Cytokine biomarkers of exacerbations in sputum from Chronic Obstructive Pulmonary Disease patients: a prospective cohort study.

BACKGROUND: We determined the relationships between cytokine expression in sputum and clinical data to characterise and understand Chronic Obstructive Pulmonary Disease (COPD) exacerbations in COPD patients. METHODS: We measured 30 cytokines in 936 sputum samples, collected at stable state (ST) and exacerbation (EX) visits from 99 participants in the Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) study (NCT01360398, www.clinicaltrials.gov). We determined their longitudinal expression and examined differential expression based on disease status or exacerbation type. RESULTS: Of the cytokines, 17 were suitable for analysis. As for disease states, in EX sputum samples, IL-17A, TNF-α, IL-1ß, and IL-10 were significantly increased compared to ST sputum samples, but a logistic mixed model could not predict disease state. As for exacerbation types, bacteria-associated exacerbations showed higher expression of IL-17A, TNF-α, IL-1ß, and IL-1α. IL-1α, IL-1ß, and TNF-α were identified as suitable biomarkers for bacteria-associated exacerbation. Bacteria-associated exacerbations also formed a cluster separate from other exacerbation types in principal component analysis. CONCLUSIONS: Measurement of cytokines in sputum from COPD patients could help identify bacteria-associated exacerbations based on increased concentrations of IL-1α, IL-1ß, or TNF-α. This finding may provide a point-of-care assessment to distinguish a bacterial exacerbation of COPD from other exacerbation types.

Cognitive domains affected post-COVID-19; a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: This review aims to characterize the pattern of post-COVID-19 cognitive impairment, allowing better prediction of impact on daily function to inform clinical management and rehabilitation. METHODS: A systematic review and meta-analysis of neurocognitive sequelae following COVID-19 was conducted, following PRISMA-S guidelines. Studies were included if they reported domain-specific cognitive assessment in patients with COVID-19 at >4 weeks post-infection. Studies were deemed high-quality if they had >40 participants, utilized healthy controls, had low attrition rates and mitigated for confounders. RESULTS: Five of the seven primary Diagnostic and Statistical Manual of Mental Disorders (DSM-5) cognitive domains were assessed by enough high-quality studies to facilitate meta-analysis. Medium effect sizes indicating impairment in patients post-COVID-19 versus controls were seen across executive function (standardised mean difference (SMD) -0.45), learning and memory (SMD -0.55), complex attention (SMD -0.54) and language (SMD -0.54), with perceptual motor function appearing to be impacted to a greater degree (SMD -0.70). A narrative synthesis of the 56 low-quality studies also suggested no obvious pattern of impairment. CONCLUSIONS: This review found moderate impairments across multiple domains of cognition in patients post-COVID-19, with no specific pattern. The reported literature was significantly heterogeneous, with a wide variety of cognitive tasks, small sample sizes and disparate initial disease severities limiting interpretability. The finding of consistent impairment across a range of cognitive tasks suggests broad, as opposed to domain-specific, brain dysfunction. Future studies should utilize a harmonized test battery to facilitate inter-study comparisons, whilst also accounting for the interactions between COVID-19, neurological sequelae and mental health, the interplay between which might explain cognitive impairment.

Neuropsychological tests associated with symptomatic HIV-associated neurocognitive disorder (HAND) in a cohort of older adults in Tanzania.

OBJECTIVE: Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) prevalence is expected to increase in East Africa as treatment coverage increases, survival improves, and this population ages. This study aimed to better understand the current cognitive phenotype of this newly emergent population of older combination antiretroviral therapy (cART)-treated people living with HIV (PLWH), in which current screening measures lack accuracy. This will facilitate the refinement of HAND cognitive screening tools for this setting. METHOD: This is a secondary analysis of 253 PLWH aged ≥50 years receiving standard government HIV clinic follow-up in Kilimanjaro, Tanzania. They were evaluated with a detailed locally normed low-literacy neuropsychological battery annually on three occasions and a consensus panel diagnosis of HAND by Frascati criteria based on clinical evaluation and collateral history. RESULTS: Tests of verbal learning and memory, categorical verbal fluency, visual memory, and visuoconstruction had an area under the receiver operating characteristic curve >0.7 for symptomatic HAND (s-HAND) (0.70-0.72; p < 0.001 for all tests). Tests of visual memory, verbal learning with delayed recall and recognition memory, psychomotor speed, language comprehension, and categorical verbal fluency were independently associated with s-HAND in a logistic mixed effects model (p < 0.01 for all). Neuropsychological impairments varied by educational background. CONCLUSIONS: A broad range of cognitive domains are affected in older, well-controlled, East African PLWH, including those not captured in widely used screening measures. It is possible that educational background affects the observed cognitive impairments in this setting. Future screening measures for similar populations should consider assessment of visual memory, verbal learning, language comprehension, and executive and motor function.

Detection and genetic characterization of chicken astrovirus and Avian Nephritis virus from hatchery to farm.

Astroviruses are an emerging hazard in hatchery management, and they are responsible for great economic losses in poultry farms worldwide. Chicken astrovirus (CAstV) and Avian Nephritis virus (ANV) are involved in hatching decrease mainly due to embryo deaths, pale and runted chicks too weak to hatch. Hatchery diseases occur through direct egg infection or through vertical transmission. However, the specific role of astroviruses in these diseases is still largely unknown. To elucidate this question, a high-quality Piedmont hatchery (Italy) was selected based on farm clinical signs and the Astrovirus serological positivity in the breeder farm. The viral dynamics was followed from the hatchery to the farm. The presence of both CAstV and ANV was monitored by evaluating the viral load, in environmental and animal samples. Interestingly, both viruses were detected in chick yolk sacs at 18th day incubation, in the gut contents of 1-day chicks, whereas the hatchery environmental samples, the external eggs' surfaces and the embryos intestinal contents were negative. The CAstV copy number was higher in animal tissues from hatchery, while a greater ANV load was detected in animal tissue from farm. Moreover, our data suggested a vertical transmission ascribed to both viruses. A frequent co-infection was also observed in samples from both hatchery and farm. Lastly, the first Italian full-length genome and molecular characterization of ANV was obtained.

Pre-pregnancy body mass index and caesarean section in Andean women in Peru: a prospective cohort study.

BACKGROUND: During the last two decades, Caesarean section rates (C-sections), overweight and obesity rates increased in rural Peru. We examined the association between pre-pregnancy body mass index (BMI) and C-section in the province of San Marcos, Northern Andes-Peru. METHODS: This is a prospective cohort study. Participants were women receiving antenatal care in public health establishments from February 2020 to January 2022, who were recruited and interviewed during pregnancy or shortly after childbirth. They answered a questionnaire, underwent a physical examination and gave access to their antenatal care card information. BMI was calculated using maternal height, measured by the study team and self-reported pre-pregnancy weight measured at the first antenatal care visit. For 348/965 (36%) women, weight information was completed using self-reported data collected during the cohort baseline. Information about birth was obtained from the health centre's pregnancy surveillance system. Regression models were used to assess associations between C-section and BMI. Covariates that changed BMI estimates by at least 5% were included in the multivariable model. RESULTS: This study found that 121/965 (12.5%) women gave birth by C-section. Out of 495 women with pre-pregnancy normal weight, 46 (9.3%) had C-sections. Among the 335 women with pre-pregnancy overweight, 53 (15.5%) underwent C-sections, while 23 (18.5%) of the 124 with pre-pregnancy obesity had C-sections. After adjusting for age, parity, altitude, food and participation in a cash transfer programme pre-pregnancy overweight and obesity increased the odds of C-section by more than 80% (aOR 1.82; 95% CI 1.16-2.87 and aOR 1.85; 95% CI 1.02-3.38) compared to women with a normal BMI. CONCLUSIONS: High pre-pregnancy BMI is associated with an increased odds of having a C-section. Furthermore, our results suggest that high BMI is a major risk factor for C-section in this population. The effect of obesity on C-section was partially mediated by the development of preeclampsia, suggesting that C-sections are being performed due to medical reasons.

The prevalence and outcomes of depression in older HIV-positive adults in Northern Tanzania: a longitudinal study.

Studies of depression and its outcomes in older people living with HIV (PLWH) are currently lacking in sub-Saharan Africa. This study aims to investigate the prevalence of psychiatric disorders in PLWH aged ≥ 50 years in Tanzania focussing on prevalence and 2-year outcomes of depression. PLWH aged ≥ 50 were systematically recruited from an outpatient clinic and assessed using the Mini-International Neuropsychiatric Interview (MINI). Neurological and functional impairment was assessed at year 2 follow-up. At baseline, 253 PLWH were recruited (72.3% female, median age 57, 95.5% on cART). DSM-IV depression was highly prevalent (20.9%), whereas other DSM-IV psychiatric disorders were uncommon. At follow-up (n = 162), incident cases of DSM-IV depression decreased from14.2 to 11.1% (χ2: 2.48, p = 0.29); this decline was not significant. Baseline depression was associated with increased functional and neurological impairment. At follow-up, depression was associated with negative life events (p = 0.001), neurological impairment (p < 0.001), and increased functional impairment (p = 0.018), but not with HIV and sociodemographic factors. In this setting, depression appears highly prevalent and associated with poorer neurological and functional outcomes and negative life events. Depression may be a future intervention target.

Prevalence and 1-year incidence of HIV-associated neurocognitive disorder (HAND) in adults aged ≥50 years attending standard HIV clinical care in Kilimanjaro, Tanzania.

OBJECTIVES: HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities. DESIGN: Longitudinal study. PARTICIPANTS: A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March-May 2016 and followed up March-May 2017. MEASUREMENTS: HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records. RESULTS: In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9-53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0-28.6 n = 16) was observed. CONCLUSIONS: HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.

First report of putative Leishmania RNA virus 2 (LRV2) in Leishmania infantum strains from canine and human visceral leishmaniasis cases in the southeast of Brazil.

BACKGROUND: Leishmania RNA virus 1 (LRV1) is commonly found in South American Leishmania parasites belonging to the subgenus Viannia, whereas Leishmania RNA virus 2 (LRV2) was previously thought to be restricted to the Old-World pathogens of the subgenus Leishmania. OBJECTIVES: In this study, we investigated the presence of LRV2 in strains of Leishmania (L.) infantum, the causative agent of visceral leishmaniasis (VL), originating from different hosts, clinical forms, and geographical regions. METHODS: A total of seventy-one isolates were screened for LRV2 using semi-nested reverse transcription-polymerase chain reaction (RT-PCR) targeting the RNA-dependent RNA polymerase (RdRp) gene. FINDINGS: We detected LRV2 in two L. infantum isolates (CUR268 and HP-EMO) from canine and human cases, respectively. MAIN CONCLUSIONS: To the best of our knowledge, this is the first detection of LRV2 in the New World.

Staphylococci isolated from cats in Italy with superficial pyoderma and allergic dermatitis: Characterisation of isolates and their resistance to antimicrobials.

BACKGROUND: In cats, superficial pyoderma traditionally is considered rare and few reports are available. There is a particular lack of studies concerning Staphylococcus species associated with pyoderma in subjects affected by allergic skin diseases. HYPOTHESIS/OBJECTIVES: (i) To evaluate the association between Staphylococcus spp. and superficial pyoderma in allergic cats and (ii) to characterise isolated staphylococci and analyse their antimicrobial resistance patterns. ANIMALS: Forty-one cats with allergic dermatitis and superficial pyoderma in Italy. MATERIALS AND METHODS: Skin swabs were cultured for the isolation of Staphylococcus spp. Species identification was performed by matrix-assisted laser desorption/ionisation time of flight mass spectrometry and 16S-rRNA sequencing. Staphylococcus aureus isolates were further characterised by staphylococcal protein A gene-typing. Antimicrobial susceptibility was performed by the disk diffusion method. RESULTS: Staphylococci were isolated from 36/41 cats sampled and 39 different isolates were identified. Uneven distribution of staphylococcal species was observed among different body locations. The 39 isolates were S. aureus (n = 15), S. felis (n = 10), S. pseudintermedius (n = 8) and other staphylococci (n = 6). Eight different S. aureus spa-types associated with human clonal complexes were identified. Antimicrobial resistance was observed to penicillin (56.4%), tetracycline (46.2%), enrofloxacin (33.3%), erythromycin (28.2%), amikacin (25.6%), clindamycin (23.1%), marbofloxacin (15.4%), gentamicin (12.8%), trimethoprim-sulfamethoxazole (10.3%), chloramphenicol (7.7%) and cefoxitin/oxacillin (5.1%). Fifteen isolates (38.4%) were multidrug-resistant while meticillin resistance was associated only with S. pseudintermedius. CONCLUSIONS AND CLINICAL RELEVANCE: These results confirm that S. aureus, S. pseudintermedius, and S. felis are frequently associated with superficial pyoderma in allergic cats. Semi-synthetic penicillins remain a suitable first-line treatment in this study, yet the high prevalence of antimicrobial resistant isolates suggests that antimicrobial susceptibility testing should be performed routinely.

Use of sisal industrial waste (Agave sisalana Perrine) in sustainable and multifunctional cosmetic products.

OBJECTIVE: Sisal is a common stiff fibre produced around the world, corresponding to approximately 70% of the commercial production of all fibres of this type. The fibres are extracted from the leaves of Agave sisalana, from which approximately 4% of their weight is obtained, with the remaining 96% considered to be residues from the process of the sisal industry. The objective of this work was to obtain a polyphenol-enriched extract from the A. sisalana residue by ultrasonically assisted extraction, characterize it chemically, evaluate in vitro antioxidant activity, and develop safe and stable photoprotective formulations for future application in cosmetic preparations. METHODS: Ultrasonic extraction of solid plant material was performed using 50% ethanol/water (v/v). The extract was chemically characterized by high-performance liquid chromatography equipment associated with classical molecular networking and evaluated for in vitro antioxidant activity by different methodologies. Ten formulations were prepared, varying the component concentrations and the shear time. The 1.0% sisal extract was incorporated into the most stable formulations, and preliminary and accelerated stability were evaluated. The emulsions were investigated for safety by assessment of primary accumulated dermal irritability and sensitization and a dermatological clinical study of phototoxicity and photosensitization. The photoprotective formulations containing or not containing the extract that were stable after 90 days had their in vivo sun protection factor (SPF), UVA protection factor, critical wavelength, and protection against visible and blue light determined. RESULTS: Ultrasound extraction using 50% ethanol/water (EH 50) as an extractor vehicle showed the best yield. The extract exhibited a concentration of phenolic compounds (77.93 mg of equivalent to the standard gallic acid/g) and showed in vitro antioxidant activity. Emulsions without and with 1.0% sisal extract remained stable and safe. The addition of the extract to the photoprotective formulation statistically increased the SPF when compared to the formulation without the extract and offered protection against UVA radiation, critical wavelengths, and absorption of visible and blue light. CONCLUSION: Based on the findings, the solid residue of A. sisalana may be indicated as a component of photoprotective and antioxidant cosmetic formulations.

OBJECTIF: Le sisal est une fibre rigide courante produite dans le monde entier, correspondant à environ 70 % de la production commerciale de toutes les fibres de ce type. Les fibres sont extraites des feuilles d'Agave sisalana dont environ 4 % du poids est obtenu, les 96 % restants étant considérés comme des résidus du procédé de l'industrie du sisal. L'objectif de ce projet était d'obtenir un extrait du résidu d'A. sisalana enrichi en polyphénols par extraction assistée par ultrasons (EAU), de le caractériser chimiquement, d'évaluer l'activité antioxydante in vitro et de développer des formulations photoprotectrices sûres et stables pour une application future dans des préparations cosmétiques. MÉTHODES: L'extraction ultrasonique de la matière végétale solide a été effectuée avec une solution à 50 % d'éthanol/eau (v/v). L'extrait a été chimiquement caractérisé avec un équipement de chromatographie en phase liquide à haute performance associé à un réseau moléculaire (RM) classique, puis évalué pour l'activité antioxydante in vitro par différentes méthodologies. Dix formulations ont été préparées en variant les concentrations des composants et le temps de cisaillement. L'extrait de sisal à 1,0 % a été incorporé dans les formulations les plus stables et la stabilité préliminaire et accélérée a été évaluée. La sécurité d'emploi des émulsions a été étudiée en évaluant l'irritabilité et la sensibilisation cutanées accumulées primaires et l'étude clinique dermatologique de la phototoxicité et de la photosensibilisation. Le facteur de protection solaire in vivo, le facteur de protection UVA, la longueur d'onde critique et la protection contre la lumière visible et bleue ont été déterminées pour les formulations photoprotectrices contenant ou non l'extrait qui étaient stables après 90 jours. RÉSULTATS: L'extraction par ultrasons utilisant une solution à 50 % d'éthanol/eau (EH 50) comme véhicule d'extraction a menée au meilleur rendement. L'extrait a présenté une concentration de composés phénoliques (77,93 mg d'EAG/g) et une activité antioxydante in vitro. Les émulsions sans et avec 1,0 % d'extrait de sisal sont restées stables et sans danger. L'ajout de l'extrait à la formulation photoprotectrice a statistiquement augmenté le SPF par rapport à la formulation sans extrait et a offert une protection contre les rayonnements UVA, la longueur d'onde critique et l'absorption de la lumière visible et bleue. CONCLUSION: D'après ces résultats, les résidus solides d'A. sisalana peuvent être indiqués comme composant des formulations cosmétiques photoprotectrices et antioxydantes.

Preliminary evaluation of a smartphone application (DelApp) for identification of delirium in sub-Saharan Africa.

OBJECTIVE: In sub-Saharan Africa, there are no validated screening tools for delirium in older adults, despite the known vulnerability of older people to delirium and the associated adverse outcomes. This study aimed to assess the effectiveness of a brief smartphone-based assessment of arousal and attention (DelApp) in the identification of delirium amongst older adults admitted to the medical department of a tertiary referral hospital in Northern Tanzania. METHOD: Consecutive admissions were screened using the DelApp during a larger study of delirium prevalence and risk factors. All participants subsequently underwent detailed clinical assessment for delirium by a research doctor. Delirium and dementia were identified against DSM-5 criteria by consensus. RESULTS: Complete data for 66 individuals were collected of whom 15 (22.7%) had delirium, 24.5% had dementia without delirium, and 10.6% had delirium superimposed on dementia. Sensitivity and specificity of the DelApp for delirium were 0.87 and 0.62, respectively (AUROC 0.77) and 0.88 and 0.73 (AUROC 0.85) for major cognitive impairment (dementia and delirium combined). Lower DelApp score was associated with age, significant visual impairment (<6/60 acuity), illness severity, reduced arousal and DSM-5 delirium on univariable analysis, but on multivariable logistic regression only arousal remained significant. CONCLUSION: In this setting, the DelApp performed well in identifying delirium and major cognitive impairment but did not differentiate delirium and dementia. Performance is likely to have been affected by confounders including uncorrected visual impairment and reduced level of arousal without delirium. Negative predictive value was nevertheless high, indicating excellent 'rule out' value in this setting.

Flipped classroom with teams-based learning in emergency higher education: methodology and results.

During the pandemic period, most of the universities shifted their curricula into fully distance learning models. Due to these Emergency Remote Education circumstances, we adopted the application of Flipped Classroom model combined with Team-based Learning pedagogical strategy in four Computer Engineering courses. Our approach was reinforced by employing LAMS Learning Activities Management System in conjunction with interactive video services. Results of the application of this approach reveal enhanced student engagement with learning resources and improved achievement when compared to the traditional, in-class, conduction of the same courses. Moreover, students report positive estimation of the adopted approach.

Homozygous CADPS2 Mutations Cause Neurodegenerative Disease with Lewy Body-like Pathology in Parrots.

BACKGROUND: Several genetic models that recapitulate neurodegenerative features of Parkinson's disease (PD) exist, which have been largely based on genes discovered in monogenic PD families. However, spontaneous genetic mutations have not been linked to the pathological hallmarks of PD in non-human vertebrates. OBJECTIVE: To describe the genetic and pathological findings of three Yellow-crowned parrot (Amazona ochrocepahala) siblings with a severe and rapidly progressive neurological phenotype. METHODS: The phenotype of the three parrots included severe ataxia, rigidity, and tremor, while their parents were phenotypically normal. Tests to identify avian viral infections and brain imaging studies were all negative. Due to their severe impairment, they were all euthanized at age 3 months and their brains underwent neuropathological examination and proteasome activity assays. Whole genome sequencing (WGS) was performed on the three affected parrots and their parents. RESULTS: The brains of affected parrots exhibited neuronal loss, spongiosis, and widespread Lewy body-like inclusions in many regions including the midbrain, basal ganglia, and neocortex. Proteasome activity was significantly reduced in these animals compared to a control (P < 0.05). WGS identified a single homozygous missense mutation (p.V559L) in a highly conserved amino acid within the pleckstrin homology (PH) domain of the calcium-dependent secretion activator 2 (CADPS2) gene. CONCLUSIONS: Our data suggest that a homozygous mutation in the CADPS2 gene causes a severe neurodegenerative phenotype with Lewy body-like pathology in parrots. Although CADPS2 variants have not been reported to cause PD, further investigation of the gene might provide important insights into the pathophysiology of Lewy body disorders. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Screening tools for common mental disorders in older adults in South Asia: a systematic scoping review.

OBJECTIVES: Common mental disorders (CMDs), particularly depression, are major contributors to the global mental health burden. South Asia, while diverse, has cultural, social, and economic challenges, which are common across the region, not least an aging population. This creates an imperative to better understand how CMD affects older people in this context, which relies on valid and culturally appropriate screening and research tools. This review aims to scope the availability of CMD screening tools for older people in South Asia. As a secondary aim, this review will summarize the use of these tools in epidemiology, and the extent to which they have been validated or adapted for this population. DESIGN: A scoping review was performed, following PRISMA guidelines. The search strategy was developed iteratively in Medline and translated to Embase, PsychInfo, Scopus, and Web of Science. Data were extracted from papers in which a tool was used to identify CMD in a South Asian older population (50+), including validation, adaptation, and use in epidemiology. Validation studies meeting the criteria were critically appraised using the Quality Assessment of Diagnostic Accuracy Studies - version 2 (QUADAS-2) tool. RESULTS: Of the 4694 papers identified, 176 met the selection criteria at full-text screening as relevant examples of diagnostic or screening tool use. There were 15 tool validation studies, which were critically appraised. Of these, 10 were appropriate to evaluate as diagnostic tests. All of these tools assessed for depression. Geriatric Depression Scale (GDS)-based tools were predominant with variable diagnostic accuracy across different settings. Methodological issues were substantial based on the QUADAS-2 criteria. In the epidemiological studies identified (n = 160), depression alone was assessed for 82% of the studies. Tools lacking cultural validation were commonly used (43%). CONCLUSIONS: This review identifies a number of current research gaps including a need for culturally relevant validation studies, and attention to other CMDs such as anxiety.

Development of a brief screening method for identification of depression in older adults in Sub-Saharan Africa.

OBJECTIVES: To develop a brief, culturally appropriate screening tool for identifying late life depression (LLD), for use by non-specialist clinicians in primary and out-patient care settings in sub-Saharan Africa (SSA). BACKGROUND: Depressive disorders are a leading contributor to the global health burden. LLD is common and cases will increase as populations' age, particularly in low- and middle-income countries (LMICs), such as those in SSA. A chronic mental health workforce shortage and the absence of culturally adapted LLD screening tools to aid non-specialist clinicians have contributed to a significant diagnostic gap. DESIGN: A systematic random sample of older people attending general medical clinics were interviewed using a 30-item LLD questionnaire, developed utilizing a Delphi consensus analysis of items from the Geriatric Depression Scale, Patient Health Questionnaire-2 and questions developed from a study of lay conceptualisations of depression in Tanzania. The items were assessed for validity against blinded DSM 5 diagnosis of depression by a research doctor. Factor and item analysis were then used to refine the questionnaire. RESULTS: The 12-item Maddison Old-age Scale for Identifying Depression (MOSHI-D) was developed. It has good internal consistency (Cronbach's α = 0.820) and construct and criterion validity (AUROC = 0.880). CONCLUSIONS: On initial evaluation, the MOSHI-D showed good internal validity. It should be easy for non-specialists to administer. External validation and further refinement will be conducted. A culturally-appropriate LLD screen may improve mental health care integration into existing healthcare settings within SSA and facilitate greater patient access to care, in accordance with current WHO strategy.

Dementia in Africa: Current evidence, knowledge gaps, and future directions.

In tandem with the ever-increasing aging population in low and middle-income countries, the burden of dementia is rising on the African continent. Dementia prevalence varies from 2.3% to 20.0% and incidence rates are 13.3 per 1000 person-years with increasing mortality in parts of rapidly transforming Africa. Differences in nutrition, cardiovascular factors, comorbidities, infections, mortality, and detection likely contribute to lower incidence. Alzheimer's disease, vascular dementia, and human immunodeficiency virus/acquired immunodeficiency syndrome-associated neurocognitive disorders are the most common dementia subtypes. Comprehensive longitudinal studies with robust methodology and regional coverage would provide more reliable information. The apolipoprotein E (APOE) ε4 allele is most studied but has shown differential effects within African ancestry compared to Caucasian. More candidate gene and genome-wide association studies are needed to relate to dementia phenotypes. Validated culture-sensitive cognitive tools not influenced by education and language differences are critically needed for implementation across multidisciplinary groupings such as the proposed African Dementia Consortium.

Low levels of frailty in HIV-positive older adults on antiretroviral therapy in northern Tanzania.

There are over 3 million people in sub-Saharan Africa (SSA) aged 50 and over living with HIV. HIV and combined antiretroviral therapy (cART) exposure may accelerate the ageing in this population, and thus increase the prevalence of premature frailty. There is a paucity of data on the prevalence of frailty in an older HIV + population in SSA and screening and diagnostic tools to identify frailty in SSA. Patients aged ≥ 50 were recruited from a free Government HIV clinic in Tanzania. Frailty assessments were completed, using 3 diagnostic and screening tools: the Fried frailty phenotype (FFP), Clinical Frailty Scale (CFS) and Brief Frailty Instrument for Tanzania (B-FIT 2). The 145 patients recruited had a mean CD4 + of 494.84 cells/µL, 99.3% were receiving cART and 72.6% were virally suppressed. The prevalence of frailty by FFP was 2.758%. FFP frailty was significantly associated with female gender (p = 0.006), marital status (p = 0.007) and age (p = 0.038). Weight loss was the most common FFP domain failure. The prevalence of frailty using the B-FIT 2 and the CFS was 0.68%. The B-FIT 2 correlated with BMI (r = - 0.467, p = 0.0001) and CD4 count in females (r = - 0.244, p = 0.02). There is an absence of frailty in this population, as compared to other clinical studies. This may be due to the high standard of HIV care at this Government clinic. Undernutrition may be an important contributor to frailty. It is unclear which tool is most accurate for detecting the prevalence of frailty in this setting as levels of correlation are low.

Screening for HIV-Associated Neurocognitive Disorder (HAND) in Adults Aged 50 and Over Attending a Government HIV Clinic in Kilimanjaro, Tanzania. Comparison of the International HIV Dementia Scale (IHDS) and IDEA Six Item Dementia Screen.

Validated screening tools for HIV-associated neurocognitive disorders (HAND) are lacking for the newly emergent ageing population of people living with HIV (PLWH) in sub-Saharan Africa (SSA). We aimed to validate and compare diagnostic accuracy of two cognitive screening tools, the International HIV dementia scale (IHDS), and the Identification and Interventions for Dementia in Elderly Africans (IDEA) screen, for identification of HAND in older PLWH in Tanzania. A systematic sample of 253 PLWH aged ≥ 50 attending a Government clinic in Tanzania were screened with the IHDS and IDEA. HAND were diagnosed by consensus American Academy of Neurology (AAN) criteria based on detailed clinical neuropsychological assessment. Strict blinding was maintained between screening and clinical evaluation. Both tools had limited diagnostic accuracy for HAND (area under the receiver operating characteristic (AUROC) curve 0.639-0.667 IHDS, 0.647-0.713 IDEA), which was highly-prevalent (47.0%). Accurate HAND screening tools for older PLWH in SSA are needed.

RESUMEN: Faltan pruebas cognitivas válidas para los trastornos neurocognitivos asociados al VIH (según sus siglas en inglés, HIV-Associated Neurocognitive Disorder (HAND) en la población emergente de personas mayores que viven con el VIH en el África subsahariana. Nuestro objetivo era validar y comparar la precisión diagnóstica de dos pruebas cognitivas, la escala internacional de demencia por VIH (según sus siglas en ingles International HIV dementia scale (IHDS) y la prueba 'IDEA', para el cribado de trastornos neurocognitivos asociados al VIH (HAND) en personas mayores viviendo con VIH en Tanzania. Una muestra sistemática de 253 personas de ≥50 años que asistieron a una clínica gubernamental en Tanzania se examinó con el IHDS y la IDEA. HAND fueron diagnosticados por consenso según los criterios de la Academia Americana de Neurología (AAN) basados en una detallada evaluación neuropsicológica y clínica. Las fases de cribado y de evaluación clínica se realizaron de forma independiente y a ciegas. Ambas herramientas tenían una precisión de diagnóstico limitada para HAND (área bajo la característica de funcionamiento del receptor (AUROC) curva 0.639 ­ 0.667 IHDS, 0.647-0.713 IDEA). HAND era altamente frecuente (47%). Se necesitan pruebas cognitivas por cribado de deterioro cognitivo en personas mayores con VIH en el África subsahariana.

Effectiveness of App-Based Cognitive Screening for Dementia by Lay Health Workers in Low Resource Settings. A Validation and Feasibility Study in Rural Tanzania.

BACKGROUND: The majority of people with dementia live in low-and middle-income countries (LMICs). In sub-Saharan Africa (SSA) human-resource shortages in mental health and geriatric medicine are well recognized. Use of technological solutions may improve access to diagnosis. We aimed to assess the diagnostic accuracy of a brief dementia screening mobile application (app) for non-specialist workers in rural Tanzania against blinded gold-standard diagnosis of DSM-5 dementia. The app includes 2 previously-validated culturally appropriate low-literacy screening tools for cognitive (IDEA cognitive screen) and functional impairment (abbreviated IDEA-IADL questionnaire). METHODS: This was a 2-stage community-based door-to-door study. In Stage1, rural primary health workers approached all individuals aged ≥60 years for app-based dementia screening in 12 villages in Hai district, Kilimanjaro Tanzania.In Stage 2, a stratified sub-sample were clinically-assessed for dementia blind to app screening score. Assessment included clinical history, neurological and bedside cognitive assessment and collateral history. RESULTS: 3011 (of 3122 eligible) older people consented to screening. Of these, 610 were evaluated in Stage 2. For the IDEA cognitive screen, the area under the receiver operating characteristic (AUROC) curve was 0.79 (95% CI 0.74-0.83) for DSM-5 dementia diagnosis (sensitivity 84.8%, specificity 58.4%). For those 358 (44%) completing the full app, AUROC was 0.78 for combined cognitive and informant-reported functional assessment. CONCLUSIONS: The pilot dementia screening app had good sensitivity but lacked specificity for dementia when administered by non-specialist rural community workers. This technological approach may be a promising way forward in low-resource settings, specialist onward referral may be prioritized.

Prevalence and associated factors of depression among older adults in rural Tanzania.

OBJECTIVES: Depression is the commonest mental disorder in older adults worldwide, affecting 7% of the world's older population and accounting for 5.7% of years lived with disability among adults aged over 60 years. We conducted a secondary data analysis to determine the point prevalence, associated risk factors and treatment gap for DSM-IV depression among older adults in the Hai District, rural Tanzania. METHODS: The primary data source was a cross-sectional two-stage community-based dementia study where older adults aged ≥70 years (n = 296) were fully-assessed for dementia and depression in the second stage. Age-adjusted prevalence of depression was determined based on the WHO standard population using the Direct Method. Univariate and multivariate logistic regression models were performed. RESULTS: Of the 296 older adults assessed for depression, 48 were diagnosed with depression based on Diagnostic and Statistical Manual of Mental Disorders-IV criteria. The median (Inter Quartile Range; QR) age was 80 (75-88) years. Age-adjusted point prevalence of depression was 21.2% (95% CI: 16.6-21.9) and the treatment gap for depression was 100%. There was reduced odds of depression in older adults who rated their physical health as good or very good (adjusted odds ratio [AOR] = 0.22; 95%CI: 0.10-0.46; p < 0.001), or moderate (AOR 0.26; 95%CI: 0.10-0.66; p = 0.005). CONCLUSIONS: Depression in older adults is associated with physical health status and there is an alarmingly high treatment gap. Future research on depression in older adults should focus on effective interventions to address physical morbidity, psychosocial factors and the treatment gap.