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Cannabis use severely affects the outcome of people with psychotic disorders, yet there is a lack of treatments. To address this, in 2019 the National Health Service (NHS) Cannabis Clinic for Psychosis (CCP) was developed to support adults suffering from psychosis to reduce and/or stop their cannabis use.
Aims
Examine outcome data from the first 46 individuals to complete the CCP's intervention.
Method
The sample (N = 46) consisted of adults (aged ≥ 18) with psychosis under the care of the South London and Maudsley NHS Foundation Trust, referred to the CCP between January 2020 and February 2023, who completed their intervention by September 2023. Clinical and functional measures were collected before (T0) and after (T1) the CCP intervention (one-to-one sessions and peer group attendance). Primary outcomes were changes in the Cannabis Use Disorders Identification Test-Revised (CUDIT-R) score and pattern of cannabis use. Secondary outcomes included T0–T1 changes in measures of delusions, paranoia, depression, anxiety and functioning.
Results
A reduction in the mean CUDIT-R score was observed between T0 (mean difference = 17.10, 95% CI = 15.54–18.67) and T1, with 73.91% of participants achieving abstinence and 26.09% reducing the frequency and potency of their use. Significant improvements in all clinical and functional outcomes were observed, with 90.70% being in work or education at T1 compared with 8.70% at T0. The variance in CUDIT-R scores explained between 34 and 64% of the variance in our secondary measures.
Conclusions
The CCP intervention is a feasible strategy to support cannabis use cessation/reduction and improve clinical and functional outcomes of people with psychotic disorders.
Venlafaxine is used to treat depression worldwide. Previous reviews have demonstrated that venlafaxine lowers scores on depression rating scales, producing statistically significant results but the relevance to patients remains uncertain. Knowledge of the incidence of the adverse effects associated with venlafaxine has previously been based on the results of non-randomised studies. Our primary objective was to assess the risks of adverse events with venlafaxine in the treatment of adults with major depressive disorder in randomised trials.
Methods
We searched relevant databases and other sources from inception to 7 March 2024 for randomised clinical trials comparing venlafaxine versus placebo or no intervention in adults with major depressive disorder. Data were synthesised using meta-analysis and Trial Sequential Analysis. The primary outcomes were suicides or suicide attempts, serious adverse events and non-serious adverse events.
Results
We included 28 trials randomising 6,253 participants to venlafaxine versus placebo. All results were at high risk of bias, and the certainty of the evidence was very low. All trials assessed outcomes at a maximum of 12 weeks after randomisation. Meta-analysis and Trial Sequential Analysis showed insufficient information to assess the effects of venlafaxine on the risks of suicides or suicide attempts. Meta-analysis showed evidence of harm of venlafaxine versus placebo on serious adverse events (risk ratio: 2.66; 95% confidence interval: 1.67–4.25; p < 0.01; 22 trials), mainly due to a higher risk of sexual dysfunction and anorexia. Meta-analysis showed that venlafaxine also increased the risk of several non-serious adverse events: nausea, dry mouth, dizziness, sweating, somnolence, constipation, nervousness, insomnia, asthenia, tremor and decreased appetite.
Conclusions
Short-term results show that venlafaxine has uncertain effects on the risks of suicides but increases the risks of serious adverse events (especially sexual dysfunction and anorexia) and many non-serious adverse events. The long-term effects of venlafaxine for major depressive disorder are unknown. It is a particular cause for concern that there are no data on the long-term adverse effects of venlafaxine given that so many people use these drugs for several years.
Adenylate kinases (AKs) are important enzymes involved in cellular energy metabolism. Among AKs, AK5 (adenylate kinase 5), a cytosolic protein, is emerging as a significant contributor to various diseases and cellular processes. This comprehensive review integrates findings from various research groups on AK5 since its discovery, shedding light on its multifaceted roles in nucleotide metabolism, energy regulation, and cellular differentiation. We investigate its implications in a spectrum of diseases, including autoimmune encephalitis, epilepsy, neurodegenerative disorders such as Alzheimer’s and Parkinson’s, diabetes, lower extremity arterial disease, celiac disease, and various cancers. Notably, AK5’s expression levels and methylation status have been associated with cancer progression and patient outcomes, indicating its potential as a prognostic indicator. Furthermore, AK5 is implicated in regulating cellular processes in breast cancer, gastric cancer, colorectal carcinoma, prostate cancer, and colon adenocarcinoma, suggesting its relevance across different cancer types. However, a limitation lies in the need for more robust clinical validation and a deeper understanding of AK5’s precise mechanisms in disease pathogenesis, despite its association with various pathophysiological conditions. Nonetheless, AK5 holds promise as a therapeutic target, with emerging evidence suggesting its potential in therapy development.
We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems.
Technical summary
The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference.
Social media summary
We highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts.
Monoclonal antibody (mAb) treatment for coronavirus disease 2019 (COVID-19) has been underutilized due to logistical challenges, lack of access, and variable treatment awareness among patients and health-care professionals. The use of telehealth during the pandemic provides an opportunity to increase access to COVID-19 care.
Methods:
This is a single-center descriptive study of telehealth-based patient self-referral for mAb therapy between March 1, 2021, and October 31, 2021, at Baltimore Convention Center Field Hospital (BCCFH).
Results:
Among the 1001 self-referral patients, the mean age was 47, and most were female (57%). White (66%), and had a primary care provider (PCP) (62%). During the study period, self-referrals increased from 14/mo in March to 427 in October resulting in a 30-fold increase. Approximately 57% of self-referred patients received a telehealth visit, and of those 82% of patients received mAb infusion therapy. The median time from self-referral to onsite infusion was 2 d (1-3 IQR).
Discussion:
Our study shows the integration of telehealth with a self-referral process improved access to mAb infusion. A high proportion of self-referrals were appropriate and led to timely treatment. This approach helped those without traditional avenues for care and avoided potential delay for patients seeking referral from their PCPs.
Low and middle-income countries (LMICs) hold the majority of disease burden attributed to major depressive disorder (MDD). Despite this, there remains a substantial gap for access to evidence-based treatments for MDD in LMICs like Pakistan. Measurement-based care (MBC) incorporates systematic administration of validated outcome measures to guide treatment decision making and is considered a low-cost approach to optimise better clinical outcomes for individuals with MDD but there is a paucity of evidence on the efficacy of MBC in LMICs.
Objectives
This protocol highlights a randomized trial which will include Pakistani outpatients with moderate to severe major depression.
Methods
Participants will be randomised to either MBC (guided by schedule), or standard treatment (guided by clinicians’ judgement), and will be prescribed with paroxetine (10–60mg/day) or mirtazapine (7.5–45mg/day) for 24 weeks. Outcomes will be evaluated by raters blind to study protocol and treatment.
Results
National Bioethics Committee (NBC) of Pakistan has given full ethics approval. The trial is being conducted and reported as per recommendation of the CONSORT statement for RCTs.
Conclusions
With increasing evidence from high-income settings supporting the effectiveness of MBC for MDD, it is now necessary to explore its feasibility, utility. and efficacy in low-resource settings. The results of the proposed trial could inform the development of a low-cost and scalable approach to efficiently optimise outcomes for individuals with MDD in Pakistan.
Bipolar disorder (BD) is a source of marked disability, morbidity, and premature death. There is a paucity of research on personalized psychosocial interventions for BD, especially in lowresource settings. A previously published pilot randomized controlled trial (RCT) of a Culturally adapted PsychoEducation (CaPE) intervention for BD in Pakistan reported higher patient satisfaction, enhanced medication adherence, knowledge and attitudes towards BD, and improvement in mood symptom scores and health-related quality of life measures compared to treatment-as-usual (TAU).
Objectives
This protocol describes a larger multicentre RCT to confirm the clinical and cost-effectiveness of CaPE in Pakistan.
Methods
A multicentre individual, parallel arm, RCT of CaPE in 300Pakistani adults with BD. Participants over the age of 18, with adiagnosis of bipolar I and II and who are currently euthymic, will berecruited from seven sites including Karachi, Lahore, Multan, Rawalpindi,Peshawar, Hyderabad and Quetta. Time to recurrence will be the primaryoutcome assessed using Longitudinal Interval Follow-up Evaluation(LIFE). Secondary measures will include mood symptomatology, qualityof life and functioning, adherence to psychotropic medications, andknowledge and attitudes towards BD.
Results
Full ethics approval has been received from National Bioethics Committee (NBC) of Pakistan and Centre for Addiction and Mental Health (CAMH), Toronto, Canada. The study has completed sixty-five screening across the seven centres, of which forty-eight participants have been randomised.
Conclusions
A successful trial will lead to rapid implementation of CaPE in clinical practice, not only in Pakistan, but also in other low-resource settings including those in high-income countries, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority patients with BD.
Background: Sex differences in treatment response to intravenous thrombolysis (IVT) are poorly characterized. We compared sex-disaggregated outcomes in patients receiving IVT for acute ischemic stroke in the Alteplase compared to Tenecteplase (AcT) trial, a Canadian multicentre, randomised trial. Methods: In this post-hoc analysis, the primary outcome was excellent functional outcome (modified Rankin Score [mRS] 0-1) at 90 days. Secondary and safety outcomes included return to baseline function, successful reperfusion (eTICI≥2b), death and symptomatic intracerebral hemorrhage. Results: Of 1577 patients, there were 755 women and 822 men (median age 77 [68-86]; 70 [59-79]). There were no differences in rates of mRS 0-1 (aRR 0.95 [0.86-1.06]), return to baseline function (aRR 0.94 [0.84-1.06]), reperfusion (aRR 0.98 [0.80-1.19]) and death (aRR 0.91 [0.79-1.18]). There was no effect modification by treatment type on the association between sex and outcomes. The probability of excellent functional outcome decreased with increasing onset-to-needle time. This relation did not vary by sex (pinteraction 0.42). Conclusions: The AcT trial demonstrated comparable functional, safety and angiographic outcomes by sex. This effect did not differ between alteplase and tenecteplase. The pragmatic enrolment and broad national participation in AcT provide reassurance that there do not appear to be sex differences in outcomes amongst Canadians receiving IVT.
Bipolar disorder is a source of marked disability, morbidity and premature death. There is a paucity of research on personalised psychosocial interventions for bipolar disorder, especially in low-resource settings. A pilot randomised controlled trial (RCT) of a culturally adapted psychoeducation intervention for bipolar disorder (CaPE) in Pakistan reported higher patient satisfaction, enhanced medication adherence, knowledge and attitudes regarding bipolar disorder, and improvement in mood symptom scores and health-related quality of life measures compared with treatment as usual (TAU).
Aims
The current protocol describes a larger multicentre RCT to confirm the clinical and cost-effectiveness of CaPE in Pakistan. Trial registration: NCT05223959.
Method
A multicentre individual, parallel-arm RCT of CaPE in 300 Pakistani adults with bipolar disorder. Participants over the age of 18, with a diagnosis of bipolar I or II disorder who are currently euthymic, will be recruited from seven sites: Karachi, Lahore, Multan, Rawalpindi, Peshawar, Hyderabad and Quetta. Time to recurrence will be the primary outcome assessed using the Longitudinal Interval Follow-up Evaluation (LIFE). Secondary measures will include mood symptoms, quality of life and functioning, adherence to psychotropic medications, and knowledge and attitudes regarding bipolar disorder.
Results
This trial will assess the effectiveness of the CaPE intervention compared with TAU in reducing the time to recurrence for people with bipolar disorder currently in remission in Pakistan and determine the effect on clinical outcomes, quality of life and functioning.
Conclusions
A successful trial might lead to rapid implementation of CaPE in clinical practice, not only in Pakistan, but also in other low-resource settings, including those in high-income countries, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority group patients with bipolar disorder.
We summarize what we assess as the past year's most important findings within climate change research: limits to adaptation, vulnerability hotspots, new threats coming from the climate–health nexus, climate (im)mobility and security, sustainable practices for land use and finance, losses and damages, inclusive societal climate decisions and ways to overcome structural barriers to accelerate mitigation and limit global warming to below 2°C.
Technical summary
We synthesize 10 topics within climate research where there have been significant advances or emerging scientific consensus since January 2021. The selection of these insights was based on input from an international open call with broad disciplinary scope. Findings concern: (1) new aspects of soft and hard limits to adaptation; (2) the emergence of regional vulnerability hotspots from climate impacts and human vulnerability; (3) new threats on the climate–health horizon – some involving plants and animals; (4) climate (im)mobility and the need for anticipatory action; (5) security and climate; (6) sustainable land management as a prerequisite to land-based solutions; (7) sustainable finance practices in the private sector and the need for political guidance; (8) the urgent planetary imperative for addressing losses and damages; (9) inclusive societal choices for climate-resilient development and (10) how to overcome barriers to accelerate mitigation and limit global warming to below 2°C.
Social media summary
Science has evidence on barriers to mitigation and how to overcome them to avoid limits to adaptation across multiple fields.
The COVID-19 pandemic may disproportionately affect the mental health of healthcare professionals (HCPs), especially patient-facing HCPs.
Aims
To longitudinally examine mental health in HCPs versus non-HCPs, and patient-facing HCPs versus non-patient-facing HCPs.
Method
Online surveys were distributed to a cohort at three phases (baseline, July to September 2020; phase 2, 6 weeks post-baseline; phase 3, 4 months post-baseline). Each survey contained validated assessments for depression, anxiety, insomnia, burnout and well-being. For each outcome, we conducted mixed-effects logistic regression models (adjusted for a priori confounders) comparing the risk in different groups at each phase.
Results
A total of 1574 HCPs and 147 non-HCPs completed the baseline survey. Although there were generally higher rates of various probable mental health issues among HCPs versus non-HCPs at each phase, there was no significant difference, except that HCPs had 2.5-fold increased risk of burnout at phase 2 (emotional exhaustion: odds ratio 2.50, 95% CI 1.15–5.46, P = 0.021), which increased at phase 3 (emotional exhaustion: odds ratio 3.32, 95% CI 1.40–7.87, P = 0.006; depersonalisation: odds ratio 3.29, 95% CI 1.12–9.71, P = 0.031). At baseline, patient-facing HCPs (versus non-patient-facing HCPs) had a five-fold increased risk of depersonalisation (odds ratio 5.02, 95% CI 1.65–15.26, P = 0.004), with no significant difference in the risk for other outcomes. The difference in depersonalisation reduced over time, but patient-facing HCPs still had a 2.7-fold increased risk of emotional exhaustion (odds ratio 2.74, 95% CI 1.28–5.85, P = 0.009) by phase 3.
Conclusions
The COVID-19 pandemic had a huge impact on the mental health and well-being of both HCPs and non-HCPs, but there is disproportionately higher burnout among HCPs, particularly patient-facing HCPs.
Qatar established its Forensic Community Mental Health Team (FCMHT) in 2019 as part of the region’s first comprehensive forensic psychiatry service. We present here the data on clinical and offending outcomes since its establishment and compare this with data from before the service was established
Objectives
To compare clinical and offending outcomes in mental health patients with criminal offending histories in Qatar before and after the establishment of Forensic Community Mental Health Team (FCMHT).
Methods
This is a retrospective study comparing the socio-demographical characteristics, clinical outcome and recidivism measures of forensic patients, under the FCMHT for the last two years with data from a similar period before the services were in place.
Results
Data for 170 patients in total was analyzed. 85 patients currently under the active care of forensic community team were matched with a comparable group before the establishment of the services. The re-admission and reoffending rates after the establishment of the service over 1 year of follow up was 15% and 20% respectively compared with 60% and 85% of the group before the service.
Conclusions
Since its inception, the FCMHT has made significant positive impact on quality of life, mental well-being and safety of patients under its care. Close working relationships with criminal justice system, families and carers has helped fight stigma and promote safer community.
The duration of immunity after first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the extent to which prior immunity prevents reinfection is uncertain and remains an important question within the context of new variants. This is a retrospective population-based matched observational study where we identified the first polymerase chain reaction (PCR) positive of primary SARS-CoV-2 infection case tests between 1 March 2020 and 30 September 2020. Each case was matched by age, sex, upper tier local authority of residence and testing route to one individual testing negative in the same week (controls) by PCR. After a 90-day pre-follow-up period for cases and controls, any subsequent positive tests up to 31 December 2020 and deaths within 28 days of testing positive were identified, this encompassed an essentially vaccine-free period. We used a conditional logistic regression to analyse the results. There were 517 870 individuals in the matched cohort with 2815 reinfection cases and 12 098 first infections. The protective effect of a prior SARS-CoV-2 PCR-positive episode was 78% (odds ratio (OR) 0.22, 0.21–0.23). Protection rose to 82% (OR 0.18, 0.17–0.19) after a sensitivity analysis excluded 933 individuals with a first test between March and May and a subsequent positive test between June and September 2020. Amongst individuals testing positive by PCR during follow-up, reinfection cases had 77% lower odds of symptoms at the second episode (adjusted OR 0.23, 0.20–0.26) and 45% lower odds of dying in the 28 days after reinfection (adjusted OR 0.55, 0.42–0.71). Prior SARS-CoV-2 infection offered protection against reinfection in this population. There was some evidence that reinfections increased with the alpha variant compared to the wild-type SARS-CoV-2 variant highlighting the importance of continued monitoring as new variants emerge.
In response to the coronavirus disease (COVID-19) pandemic, the State of Maryland established a 250-bed emergency response field hospital at the Baltimore Convention Center to support the existing health care infrastructure. To operationalize this hospital with 65 full-time equivalent clinicians in less than 4 weeks, more than 300 applications were reviewed, 186 candidates were interviewed, and 159 clinicians were credentialed and onboarded. The key steps to achieve this undertaking involved employing multidisciplinary teams with experienced personnel, mass outreach, streamlined candidate tracking, pre-interview screening, utilizing all available expertise, expedited credentialing, and focused onboarding. To ensure staff preparedness, the leadership developed innovative team models, applied principles of effective team building, and provided “just in time” training on COVID-19 and non-COVID-19-related topics to the staff. The leadership focused on staff safety and well-being, offered appropriate financial remuneration, and provided leadership opportunities that allowed retention of staff.
Cold dissection is the most commonly used tonsillectomy technique, with low post-operative haemorrhage rates. Coblation is an alternative technique that may cause less pain, but could have higher post-operative haemorrhage rates.
Objective
This study evaluated the peri-operative outcomes in paediatric tonsillectomy patients by comparing coblation and cold dissection techniques.
Methods
A systematic review was conducted of all comparative studies of paediatric coblation and cold dissection tonsillectomy, up to December 2018. Any studies with adults were excluded. Outcomes such as pain, operative time, and intra-operative, primary and secondary haemorrhages were recorded.
Results
Seven studies contributed to the summative outcome. Coblation tonsillectomy appeared to result in less pain, less intra-operative blood loss (p < 0.01) and a shorter operative time (p < 0.01). There was no significant difference between the two groups for post-operative haemorrhage (p > 0.05).
Conclusion
The coblation tonsillectomy technique may offer better peri-operative outcomes when compared to cold dissection, and should therefore be offered in paediatric cases, before cold dissection tonsillectomy.
There are few longitudinal studies about South Asians (SAs) and little information about recruitment and retention approaches for this ethnic group.
Methods:
We followed 906 SAs enrolled in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort for 5 years. Surviving participants were invited for a second clinical exam from 2015 to 2018. A new wave of participants was recruited during 2017–2018. We assessed the yields from different methods of recruitment and retention.
Results:
A total of 759 (83%) completed the second clinical exam, and 258 new participants were enrolled. Providing a nearby community hospital location for the study exam, offering cab/shared ride reimbursement, and conducting home visits were the most effective methods for enhancing retention. New participant recruitment targeted women and individuals with lower socioeconomic status, and we found that participant referrals and active community engagement were most effective. Mailing invitational letters to those identified by electronic health records had very low yield.
Conclusion:
Recruitment and retention strategies that address transportation barriers and increase community engagement will help increase the representation of SAs in health research.