 23, 102-113]. Adolescents (N=67; ages 10-14; 52% male) provided 2 saliva samples before, and 4 samples after, a modified Trier Social Stress Test (TSST; Kirschbaum, C., Pirke, K., Hellhammer, D.H., 1993. The "Trier Social Stress Test": a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28, 76-81). Samples were assayed for cortisol (C) and alpha-amylase (A-A), a surrogate marker of sympathetic nervous system (SNS) activity. Parents/guardians and adolescents reported on adolescents' aggressive behavior. Both salivary A-A and C increased in response to the TSST, with a peak response for A-A immediately post-TSST and for C 10 min post-TSST. A-A and C stress reactivity were estimated using area under the curve (AUC). Asymmetrical C and A-A reactivity accounted for 7% of the variance in parent-reported adolescent aggression. At lower levels of A-A reactivity, lower C reactivity corresponded to higher aggression ratings, but at high A-A reactivity levels, C reactivity was not related to aggression. These results support the hypothesis of Bauer et al. and underscore the importance of a multiple systems measurement approach in biosocial models of adolescent aggression.

Psychoneuroendocrinology · 266 citationsread the source →

Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects.

Radical radiotherapy is a standard form of management of localised prostate cancer. Conformal treatment planning spares adjacent normal tissues reducing treatment-related side effects and may permit safe dose escalation. We have tested the effects on tumour control and side effects of escalating radiotherapy dose and investigated the appropriate target volume margin. After an initial 3-6 month period of androgen suppression, 126 men were randomised and treated with radiotherapy using a 2 by 2 factorial trial design. The initial radiotherapy tumour target volume included the prostate and base of seminal vesicles (SV) or complete SV depending on SV involvement risk. Treatments were randomised to deliver a dose of 64 Gy with either a 1.0 or 1.5 cm margin around the tumour volume (1.0 and 1.5 cm margin groups) and also to treat either with or without a 10 Gy boost to the prostate alone with no additional margin (64 and 74 Gy groups). Tumour control was monitored by prostate-specific antigen (PSA) testing and clinical examination with additional tests as appropriate. Acute and late side effects of treatment were measured using the Radiation Treatment and Oncology Groups (RTOG) and LENT SOM systems. The results showed that freedom from PSA failure was higher in the 74 Gy group compared to the 64 Gy group, but this did not reach conventional levels of statistical significance with 5-year actuarial control rates of 71% (95% CI 58-81%) in the 74 Gy group vs 59% (95% CI 45-70%) in the 64 Gy group. There were 23 failures in the 74 Gy group and 33 in the 64 Gy group (Hazard ratio 0.64, 95% CI 0.38-1.10, P=0.10). No difference in disease control was seen between the 1.0 and 1.5 cm margin groups (5-year actuarial control rates 67%, 95% CI 53-77% vs 63%, 95% CI 50-74%) with 28 events in each group (Hazard ratio 0.97, 95% CI 0.50-1.86, P=0.94). Acute side effects were generally mild and 18 weeks after treatment, only four and five of the 126 men had persistent > or =Grade 1 bowel or bladder side effects, respectively. Statistically significant increases in acute bladder side effects were seen after treatment in the men receiving 74 Gy (P=0.006), and increases in both acute bowel side effects during treatment (P=0.05) and acute bladder sequelae (P=0.002) were recorded for men in the 1.5 cm margin group. While statistically significant, these differences were of short duration and of doubtful clinical importance. Late bowel side effects (RTOG> or =2) were seen more commonly in the 74 Gy and 1.5 cm margin groups (P=0.02 and P=0.05, respectively) in the first 2 years after randomisation. Similar results were found using the LENT SOM assessments. No significant differences in late bladder side effects were seen between the randomised groups using the RTOG scoring system. Using the LENT SOM instrument, a higher proportion of men treated in the 74 Gy group had Grade > or =3 urinary frequency at 6 and 12 months. Compared to baseline scores, bladder symptoms improved after 6 months or more follow-up in all groups. Sexual function deteriorated after treatment with the number of men reporting some sexual dysfunction (Grade> or =1) increasing from 38% at baseline to 66% at 6 months and 1 year and 81% by year 5. However, no consistent differences were seen between the randomised groups. In conclusion, dose escalation from 64 to 74 Gy using conformal radiotherapy may improve long-term PSA control, but a treatment margin of 1.5 cm is unnecessary and is associated with increased acute bowel and bladder reactions and more late rectal side effects. Data from this randomised pilot study informed the Data Monitoring Committee of the Medical Research Council RT 01 Trial and the two studies will be combined in subsequent meta-analysis.

British journal of cancer · randomised controlled trial · 155 citationsread the source →

Improvements in advance care planning in the Veterans Affairs System: results of a multifaceted intervention.

Background: Advance care planning (ACP) aims to guide health care in the event of decisional incapacity. Interventions to promote ACP have had limited effectiveness. We conducted an educational and motivational intervention in Department of Veterans Affairs outpatient clinics to increase ACP use and proxy and health care provider understanding of patients' preferences and values. Methods: We recruited 23 providers and up to 14 of each of their patients; the patients were randomized to the control or intervention group. Eligibility criteria included a preexisting relationship with the provider, age 55 years or older, chronic health condition(s), and no recorded advance directive. The intervention group (n = 119) received an ACP workbook, motivational counseling by social workers, and cues to providers to discuss ACP. The control group (n = 129) received an advance directive booklet. Results: The intervention patients reported more ACP discussions with their providers (64% vs 38%; P<.001). Living wills were filed in the medical record twice as often in the intervention group (48% vs 23%; P<.001). Provider-patient dyads in the intervention group had higher agreement scores than the control group for treatment preferences, values, and personal beliefs (58% vs 48%, 57% vs 46%, and 61% vs 47%, respectively; P<.01 for all comparisons). The agreement scores for the proxy-patient dyads did not differ between groups for treatment preferences and values, but were higher in the intervention than the control group for personal beliefs (67% vs 56%). Conclusion: This intervention demonstrates mixed results and highlights the ongoing challenges of helping health care providers and potential proxy decision makers represent patient preferences and values.

Archives of internal medicine · randomised controlled trial · 89 citationsread the source →

Priority-setting dilemmas, moral distress and support experienced by nurses and physicians in the early phase of the COVID-19 pandemic in Norway.

Background: The global COVID-19 pandemic has imposed challenges on healthcare systems and professionals worldwide and introduced a ´maelstrom´ of ethical dilemmas. How ethically demanding situations are handled affects employees' moral stress and job satisfaction. Aim: Describe priority-setting dilemmas, moral distress and support experienced by nurses and physicians across medical specialties in the early phase of the COVID-19 pandemic in Western Norway. Research design: A cross-sectional hospital-based survey was conducted from 23 April to 11 May 2020. Ethical considerations: Ethical approval granted by the Regional Research Ethics Committee in Western Norway (131421). Findings: Among the 1606 respondents, 67% had experienced priority-setting dilemmas the previous two weeks. Healthcare workers who were directly involved in COVID-19 care, were redeployed or worked in psychiatry/addiction medicine experienced it more often. Although 59% of the respondents had seen adverse consequences due to resource scarcity, severe consequences were rare. Moral distress levels were generally low (2.9 on a 0-10 scale), but higher in selected groups (redeployed, managers and working in psychiatry/addiction medicine). Backing from existing collegial and managerial structures and routines, such as discussions with colleagues and receiving updates and information from managers that listened and acted upon feedback, were found more helpful than external support mechanisms. Priority-setting guidelines were also helpful. Discussion: By including all medical specialties, nurses and physicians, and various institutions, the study provides information on how the COVID-19 mitigation also influenced those not directly involved in the COVID-19 treatment of patients. In the next stages of the pandemic response, support for healthcare professionals directly involved in outbreak-affected patients, those redeployed or those most impacted by mitigation strategies must be a priority. Conclusion: Empirical research of healthcare workers experiences under a pandemic are important to identify groups at risks and useful support mechanisms.

Nursing ethics · cohort or longitudinal · 92 citationsread the source →

Improving newborn preventive services at the birth hospitalization: a collaborative, hospital-based quality-improvement project.

Objective: The goal was to test the effectiveness of a statewide, collaborative, hospital-based quality-improvement project targeting preventive services delivered to healthy newborns during the birth hospitalization. Methods: All Vermont hospitals with obstetric services participated. The quality-improvement collaborative (intervention) was based on the Breakthrough Series Collaborative model. Targeted preventive services included hepatitis B immunization; assessment of breastfeeding; assessment of risk of hyperbilirubinemia; performance of metabolic and hearing screens; assessment of and counseling on tobacco smoke exposure, infant sleep position, car safety seat fit, and exposure to domestic violence; and planning for outpatient follow-up care. The effect of the intervention was assessed at the end of an 18-month period. Preintervention and postintervention chart audits were conducted by using a random sample of 30 newborn medical charts per audit for each participating hospital. Results: Documented rates of assessment improved for breastfeeding adequacy (49% vs 81%), risk for hyperbilirubinemia (14% vs 23%), infant sleep position (13% vs 56%), and car safety seat fit (42% vs 71%). Documented rates of counseling improved for tobacco smoke exposure (23% vs 53%) and car safety seat fit (38% vs 75%). Performance of hearing screens also improved (74% vs 97%). No significant changes were noted in performance of hepatitis B immunization (45% vs 30%) or metabolic screens (98% vs 98%), assessment of tobacco smoke exposure (53% vs 67%), counseling on sleep position (46% vs 68%), assessment of exposure to domestic violence (27% vs 36%), or planning for outpatient follow-up care (80% vs 71%). All hospitals demonstrated preintervention versus postintervention improvement of > or = 20% in > or = 1 newborn preventive service. Conclusions: A statewide, hospital-based quality-improvement project targeting hospital staff members and community physicians was effective in improving documented newborn preventive services during the birth hospitalization.

Pediatrics · cohort or longitudinal · 30 citationsread the source →

Common themes and emerging trends for the use of technology to support mental health and psychosocial well-being in limited resource settings: A review of the literature.

There are significant disparities in access to mental health care. With the burgeoning of technologies for health, digital tools have been leveraged within mental health and psychosocial support programming (eMental health). A review of the literature was conducted to understand and identify how eMental health has been used in resource-limited settings in general. PubMed, Ovid Medline and Web of Science were searched. Six-hundred and thirty full-text articles were identified and assessed for eligibility; of those, 67 articles met the inclusion criteria and were analyzed. The most common mental health use cases were for depression (n = 25) and general mental health and well-being (n = 21). Roughly one-third used a website or Internet-enabled intervention (n = 23) and nearly one-third used an SMS intervention (n = 22). Technology was applied to enhance service delivery (n = 32), behavior change communication (n = 26) and data collection (n = 8), and specifically dealt with adherence (n = 7), ecological momentary assessments (n = 7), well-being promotion (n = 5), education (n = 8), telemedicine (n = 28), machine learning (n = 5) and games (n = 2). Emerging trends identified wearables, predictive analytics, robots and virtual reality as promising areas. eMental health interventions that leverage low-tech tools can introduce, strengthen and expand mental health and psychosocial support services and can be a starting point for future, advanced tools.

Psychiatry research · review · 30 citationsread the source →

Evaluation of Parental Dental Fear and Anxiety (DFA) on Adolescent Dental Treatment

INTRODUCTION Dental anxiety is a negative state of mind of a dental patient, which is shown to be excessive and unreasonable.[1] Dental fear is a normal emotional response to particularly alarming stimuli in situations related to dental treatment.[1] Dental fear and anxiety (DFA) are often used together to describe different types of fear experienced in the dental environment.[2] American Academy of Pediatrics divides adolescents into three age groups: early 11–14 years, middle 15–17 years, and late 18–21 years.[3] Five specific pathways for DFA were seen in adolescent dental patients. One of which being the parental pathway plays an important role in the transmission of fear hindering their child’s dental treatment.[4] Parental DFA is usually an excessive perturbing of the things that could go wrong in child’s oral health and is an important factor that has an impact on adolescents receiving dental treatment and maintenance of their oral health. It is necessary to recognize and know how parental DFA affects the dental treatment of adolescents. Thus, this review aimed at evaluating the parental influence of DFA on dental treatment of adolescents. MATERIALS AND METHODS DATA EXTRACTION AND LITERATURE SEARCH STRATEGY A broad search of literature published between 2005 and 2021 from electronic databases through Scopus, PubMed, Google Scholar, and Web of Science was performed. These studies were conducted in different countries as mentioned in Table 1. This review article includes eight cross-sectional studies, three longitudinal studies, and one descriptive study. The age group of children included ranged from 10 to 19 years. Table 1: Summary study design, data collection, dental fear and anxiety assessment scales used analysis, and interpretation of reviewed articlesThe search was carried out using the following keywords: dental anxiety, parental dental anxiety, adolescent, and dental treatment. The terms used to formulate the search strategies were parent OR mother OR father AND dental fear OR dental anxiety AND adolescent AND dental treatment. Data extracted were independently reviewed and disagreements were solved by discussion. A flowchart representing the method of article selection for the review is shown in Figure 1.Figure 1: Flowchart representing the method of article selectionINCLUSION CRITERIA We included the studies in which parental dental anxiety was a major criterion affecting different dental health conditions. Articles referring to adolescents (10–19 years) facing different oral health problems were also included in the study. EXCLUSION CRITERIA Abstracts that were not giving relevant data, data from unpublished articles, parental dental anxiety in medically compromised and specially challenged adolescents, and articles that did not include the adolescent age group were excluded from the study. RESULTS Approximately 83 publications were found related. Screening identified 10 articles that fulfilled the criteria of inclusion; full-text versions were retrieved and their references were screened for further relevant articles. Checking the subreference list, another two relevant articles were found. Thus, 12 articles were considered for this review that met the final inclusion criteria. Of 12 articles reviewed, 8 studies[56789101112] used validated assessment scales as mentioned by authors for measuring parental DFA. The authors have not specified the validation of assessment scales used for the other four studies.[13141516] The various DFA assessment scales used in the reviewed articles are mentioned in Table 2. Summary study design, data collection, analysis, and interpretation of reviewed articles are mentioned in Table 1.Table 2: Tabular representation of dental fear and anxiety assessment scales usedDISCUSSION Dental anxiety being primarily a negative parental factor was found to affect children from assessing regular dental care. Among the reviewed articles based on the outcome, we found that three articles explained about a relationship between parental DFA and adolescent dental treatment,[67,13] and the remaining nine articles explained about the correlation between parental DFA scores with adolescent DFA scores.[6891011,13141516] No significant association was observed between parental DFA and adolescent DFA scores in two of the studies,[78] whereas two studies showed positive association only during early adolescence.[914] Other five studies showed a significant positive correlation of parental DFA with their children’s dental anxiety,[10111215,16] of which three studies also suggested fathers as mediating role in transmission of DFA to their children.[1011,15] RELATIONSHIP BETWEEN PARENTAL DENTAL FEAR AND ANXIETY AND ADOLESCENT DENTAL TREATMENT Adolescent dental treatment utilization mainly depends on parental/caretaker’s decision-making and their dental care obtaining habits. In childhood and even adolescence, this becomes very crucial for the development of good oral health behavior like regular visits to the dentist and preventive dental care.[17] Another postulated process is “social learning” wherein, media, friends, and relatives portray dentists in negative light or image leading to formation of DFA. These processes of information transmission and vicarious experience lead to negative portrayal of dentists and pessimistic expectations about the dentist’s role. All these predispose to DFA.[18] The absence of anxiety among parents would have a positive influence on a child.[19] Parental dental anxiety along with family income, economic stability, parental oral health literacy, and oral health practices is found to be a few factors that affect adolescent’s oral health-related quality of life (QOL).[202122] Dental anxiety being primarily a negative parental factor was found to affect children from accessing regular dental care, whereas parental self-dental utilization being a positive parental factor showed a positive impact on a child’s dental utilization.[23] Parents with higher anxiety levels were found to start brushing their children’s teeth at an earlier age; hence, a significant correlation was found between parent’s anxiety levels and the age at which the child starts to brush.[24] Dental health status of children was found to be better with more a positive attitude of parents toward dentistry.[25] Among the articles reviewed, two articles were found to have parental DFA during fixed orthodontic treatment of the adolescents which included the use of extraoral appliances. These two studies used different anxiety measurement scales for assessing parental DFA before and during the treatment procedures.[513] Poorer QOL is seen in families of adolescents with malocclusion as compared with the families of adolescents without any occlusal variation; the impact may have effects on parental or guardian’s emotions.[26] Both of the studies assessed state and trait dental anxiety of parents (STAI scale). State anxiety is transient, fluctuates, and varies in intensity. Trait anxiety is a personality trait; it is stable with time.[2728] The result showed that parent’s trait anxiety levels did not change during orthodontic treatment.[513] State anxiety was found to be within normal range and changed according to intensity of pressure.[13] There was an incidence of high levels of state anxiety and depression in both parents and patients under treatment with extra oral orthodontic appliances after 1 year of active treatment. Among patients waiting for orthodontic treatment and among their parents no statistically significant differences were noted in their trait anxiety levels.[5] The extra oral appliances had a negative effect on patient’s and parent’s anxiety levels which might indirectly affect the ongoing dental treatment. It was therefore recommended for clinicians to have alternate treatment modalities in mind to address this challenge.[5] Apart from orthodontic treatment, adolescents are also found commonly with traumatic dental injuries (TDIs) involving dentine/pulp or fracture of the root. A family’s QOL in such conditions was assessed using the family impact scale (FIS). This scale had four subscales, in which parental emotion was one of the subscales assessed. Parental emotion had a significant negative impact on the severity of TDI and severe untreated TDI of an adolescent can be a source of family distress.[629,30] EVIDENCE OF ASSOCIATION OF DENTAL FEAR AND ANXIETY BETWEEN PARENTS AND THEIR ADOLESCENTS Previous studies have shown that parents exhibit an influence on their children’s DFA through modeling and information.[31] The DFA experienced in childhood may lead into adulthood causing a predictor for dental treatment avoidance in adulthood.[3233] Among the reviewed articles, we found a correlation between the parental dental DFA scores with their adolescent’s DFA scores. Parent’s DFA and children’s DFA were assessed using the same dental anxiety measuring scale in nine of the studies,[6891011,13141516] and three studies[57,12] used different scales to measure anxiety levels in parents and children’s. Two of the studies showed no significant association between the anxiety level of adolescents and that of their parents.[78] One of the studies suggested that when a child reached adolescence, parental DFA does not directly contribute to child DFA. Other factors such as the presence of a sibling and family structure (single-parent family, nuclear) are found to play a significant role.[7] Lending support to the former findings, there was no relation between anxiety levels of adolescents (12–17 years) and that of their parents, whereas in the same study a positive association was found when the child is 8–11 years of age.[8] Two studies suggested a positive association in early adolescence.[914] In one of these two studies, mother’s and adolescents dental fear scores had a significant association at the age of 12 years and 18 years in given treatment scenarios such as “feeling about having their teeth scraped and polished, having teeth drilled and having an injection in gum,” whereas there was no significant association between dental fear scores of mother’s and adolescence at 15 years of age.[9] In another study reviewed, in early adolescence (11–12 years), there was a statistically significant association between parental and adolescent dental fear but in mid-adolescence (15–16 years) there was only an association with parental dental fear with their daughters.[14] It was found in the Finnish population, by eliminating dental fear among 30 years and elderly population, 41% of irregular attendees could become regular attenders.[34] In contrast, other five studies showed a significant positive correlation of parental DFA with their children’s dental anxiety.[10111215,16] Fearful parents of adolescents of age (11–16 years) assumed that their child had fear irrespective of whether the child had fear or not.[16] Three of these studies, where parental DFA was assessed in both the parents, suggested that the father also has a mediating role in the transmission of DFA to the children of age group 11–17 years,[10] 7–15 years,[11] and 7–12 years,[15] respectively. Father’s DFA is one of the best predictors of adolescence DFA[1035] and it is also found that child’s dental anxiety is best predicted by the parent’s fear of pain.[12] Previous studies have suggested that children experience fear and anxiety in their early life due to a lack of cognitive ability without having a clear perception of fearful situation and have been influenced by their parent’s fear and anxiety.[36] It is still unclear of the association of DFA between parents and late adolescents.[9] It was found that limited studies were found in the area of adolescent oral health. In the available literature, definite assessment methods were not used to assess the anxiety levels among parents. Furthermore, studies focused on late adolescence are indicated to establish the changes in oral health due to parental DFA. Adolescence is the transitional phase between childhood and adulthood and is a crucial period where they develop decision-making and independence; this has an impact on dental treatment-seeking behavior. The influence of parental dental anxiety might worsen the scenario. Parental DFA is seen to have a direct impact on the treatment itself.[56,20] Previously reviewed articles show a strong association of parental DFA and child’s DFA below 8 years of age.[37] In this study, we found parental DFA showed a positive association with their adolescent’s DFA, which thus hinders their dental treatment. There is a need to give attention to psychological parameters before and during the treatment of both parents and adolescents. Therefore, identifying parental dental anxiety prior to the treatment and intervention helps to reduce or eliminate DFA in children and further improves their dental treatment utilization. This study adds value in sensitizing dental professionals toward addressing parental concerns while treating adolescents and recommendations for appropriate implementations in teaching curricula and policies regarding the same. There is more potential to understand the background of parental DFA in single parents and in mother and father alone and also the factors that made them vulnerable. Parental education/counselling regarding various dental treatment procedures using appropriate methods such as focus group discussion will help to reduce DFA among the parental populations. ACKNOWLEDGEMENT We thank Health Sciences Library, Manipal Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India and Department of Psychiatry, Kasturba Medical College and Hospital, Manipal, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, India. FINANCIAL SUPPORT AND SPONSORSHIP This study was self-funded. CONFLICTS OF INTEREST There are no conflicts of interest. AUTHORS CONTRIBUTIONS Idea and conceptualization: Ramprasad Vasthare. Literature search: Thrisha Hegde, Bhavyashri P. Manuscript writing: Thrisha Hegde, Bhavyashri P, Ramprasad Vasthare, Karthik M, Ravindra Munoli. Editing of the review: Ramprasad Vasthare, Thrisha Hegde, Bhavyashri P, Karthik M, Ravindra Munoli. Intellectual inputs: Ramprasad Vasthare, Ravindra Munoli, Karthik M. ETHICAL POLICY AND INSTITUTIONAL REVIEW BOARD STATEMENT Not applicable as this was a narrative review. PATIENT DECLARATION OF CONSENT Not applicable. DATA AVAILABILITY STATEMENT Data of literature search is available on appropriate request to the corresponding author.

Journal of International Society of Preventive and Community Dentistry · review · 16 citationsread the source →

Outcomes in people with eating disorders: a transdiagnostic and disorder-specific systematic review, meta-analysis and multivariable meta-regression analysis.

Eating disorders (EDs) are known to be associated with high mortality and often chronic and severe course, but a recent comprehensive systematic review of their outcomes is currently missing. In the present systematic review and meta-analysis, we examined cohort studies and clinical trials published between 1980 and 2021 that reported, for DSM/ICD-defined EDs, overall ED outcomes (i.e., recovery, improvement and relapse, all-cause and ED-related hospitalization, and chronicity); the same outcomes related to purging, binge eating and body weight status; as well as mortality. We included 415 studies (N=88,372, mean age: 25.7±6.9 years, females: 72.4%, mean follow-up: 38.3±76.5 months), conducted in persons with anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), other specified feeding and eating disorders (OSFED), and/or mixed EDs, from all continents except Africa. In all EDs pooled together, overall recovery occurred in 46% of patients (95% CI: 44-49, n=283, mean follow-up: 44.9±62.8 months, no significant ED-group difference). The recovery rate was 42% at <2 years, 43% at 2 to <4 years, 54% at 4 to <6 years, 59% at 6 to <8 years, 64% at 8 to <10 years, and 67% at ≥10 years. Overall chronicity occurred in 25% of patients (95% CI: 23-29, n=170, mean follow-up: 59.3±71.2 months, no significant ED-group difference). The chronicity rate was 33% at <2 years, 40% at 2 to <4 years, 23% at 4 to <6 years, 25% at 6 to <8 years, 12% at 8 to <10 years, and 18% at ≥10 years. Mortality occurred in 0.4% of patients (95% CI: 0.2-0.7, n=214, mean follow-up: 72.2±117.7 months, no significant ED-group difference). Considering observational studies, the mortality rate was 5.2 deaths/1,000 person-years (95% CI: 4.4-6.1, n=167, mean follow-up: 88.7±120.5 months; significant difference among EDs: p<0.01, range: from 8.2 for mixed ED to 3.4 for BN). Hospitalization occurred in 26% of patients (95% CI: 18-36, n=18, mean follow-up: 43.2±41.6 months; significant difference among EDs: p<0.001, range: from 32% for AN to 4% for BN). Regarding diagnostic migration, 8% of patients with AN migrated to BN and 16% to OSFED; 2% of patients with BN migrated to AN, 5% to BED, and 19% to OSFED; 9% of patients with BED migrated to BN and 19% to OSFED; 7% of patients with OSFED migrated to AN and 10% to BN. Children/adolescents had more favorable outcomes across and within EDs than adults. Self-injurious behaviors were associated with lower recovery rates in pooled EDs. A higher socio-demographic index moderated lower recovery and higher chronicity in AN across countries. Specific treatments associated with higher recovery rates were family-based therapy, cognitive-behavioral therapy (CBT), psychodynamic therapy, and nutritional interventions for AN; self-help, CBT, dialectical behavioral therapy (DBT), psychodynamic therapy, nutritional and pharmacological treatments for BN; CBT, nutritional and pharmacological interventions, and DBT for BED; and CBT and psychodynamic therapy for OSFED. In AN, pharmacological treatment was associated with lower recovery, and waiting list with higher mortality. These results should inform future research, clinical practice and health service organization for persons with EDs.

World psychiatry : official journal of the World Psychiatric Association (WPA) · 148 citationsread the source →

Potential impact of midwives in preventing and reducing maternal and neonatal mortality and stillbirths: a Lives Saved Tool modelling study.

Background: Strengthening the capacity of midwives to deliver high-quality maternal and newborn health services has been highlighted as a priority by global health organisations. To support low-income and middle-income countries (LMICs) in their decisions about investments in health, we aimed to estimate the potential impact of midwives on reducing maternal and neonatal deaths and stillbirths under several intervention coverage scenarios. Methods: For this modelling study, we used the Lives Saved Tool to estimate the number of deaths that would be averted by 2035, if coverage of health interventions that can be delivered by professional midwives were scaled up in 88 countries that account for the vast majority of the world's maternal and neonatal deaths and stillbirths. We used four scenarios to assess the effects of increasing the coverage of midwife-delivered interventions by a modest amount (10% every 5 years), a substantial amount (25% every 5 years), and the amount needed to reach universal coverage of these interventions (ie, to 95%); and the effects of coverage attrition (a 2% decrease every 5 years). We grouped countries in three equal-sized groups according to their Human Development Index. Group A included the 30 countries with the lowest HDI, group B included 29 low-to-medium HDI countries, and group C included 29 medium-to-high HDI countries. Findings: We estimated that, relative to current coverage, a substantial increase in coverage of midwife-delivered interventions could avert 41% of maternal deaths, 39% of neonatal deaths, and 26% of stillbirths, equating to 2·2 million deaths averted per year by 2035. Even a modest increase in coverage of midwife-delivered interventions could avert 22% of maternal deaths, 23% of neonatal deaths, and 14% of stillbirths, equating to 1·3 million deaths averted per year by 2035. Relative to current coverage, universal coverage of midwife-delivered interventions would avert 67% of maternal deaths, 64% of neonatal deaths, and 65% of stillbirths, allowing 4·3 million lives to be saved annually by 2035. These deaths averted would be particularly concentrated in the group B countries, which currently account for a large proportion of the world's population and have high mortality rates compared with group C. Interpretation: Midwives can help to substantially reduce maternal and neonatal mortality and stillbirths in LMICs. However, to realise this potential, midwives need to have skills and competencies in line with recommendations from the International Confederation of Midwives, to be part of a team of sufficient size and skill, and to work in an enabling environment. Our study highlights the potential of midwives but there are many challenges to the achievement of this potential. If increased coverage of midwife-delivered interventions can be achieved, health systems will be better able to provide effective coverage of essential sexual, reproductive, maternal, newborn, and adolescent health interventions. Funding: New Venture Fund.

The Lancet. Global health · 263 citationsread the source →

Reproductive, obstetric, and long-term health outcome after uterus transplantation: results of the first clinical trial.

Objective: To evaluate reproductive, obstetric, and long-term health of the first completed study of uterus transplantation (UTx). Design: Prospective. Setting: University hospital. Patient(s): Nine live donor UTx procedures were conducted and seven were successful. Donors, recipients, and children born were observed. Intervention(s): In vitro fertilization was performed with embryo transfer (ET) of day 2 or day 5 embryos in natural cycles. Pregnancies and growth trajectory of the children born were observed. Health-related quality of life, psychosocial outcome, and medical health of donors and recipients were evaluated by questionnaires. Main outcome measure(s): The results of in vitro fertilization, pregnancies, growth of children, and long-term health of patients were reported. Result(s): Six women delivered nine infants, with three women giving birth twice (cumulative birth rates of 86% and 67% in surgically successful and performed transplants, respectively). The overall clinical pregnancy rate (CPR) and live birth rate (LBR) per ET were 32.6% and 19.6%, respectively. For day 2 embryos, the CPR and LBR per ET were 12.5% and 8.6%, respectively. For day 5 embryos, the CPR and LBR per ET were 81.8% and 45.4%, respectively. Fetal growth and blood flow were normal in all pregnancies. Time of delivery (median in full pregnancy weeks + days [ranges]) by cesarean section and weight deviations was 35 + 3 (31 + 6 to 38 + 0) and -1% (-13% to 23%), respectively. Three women developed preeclampsia and four neonates acquired respiratory distress syndrome. All children were healthy and followed a normal growth trajectory. Measures of long-term health in both donors and recipients were noted to be favorable. When UTx resulted in a birth, scores for anxiety, depression, and relationship satisfaction were reassuring for both the donors and recipients. Conclusion(s): The results of this first complete UTx trial show that this is an effective infertility treatment, resulting in births of healthy children and associated with only minor psychological and medical long-term effects for donors and recipients. Clinical trial registration number: NCT02987023.

Fertility and sterility · 42 citationsread the source →

Combat sports and wellbeing: advancing health and inclusion in athletes and practitioners. An opinion paper

Historically, combat sports have been predominantly conceptualized within the framework of elite competition, emphasizing physical aptitude, technical proficiency, and strategic execution (1-3). Despite their traditional and peculiar constitutions and developments, disciplines such as judo, karate, taekwondo, wrestling, fencing, boxing, and mixed martial arts have commonly been associated with high-performance athletes striving for competitive excellence on national and international stages (1, 4-6). However, contemporary discourse increasingly recognizes their expansive role in contributing to physical and psychological well-being, and social inclusion of the practitioners (7, 8). This paradigmatic shift underscores the capacity of combat sports to function as inclusive and accessible modalities for fostering multidimensional health benefits across diverse populations, including individuals with disabilities and other marginalized groups (9-13).The interdisciplinary exploration of physical activity and health highlights the intricate interrelationship between structured sports engagement and holistic well-being (14). Whilst conventional team and individual sports have long been acknowledged for their physiological and psychosocial benefits, combat sports exhibit distinct characteristics that might amplify these advantages (15, 16). Within combat sports, the synergistic interplay of rigorous physical conditioning, the cognitive engagement, adherence to rules, competition dynamics, respect, externalizing emotions regulation, are intertwined with pedagogical and philosophical values, thus presenting a unique framework for enhancing psychological resilience, cognitive adaptability, and emotional control. Consequently, the systematic practice of combat sports has been increasingly examined as a way of promoting mental health, stress modulation, and social cohesion (17, 18).The inclusive nature of many combat sports programmes further accentuates their relevance in dismantling stereotypes, facilitating integration, and fostering equity and social integration (19-21). In fact, they demonstrated significant adaptability to accommodate individuals with disabilities (e.g., physical impairments, developmental, emotional, intellectual disorders), thereby ensuring equitable access and fostering empowerment (9, 22). Adapted judo, para-taekwondo, and other modified combat disciplines provide individuals with disabilities a structured platform to engage in physical activity, cultivate self-efficacy, and develop meaningful social connections within a supportive and adaptive environment (23). From a public health perspective, the integration of combat sports within community-based health initiatives offers a compelling opportunity to engage populations that may not traditionally participate in structured physical activity programmes (7, 8, 19). The distinctive accessibility of combat sports, which cater to practitioners of all skill levels (e.g., from novices to elite athletes) sets them apart from many other sports. While their structured progression, adaptability, and emphasis on holistic development make them a viable option for lifelong and intergenerational participation (19, 24, 25), the mentorship and pedagogical frameworks cultivate positive role modeling, discipline, and intrinsic motivation, which are integral for sustaining long-term adherence to health-promoting behaviors (8).Furthermore, the intersection between combat sports and mental health has increasingly emerged as a focal point within academic and clinical research (17) with empirical evidence suggesting an association between participation and enhanced self-regulation and self-efficacy, and reduction in anxiety and depressive symptomatology (8, 26, 27). In necessitating sustained focus, adaptability, and emotional equilibrium, combat sports inherently require cognitive and affective demands, which align closely with established psychological frameworks that underpin mental well-being (28, 29). Moreover, the integration of mindfulness techniques, stress management strategies, and resilience-building paradigms within combat sports training substantiates their potential as a non-pharmacological intervention for addressing various mental health challenges (e.g., autism spectrum and oppositional defiant disorders) (30, 31).Despite these advantages, the discourse surrounding combat sports and well-being necessitates a critical examination of inherent risks and potential challenges. Issues related to injury risk, hypercompetitive environments, eating disorders, sexual harassment, and the psychological stressors associated with high-intensity training warrant careful scrutiny (32-36). The implementation of evidence-based injury prevention protocols, the establishment of ethically responsible coaching methodologies, and the promotion of safe training environments are imperative to ensure that the benefits of combat sports are maximized while minimizing adverse outcomes. Against this backdrop, this opinion paper seeks to examine the role of combat sports in advancing health and social inclusion among athletes and practitioners. Through a synthesis of contemporary empirical findings, theoretical paradigms, and applied insights, this paper aims to contribute to the evolving discourse on the potential of combat sports as a catalyst for holistic well-being. By delineating the multidimensional impact of combat sports on physical, psychological, and social health, this paper endeavors to underscore their transformative potential as an instrument for fostering individual and community well-being within different populations. DiscussionWhilst an expanding body of research and an evolution in scholarly discourse is recognizing the combat sports’ broader implications for holistic well-being (30, 37), a rigorous evaluation of the investigation methodologies, the validity of hypotheses, and the translational potential of recent findings is necessary to contextualize their significance within the sports and public health sciences, considering their strengths, weaknesses, opportunities, and threats (Figure 1).----------------------------------------ADD FIGURE 1 ABOUT HERE----------------------------------------Empirical evidence robustly shows the positive impact of combat sports on physical fitness, motor coordination, and cardiovascular health (3, 38). These benefits are attributed to the high-intensity, intermittent nature of combat sports training, which enhances aerobic and anaerobic endurance, muscular strength, and neuromuscular control (39). However, concerns regarding injury risk, particularly in striking and contact-intensive disciplines such as boxing, taekwondo, and mixed martial arts, necessitate continued research into injury mitigation strategies, particularly those targeting concussion and repetitive head trauma (6, 35, 40, 41). Moreover, many combat sports have developed styles with reduced or simulated contact to minimize injury risk. For example, the French "boxe éducative" emphasizing technique and control, penalizing any violent behaviors (42) and the value and application of kata (i.e., forms; prearranged, pattern practices) to learning and adopting judo technique in a safe way educating the athlete culturally, to enrich her/him as a person (43).Beyond physical health, recent studies highlight the psychological benefits of combat sports, including reductions in anxiety and depression and improvements in self-efficacy, emotional regulation, resilience, and stress management (27, 44-47). Therefore, combat sports-based interventions for individuals with mental health conditions have yielded promising outcomes (23). Despite these encouraging findings, variability in study designs, participant demographics, and intervention protocols limits their external validity, underscoring the need for further rigorously controlled investigations. Furthermore, some authors claimed that combat sport athletes might present symptoms of low energy availability and high anxiety levels associated with competition- and injury-related psychological stressors, deficits in executive functions and neuropsychological impairments associated with occurrence of concussions, disordered eating and eating disorders associated with weight-loss, and might suffer offensive, frightening, hostile, degrading, humiliating experiences, or sexual harassment, which urge safeguarding actions (32-36).The role of combat sports in fostering social inclusion has gained empirical support, particularly in programmes aimed at individuals with disabilities and marginalized communities (25, 48). For instance, a recent systematic review shows that judo interventions adapted for intellectual disabilities help improve social integration and self-perception and enhance participants' quality of life (49). The development of para-combat sports demonstrates enhanced physical and motor abilities while providing psychosocial benefits to various populations with different disabilities, promoting social integration, self-perception, and community belonging (50, 51). However, longitudinal research is needed to assess the long-term retention rates and sustainability of these benefits. Furthermore, there is a need of studies focused on the most appropriate adapted rules to achieve a fairer competition for ensuring a sense of success in individuals with physical, emotional, mental, hearing or visual impairments participating in adapted sports competitions at local, national, and international levels. Methodological approaches in combat sports research encompass experimental, longitudinal, qualitative, and systematic review designs. While randomized controlled trials remain the gold standard for establishing causality, their application in combat sports research is constrained by ethical concerns, logistical challenges, and the inherently dynamic nature of training environments (52, 53). Consequently, many studies rely on observational designs, which, despite their value in identifying associations, are susceptible to confounding variables and biases (24, 54).Qualitative methodologies have provided critical insights into the lived experiences of combat sports practitioners, offering perspectives on psychological and social dimensions that are often overlooked in quantitative studies (28). Ethnographic research has been particularly instrumental in elucidating the role of combat sports in shaping identity, discipline, and personal development (55). However, limitations in reproducibility and generalizability highlight the need for mixed-methods approaches to generate a more comprehensive understanding of combat sports' impact (25, 56).Additionally, the incorporation of biometric and neurocognitive assessments, such as heart rate variability analysis, functional MRI, and salivary cortisol measurements, has advanced our understanding of the physiological and psychological mechanisms underlying combat sports participation (47, 57, 58). Despite their objective precision, these techniques often face challenges related to cost, accessibility, and limited sample sizes, necessitating the development of scalable and cost-effective methodologies for broader research application. Finally, recent studies show that virtual reality (VR) technology and digital platforms are increasingly becoming part of combat sports training methods. Due to COVID-19 restrictions, martial arts schools and organizations implemented hybrid or online training models, which allowed athletes to stay engaged. VR boxing programmes provide users with virtual sparring simulations to enhance their motor skills without needing physical interaction. Initial results indicate that VR training enhances response behavior in karate athletes (59). Digital adaptations offer great potential, especially for people with limited mobility or remote locations. However, further studies are necessary to prove their enduring effects on physical health and psychological and social aspects (59-61).Strengths and Weaknesses of Scientific HypothesesThe hypothesis that combat sports confer multidimensional health benefits is strongly supported by empirical evidence spanning physiological, psychological, and social domains (8, 62-64). The integration of physical exertion, cognitive engagement, and structured discipline inherent in combat sports aligns with established theories of exercise psychology, neuroplasticity, and social identity formation (65, 66). This multidimensional perspective provides a robust theoretical foundation for advocating combat sports as a health-promoting activity. Nevertheless, several limitations warrant consideration. The heterogeneity of disciplines, which vary highly in intensity, contact level, and training methodologies, is often inadequately addressed in research, leading to overgeneralized conclusions (17, 39). Often underexamined, individual differences in personality, motivation, and previous trauma history may strongly moderate the psychological outcomes of combat sports participation (35, 67, 68).Additionally, a research focus is needed on concerns regarding the potential for adverse psychological effects (e.g., anxiety, depression, disordered eating behaviors, burnout, and decreased self-esteem), particularly in competitive environments where performance pressure, extreme weight-cutting practices, and aggressive coaching styles are prevalent (69, 70). Indeed, a balanced perspective that considers both benefits and risks is essential for the development of evidence-based recommendations (10, 71).Future DirectionsTo enhance the field, future research should prioritize well-structured longitudinal studies that assess the long-term impact of combat sports participation on physical, psychological, and social health. Standardization of outcome measures, intervention protocols, and participant demographics would facilitate cross-study comparisons and strengthen the reliability of findings (72, 73). Moreover, interdisciplinary collaborations incorporating sports science, psychology, and sociology could provide a more holistic perspective on combat sports' broader implications on practitioners (74).From a policy perspective, to yield valuable insights into combat sports’ practical applications research should investigate their efficacy within public health, educational, and rehabilitation initiatives, particularly for underserved and vulnerable populations (23, 75, 76).Furthermore, while safety remains a primary concern, advancements in protective equipment, training methodologies, education for athletes, coaches, referees and tournament directors, and regulatory frameworks should be continually evaluated to optimize benefits while mitigating risks (40, 41, 58, 77, 78). Ethical considerations, particularly concerning athlete well-being and inclusive participation, should remain a central focus in both research and practical implementation (17, 34, 36).Therefore, key research challenges to be addressed are: 1. Injury risk and safety: a need for injury prevention strategies, especially for concussions and head trauma in striking sports. 2. Psychological wellbeing: risks of stress, anxiety, burnout, and negative self-perception in competitive environments. 3. Inclusion and accessibility: a need for more research on long-term social and psychological benefits for marginalized groups and individuals with disabilities. 4. Methodological limitations: lack of standardized protocols, variability in study designs, and limited reproducibility of findings. 5. Ethical and regulatory issues: concerns over coaching practices, extreme weight-cutting, and athlete wellbeing in high-pressure environments. 6. Technological innovations: more research required on the effectiveness of VR and digital training tools in combat sports. 7. Public health and policy: exploration of combat sports' role in health initiatives, rehabilitation, and educational programs. ConclusionThe evolving discourse on combat sports highlights their potential as a multidimensional tool for well-being promotion. While a substantial body of evidence supports their benefits, a critical examination of methodological limitations, scientific hypotheses, and practical applications is essential for further refine our understanding and enhance their effectiveness. Finally, this article makes a significant contribution not only to the field of martial arts but also to public health and sports psychology. Its interdisciplinary approach calls for scientific collaboration and methodological rigor, reinforces the need for evidence-based policies and can serve as a valuable guide for researchers and policymakers looking to integrate combat sports into strategies for promoting health and social inclusion.

Frontiers in Psychology · 12 citationsread the source →

Mental Health Response to the COVID-19 Outbreak in China

Back to table of contents Previous article Next article CommentaryFull AccessMental Health Response to the COVID-19 Outbreak in ChinaJunying Zhou, M.D., Ph.D., Liu Liu, M.D., Pei Xue, M.D., Xiaorong Yang, B.N., Xiangdong Tang, M.D., Ph.D.Junying Zhou, M.D., Ph.D., Liu Liu, M.D., Pei Xue, M.D., Xiaorong Yang, B.N., Xiangdong Tang, M.D., Ph.D.Published Online:7 May 2020https://doi.org/10.1176/appi.ajp.2020.20030304AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Transmission of the 2019 novel coronavirus (COVID-19) (1) has now widely and rapidly spread around the world. On March 11, 2020, the World Health Organization announced that COVID-19 is a pandemic (2). The rapid transmission and mortality risk of the COVID-19 infection may increase the risk of mental health problems among healthy individuals in the general public and worsen preexisting psychiatric problems in psychiatric patients, although data are still being gathered. A constellation of difficult feelings and psychological distress, including panic, worries, and depression, could be triggered by the fear of possible infection, being quarantined at hospitals and home, social isolation, and even the shortage of protective gear.A number of mental health surveys associated with the COVID-19 outbreak are being conducted in different vulnerable populations, which include infected patients, medical staff, students, and the general population. Liu et al. have reported results from a multicenter survey conducted among 1,563 medical staff members and found that the prevalence of depression and anxiety was 51% and 45%, respectively (3). So far, data on the mental health repercussions of the COVID-19 pandemic in outpatient populations have not been available. Thus, we conducted a questionnaire survey, from February 25 to March 9, 2020, among outpatients who sought care in the Departments of Psychiatry, Neurology, and Sleep Medicine in West China Hospital of Sichuan University (Chengdu, China). A self-report questionnaire was completed by outpatients, who provided consent, via the WeChat-based survey program Questionnaire Star. A total of 2,065 out of 3,441 patients completed the survey, including 589 new patients and 1,476 existing patients. The prevalence rates of mental health problems related to the COVID-19 outbreak, including anxiety (defined as a total score ≥5 on the Generalized Anxiety Disorder 7-item scale), depression (defined as a total score ≥5 on the Patient Health Questionnaire 9-item scale), and insomnia (defined as a total score ≥8 on the Insomnia Severity Index), were 25.5%, 16.9%, and 26.2%, respectively. Furthermore, 20.9% of patients (N=300) with preexisting psychiatric disorders (N=1,434) reported a deterioration of their mental health condition related to the pandemic. In particular, transportation restrictions, isolation at home, and fear of cross-infection in hospitals have inevitably become major concerns and barriers to treatment for these patients during the outbreak. Our survey also showed that 24.5% of new patients, including those with anxiety (N=46), depression (N=37), insomnia (N=79), and psychosis (N=21), could not receive timely diagnoses and treatment. Similarly, 22.0% of existing patients with diagnosed mental disorders, including depression, bipolar disorders, and schizophrenia (N=315), could not receive routine psychiatric care because of suspended hospital visits. Consequently, 18.1% of patients (N=259) have self-reduced medication dosages, and 17.2% of patients (N=247) stopped taking their medication because they could not gain access to prescriptions from physicians during the outbreak. As the lifetime prevalence of mental disorders is 16.6% among adults in China (4), millions of psychiatric patients may face barriers to help seeking for timely management of their mental health condition. The long-term repercussions of the viral pandemic on the management of psychiatric patients warrant further investigation. Nonetheless, our data reiterate the importance of implementing appropriate mental health care measures in the face of the COVID-19 pandemic. In response to the COVID-19 outbreak, there have been ongoing measures and concerted efforts in China that emphasize the importance of dealing with the potentially concurrent mental health crisis. On January 26, 2020, the National Health Commission of China released principles for emergency psychological crisis intervention for the COVID-19 pandemic (5). Mental health hotlines were quickly established across China and provided the public with counseling and psychological services. The telephone and Internet have been widely used to deliver mental health care services, and social media platforms (e.g., WeChat, Weibo) have been used to share strategies, guidelines, and education programs for managing potential mental distress. In addition, a series of self-help handbooks for psychological care associated with COVID-19 have been published by the China Association for Mental Health, medical institutions, and universities. Furthermore, a number of hospitals in China have initiated telemedicine services for patients in need during the outbreak of COVID-19. On January 26, 2020, West China Hospital of Sichuan University, as one of the leading hospitals in China, opened a free online outpatient service involving more than 100 medical doctors across specialties. This online outpatient service was created mainly to provide prescriptions to existing patients and to offer consultation to new patients. Our hospital collaborated with commercial courier services to deliver medication to patients' homes at no cost. To date, thousands of patients have received health care provided by this online outpatient service. Interestingly, only 7.4% of patients with mental disorders (N=136) in our survey have sought online help for medical care. Thus, there is a need to promote online mental health care services across China to manage mental health problems during the pandemic. The long-term outcomes of the mental health interventions in both community and hospital settings need further evaluation to determine how we can ameliorate the negative effects of viral outbreaks in the general public, especially among vulnerable patients with mental health problems. Sleep Medicine Center (Zhou, Xue, Tang), Department of Anesthesiology, Translational Neuroscience Center (Liu), and Outpatient Department (Yang), West China Hospital, Sichuan University, Chengdu, China. Send correspondence to Dr. Zhou ([email protected]).The authors report no financial relationships with commercial interests. The authors thank the clinic nurses in the Departments of Psychiatry, Neurology, and Sleep Medicine, West China Hospital, Sichuan University. References1 Lu R, Zhao X, Li J, et al.: Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395:565–574Crossref, Medline, Google Scholar2 World Health Organization (WHO): WHO director-general's opening remarks at the media briefing on COVID-19: 11 March 2020 (https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020)Google Scholar3 Liu S, Yang L, Zhang C, et al.: Online mental health services in China during the COVID-19 outbreak. Lancet Psychiatry 2020; 7:e17–e18Crossref, Medline, Google Scholar4 Huang Y, Wang Y, Wang H, et al.: Prevalence of mental disorders in China: a cross-sectional epidemiological study. Lancet Psychiatry 2019; 6:211–224Crossref, Medline, Google Scholar5 National Health Commission of China: [Principles for emergency psychological crisis intervention for the new coronavirus pneumonia.] http://www.nhc.gov.cn/jkj/s3577/202001/6adc08b966594253b2b791be5c3b9467.shtml (Chinese)Google Scholar FiguresReferencesCited byDetailsCited byRelationship between depression and burnout among nurses in Intensive Care units at the late stage of COVID-19: a network analysis1 April 2024 | BMC Nursing, Vol. 23, No. 1Effects of Long COVID on Psycho-Physical Conditions in the Italian Population: A Statistical and Large Language Model Combined Description27 April 2024 | European Journal of Investigation in Health, Psychology and Education, Vol. 14, No. 5The efficacy of internet-delivered cognitive-behavioral therapy for posttraumatic stress disorder according to the mean age of patients: a systematic review and meta-analysis11 December 2023 | Psychology, Health & Medicine, Vol. 29, No. 4Descripción de un Programa de Telesalud Mental en el Marco de la Pandemia de COVID-19 en ColombiaRevista Colombiana de Psiquiatría, Vol. 53, No. 2Longitudinal trajectories of anxiety and depression in subjects with different mental disorders after one year in the COVID-19 pandemicPsychiatry Research, Vol. 334The Impact of the COVID-19 Pandemic on the Mental Health of Families16 April 2024Effect of anxiety and depression on self-reported adverse reactions to COVID-19 vaccine: a cross-sectional study in Shanghai, China3 March 2023 | BMC Public Health, Vol. 23, No. 1Evaluation of cognitive functions in a group of Egyptian recovered COVID-19 patients22 May 2023 | Middle East Current Psychiatry, Vol. 30, No. 1Trends in telemedicine utilization for mental illness during the COVID-19 pandemic: an analysis of a nationwide database in Korea24 October 2023 | BMC Psychiatry, Vol. 23, No. 1Investigating the dynamic relationship between stigma of fear, discrimination and employees performance among healthcare workers during Covid-19 pandemic31 July 2023 | Cognition, Technology & Work, Vol. 25, No. 4"I Can't See an End in Sight." How the COVID-19 Pandemic May Influence Suicide RiskCrisis, Vol. 44, No. 6Mental Distress Among Norwegian Adults During the COVID-19 Pandemic: Predictors in Initial Response and Subsequent Trajectories25 October 2023 | International Journal of Public Health, Vol. 68The mediating effect of family health on the relationship between health literacy and mental health: A national cross-sectional survey in China24 April 2023 | International Journal of Social Psychiatry, Vol. 69, No. 6Coronavirus anxiety, fear level, and awareness of nursing students starting face-to-face education28 August 2023 | Journal of Public Health, Vol. 20Unleashing the link between the relaxation of the COVID-19 control policy and residents' mental health in China: the mediating role of family tourism consumption22 August 2023 | Frontiers in Public Health, Vol. 11Impact of the first wave of COVID-19 pandemic on the Hungarian university students' social and health behaviour28 October 2021 | Journal of Public Health, Vol. 31, No. 7Is psychologically vulnerable rural-to-urban migrants' mental health further at stake under China's tightened COVID-19 measures: how should the government respond?5 May 2023 | Frontiers in Sociology, Vol. 8The impact of the COVID-19 pandemic and earthquake on mental health of persons with severe mental illness: A survey study among people receiving community mental health care versus treatment as usual in Croatia1 November 2022 | International Journal of Social Psychiatry, Vol. 69, No. 3Prosocial behavior predicts meaning in life during the COVID-19 pandemic: The longitudinal mediating role of perceived social support16 March 2023 | Frontiers in Public Health, Vol. 11Inter-relationships of depressive and anxiety symptoms with suicidality among adolescents: A network perspectiveJournal of Affective Disorders, Vol. 324The Racial Differences in Impact and Knowledge of COVID-19 Among Patients with Psychiatric IllnessesCurrent Psychiatry Research and Reviews, Vol. 19, No. 1Codesign of a digital health tool for suicide prevention: protocol for a scoping review10 March 2023 | BMJ Open, Vol. 13, No. 3Chinese adolescents' depression, anxiety, and family mutuality before and after COVID ‐19 lockdowns: Longitudinal cross‐lagged relations2 September 2022 | Family Relations, Vol. 72, No. 1Public psychological crisis reports: an investigation during the remission of COVID-19 in China21 January 2022 | Chinese Management Studies, Vol. 17, No. 1"Nice You Share in Return": Informational Sharing, Reciprocal Sharing, and Life Satisfaction Amid COVID-19 Pandemic29 October 2022 | Social Indicators Research, Vol. 165, No. 2Psychological Distress of Healthcare Workers in 4 Hospitals Compared to General Population During the First Italian Wave of COVID-19 Pandemic27 January 2023 | INQUIRY: The Journal of Health Care Organization, Provision, and Financing, Vol. 60Effect of the COVID-19 Lockdown and Post-lockdown on Mental Health Among Diploma in Pharmacy Students27 July 2023Evaluation and Application of Cloud Computing in Mental Health Service PlatformProcedia Computer Science, Vol. 228A mathematical model of coronavirus transmission by using the heuristic computing neural networksEngineering Analysis with Boundary Elements, Vol. 146Complicaciones neuropsiquiátricas por COVID-1931 December 2022 | Salud, Ciencia y Tecnología, Vol. 2, No. S1Network analysis of depressive and anxiety symptoms in adolescents during the later stage of the COVID-19 pandemic10 March 2022 | Translational Psychiatry, Vol. 12, No. 1Impact of housing conditions on changes in youth's mental health following the initial national COVID-19 lockdown: a cohort study4 February 2022 | Scientific Reports, Vol. 12, No. 1COVID-19 behavioral health and quality of life19 January 2022 | Scientific Reports, Vol. 12, No. 1RETRACTED ARTICLE: Type 1 diabetes and the challenges of emotional support in crisis situations: results from a randomized clinical trial of a multidisciplinary teleintervention23 February 2022 | Scientific Reports, Vol. 12, No. 1Type 1 diabetes and the challenges of emotional support in crisis situations: results from a feasibility study of a multidisciplinary teleintervention20 May 2022 | Scientific Reports, Vol. 12, No. 1Prevalence of post-traumatic stress disorder symptoms among patients with mental disorder during the COVID-19 pandemic1 March 2022 | BMC Psychiatry, Vol. 22, No. 1COVID-19 and substance use disorders: a review of international guidelines for frontline healthcare workers of addiction services31 March 2022 | BMC Psychiatry, Vol. 22, No. 1Anxiety and depression in the post-pandemic era: concerns about viral mutation and re-outbreak3 November 2022 | BMC Psychiatry, Vol. 22, No. 1Gender differences in psychiatric outpatients: a before and during COVID-19 pandemic study in general hospitals from China7 September 2022 | Annals of General Psychiatry, Vol. 21, No. 1Public wellbeing analytics framework using social media chatter data3 November 2022 | Social Network Analysis and Mining, Vol. 12, No. 1Association between sedentary time and metabolic syndrome: A cross-sectional study among Chinese Garze Tibetans17 November 2022 | Frontiers in Public Health, Vol. 10COVID-19 pandemic and adolescent mental health in China: Micro evidence and socioeconomic mechanisms14 November 2022 | Frontiers in Psychology, Vol. 13A deep learning-based model for detecting depression in senior population7 November 2022 | Frontiers in Psychiatry, Vol. 13Einfluss der COVID-19-Pandemie auf die ambulante psychotherapeutische Versorgung von Kindern und Jugendlichen27 June 2022 | Die Psychotherapie, Vol. 67, No. 6Family Resilience, Media Exposure, and Children's Mental Health in China During COVID-196 December 2021 | The Family Journal, Vol. 30, No. 4The associations among the stress symptoms, depressive symptoms, anxiety symptoms and insomnia symptoms in depressed patients after the first COVID-19 outbreak was initially controlled in China: A prospective cohort studyJournal of Affective Disorders, Vol. 314Minority and low-SES families' experiences during the early phases of the COVID-19 pandemic crisis: A qualitative studyChildren and Youth Services Review, Vol. 140Network analysis of depression, anxiety, insomnia and quality of life among Macau residents during the COVID-19 pandemicJournal of Affective Disorders, Vol. 311Prevalence of problematic Internet use during the coronavirus disease 2019 pandemicCurrent Opinion in Behavioral Sciences, Vol. 46Prevalence of anxiety symptoms among Chinese university students amid the COVID-19 pandemic: A systematic review and meta-analysisHeliyon, Vol. 8, No. 8Machine learning approach for anxiety and sleep disorders analysis during COVID-19 lockdown30 May 2022 | Health and Technology, Vol. 12, No. 4Mental health of patients with mental illness during the COVID-19 pandemic lockdown: a questionnaire-based survey weighted for attrition17 September 2021 | Nordic Journal of Psychiatry, Vol. 76, No. 5Proposal of a Model for the Analysis of the State of the Use of ICT in Education Applied to Technological Institutes of Higher Education8 July 2022 | Computers, Vol. 11, No. Mental and COVID-19 A in the June 2022 | Frontiers in Public Health, Vol. of Psychiatric in Patients in Hospitals to COVID-19 Outbreak in A Center Longitudinal April 2022 | Vol. No. Use and Mental Health During the COVID-19 Health Vol. No. for During the COVID-19 Pandemic: A April 2022 | Frontiers in Psychiatry, Vol. post-traumatic in the general a cross-sectional study from August 2021 | Psychology, Health & Medicine, Vol. No. as in a with A Reports, Vol. 17, No. of symptoms in Internet and depression among adolescents in A network of Affective Disorders, Vol. March 2022 | University Journal of and of Social Media in for the of the Pandemic among Students27 February 2022 | International Journal of Research and Public Health, Vol. 19, No. of the during the COVID-19 Lockdown by the Mental Health by the of Psychology of March 2022 | International Journal of Research and Public Health, Vol. 19, No. symptoms during the early and late of the COVID-19 pandemic in China: a systematic review and Medicine, Vol. and Sleep of Patients with Sleep February 2022 | Journal of Sleep Medicine, Vol. 9, No. of and psychiatric symptoms in patients with psychiatric disorders during the Covid-19 May 2021 | European of Psychiatry and Vol. No. the Care and Anxiety of Patients with COVID-19 in November 2021 | Journal of and Health, Vol. No. impact of the pandemic on in the with preexisting mental health A longitudinal October 2021 | Journal of Vol. No. of Psychiatric and Psychiatric Among for During the Initial of COVID-19 Pandemic in Vol. 19, No. of the COVID-19 September to the Prevalence of of Mental in the During the COVID-19 Pandemic: December 2022 | Research, Vol. No. in the of the COVID-19 Pandemic in January 2022 | Journal of Science, Vol. No. 6Mental Health and among University during the COVID-19 Pandemic in January 2022 | Journal of Sciences, Vol. No. in the and COVID-19 among patients with psychiatric illness A study from of Psychiatry, Vol. No. on Impact of COVID-19 Pandemic on with their and with Social Psychiatry, Vol. No. and of to Department during COVID-19 Pandemic of December 2021 | Journal of Care Medicine, Vol. 25, No. impact of the COVID-19 pandemic on depression in a prospective cohort December 2021 | Medicine, Vol. impact in patients with mental disorders after of COVID-19 Vol. to the COVID-19 Pandemic Among the General February 2021 | Journal of and Studies, Vol. No. 8The impact of COVID-19 pandemic on symptoms and among patients with medication a cross-sectional May 2021 | The Journal of and Vol. 22, No. reactions and insomnia in adults with mental health disorders during the COVID-19 January 2021 | BMC Psychiatry, Vol. 21, No. and anxiety symptoms in adults before and during the COVID-19 pandemic: evidence from a September 2021 | Annals of General Psychiatry, Vol. No. 1Prevalence of psychiatric and related symptoms among patients with COVID-19 during the wave of the April 2021 | and Health, Vol. 17, No. anxiety, and post-traumatic stress symptoms and COVID-19 patients: a cross-sectional study4 May 2021 | Middle East Current Psychiatry, Vol. No. of a of patients with disorders during the first COVID-19 December 2021 | Scientific Reports, Vol. 11, No. 1Effects of COVID ‐19 pandemic on mental health outcomes in a cohort of early psychosis January 2021 | in Psychiatry, Vol. No. the psychological therapy treatment outcomes for adults who are not in of and be to November 2021 | Medicine, Vol. Health to Social During the COVID-19 Pandemic in a November 2021 | Frontiers in Public Health, Vol. between the COVID-19 and and symptoms in people with November 2021 | impact of and mental health on health during of Psychiatric Research, Vol. and of public health on public new A systematic March 2021 | International Journal of Social Psychiatry, Vol. 67, No. and disorders associated with COVID-19. disorders and Vol. of mental disorders on COVID-19 October 2021 | Neurology, Vol. 13, No. of COVID-19 pandemic on emergency community Psychiatry, Vol. and psychological impact of COVID-19 pandemic in a cohort study Vol. mental health and need for care among psychiatric outpatients during the COVID-19 pandemic: from an in Research, Vol. pandemic in January 2021 | Journal of Social and Vol. 23, No. Psychiatric and the of Mental during the COVID-19 Pandemic: A et la de la COVID-19: January 2021 | The Journal of Psychiatry, Vol. No. Media and Analysis during the Covid-19 September 2021 | Vol. 13, No. Distress During the COVID-19 Pandemic in Patients Mental August 2021 | Frontiers in Psychology, Vol. to Analysis of the of July 2021 | Vol. 13, No. of COVID-19: of and July 2021 | No. 29, of Health for the of July 2021 | Frontiers in Health, Vol. of the Patients in Hospital to the COVID-19 A July 2021 | Frontiers in Psychology, Vol. during the COVID-19 pandemic social July 2021 | Vol. No. COVID-19 in Chinese July 2021 | Frontiers in Medicine, Vol. experiences of and mental health services during the first Covid-19 of Health Vol. 9, No. Health and during the Pandemic in A Questionnaire of Mental Health and Psychiatric July 2021 | International Journal of Research and Public Health, Vol. No. of the COVID-19 pandemic on mental health service use among psychiatric outpatients in a of Affective Disorders, Vol. and Association of Life Among of Patients Psychiatric Services During the COVID-19 June 2021 | Frontiers in Psychiatry, Vol. of Anxiety to the COVID-19 Ph.D., Yang, Ph.D., Ph.D., Ph.D., Ph.D., Yang, Ph.D., Ph.D., Ph.D., Ph.D., Ph.D., Ph.D., Ph.D., Ph.D., Ph.D., Ph.D., Ph.D., M.D., Ph.D., April 2021 | Journal of Psychiatry, Vol. No. in depression & anxiety among mental health service during the COVID-19 pandemicJournal of Affective Disorders, Vol. symptoms and seeking during the Covid-19 May 2021 | Translational Psychiatry, Vol. 11, No. und und February 2021 | der Vol. No. prevalence of depressive and anxiety symptoms and their associations with quality of life among patients with psychiatric disorders during the COVID-19 January 2021 | Translational Psychiatry, Vol. 11, No. COVID-19 pandemic and mental of The Vol. of COVID-19 pandemic on the mental health of May 2021 | Journal of associated with mental health and quality of life during the COVID-19 pandemic in May 2021 | Open, Vol. No. and risk of psychiatric symptoms and diagnoses before and during the COVID-19 pandemic: from the COVID-19 mental health April 2021 | Medicine, Vol. in The impact of protective and on and Medicine in Psychiatry, Vol. COVID-19 the of March 2021 | Current Psychiatry Reports, Vol. 23, No. Medicine in Psychiatry in the COVID-19 era: the impact of the pandemic on mental Medicine in Psychiatry, Vol. and in the age of October 2020 | Psychology & Vol. No. in mental health problems related to COVID-19 in Hospital Psychiatry, Vol. mental health and novel coronavirus: The risk of the Journal of Psychiatry, Vol. for and Mental On the of COVID-19 February 2021 | Frontiers in Vol. of during COVID-19: a an January 2021 | Vol. 44, No. and psychological of students during the early stage of COVID-19 outbreak in China: a cross-sectional February 2021 | BMJ Open, Vol. 11, No. an to Mental Health, and among Youth and February 2021 | International Journal of Research and Public Health, Vol. No. in the and of Mental Health November from July Disorders, and and mental illness: A systematic review and & Health, Vol. and in pandemic: the in mental health October 2020 | International Journal of Vol. No. 1Prevalence and with Insomnia Among the Chinese General Public the 2019 June 2021 | and of Vol. the of December 2021 | and of Vol. Health for to Patients in a of Pandemic: and of Patient July 2021 | Mental Health, Vol. 8, No. impact of COVID-19 pandemic on the of depression among health care cross-sectional May 2021 | Vol. Mental Health the of in the April 2021 | Journal of Education in the Health Vol. No. from November to the Mental Health of by COVID-19 in China: A December 2020 | Frontiers in Psychiatry, Vol. of in 100 Patients Disorder During the COVID-19 Pandemic in December 2020 | Frontiers in Psychiatry, Vol. in of November 2020 | Current Psychiatry Reports, Vol. 22, No. adverse with during COVID-19 Journal of Psychiatry, Vol. of patients with Journal of Psychiatry, Vol. health response for and adolescents during the COVID-19 outbreak in Research, Vol. to COVID-19 to in and from a for Sleep in December 2020 | International Journal of Research and Public Health, Vol. 17, No. awareness of suicide during the October 2020 | Reports, Vol. No. of and health anxiety during COVID pandemic among of a psychiatric an Journal of impact of COVID ‐19 on individuals with disorders: A survey of individuals in the and the July 2020 | International Journal of Disorders, Vol. 53, No. and Distress COVID-19 Among University in the October 2020 | Frontiers in Psychiatry, Vol. pandemic and mental health review of the and Vol. and to the COVID-19 crisis in the of Psychiatric Research, Vol. of COVID-19 on Youth Mental Health, and A of and de la COVID-19 la de et adolescents un et July 2020 | The Journal of Psychiatry, Vol. No. Network Analysis of During the COVID-19 October 2020 | Frontiers in Psychology, Vol. of suicide during and after the COVID ‐19 September 2020 | World Psychiatry, Vol. 19, No. psychological and mental impact of coronavirus disease 2019 (COVID-19) on medical staff and general public A systematic review and Research, Vol. changes during COVID-19 and the potential A June 2020 | Journal of Health Psychology, Vol. 25, No. and July 2020 | Journal of Psychiatry, Vol. No. COVID-19-Pandemie die und Psychotherapie, Vol. No. 2019 (COVID-19) and Psychiatric in Anxiety and Journal of Medicine, Vol. 2, No. of COVID-19 on Mental Health in the September 2020 | Journal of Internet Research, Vol. 22, No. an Outpatient Psychiatric to During the COVID-19 Pandemic: A October 2020 | Journal of Internet Research, Vol. 22, No. disorders in people infected with the coronavirus September 2020 | Journal of Public Health, Vol. No. 4 July authors thank the clinic nurses in the Departments of Psychiatry, Neurology, and Sleep Medicine, West China Hospital, Sichuan April 2020 online May 2020 in 1 July 2020

American Journal of Psychiatry · 294 citationsread the source →

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings: In 2019, there were 12·2 million (95% UI 11·0-13·6) incident cases of stroke, 101 million (93·2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6·55 million (6·00-7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8-12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1-6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0-73·0), prevalent strokes increased by 85·0% (83·0-88·0), deaths from stroke increased by 43·0% (31·0-55·0), and DALYs due to stroke increased by 32·0% (22·0-42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0-18·0), mortality decreased by 36·0% (31·0-42·0), prevalence decreased by 6·0% (5·0-7·0), and DALYs decreased by 36·0% (31·0-42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0-24·0) and incidence rates increased by 15·0% (12·0-18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5-3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5-3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57-8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97-3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01-1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7-90·8] DALYs or 55·5% [48·2-62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3-48·6] DALYs or 24·3% [15·7-33·2]), high fasting plasma glucose (28·9 million [19·8-41·5] DALYs or 20·2% [13·8-29·1]), ambient particulate matter pollution (28·7 million [23·4-33·4] DALYs or 20·1% [16·6-23·0]), and smoking (25·3 million [22·6-28·2] DALYs or 17·6% [16·4-19·0]). Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding: Bill & Melinda Gates Foundation.

The Lancet. Neurology · 5441 citationsread the source →

Using social risk factors to predict allostatic biotypes of depression: A latent profile and multinomial regression analysis.

Objective: Major depression is often difficult to treat, particularly among individuals exposed to psychosocial risks like childhood maltreatment, loneliness, and recent stress. These experiences may lead to biological dysregulation consistent with allostatic load theory. This study explored whether distinct biological profiles among adults with depression are associated with specific psychosocial and health-related factors. Method: Data were drawn from the Midlife in the United States study (MIDUS), including 367 participants with clinically significant depressive symptoms (CES-D ≥ 16). Latent profile analysis identified biological profiles based on 23 biomarkers across seven systems: inflammation, glucose, sympathetic and parasympathetic nervous systems, HPA-axis, cardiovascular, and lipids. Multinomial regression models examined associations between profile membership and psychosocial (childhood maltreatment, loneliness, recent stress), health (alcohol use, smoking, exercise), and demographic variables (sex, race/ethnicity, age, education). Results: A five-profile solution best fit the data: High Inflammation & Glucose (n = 74), Low PNS (n = 83), High PNS (n = 73), Healthy Depression (n = 67), and High HPA-Axis (n = 70). Childhood maltreatment significantly predicted membership in the High Inflammation & Glucose and Low PNS profiles compared to the Healthy Depression group, even after controlling for health behaviors and demographics. Loneliness and recent stress were not significant predictors. Conclusion: Childhood maltreatment is a predictor of biological dysregulation in depression, differentially predicting profiles characterized by inflammatory and metabolic vs parasympathetic functioning. These may represent different vulnerability pathways from social experiences to depressive illness. Incorporating measurement strategies specific to these pathways may aide in selecting treatment options for people who have depression and a history of childhood maltreatment.

Brain, behavior, and immunityread the source →

Exceptional longevity in men: modifiable factors associated with survival and function to age 90 years.

Background: Prospective data on nongenetic determinants of exceptional longevity are limited, and information on long-lived men and their functional status is particularly sparse. We examined modifiable factors associated with a life span of 90 or more years and late-life function in men. Methods: In this prospective cohort study of 2357 healthy men (mean age, 72 years) within the Physicians' Health Study (1981-2006), biological and lifestyle factors and comorbid conditions were assessed by self-report with baseline and annual questionnaires. Mortality and incidence of major diseases were confirmed by medical record review. Late-life function was assessed 16 years after baseline by the Medical Outcomes Study 36-Item Short-Form Health Survey. Results: A total of 970 men (41%) survived to at least age 90 years. Smoking was associated with increased risk of mortality before age 90 years (hazard ratio [HR]; 2.10; 95% confidence interval [CI], 1.75-2.51), and similar associations were observed with diabetes (HR, 1.86; 95% CI, 1.52-2.26), obesity (HR, 1.44; 95% CI, 1.10-1.90), and hypertension (HR, 1.28; 95% CI, 1.15-1.43). Regular exercise was associated with a nearly 30% lower mortality risk (HR, 0.72; 95% CI, 0.62-0.83). The probability of a 90-year life span at age 70 years was 54% in the absence of smoking, diabetes, obesity, hypertension, or sedentary lifestyle. It ranged from 36% to 22% with 2 adverse factors and was negligible (4%) with 5. Compared with nonsurvivors, men with exceptional longevity had a healthier lifestyle (67% vs 53% had <or=1 adverse factor), had a lower incidence of chronic diseases, and were 3 to 5 years older at disease onset. They had better late-life physical function (mean +/- SD score [maximum 100], 73 +/- 23 vs 62 +/- 30; P < .001) and mental well-being (mean score, 84 +/- 14 vs 81 +/- 17; P = .03). More than 68% (vs 45%) rated their late-life health as excellent or very good, and less than 8% (vs 22%) reported fair or poor health (P < .001 for trend). Regular exercise was associated with significantly better-and smoking and overweight with significantly worse-late-life physical function. Smoking also was associated with a significant decrement in mental function. Conclusion: Modifiable healthy behaviors during early elderly years, including smoking abstinence, weight management, blood pressure control, and regular exercise, are associated not only with enhanced life span in men but also with good health and function during older age.

Archives of internal medicine · editorial or comment · 143 citationsread the source →

PATHOPHYSIOLOGY OF DEPRESSION: DO WE HAVE ANY SOLID EVIDENCE OF INTEREST TO CLINICIANS?

Major depressive disorder (MDD) is a common and costly disorder which is usually associated with severe and persistent symptoms leading to important social role impairment and increased mortality 1,2. It is one of the most important causes of disability worldwide 3. The high rate of inadequate treatment of the disorder remains a serious concern 1. This review is aimed at summarizing the solid evidence on the etiology and pathophysiology of MDD that is likely relevant for clinical psychiatry. Neurobiological findings are regarded as solid when they are consistent and convergent, i.e., they have been confirmed by several studies using the same method and fit into results from studies using different methodological approaches. Family, twin, and adoption studies provide very solid and consistent evidence that MDD is a familial disorder and that this familiality is mostly or entirely due to genetic factors 4. This important finding suggests that parental social behavior and other familial environmental risk factors are not as important in the pathogenesis of MDD as previously assumed and should not be the major focus of the treatment of the disorder. The above-mentioned studies consistently show that the influence of genetic factors is around 30–40% 4. Non-genetic factors, explaining the remaining 60–70% of the variance in susceptibility to MDD, are individual-specific environmental effects (including measurement error effects and gene-environment interactions). These effects are mostly adverse events in childhood and ongoing or recent stress due to interpersonal adversities, including childhood sexual abuse, other lifetime trauma, low social support, marital problems, and divorce 5,6. These results suggest that there is a huge potential in the prevention of MDD by means of psychosocial interventions (e.g., in schools, at workplace). In addition, these results mirror the clinical practice of empirically validated psychotherapies to treat depression 7,8,9, including interpersonal, psychodynamic and cognitive behavioral psychotherapies and cognitive behavioural analysis system of psychotherapy, which all focus directly or indirectly on interpersonal difficulties and skills. This does not exclude the fact that unidentified non-genetic, non-psychosocial risk factors may also play important roles in some patients (e.g., climatic change, medical conditions). Stress sensitivity in depression is partly gender-specific. While men and women are, in general, equally sensitive to the depressogenic effects of stressful life events, their responses vary depending upon the type of stressor. Specifically, men are more likely to have depressive episodes following divorce, separation, and work difficulties, whereas women are more sensitive to events in their proximal social network, such as difficulty getting along with an individual, serious illness, or death 10. These findings point to the importance of gender-sensitive psychosocial approaches in the prevention and treatment of MDD. In contrast to the very solid evidence from epidemiological studies on broad risk factor domains, there is no solid evidence for specific genes and specific gene-by-environment interactions in the pathogenesis of MDD. Genome-wide association studies have indicated that many genes with small effects are involved in complex diseases, increasing the difficulty in identifying such genes 11. While there has been progress in the search for risk genes for several complex diseases despite this methodological problem 12, psychiatric conditions have turned out to be very resistant to robust gene identification. For example, based on a community-based prospective study, it has been proposed that a specific genetic variation in the promoter region of the serotonin transporter (a target of antidepressant drugs) interacts with stressful life events in the pathogenesis of depression 13. Although there is high clinical and neurobiological plausibility of this interaction, a recent meta-analysis yielded no evidence that the serotonin transporter gene alone or in interaction with psychological stress was associated with the risk of depression 14. The limited success of genetic studies of depression has been related to use of current classification schemas including ICD-10 and DSM-IV. These diagnostic manuals are based on clusters of symptoms and characteristics of clinical course that do not necessarily describe homogenous disorders but instead reflect common final pathways of different pathophysiolgical processes 15,16. The clinician should be aware that family history will continue to be the most solid source of information to estimate the genetic risk of MDD. Corticotropin-releasing hormone (CRH) is released from the hypothalamus in response to the perception of psychological stress by cortical brain regions. This hormone induces the secretion of pituitary corticotropin, which stimulates the adrenal gland to release cortisol into the plasma. The physiologic response to stress is partly gender-specific: women show generally greater stress responsiveness than men, which is consistent with the greater incidence of major depression in women 17. Moreover, men show greater cortisol responses to achievement challenges, whereas women show greater cortisol responses to social rejection challenges 18. Although MDD is considered as a stress disorder, most subjects treated for MDD have no evidence of dysfunctions of the hypothalamic-pituitary-adrenal axis (HPA) 19. However, some subjects with MDD do show abnormalities of that axis and of the extrahypothalamic CRH system 20. Altered stress hormone secretion appeared to be most prominent in depressed subjects with a history of childhood trauma 21. Elevated cortisol may act as a mediator between major depression and its physical long-term consequences such as coronary heart disease, type II diabetes, and osteoporosis 22. The importance of HPA axis dysfunction for the efficacy of antidepressants is a matter of debate 23. This axis is regulated through a dual system of mineralocorticoid (MR) and glucocorticoid (GR) receptors. Decreased limbic GR receptor function 24,25 and increased functional activity of the MR system 26 suggest an imbalance in the MR/GR ratio in stress-related conditions such as MDD. Epigenetic regulation of the glucocorticoid receptors has been associated with childhood abuse 27. Such environmental programming of gene expression may represent one possible mechanism that links early life stress to abnormal HPA axis function and increased risk of MDD in adults. While the CRH stimulation test (dex/CRH test) 28 is a sensitive measure of the HPA axis dysfunction in depression, the specificity of this test for MDD is low. However, non-suppression in the dex/CRH test has consistently predicted increased risk for depressive relapse during clinical remission 23. Additionally, the measurement of waking salivary cortisol concentration has been shown to be a simple and sensitive test for HPA axis hyperactivity in depression 29. Hypercortisolemia is almost exclusively found in subjects with severe and psychotic depression, in whom glucocorticoid antagonists may have some therapeutic effect 30. There is convergent evidence for CRH to play a major role in the pathogenesis of certain types of depression. Levels of CRH in the cerebrospinal fluid are elevated in some depressed subjects 31. Post-mortem studies reported an increased number of CRH secreting neurons in limbic brain regions in depression 32, likely reflecting a compensatory response to increased CRH concentrations 33. In addition, CRH produces a number of physiological and behavioral alterations that resemble the symptoms of major depression, including decreased appetite, disrupted sleep, decreased libido, and psychomotor alterations 34. There is also preliminary evidence that CRH1 receptor antagonists reduce symptoms of depression and anxiety 35. “Sickness behavior” as a result of an activation of the inflammatory response system shares many symptoms with depression, including fatigue, anhedonia, psychomotor retardation, and cognitive impairment. Sickness is mediated by pro-inflammatory cytokines such as interleukin-1α, tumor necrosis factor-α, and interleukin-6, which activate the HPA axis and impair the central serotonin system 36. The prevalence of depression as an unwanted effect of recombinant interferons is around 30% 37. In animals, blocking pro-inflammatory cytokine-mediated signaling produces antidepressant-like effects 38. Clinical data suggest that cytokines may play a role in the pathophysiology of a subgroup of depressed subjects, particularly those with comorbid physical conditions 36. The antidepressant enhancing effect of acetylsalicylic acid 39 points to the possible clinical relevance of psychoneuroimmunology in clinical depression research. Taken together, the laboratory tests with the highest potential to be clinically useful in the care of depressed individuals are based on abnormalities of the neuroendocrine and neuroimmune systems. Despite the large amount of basic science data suggesting that the HPA axis is importantly involved in the pathophysiology of depression, the effect of pharmacological modulation of this neuroendocrine system as antidepressant therapy has been disappointing. The link between childhood trauma and a permanently altered physiologic stress system points to the use of specific psychotherapies in the treatment of depressed patients with a history of early life trauma 40. Most of the serotonergic, noradrenergic and dopaminergic neurons are located in midbrain and brainstem nuclei and project to large areas of the entire brain. This anatomy suggests that monoaminergic systems are involved in the regulation of a broad range of brain functions, including mood, attention, reward processing, sleep, appetite, and cognition. Almost every compound that inhibits monoamine reuptake, leading to an increased concentration of monoamines in the synaptic cleft, has been proven to be a clinically effective antidepressant 19. Inhibiting the enzyme monoamine oxidase, which induces an increased availability of monoamines in presynaptic neurons, also has antidepressant effects. These observations led to the pharmacologically most relevant theory of depression, referred to as the monoamine-deficiency hypothesis. The monoamine-deficiency theory posits that the underlying pathophysiological basis of depression is a depletion of the neurotransmitters serotonin, norepinephrine or dopamine in the central nervous system. Serotonin is the most extensively studied neurotransmitter in depression. The most direct evidence for an abnormally reduced function of central serotonergic system comes from studies using tryptophan depletion, which reduces central serotonin synthesis. Such a reduction leads to the development of depressive symptoms in subjects at increased risk of depression (subjects with MDD in full remission, healthy subjects with a family history of depression) 41,42, possibly mediated by increased brain metabolism in the ventromedial prefrontal cortex and subcortical brain regions 42. Experimentally reduced central serotonin has been associated with mood congruent memory bias, altered reward-related behaviors, and disruption of inhibitory affective processing 16, all of which add to the clinical plausibility of the serotonin deficiency hypothesis. There is also evidence for abnormalities of serotonin receptors in depression, with the most solid evidence pointing to the serotonin-1A receptor, which regulates serotonin function. Decreased availability of this receptor has been found in multiple brain areas of patients with MDD 43, although this abnormality is not highly specific for MDD and has been found in patients with panic disorder 44 and temporal lobe epilepsy 45, possibly contributing to the considerable comorbidity among these conditions. However, there is no explanation for the mechanism of serotonin loss in depressed patients, and studies of serotonin metabolites in plasma, urine and cerebrospinal fluid, as well as post-mortem research on the serotonergic system in depression, have yielded inconsistent results. There is preliminary evidence that an increased availability of the brain monoamine oxidase, which metabolizes serotonin, may cause serotonin deficiency 46. In addition, loss-of-function mutations in the gene coding for the brain-specific enzyme tryptophan hydroxylase-2 may explain the loss of serotonin production as a rare risk factor for depression 47. Dysfunction of the central noradrenergic system has been hypothesized to play a role in the pathophysiology of MDD, based upon evidence of decreased norepinephrine metabolism, increased activity of tyrosine hydroxylase, and decreased density of norepinephrine transporter in the locus coeruleus in depressed patients 48. In addition, decreased neuronal counts in the locus coeruleus, increased alpha-2 adrenergic receptor density, and decreased alpha-1 adrenergic receptor density have been found in the brains of depressed suicide victims post-mortem 49. Since there is no method to selectively deplete central norepinephrine and no imaging tool to study the central norepinephrine system, solid evidence for abnormalities of this system in depression is lacking. While the classical theories of the neurobiology of depression mainly focused on serotonin and norepinephrine, there is increasing interest in the role of dopamine 50. Dopamine reuptake inhibitors (e.g., nomifensine) and dopamine receptor agonists (e.g., pramipexole) had antidepressant effects in placebo-controlled studies of MDD 51. In the cerebrospinal fluid and jugular vein plasma, levels of dopamine metabolites were consistently reduced in depression, suggesting decreased dopamine turnover 52. Striatal dopamine transporter binding and dopamine uptake were reduced in MDD, consistent with a reduction in dopamine neurotransmission 53. Degeneration of dopamine projections to the striatum in Parkinson's disease was associated with a major depressive syndrome in about one half of cases, which usually preceded the appearance of motor signs 54. Experimentally reduced dopaminergic transmission into the accumbens has been associated with anhedonic symptoms and performance deficits on a reward processing task in subjects at increased risk of depression 55,56. These findings are consistent with the clinical observation that depressed patients have a blunted reaction to positive reinforcers and an abnormal response to negative feedback 57. Almost all established antidepressants target the monoamine systems 58. However, full and partial resistance to these drugs and their delayed onset of action suggest that dysfunctions of monoaminergic neurotransmitter systems found in MDD represent the downstream effects of other, more primary abnormalities. Despite this limitation, the monoamine-deficiency hypothesis has proved to be the most clinically relevant neurobiological theory of depression. New findings on the role of dopamine in depression emphasize the scientific potential of this theory, and promising reports of antidepressant effects of drugs that modulate the dopaminergic system (e.g., pramipexole, modafinil) in difficult-to-treat depression underline its clinical relevance 51,59. Although many historical attempts to localize mental functions have failed, they have considerably contributed to a modern neuroscientific understanding of mental disorders 60. The development of neuroimaging techniques has opened up the potential to investigate structural and functional abnormalities in living depressed patients. Unfortunately, the diversity of imaging techniques used, the relatively small and heterogeneous study samples studied, and the limited overlap of results across imaging paradigms 61 make it difficult to reliably identify neuronal regions or networks with consistently abnormal structure or function in MDD. Functional imaging studies have provided the most limited overlap of findings. This may be due to methodological limitations and/or the complexity of neurocircuitry involved in MDD. A recent meta-analytic study found the best evidence for abnormal brain activity in MDD in lateral frontal and temporal cortices, insula, and cerebellum. In these brain regions activity was decreased at rest, they showed a relative lack of activation during induction of negative emotions, and an increase in activity following treatment with serotonin reuptake inhibitors. Opposite changes may exist in ventromedial frontal areas, striatum and possibly other subcortical brain regions 61. More solid evidence has been provided by structural imaging and post-mortem studies. A recent meta-analytic study on brain volume abnormalities in MDD revealed relatively large volume reductions in the ventromedial prefrontal cortex, particularly in the left anterior cingulate and in the orbitofrontal cortex. Moderate volume reductions were found in the lateral prefrontal cortex, hippocampus and striatum 62. Post-mortem studies consistently identified a reduction in glia cell density in dorsal, orbital and subgenual prefrontal cortices, as well as in the amygdala 63,64. Overall, functional, structural and post-mortem studies suggest that structural and functional abnormalities in the left subgenual cingulate cortex are the most solid neuroanatomical finding in MDD. Volume reduction in this region was found early in illness and in young adults at high familial risk for MDD 65, suggesting a primary neurobiological abnormality associated with the etiology of the illness. Humans with lesions that include the subgenual prefrontal cortex showed abnormal autonomic responses to social stimuli 66, and rats with left-sided lesions in this region had increased sympathetic arousal and corticosterone responses to restraint stress 67. Most importantly, chronic deep brain stimulation to reduce the potentially elevated activity in the subgenual cingulated cortex produced clinical benefits in patients with treatment-resistant depression 68. In summary, despite the considerable heterogeneity of findings from neuroimaging studies, there is convergent evidence for the presence of abnormalities in the subgenual prefrontal cortex in some patients with MDD. Neuroanatomical research in depression is of great clinical interest, since novel antidepressant treatments such as deep brain stimulation can target specific brain regions. In addition, there are promising leads for neuroimaging findings to predict the likelihood of responses to specific treatments 69. Risk factors for depressive episodes change during the course of the illness. The first depressive episode is usually “reactive”, i.e., triggered by important psychosocial stressors, while subsequent episodes become increasingly “endogenous”, i.e., triggered by minor stressors or occurring spontaneously 70. There is consistent evidence that the volume loss of the hippocampus and other brain regions is related to the duration of depression 71, suggesting that untreated depression leads to hippocampal volume loss, possibly resulting in increased stress sensitivity 72 and increased risk of recurrence 73. Glucocorticoid neurotoxicity, glutamatergic toxicity, decreased neurotrophic factors, and decreased neurogenesis have been proposed as possible mechanisms explaining brain volume loss in depression. There is no solid evidence on of these since there are no imaging to directly and neurotrophic processes in neurotrophic factor has considerable Specifically, studies have shown between and in hippocampal as well as expression of following antidepressant treatment The clinician should be aware of the potentially effect of depression and treat depressed patients as early and as A of studies consistently showed reductions in acid concentrations in the prefrontal and cortex in depression This may reflect stress since psychological stress to presynaptic of prefrontal neurotransmission low concentration may reflect reduction in the density and of In addition, chronic stress may reduce receptor possibly through changes in evidence of the hypothesis of depression the lack of effects of drugs on depressive symptoms and prefrontal concentration in subjects with MDD of evidence suggest a dysfunction of the neurotransmitter system in a of the receptor produced and large antidepressant effects in patients with treatment-resistant MDD inhibitors of release (e.g., antidepressant abnormal levels were found in depressed subjects as by and there is evidence for abnormal signaling in post-mortem Since is the major neurotransmitter involved in almost every brain the of the specific role of in depression (e.g., there are promising leads that the receptor is involved in MDD and are diagnostic for MDD, suggesting regulation in depressed patients. In addition, some depressive symptoms may show psychomotor of of positive and negative and a subgroup of patients with MDD may have a disorder In healthy young subjects, changes in the of the had specific effects on subsequent mood In depressed patients, of can have antidepressant on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of The and of the neurobiological of depression are in 1. The many theories of depression and the relatively low response rate of all antidepressant treatments a hypothesis of and suggest that depression is a clinically and heterogeneous disorder. This research on of the response to therapeutic interventions using such as neuroimaging and neuroendocrine tests in with for with to stress sensitivity and antidepressant The of of therapeutic will for the development of that has the potential to interventions and to up pathways in the of novel therapeutic approaches.

World Psychiatry · editorial or comment · 607 citationsread the source →

Atypical Antipsychotics: CATIE Study, Drug-Induced Movement Disorder and Resulting Iatrogenic Psychiatric-Like Symptoms, Supersensitivity Rebound Psychosis and Withdrawal Discontinuation Syndromes

Chronic illness can result in chronicity of clinical practice. As we have moved away from prescribing classical antipsychotics and tricyclic antidepressants, issues remain with the use of atypical antipsychotics and second-generation antidepressants that need to be addressed, namely, iatrogenic discontinuation syndromes and supersensitivity psychiatric symptoms. An optimal maintenance drug treatment consists of regular attempts to reduce the dose by finding a minimal therapeutic dose, regularly asking the question of when to reduce or withdraw treatment and for which patients, and moreover, why it is difficult to decrease a given drug treatment. Recently, Falloon [1] proposed that maintenance pharmacotherapy in schizophrenia will depend on finally finding minimally effective doses through ‘extensive training in stress management’. In the long-term treatment of major depression, Fava [2] has hypothesized that antidepressants can aggravate the course of depressive illness. Lambert [3] recently suggested that ‘antipsychotic-switching syndromes’, which include discontinuation syndromes, are a ‘major barrier’ to adjusting antipsychotic treatment. In this paper, we propose that to achieve optimal maintenance treatment with antipsychotics, and to reduce or withdraw antipsychotics effectively, we must distinguish syndromes associated with discontinuing antipsychotics, such as supersensitivity psychosis, from true relapse. While the prevalence and incidence of drug-induced movement disorder(s) (DIMD) has continuously decreased with atypical antipsychotics, DIMD persist as do psychiatric and psychiatric-like symptoms associated with DIMD, and these must also be identified and evaluated. Persistent DIMD have been found to be a predictor of the later emergence of tardive dyskinesia (TD) and supersensitivity psychosis [4]. At present, we need to determine the relative risk of iatrogenic discontinuation syndromes, DIMD and DIMD psychiatric symptoms resulting from atypical antipsychotics. Although atypical antipsychotics are now most commonly prescribed, a debate has emerged on the differences between classical and atypical antipsychotics following the results of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study [5]. The question that comes to the forefront is why recent studies are no longer finding well-established differences between these two generations in terms of efficacy and DIMD. Reasons to explain why recent schizophrenia studies have found reduced drug and placebo differences were examined at the International Society for CNS Clinical Trials and Methodology Annual Mid-Year Conference [6]. While the fact must be considered that patients included in recent studies have less severe illness with symptoms that are better controlled than in past studies (likely due to earlier treatment), the issue that psychiatric symptoms specific to schizophrenia are not being adequately measured nor differentiated from psychiatric and psychiatric-like symptoms associated with DIMD is crucial to answering this question. For example, it is hard to believe that in a recent review of psychomotor slowing in schizophrenia, the authors, when evaluating its effect on measurement and treatment research to improve cognition in schizophrenia (MATRICS), nearly completely ignored the influence of akinesia and DIMD on neuropsychological tests in schizophrenia and the importance of accurate DIMD measurements [7]. As we pursue this ongoing discussion, we recommend the discontinuation of all classical antipsychotics due to their neurotoxic association with a high prevalence of DIMD and increases in basal ganglia volumes [8], and now address how to prescribe atypical antipsychotics most effectively, by taking into account DIMD-associated psychiatric symptoms and iatrogenic discontinuation syndromes. The first widely prescribed atypical antipsychotic, risperidone, was first approved in Canada in 1993 following the publication of the Canadian Multicenter Risperidone Study, which reported clear advantages of risperidone over haloperidol and the placebo, and significantly less appearance of DIMD with risperidone than haloperidol [9]. DIMD includes the 4 types of movement disorders induced by antipsychotics: parkinsonism, dystonia, dyskinesia and akathisia [10]. These findings were confirmed by the American Risperidone Study [11] and several other studies reporting greater efficacy of risperidone over classical antipsychotics in terms of cost-efficiency [12] and the clinical management of patients with schizophrenia [13,14,15,16,17]. However, the CATIE study [5] challenged these results. The CATIE study found that of the 4 atypical antipsychotics studied, olanzapine was the only atypical to be more efficacious than the classical antipsychotic perphenazine, and to be highly superior to risperidone for discontinuation of treatment, due to lack of efficacy [5]. Olanzapine is known to produce less DIMD compared to risperidone, therefore one would expect psychiatric symptoms caused by DIMD to be less frequent with olanzapine than risperidone. The expected higher rate of DIMD-induced emergent psychiatric symptoms associated with risperidone would explain the CATIE results, showing risperidone to be significantly less efficacious than olanzapine [5], despite risperidone being known to be at least as efficacious as olanzapine for true schizophrenic symptoms. Furthermore, the rating scales used to measure DIMD did not find the well-established differences between the 5 antipsychotics for DIMD rates [5]. Thus, we propose that DIMD and DIMD-induced psychiatric symptoms were confounded with true schizophrenic symptoms in the CATIE study. DIMD-associated psychiatric symptoms could be classified into 3 types: (1) emergent psychiatric symptoms caused by DIMD, such as akinesia inducing depression, akathisia inducing anxiety; (2) iatrogenic psychiatric-like symptoms resulting from confounding DIMD with psychiatric symptoms, such as akinesia confounded with psychomotor retardation, akathisia with agitation; (3) supersensitivity psychosis symptoms associated with DIMD. In the CATIE study, quetiapine (mean dose = 543.4 mg/day), which shares a low rate of DIMD with olanzapine, was also found to be significantly less efficacious compared to olanzapine, but in contrast to risperidone, this lack of efficacy could be due to psychiatric symptoms related to supersensitivity psychosis explained by quetiapine’s loose binding properties at the D2 receptor [18]. Patients taking quetiapine had a completion rate of 18% out of 329 patients, whereas in our 3-year prospective study of quetiapine monotherapy with a lower mean dose of 487 mg/day (thus less likely to develop therapeutic tolerance), the completion rate was 21.7% out of 23 patients; 6 of 7 patients who relapsed, after a minimum 3 months of stabilized quetiapine treatment, met the criteria for supersensitivity psychosis [19]. Without distinguishing these DIMD-associated psychiatric symptoms from symptoms due to the original illness, the major impact of atypical antipsychotics is on the reduction of DIMD and TD [10, 20,] and their beneficial effects on psychosis are masked by DIMD emergent psychiatric symptoms, including supersensitivity psychosis. We will review 4 multicenter trials, which include a total of 14,497 patients, to illustrate how psychiatric and schizophrenic symptoms are confounded with DIMD-associated psychiatric symptoms.TD epidemiology has changed significantly since the introduction of atypical antipsychotics, with a constant decline in its prevalence [10]. TD, classified as a DIMD, is a hyperkinetic, involuntary and purposeless movement disorder [10, 20]. Considered as the most significant side effect of classical antipsychotics, TD has been associated with antipsychotics and gastrointestinal neuroleptics, and usually occurs after several years of treatment. Persistent TD can also occur after short-term exposure to classical antipsychotics and gastrointestinal neuroleptics even at low doses and for as few as 2 months [8,21,22,23], while reversible and withdrawal dyskinesias share properties with levodopa-induced dyskinesia [24]. We conducted several epidemiological studies of TD [4,25,26,27] and in 1975, using the National Institute of Mental Health (NIMH) psychopharmacology criteria, we found a 31% prevalence of TD in 261 outpatients with schizophrenia [25]. We also evaluated these patients according to the Schooler and Kane research diagnostic criteria and found a 22% prevalence of TD. This variability of findings related to defining criteria complicates comparisons across studies [10]. In a 5-year follow-up study of 169 of the same patients [4, 25], 45% met the research diagnostic criteria for TD. In 1975, 131 of the 261 patients did not meet the research diagnostic for TD, and in 1980 treatment-emergent TD was found in 46 of the patients who did not have it in 1975, for a 5-year cumulative incidence rate of 35% and a mean annual incidence rate of 8.4%. When corrected for remissions, the mean annual incidence rate decreased to 2.9%. This incidence rate, which includes both patients who developed and remitted from TD over time, is similar to results found by other studies during the same time period [28, 29]. The cumulative incidence of treatment-emergent TD in the study by Kane et al. [29] was 12% after 4 years and 40% after 8 years of neuroleptic exposure, which is similar to our finding of an annual incidence rate (corrected for remissions) of 3% for classical antipsychotics. In a study carried out in 130 lithium-treated affective disorder patients previously, but less, exposed to antipsychotics, we found a TD prevalence of 9.2% [26], which was a quarter of the incidence reported in our previous studies on patients with schizophrenia who had greater exposure to antipsychotics. In this time period of classical antipsychotics, 2 meta-analyses (including mostly patients with schizophrenia) reported mean TD prevalences of 23% [30] and 20% [31]. In view of the fact that 58% of patients treated with classical antipsychotics will develop treatment-emergent TD after 10–15 years of treatment [4], and the known beneficial neuroprotective effects of atypical antipsychotics on TD [32] and on increased basal ganglia volumes induced by classical antipsychotics [8], we recommend the discontinuation of all classical antipsychotics due to their neurotoxic effects. In the time period of both classical and atypical antipsychotics, the following multicenter studies (n = 3,753) evaluated the incidence and prevalence of TD, using the same definitions, Extrapyramidal Symptom Rating Scale [20] and training videotapes as in the previous time period. In the first study, an annual TD incidence of 0.68% was reported prospectively in 725 patients with schizophrenia, treated with the long-acting injectable atypical antipsychotic risperidone [27, 33]. Treatment-emergent TD was found in 12 of 587 patients without dyskinesia at the baseline [33]; however, expert case assessment determined 7 cases (1.19%) of withdrawal dyskinesia (3 cases resolved, 4 cases unchanged), 1 case (0.17%) of reversible dyskinesia and 4 cases (0.68%) of persistent treatment-emergent TD. Of the patients with baseline dyskinesia, 28.4% improved, no longer met TD criteria and maintained this response [33]. This annual treatment-emergent TD incidence of 0.68% with atypical antipsychotics is only 22% of the annual incidence of 3% reported with classical antipsychotics [4]. In the second study, the Schizophrenia International Suicide Prevention Trial (67 centers in 11 countries) [34], 980 patients with schizophrenia, or schizoaffective disorders, taking an atypical alone (25.6%), a classical alone (31.5%) or both a classical and an atypical antipsychotic (42.9%) were included from March 19, 1998, to February 14, 1999, and TD was found at the baseline in 115 (12%) patients [27, 35]. Thus, after 10 years in the time period of both classical and atypical antipsychotics, the overall prevalence of TD decreased by at least twofold compared to our previous 1979–1988 studies with classical antipsychotics [4, 25], using the same definitions, Extrapyramidal Symptom Rating Scale and training videotapes. In the third study (baseline data from three Ris-Consta multicenter studies) [27, 36] carried out 1 year later, 2,048 patients were included from March 21, 1999, to December 15, 2000, and TD was found at the baseline in 209 patients (10.2%), using the same methodology. This study showed a further decrease in the prevalence of TD after an additional year of atypical use. This changing epidemiology of TD with atypical antipsychotics is confirmed by Correll et al. [37] in a systematic review of 1-year prospective studies with atypical antipsychotics, and by Jeste et al. [38] in a 1-year study of elderly patients treated with risperidone. In conclusion, following the introduction of atypical antipsychotics, the prevalence and incidence of TD have significantly decreased. However, the risk for TD still exists with both atypical and classical antipsychotics, and there is a need for continued surveillance of emerging cases of TD in patients taking antipsychotics [39], especially as the current debate continues on the differences in efficacy between these two generations of antipsychotics following results from studies such as the CATIE [5, 39]. Furthermore, Kane [39] has pointed out that newly trained clinicians using mostly atypical antipsychotics may not have had the same exposure to TD as previously trained clinicians.A high prevalence of all 4 types of DIMD (parkinsonism, dystonia, dyskinesia and akathisia) remains. In the Schizophrenia International Suicide Prevention Trial (n = 980), a prevalence of 57.5% of DIMD (n = 551 patients) was found [27, 35]. In the Ris-Consta studies (n = 2,048) [27, 36], 970 patients (47.4%) had DIMD at the baseline, which consisted of 778 patients with parkinsonism (38.0%), 285 patients with akathisia (14%) and 209 patients with TD (10.2%). Thus, nearly 1 patient out of 2 had a definite DIMD in this time period of classical and atypical antipsychotics. In addition, DIMD have been consistently associated with significant psychiatric symptoms as measured by the positive and negative syndrome scale (PANSS) [40, 41]. In the InterSept study (n = 980), which included patients with schizophrenia and schizoaffective disorder who were at risk of suicide, suicidality was associated at baseline with DIMD, parkinsonism, TD and akathisia, and depression was associated with TD and akathisia [27, 35]. Based on these results, we recommend routinely assessing DIMD in patients with schizophrenia with suicidal and depressive symptoms. In the Ris-Consta studies (n = 2,048), baseline DIMD were also significantly associated with the PANSS total score, positive, negative and anxiety/depression symptoms [27, 36]. Greater anxiety and depression were seen in patients with severer DIMD, akathisia and parkinsonism. Higher PANSS negative symptom rating was associated with parkinsonism and higher PANSS total scores were associated with akathisia. In this time period, these last two studies (n = 3,028) show that DIMD persists with atypical antipsychotics, and that patients with DIMD have significantly higher PANSS scores compared to patients without DIMD.These results are in agreement with findings from 2 other multicenter studies: the American CATIE study [5] and the European Schizophrenia Outpatient Health Outcomes (SOHO) study [42]. In the CATIE baseline data, patients with TD (n = 212) were found to have significantly more psychopathology than patients without TD (n = 1,098) as measured by the PANSS total score and PANSS general psychopathology subscale [43]. In the 3-year prospective SOHO study, emergent cases of TD were associated with greater overall psychopathology. An increase in clinical global impression overall symptom severity was longitudinally associated with cases of TD in patients without TD at the baseline (n = The SOHO and the CATIE studies have also examined other for TD. the CATIE and SOHO studies found that other DIMD were associated with TD the CATIE study showed that patients with TD had more parkinsonism akathisia while the SOHO study found that baseline symptoms TD our findings in a prospective study of TD [4]. In to reporting that the incidence of TD was lower in patients taking atypical compared to classical antipsychotics after 6 months the SOHO study showed that the incidence of TD was associated with the incidence of of drug-induced in is crucial to that there is a of DIMD with atypical antipsychotics, which are not and confounded with psychiatric symptoms rating scales used routinely in clinical to DIMD do not DIMD from psychiatric symptoms from the 4 multicenter (n = 14,497 patients) into this the CATIE the [27, the Ris-Consta [27, 36] and the SOHO studies have all confirmed the association of DIMD with psychiatric symptoms. most of the studies included in this measure psychiatric symptoms according to the we propose the following of PANSS psychiatric symptoms associated with emergent psychiatric symptoms caused by DIMD, such as depression and suicidality example, akinesia is known to produce depression, psychomotor and suicidal while akathisia psychomotor and suicidal and TD is also associated with suicidal iatrogenic psychiatric-like symptoms resulting from confounding and DIMD with psychiatric symptoms, such as confounding and with and retardation, akathisia with anxiety and and and dyskinesias with and schizophrenic psychiatric schizophrenic symptoms associated with DIMD caused by supersensitivity psychosis, which we are now to first reported drug-induced associated with TD a in and increased receptor after long-term treatment with classical antipsychotics, and we this supersensitivity psychosis. We that TD and supersensitivity psychosis with the decrease or withdrawal of an antipsychotic, given risk not and at the same The debate continues on how to most withdraw antipsychotic [1] and and psychiatric syndromes associated with types of syndromes have been with the discontinuation of (1) withdrawal syndromes and major (2) syndromes anxiety and which have been reported with and (3) supersensitivity syndromes such as TD and supersensitivity psychosis These discontinuation syndromes all produce psychiatric symptoms that can be confounded with true of the original illness. In a recent review of the on psychosis the importance of between antipsychotic withdrawal effects related to the course of the original illness and drug-induced effects such as supersensitivity psychosis. due to the discontinuation of a drug can be differentiated from the course of original illness and more long-term maintenance treatment could be reduced and in patients The long-term maintenance with second-generation antidepressants and of a major depressive disorder is of the in and during long-term maintenance treatment. The has also recently been to produce a persistent disorder following withdrawal to be related to supersensitivity When discontinuing antipsychotics and antidepressants, the of supersensitivity syndromes and other iatrogenic discontinuation syndromes must be to high doses or of outpatients and with schizophrenia treated with a classical antipsychotic treatment also included 1 but no antidepressants, no and no showed a prevalence of 22% for supersensitivity psychosis The prevalence of TD using Schooler and Kane criteria, was that found for supersensitivity psychosis. cases of supersensitivity psychosis increased the prevalence of supersensitivity psychosis to psychosis was associated with a higher maintenance dose of classical antipsychotics, high and schizophrenia with a The higher antipsychotic dose and higher associated with supersensitivity psychosis to the of supersensitivity and these results that lower doses of antipsychotics could the appearance of supersensitivity psychosis. In this study, there was no found between TD and supersensitivity psychosis, due to TD being associated with schizophrenia and supersensitivity psychosis with higher antipsychotic dose was not to be a risk for TD, whereas increased was associated with TD but not associated with supersensitivity psychosis. is that most patients in this study were treated with which has a high for the D2 which could to both a high incidence of supersensitivity psychosis and DIMD as the drug is known to produce a high incidence of symptoms psychosis, in its masked and withdrawal is known to occur 6 following the decrease or withdrawal of an antipsychotic or 3 months for a long-acting injectable We have proposed that TD and supersensitivity psychosis can result from the of in the caused by following in D2 with high for The of supersensitivity psychosis and TD share can both occur after long-term use of antipsychotics and can and difficult to with of the antipsychotic stress both TD and supersensitivity psychosis and both can be by and by and TD was to be the predictor of supersensitivity psychosis in our and follow-up study of supersensitivity psychosis [4, TD and supersensitivity psychosis may or may not occur in the same time but TD is associated with supersensitivity psychosis when it occurs during withdrawal of antipsychotics These two supersensitivity syndromes have been difficult to study due to the fact that antipsychotics can their appearance further with supersensitivity psychosis is that symptoms the original illness and true however, supersensitivity psychosis can be as it more after of the antipsychotic than true occurs with high doses of antipsychotics and not with antipsychotic treatment and therapeutic to antipsychotic treatment after drug response time, as therapeutic there is further of supersensitivity and further syndromes, TD, can (1) or (2) persistent or (3) reversible or symptoms can persist for several months or years and can still be reversible or When persistent and supersensitivity symptoms symptoms, being severer than the original symptoms, but these supersensitivity symptoms persist in contrast to symptoms and may include symptoms atypical antipsychotics, it has been proposed that supersensitivity psychosis occurs more with antipsychotics with from the D2 receptor The 2 atypical antipsychotics most associated with supersensitivity psychosis are quetiapine and which both have loose binding properties at the D2 receptor An additional which and severe in the withdrawal of is its effect as an receptor Thus, for the withdrawal would be by the receptor following of at this drug in the of the a and psychosis results cases of supersensitivity psychosis have also been reported with olanzapine psychosis was found to be associated with quetiapine in our 3-year study of quetiapine in 23 outpatients with schizophrenia and schizoaffective disorder who had previously been treated with classical antipsychotics risperidone, and had symptoms and of side effects [19]. As in our of the CATIE study, 7 patients after a minimum of 3 months of stabilized treatment and 6 of these patients met the criteria for supersensitivity psychosis [19]. the 11 of patients with baseline TD relapsed, the that TD to supersensitivity psychosis and have been to be efficacious in of patients with supersensitivity psychosis We also recommend the use of in supersensitivity and anxiety disorder induced by the discontinuation of the An can be used in with an antipsychotic or an in to more decrease or withdraw these and find the minimal therapeutic dose for patients who still need long-term treatment. a minimal therapeutic dose with an has an additional for a drug olanzapine, as the dose will significant side In in the of Mental Health psychiatric 35% of patients with a of schizophrenia and For severe cases of schizophrenia, the use of or is in to drug to antipsychotic While is less than or it is superior to for anxiety and the of optimal minimal maintenance drug treatment. proposed the beneficial results of treatment in schizophrenia is their effect We have also related their beneficial effects to an of a We recommend treatment as a first for from treatment, can also be prescribed as with as it has a In a and that and had than other in addition, emerging that may improve DIMD has also been to be effective as an to antipsychotic monotherapy in patients with schizophrenia who treatment We that of cases of schizophrenia can be related to supersensitivity psychosis. In patients for maintenance treatment is a minimal therapeutic dose can be with the use of an that will patients from antipsychotic or conclusion, DIMD-induced psychiatric symptoms and supersensitivity syndromes will to to results such as found in the CATIE study which show that olanzapine is the only atypical antipsychotic more efficacious than a classical The proposed for psychiatric and psychiatric-like symptoms associated with DIMD may to the of all classical antipsychotics and the use of higher doses and longer than of atypical antipsychotics. research is in to develop to distinguish between true and iatrogenic discontinuation syndromes and to to more withdraw antipsychotics and antidepressants by and supersensitivity syndromes, for the antipsychotics and quetiapine and for the may to further of DIMD, TD and supersensitivity psychosis as we to more differences in the of As most of antipsychotics and second-generation antidepressants are not routinely or for more differences in drug will also to prescribe minimal therapeutic doses of antipsychotics and antidepressants for greater efficacy and better in the maintenance has and the last 3 years from and

Psychotherapy and Psychosomatics · editorial or comment · 168 citationsread the source →

A grander challenge: the case of how Makerere University College of Health Sciences (MakCHS) contributes to health outcomes in Africa.

Background: "Grand challenges" in global health have focused on discovery and development of technologies to save lives. The "grander challenge" involves building institutions, systems, capacity and demand to effectively deliver strategies to improve health. In 2008, Makerere University began a radical institutional change to bring together four schools under one College of Health Sciences. This paper's objective is to demonstrate how its leadership in training, research, and services can improve health in Uganda and internationally, which lies at the core of the College's vision. Methods: A comprehensive needs assessment involved five task forces that identified MakCHS's contribution to the Ugandan government health priorities. Data were collected through analysis of key documents; systematic review of MakCHS publications and grants; surveys of patients, students and faculty; and key informant interviews of the College's major stakeholders. Four pilot projects were conducted to demonstrate how the College can translate research into policy and practice, extend integrated outreach community-based education and service, and work with communities and key stakeholders to address their priority health problems. Results: MakCHS inputs to the health sector include more than 600 health professionals graduating per year through 23 degree programs, many of whom assume leadership positions. MakCHS contributions to processes include strengthened approaches to engaging communities, standardized clinical care procedures, and evidence-informed policy development. Outputs include the largest number of outpatients and inpatient admissions in Uganda. From 2005-2009, MakCHS also produced 837 peer-reviewed research publications (67% in priority areas). Outcomes include an expanded knowledge pool, and contributions to coverage of health services and healthy behaviors. Impacts include discovery and applications of global significance, such as the use of nevirapine to prevent HIV transmission in childbirth and male circumcision for HIV prevention. Pilot projects have applied innovative demand and supply incentives to create a rapid increase in safe deliveries (3-fold increase after 3 months), and increased quality and use of HIV services with positive collateral improvements on non-HIV health services at community clinics. Conclusion: MakCHS has made substantial contributions to improving health in Uganda, and shows great potential to enhance this in its new transformational role - a model for other Universities.

BMC international health and human rights · 21 citationsread the source →

Descriptive cross sectional study on prevalence, perceptions, predisposing factors and health seeking behaviour of women with stress urinary incontinence.

Background: Stress urinary incontinence (SUI) leads to considerable physical and psychological morbidity. The highest prevalence reported was found in Caucasian Americans (range 23% -67%) and the lowest in Singaporean females (4.8%). The study assessed the prevalence, perceptions, predisposing factors and health seeking behaviour of women with SUI in an Asian setting which may have different sociocultural implications. Methods: 400 consecutive women >20 years of age attending the outpatient department of a tertiary care hospital in Sri Lanka, for non-urinary conditions were studied over a 3 week period using an interviewer administered questionnaire. SUI was diagnosed on clinical history alone when leakage of urine occurred either with coughing, sneezing, walking or lifting heavy objects. The severity was graded using the Finnish Gynaecological Society's Urinary Incontinence Severity Score (UISS). Data were analysed using SPSS version 20. Odds ratios were calculated using univariate and multivariate analysis. Results: Ninety three (23.33%) had SUI and only 12 (12.9%) had sought treatment. The prevalence among women >50 years of age was 34.71% ( n = 121) compared to 18.28% (n = 279) in those ≤50 years. 25 (26.88%) had mild SUI, 66 (70.97%) moderate and 2 (2.15%) severe as per UISS. SUI was perceived as an illness by 210 (52.5%). SUI was significantly associated with pregnancy, parity, vaginal delivery, complicated labour, diabetes mellitus, chronic cough, constipation and faecal incontinence (p < 0.05).Among those affected main reasons for not seeking medical advice included; being embarrassed (n = 27, 33.33%), not knowing that it is remediable (n = 23, 28.40%), perceiving SUI to be a normal consequence of childbirth (n = 19, 23.46%) and having to attend to needs of the family (n = 12, 14.81%). None who had been pregnant (n = 313) had received advice on postnatal pelvic floor exercises. SUI interfered with social activities (71;76.34%), sexual function (21; 22.58%) and resulted in despair (67; 72.09%). It was associated with clinically diagnosed candidiasis (50; 53.76%) and soreness in the perineal region (49; 52.69%). Conclusions: SUI is a common and neglected gynaecological problem with poor healthcare seeking behaviour. Community based education may help to minimize the occurrence and improve the quality of life of those affected.

BMC women's health · 46 citationsread the source →

Spirituality, religiosity, and spiritual pain among caregivers of patients with advanced cancer.

Background: Caregivers of patients with advanced cancer often face physical, social, and emotional distress as well as spiritual pain. Limited research has focused on the spiritual aspects of caregivers' suffering in the palliative care setting. Methods: We interviewed 43 caregivers of patients with advanced cancer in our palliative care outpatient clinic. We determined demographic characteristics, religious affiliation, and relationship to the patient. Levels of spirituality, religiosity, and spiritual pain were self-reported using numeric rating scales (0 = lowest; 10 = highest). The participants completed various validated questionnaires to assess sleep disturbances, psychosocial distress, coping skills, and quality of life (QOL). Results: The median age was 52 years (range, 21-83); 29 (67%) were women, 34 (78%) were white, 7 (17%) were African American, and 2 (5%) were Hispanic; 39 (91%) were Christian, 1 (2%) was Jewish, and 1 (2%) was agnostic; 37 (86%) were married; 18 (42%) were working full time; and 25 (58%) were spouses. All considered themselves spiritual, and 98% considered themselves religious, with median scores of 8 (interquartile range, 6-10) and 8 (interquartile range, 4-9), respectively. All the caregivers reported that spirituality and religiosity helped them cope with their loved one's illness, and many reported that spirituality and religiosity had a positive impact on their loved one's physical (58%) and emotional (76%) symptoms. Spiritual pain was reported by 23 (58%), with a median score of 5 (interquartile range, 2-8). Caregivers with spiritual pain had higher levels of anxiety (median 10 vs 4; P = .002), depression (6 vs 2; P = .006), and denial (3 vs 2; P = .01); more behavioral disengagement (3 vs 2; P = 0.011) more dysfunctional coping strategies (19 vs 16; P < .001) and worse QOL (70 vs 51; P < .001) than those who did not have spiritual pain. Conclusions: The majority of caregivers of patients with advanced cancer considered themselves spiritual and religious. Despite this, there is high prevalence of spiritual pain in this population. Caregivers with spiritual pain experienced worse psychological distress and worse QOL. These findings support the importance of spiritual assessment of and spiritual support for caregivers in this setting.

The American journal of hospice & palliative care · 65 citationsread the source →

Psychological and pharmacological interventions for social anxiety disorder in adults: a systematic review and network meta-analysis.

Background: Social anxiety disorder-a chronic and naturally unremitting disease that causes substantial impairment-can be treated with pharmacological, psychological, and self-help interventions. We aimed to compare these interventions and to identify which are most effective for the acute treatment of social anxiety disorder in adults. Methods: We did a systematic review and network meta-analysis of interventions for adults with social anxiety disorder, identified from published and unpublished sources between 1988 and Sept 13, 2013. We analysed interventions by class and individually. Outcomes were validated measures of social anxiety, reported as standardised mean differences (SMDs) compared with a waitlist reference. This study is registered with PROSPERO, number CRD42012003146. Findings: We included 101 trials (13 164 participants) of 41 interventions or control conditions (17 classes) in the analyses. Classes of pharmacological interventions that had greater effects on outcomes compared with waitlist were monoamine oxidase inhibitors (SMD -1·01, 95% credible interval [CrI] -1·56 to -0·45), benzodiazepines (-0·96, -1·56 to -0·36), selective serotonin-reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs; -0·91, -1·23 to -0·60), and anticonvulsants (-0·81, -1·36 to -0·28). Compared with waitlist, efficacious classes of psychological interventions were individual cognitive-behavioural therapy (CBT; SMD -1·19, 95% CrI -1·56 to -0·81), group CBT (-0·92, -1·33 to -0·51), exposure and social skills (-0·86, -1·42 to -0·29), self-help with support (-0·86, -1·36 to -0·36), self-help without support (-0·75, -1·25 to -0·26), and psychodynamic psychotherapy (-0·62, -0·93 to -0·31). Individual CBT compared with psychological placebo (SMD -0·56, 95% CrI -1·00 to -0·11), and SSRIs and SNRIs compared with pill placebo (-0·44, -0·67 to -0·22) were the only classes of interventions that had greater effects on outcomes than appropriate placebo. Individual CBT also had a greater effect than psychodynamic psychotherapy (SMD -0·56, 95% CrI -1·03 to -0·11) and interpersonal psychotherapy, mindfulness, and supportive therapy (-0·82, -1·41 to -0·24). Interpretation: Individual CBT (which other studies have shown to have a lower risk of side-effects than pharmacotherapy) is associated with large effect sizes. Thus, it should be regarded as the best intervention for the initial treatment of social anxiety disorder. For individuals who decline psychological intervention, SSRIs show the most consistent evidence of benefit. Funding: National Institute for Health and Care Excellence.

The lancet. Psychiatry · 328 citationsread the source →

2014 Alzheimer's disease facts and figures.

This report discusses the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality rates, costs of care, and overall effect on caregivers and society. It also examines the impact of AD on women compared with men. An estimated 5.2 million Americans have AD. Approximately 200,000 people younger than 65 years with AD comprise the younger onset AD population; 5 million are age 65 years or older. By mid-century, fueled in large part by the baby boom generation, the number of people living with AD in the United States is projected to grow by about 9 million. Today, someone in the country develops AD every 67 seconds. By 2050, one new case of AD is expected to develop every 33 seconds, or nearly a million new cases per year, and the total estimated prevalence is expected to be 13.8 million. In 2010, official death certificates recorded 83,494 deaths from AD, making AD the sixth leading cause of death in the United States and the fifth leading cause of death in Americans aged 65 years or older. Between 2000 and 2010, the proportion of deaths resulting from heart disease, stroke, and prostate cancer decreased 16%, 23%, and 8%, respectively, whereas the proportion resulting from AD increased 68%. The actual number of deaths to which AD contributes (or deaths with AD) is likely much larger than the number of deaths from AD recorded on death certificates. In 2014, an estimated 700,000 older Americans will die with AD, and many of them will die from complications caused by AD. In 2013, more than 15 million family members and other unpaid caregivers provided an estimated 17.7 billion hours of care to people with AD and other dementias, a contribution valued at more than $220 billion. Average per-person Medicare payments for services to beneficiaries aged 65 years and older with AD and other dementias are more than two and a half times as great as payments for all beneficiaries without these conditions, and Medicaid payments are 19 times as great. Total payments in 2014 for health care, long-term care, and hospice services for people aged 65 years and older with dementia are expected to be $214 billion. AD takes a stronger toll on women than men. More women than men develop the disease, and women are more likely than men to be informal caregivers for someone with AD or another dementia. As caregiving responsibilities become more time consuming and burdensome or extend for prolonged durations, women assume an even greater share of the caregiving burden. For every man who spends 21 to more than 60 hours per week as a caregiver, there are 2.1 women. For every man who lives with the care recipient and provides around-the-clock care, there are 2.5 women. In addition, for every man who has provided caregiving assistance for more than 5 years, there are 2.3 women.

Alzheimer's & dementia : the journal of the Alzheimer's Association · 685 citationsread the source →