Anti-dementia drugs: what is the evidence in advanced stages?

Dementia is a major public health concern due to its increasing prevalence, substantial caregiver burden, and high financial costs. Currently, the anti-dementia drugs aim only at a symptomatic effect. The subject of prescribing these drugs in advanced stages is a matter of considerable debate, with different countries making distinct recommendations. In this review article, we analyzed the evidence regarding cognitive and functional outcomes, adverse events, health-related costs, and caregiver burden in patients with advanced Alzheimer disease (AD) and mixed dementia. We included 35 studies. Most studies are heterogeneous, focus exclusively on AD, and show small benefits in terms of cognitive and functional scales. The overall evidence seems to suggest a benefit in introducing or maintaining anti-dementia drugs in patients with advanced dementia, but clinical meaningfulness is difficult to ascertain. The issue of costs and caregiver burden is significantly underexplored in this field but also seems to favor treatment continuation, despite a reduced overall effect. The decision of introducing or withdrawing anti-dementia drugs in advanced stages of dementia should be individualized. Future studies with homogeneous designs and outcomes are warranted.

Perspectives on the diagnosis and management of functional cognitive disorder: An international Delphi study.

BACKGROUND: Current proposed criteria for functional cognitive disorder (FCD) have not been externally validated. We sought to analyse the current perspectives of cognitive specialists in the diagnosis and management of FCD in comparison with neurodegenerative conditions. METHODS: International experts in cognitive disorders were invited to assess seven illustrative clinical vignettes containing history and bedside characteristics alone. Participants assigned a probable diagnosis and selected the appropriate investigation and treatment. Qualitative, quantitative and inter-rater agreement analyses were undertaken. RESULTS: Eighteen diagnostic terminologies were assigned by 45 cognitive experts from 12 countries with a median of 13 years of experience, across the seven scenarios. Accurate discrimination between FCD and neurodegeneration was observed, independently of background and years of experience: 100% of the neurodegenerative vignettes were correctly classified and 75%-88% of the FCD diagnoses were attributed to non-neurodegenerative causes. There was <50% agreement in the terminology used for FCD, in comparison with 87%-92% agreement for neurodegenerative syndromes. Blood tests and neuropsychological evaluation were the leading diagnostic modalities for FCD. Diagnostic communication, psychotherapy and psychiatry referral were the main suggested management strategies in FCD. CONCLUSIONS: Our study demonstrates the feasibility of distinguishing between FCD and neurodegeneration based on relevant patient characteristics and history details. These characteristics need further validation and operationalisation. Heterogeneous labelling and framing pose clinical and research challenges reflecting a lack of agreement in the field. Careful consideration of FCD diagnosis is advised, particularly in the presence of comorbidities. This study informs future research on diagnostic tools and evidence-based interventions.

'If we take the engine out, how will the car go?': beliefs, understanding and access to vasectomy services in Timor-Leste.

Vasectomy is a safe, highly effective and affordable method of permanent contraception, and one of the few currently available contraceptive methods for men. Despite this, vasectomy uptake remains overall low, making up just 2% of the global contraceptive method mix. To better understand access to vasectomy in a country with negligible uptake, we conducted participatory and operational research in the Democratic Republic of Timor-Leste (Timor-Leste). We held 14 participatory group discussions with 175 community participants (84 men, 91 women; aged 18-72) across seven municipalities (Ainaro, Baucau, Bobonaro, Dili, Lautem, Manufahi, and Oecusse), and individual in-depth interviews with 24 healthcare providers (16 women, 8 men; aged 25-56 years). Data were analysed using reflexive thematic analysis. Community awareness and understanding about vasectomy were limited, with concerns expressed about physical and social side effects. Healthcare providers had limited experience and knowledge about vasectomy, and about male sexual and reproductive health more generally. However, our findings also indicate a small but existing demand for vasectomy services that could be grown and better met through health systems strengthening initiatives. Insights from our research have informed programmatic decision-making in Timor-Leste and can be further used to inform national health policy and practice.

A simple protocol for the synthesis of perylene bisimides from perylene tetracarboxylic dianhydride.

Perylene bisimides are highly attractive polycyclic aromatic hydrocarbons due to their photostability associated to unique and characteristic photochemical properties. They have been widely used for analytical purposes, despite the hydrophobicity of most of these compounds. The ring substitution pattern plays an important role in fine-tuning the physicochemical properties that govern solubility and aggregation. In this work, a selection of perylene bisimides were prepared from the reaction of perylenetetracarboxylic dianhydride with α-amino acids or primary aliphatic and aromatic amines. These molecules were obtained in good yield by a simple synthetic protocol based on the use of imidazole as a green solvent and avoiding the need for complex purification methods, a major advantage for future applications. Functionalization of the exocyclic substituent can also be performed and was exemplified by the incorporation of the maleimide and anthraquinone moieties.

The sound of Parkinson's disease: A model of audible bradykinesia.

INTRODUCTION: Evaluation of bradykinesia is based on five motor tasks from the MDS-UPDRS. Visually scoring these motor tasks is subjective, resulting in significant interrater variability. Recent observations suggest that it may be easier to hear the characteristic features of bradykinesia, such as the decrement in sound intensity or force of repetitive movements. The objective is to evaluate whether audio signals derived during four MDS-UPDRS tasks can be used to detect and grade bradykinesia, using two machine learning models. METHODS: 54 patients with Parkinson's disease and 28 healthy controls were filmed while executing the bradykinesia motor tasks. Several features were extracted from the audio signal, including number of taps, speed, sound intensity, decrement and freezes. For each motor task, two supervised machine learning models were trained, Logistic Regression (LR) and Support Vector Machine (SVM). RESULTS: Both classifiers were able to separate patients from controls reasonably well for the leg agility task, area under the receiver operating characteristic curve (AUC): 0.92 (95%CI: 0.78-0.99) for LR and 0.93 (0.81-1.00) for SVM. Also, models were able to differentiate less severe bradykinesia from severe bradykinesia, particularly for the pronation-supination motor task, with AUC: 0.90 (0.62-1.00) for LR and 0.82 (0.45-0.97) for SVM. CONCLUSION: This audio-based approach discriminates PD from healthy controls with moderate-high accuracy and separated individuals with less severe bradykinesia from those with severe bradykinesia. Sound analysis may contribute to the identification and monitoring of bradykinesia.

It's in the game: A review of neurological lesions associated with sports.

INTRODUCTION: The practice of sports may lead to neurological injuries. While relatively uncommon (overall incidence of approximately 2.5%), and mostly benign and transient, some conditions may be life-threatening and permanent. Thus, both clinical neurologists and sports physicians should be aware of their existence and relevance. We aimed to review all sports-related neurological injuries and illnesses reported in the literature. METHODS: Following SANRA guidelines, we performed a narrative review and searched PubMed and Scopus databases. Relevant sports were selected based on their recognition as an Olympic sport by the International Olympic Committee. Chronic traumatic encephalopathy (CTE) and other neurodegenerative disorders were not included. RESULTS: A total of 292 studies were included concerning 33 different sports. The most reported neurological injury was damage to the peripheral nervous system. Traumatic injuries have also been extensively reported, including cerebral haemorrhage and arterial dissections. Non-traumatic life-threatening events are infrequent but may also occur, e.g. posterior reversible encephalopathy syndrome, cerebral venous thrombosis, and arterial dissections. Some conditions were predominantly reported in specific sports, e.g. yips in baseball and golf, raising the possibility of a common pathophysiology. Spinal cord infarction due to fibrocartilaginous embolism was reported in several sports associated with minor trauma. CONCLUSION: Sports-related neurological injuries are increasingly receiving more social and medical attention and are an important cause of morbidity and mortality. This review may serve as a guide to physicians managing these challenging situations.

The response to COVID-19 in Timor-Leste: lessons learnt.

The response to the COVID-19 pandemic in Timor-Leste offers lessons that may be useful for incorporating into future responses to infectious disease outbreaks in similar resource-limited settings. In this paper, we identify nine key areas for learning from Timor-Leste's experience of the COVID-19 pandemic: (1) the importance of prior preparation for health emergencies, (2) the establishment of effective leadership and governance structures, (3) the protective impact of early border restrictions, (4) the rapid expansion of diagnostic laboratory capacity, (5) the impact of effective health communications in supporting the vaccine roll-out, (6) the opportunity to build capacity for clinical care, (7) the use of public health interventions that were found to have limited public health impact, (8) the broader effects of the pandemic and the public health response and (9) translation of lessons from COVID-19 to other public health priorities.

'It depends on who is asking and why they will use it': Access to male condoms in Timor-Leste.

The uptake of male condoms remains markedly low in The Democratic Republic of Timor-Leste (Timor-Leste), an island nation in South-East Asia. To understand why, we conducted participatory and operational research about beliefs, understanding and access to male condoms from both a community and healthcare provider perspective. We held 14 participatory group discussions (PGDs) with 175 community participants (84 men, 91 women; aged 18-72) across seven municipalities (Ainaro, Baucau, Bobonaro, Dili, Lautem, Manufahi, and Oecusse) in 2019. We held individual in-depth interviews (IDIs) with 24 healthcare providers working in the same community catchment areas as the PGDs. Two counsellors, four doctors, fifteen midwives, and three nurses participated (16 women, 8 men; aged 25-56 years). Data were analysed using reflexive thematic analysis. PGD and IDI participant awareness, understanding and beliefs about male condoms were diverse. Male condoms were often discussed as something negative and taboo, and as something that is highly regulated and discouraged within society and the health system. However, many PGD and IDI participants also challenged this narrative by providing a more rights-based perspective about universal access to sexual and reproductive health information and services, including male condoms. Insights from our research have been used to inform programmatic decision-making in Timor-Leste, including health promotion and service delivery initiatives. Our findings can be further used to inform national health policy, healthcare provider training, and advocacy and communication work.

Risk factors associated with post-intensive care syndrome in family members (PICS-F): A prospective observational study.

Background: The family members of intensive care unit (ICU) patients play a crucial role in modern ICUs. These individuals are predisposed to the development of post-intensive care syndrome in family members (PICS-F), a syndrome experienced by family members of ICU patients in response to critical illness and characterised by new or worsening psychological symptoms. This study sought to evaluate the levels of anxiety and depression exhibited by the family members of patients hospitalised in the ICU. It also aimed to identify the risk factors associated with the experience of PICS-F, which should assist with its prevention in the future. Methods: The study sample comprised 164 ICU patients and their family members. Sociodemographic data were gathered at the time of ICU admission and 3 months after discharge, and the family members were screened for emotional distress using the Hospital Anxiety and Depression Scale (HADS). Comparison tests were used to test for an association between family/patient characteristics and a positive HADS score. In addition, a multivariable logistic regression model was constructed to identify the independent factors associated with a positive HADS score. Results: Emotional distress was identified in 24% of the family members 3 months after their relatives had been discharged from the ICU. A number of personal traits were found to be associated with emotional distress in the family members, namely unemployment (p = .008), smoking/drinking habits (p = .036) and personal history of psychopathology (p = .045). In the multiple logistic regression analyses, only unemployment was found to be an independent factor associated with both anxiety and depression in the family members (OR = 2.74, CI 95%: 1.09-6.93). No association was found between the patients' characteristics and emotional distress in the family members. Conclusions: The findings of this study indicate an association between emotional distress in the family members of ICU patients and their personal traits, thereby building on the prior literature by suggesting that patient characteristics are less pertinent to the experience of PICS-F. Unemployment may represent a meaningful risk factor for emotional distress in family members (a potential marker of PICS-F), given its relationship with family members' positive HADS scores post-ICU discharge. These findings should influence preventative strategies concerning PICS-F by illustrating the need to assess family characteristics and demographics early in a patient's ICU stay and, consequently, allowing for the early identification of at-risk individuals and the prompt implementation of adequate support services.

Augenblickdiagnose in neurology: Revisiting 'diagnosis in the blink of an eye'.

BACKGROUND AND PURPOSE: The art of diagnosis in clinical neurology requires attentive listening and careful observation. In certain situations, a fragment of the history or a physical sign may be so distinctive that it allows clinicians to evoke a specific diagnosis. This quick mental process was previously referred to as 'Augenblickdiagnose' ('diagnosis in the blink of an eye') in a seminal paper by Dr. William Campbell in 1998. We aimed to revisit this concept by providing additional clinical vignettes. METHODS: The authors wrote clinical vignettes using examples from their own clinical practice and performed a non-systematic review of influential neurology textbooks using the words 'pathognomonic' and 'highly suggestive'. RESULTS: Twenty examples from various fields of neurology are presented in a table, stratified by major fields of neurology. A short educational reflection is provided for each diagnosis considered. CONCLUSION: 'Augenblickdiagnose' is an engaging teaching resource that also contributes to 'neurophilia', that is, a fascination for neurology, perhaps increasingly in today's modern neurology practice. However, multiple cognitive biases underlying mental shortcuts may lead to an incorrect diagnosis. It is important to stress that good clinical practice in neurology requires taking a thorough history and performing a careful neurological examination.

The epidemiology of the COVID-19 pandemic in the small, low-resource country of Timor-Leste, January 2020 - June 2022.

Abstract: Timor-Leste, a small, mountainous half-island nation which shares a land border with Indonesia and which is 550 km from Australia, has a population of 1.3 million and achieved independence for the second time in 2002. It is one of the poorest nations in Asia. In response to the global coronavirus disease 2019 (COVID-19) pandemic, the Timor-Leste Ministry of Health undertook surveillance and contact tracing activities on all notified COVID-19 cases. Between 1 January 2020 and 30 June 2022, there were 22,957 cases of COVID-19 notified which occurred in three waves, the first which was delayed until April 2021 (community transmission of B.1.466.2 variant following major flooding), followed by waves in August 2021 (B.1.617.2 Delta variant transmission) and February 2022 (B.1.1.529 Omicron variant transmission). There were 753 people hospitalised due to COVID-19 and 133 deaths. Of the 133 deaths, 122 (92%) were considered not fully vaccinated (< 2 COVID-19 vaccines) and none had received boosters. Timor-Leste implemented measures to control COVID-19, including: rapid closure of international borders; isolation of cases; quarantining of international arrivals and close contacts; restrictions on internal travel; social and physical distancing; and, finally, a country-wide vaccination program. The health system's capacity was never exceeded.