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Introduction: Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran, potentially allowing for thrombolysis. This nation-wide observational cohort study, systematic review, and meta-analysis evaluated the efficacy and safety of thrombolysis preceded by dabigatran-reversal in people with acute ischemic stroke. Patients and methods: We recruited people undergoing thrombolysis following dabigatran-reversal at 17 stroke centers in Italy (reversal-group), people on dabigatran treated with thrombolysis without reversal (no-reversal group), and age, sex, hypertension, stroke severity, and reperfusion treatment-matched controls in 1:7 ratio (control-group). We compared groups for symptomatic intracranial hemorrhage (sICH, main outcome), any brain hemorrhage, good functional outcome (mRS 0–2 at 3 months), and death. The systematic review followed a predefined protocol (CRD42017060274), and odds ratio (OR) meta-analysis was implemented to compare groups. Results: Thirty-nine patients in dabigatran-reversal group and 300 matched controls were included. Reversal was associated with a non-significant increase in sICH (10.3% vs 6%, aOR = 1.32, 95% CI = 0.39–4.52), death (17.9% vs 10%, aOR = 0.77, 95% CI = 0.12–4.93) and good functional outcome (64.1% vs 52.8%, aOR = 1.41, 95% CI = 0.63–3.19). No hemorrhagic events or deaths were registered in no-reversal group (n = 12). Pooling data from 3 studies after systematic review (n = 1879), reversal carried a non-significant trend for sICH (OR = 1.53, 95% CI = 0.67–3.50), death (OR = 1.53, 95% CI = 0.73–3.24) and good functional outcome (OR = 2.46, 95% CI = 0.85–7.16). Discussion and conclusion: People treated with reperfusion strategies after dabigatran reversal with idarucizumab seem to have a marginal increase in the risk of sICH but comparable functional recovery to matched patients with stroke. Further studies are needed to define treatment cost-effectiveness and potential thresholds in plasma dabigatran concentration for reversal.

Schistosomiasis is a helminthiasis infecting approximately 250 million people worldwide. In 2001, the World Health Assembly (WHA) 54.19 resolution defined a new global strategy for control of schistosomiasis through preventive chemotherapy programmes. This resolution culminated in the 2006 WHO guidelines that recommended empirical treatment by mass drug administration with praziquantel, predominately to school-aged children in endemic settings at regular intervals. Since then, school-based and community-based preventive chemotherapy programmes have been scaled-up, reducing schistosomiasis-associated morbidity. Over the past 15 years, new scientific evidence-combined with a more ambitious goal of eliminating schistosomiasis and an increase in the global donated supply of praziquantel-has highlighted the need to update public health guidance worldwide. In February, 2022, WHO published new guidelines with six recommendations to update the global public health strategy against schistosomiasis, including expansion of preventive chemotherapy eligibility from the predominant group of school-aged children to all age groups (2 years and older), lowering the prevalence threshold for annual preventive chemotherapy, and increasing the frequency of treatment. This Review, written by the 2018-2022 Schistosomiasis Guidelines Development Group and its international partners, presents a summary of the new WHO guideline recommendations for schistosomiasis along with their historical context, supporting evidence, implications for public health implementation, and future research needs.

Mini-Mental State Examination (MMSE) lacks of sensitivity in detecting cognitive deficits associated with subcortical damage. The HIV-Dementia Scale (HDS), a screening tool originally created for detecting cognitive impairment due to subcortical damage in HIV + patients, has proved to be useful in other neurological diseases. Until now, an Italian version of the HDS is not available. We aimed at: (1) validating the HDS Italian version (HDS-IT) in a cohort of cognitively healthy subjects (CN); (2) exploring the suitability of HDS-IT in detecting cognitive impairment due to subcortical damage (scCI). The psychometric properties of the HDS-IT were assessed in 180 CN (mean age 67.6 ± 8.3, range 41–84) with regard to item-total correlation, test–retest reliability and convergent validity with MMSE. Item-total correlations ranged 0.44–0.72. Test–retest reliability was 0.70 (p p scCI subjects (mean age 64.9 ± 10.6, range 41–84). Mean HDS-IT total score was close to the original version and significantly lower in the scCI group compared to CN (8.6 ± 3.6 vs. 12.6 ± 2.5, p p

Objectives Cerebrospinal fluid α-synuclein (CSF α-syn) represents a possible biomarker in Parkinson’s disease (PD) diagnosis. CSF blood contamination can introduce a bias in α-syn measurement. To date, CSF samples with a red blood cells (RBC) count >50 RBC × 106/L or haemoglobin (Hb) concentration >200 μg/L are excluded from biomarker studies. However, investigations for defining reliable cut-off values are missing. Methods We evaluated the effect of blood contamination on CSF α-syn measurement by a systematic approach in a cohort of 42 patients with different neurological conditions who underwent lumbar puncture (LP) for diagnostic reasons. CSF samples were spiked with whole blood and serially diluted to 800, 400, 200, 100, 75, 50, 25, 5, 0 RBC × 106/L. CSF α-syn and Hb levels were measured by ELISA. Results In neat CSF, the average concentration of α-syn was 1,936 ± 636 ng/L. This value increased gradually in spiked CSF samples, up to 4,817 ± 1,456 ng/L (+149% α-syn variation) in samples with 800 RBC × 106/L. We established different cut-offs for discriminating samples with α-syn level above 5, 10, and 20% variation, corresponding to a Hb (RBC) concentration of 1,569 μg/L (37 RBC × 106/L), 2,082 μg/L (62 RBC × 106/L), and 3,118 μg/L (87 RBC × 106/L), respectively. Conclusions Our data show the high impact of CSF blood contamination on CSF α-syn levels, highlighting the measurement of Hb concentration as mandatory when assessing CSF α-syn. The thresholds we calculated are useful to classify CSF samples for blood contamination, considering as reliable only those showing a Hb concentration

The objective was to estimate the diagnostic accuracy of real time polymerase chain reaction (RT-PCR) and lateral flow immunoassay (LFIA) tests for COVID-19, depending on the time post symptom onset. Based on the cross-classified results of RT-PCR and LFIA, we used Bayesian latent class models (BLCMs), which do not require a gold standard for the evaluation of diagnostics. Data were extracted from studies that evaluated LFIA (IgG and/or IgM) assays using RT-PCR as the reference method. \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${Se}_{RT- PCR}$\end{document} was 0.68 (95% probability intervals: 0.63; 0.73). \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${Se}_{IgG/M}$\end{document} was 0.32 (0.23; 0.41) for the first week and increased steadily. It was 0.75 (0.67; 0.83) and 0.93 (0.88; 0.97) for the second and third week post symptom onset, respectively. Both tests had a high to absolute Sp, with higher point median estimates for \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${Sp}_{RT- PCR}$\end{document} and narrower probability intervals: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${Sp}_{RT- PCR}$\end{document} was 0.99 (0.98; 1.00) and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}${Sp}_{IgG/M}$\end{document} was 0.97 (0.92; 1.00), 0.98 (0.95; 1.00) and 0.98 (0.94; 1.00) for the first, second and third week post symptom onset. The diagnostic accuracy of LFIA varies with time post symptom onset. BLCMs provide a valid and efficient alternative for evaluating the rapidly evolving diagnostics for COVID-19, under various clinical settings and different risk profiles.

Millions of praziquantel doses have been delivered in schistosomiasis endemic populations through preventive chemotherapy. However, no comprehensive assessment of short and long-term safety has been conducted. This systematic review assessed safety of praziquantel in persons with and without schistosome infections who received praziquantel treatment.MethodsWe identified relevant studies (published, unpublished, in press or preprint) that assessed safety of praziquantel without language restriction. We searched MEDLINE, EMBASE, CINAHL, and LILACS from 1978 to 31stOctober 2021, using well-formulated and piloted search strategy. We also searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2021), mRCT, Google Scholar, Hinari and Africa Journals Online. References of relevant studies were checked and experts were contacted for additional studies. One author searched and managed the search output. Two authors selected studies, extracted data and assessed quality of the included studies for risk of bias. Activities at all stages were checked independently by a third reviewer. Discrepancies were resolved through discussion among the authors. Data were analysed with RevMan v5.4 and STATA v17. Binary outcomes were reported as risk ratio using random-effects model and continuous outcomes as mean difference, all presented with their 95% confidence intervals. P-value was set at 0.05. Heterogeneity was assessed using I2-static and where possible sensitivity analysis was conducted. When pooling of data was not possible, we presented data in a narrative synthesis and as tables.Main resultsThe search retrieved 3202 studies of which 134 met the inclusion criteria; 94 (70.1%) were conducted in Africa, 17 (12.7%) in Asia, 15 (11.2%) in the Americas (14 from Brazil), 4 (3.0%) in the Middle East and 3 (2.2%) in Europe. Praziquantel mostly resulted in mild-to-moderate and transient adverse events, however, majority of the included studies had design issues, including very short follow-up times (mostly few hours) for assessing incidence of adverse events. Less than 2= 98%, p < 0.00001), dizziness (RR 1.80, 95% CI 1.36 to 2.37, p = 0.0001), vomiting (RR 2.43, 95% CI 1.87 to 3.14, I2= 98%; p < 0.00001), four time for abdominal pain (RR 3.97, 95% CI 3.09 to 5.10, I2= 96%, p < 0.00001), nausea (RR 1.67, 95% CI 1.32 to 2.12, I2= 97%, p < 0.0001), general discomfort (RR 1.32, 95% CI 1.03 to 1.68, I2= 97%, p < 0.00001), fever (RR 4.78, 95% CI 3.04 to 7.52, I2= 98%, p < 0.00001), diarrhoea (RR 1.41, 95% CI 1.12 to 1.78, I2= 92%, p < 0.00001), itching (RR 2.42, 95% CI 1.58 to 3.70, I2= 93%, p 2= 92%, p = 0.002). There was no statistically significant difference in incidence of swelling. Some of the studies that assessed safety in pregnant women reported serious events including miscarriages, foetal deaths and congenital anomalies, but the evidence is incoclusive given the limited numbers. Some studies reported praziquantel-related visual adverse events, but evidence is limited and remains inconclusive. There was paucity of data on long term adverse events, and events in co-morbidity, polypharmacy, co-infection with taeniasis. Generally, adverse events research in this area lacked methodological rigour.ConclusionsThe evidence generated from this review involving millions of people and millions of doses from different geographic locations with mostly mild-to-moderate and transient adverse events shows praziquantel is safe. However, given that the primary studies included in the review had design issues, including over 95% assessing adverse events over very short follow-up times, means serious long-term adverse events would have been missed. Also, the fact that some pregnant women who received praziquantel experienced serious events including miscarriages, foetal deaths and congenital anomalies calls for caution in the inclusion of pregnant women, particularly in their first trimester, in preventive chemotherapy campaigns. Additionally, the studies that reported severe visual adverse events raise safety concerns. Praziquantel is now offered repeatedly in endemic communities and the fact that in some settings up to 90% of those without infection could be offered the drug and the fact that there was no study that compared safety between infected and non-infected recipients, warrants further research. Evidence on safety in pregnant women and their foetuses, co-morbidity, polypharmacy, co-infection with taeniasis, as well as co-administration with drugs used in other preventive chemotherapy programmes, remain inconclusive and further research with long follow-up that should include blood chemistry analysis to provide additional evidence on long term safety, is warranted. This systematic review has exposed the lack of methodological rigour in adverse events studies and recommends future research should use robust and standardized design, methods, conduct and reporting.

The role of patent foramen ovale (PFO) in cryptogenic stroke (CS) is debated. Tools to predict PFO occurrence and attributable fraction are needed to guide cost-effective diagnostics and treatment. Risk of Paradoxical Embolism (RoPE) score relies on neuroimaging findings, which might be inconclusive in up to 30% of cases. We developed a clinical-based easy tool to predict the presence and attributable fraction of PFO in CS patients, without using neuroimaging. The clinical RoPE (cRoPE) score, ranging 1–10, was elaborated through Delphi method from the original RoPE score, replacing cortical infarction with the Oxfordshire Community Stroke Project (OCSP) classification (lacunar stroke = 0 points, other subtypes = 1 point). Then, from the SISIFO (Studio Italiano di prevalenza nello Stroke Ischemico di pervieta del Forame Ovale, or Prevalence of Patent Foramen Ovale in Ischemic Stroke in Italy) study, a multicenter, prospective study on consecutive acute ischemic stroke patients (n = 1130) classified by Trial of Org 10172 in Acute Stroke Treatment (TOAST) and OCSP criteria and undergoing PFO testing, we selected the VV-CDC cohort (Vibo Valentia, Citta di Castello, n = 323) to test the accuracy of cRoPE in predicting PFO detection. We compared cRoPE with RoPE to verify cRoPE reliability. Finally, we tested, through ROC analysis, the performance of cRoPE depending on TOAST classification. Overall, PFO was detected in 21% in VV-CDC and in 23.4% in remaining SISIFO cohort (n = 807). cRoPEAUC and RoPEAUC were similar in VV-CDC. cRoPE performance was comparable with RoPE among CS (cRoPEAUC 0.76, 95%CI 0.67–0.85, RoPEAUC 0.75, 95%CI 0.66–0.84). Moving to the remaining SISIFO cohort, cRoPE confirmed satisfactory accuracy in predicting PFO detection in CS patients (cRoPEAUC 0.71, 95%CI 0.66–0.78, p = 0.032). Conclusions: cRoPE might help in stratification of patients with CS, allowing accurate esteem of the likelihood of PFO to be found, especially in cases when neuroimaging is inconclusive.

Since closure has restrictive eligibility criteria, the vast majority of patients with cryptogenic stroke and patent foramen ovale (PFO) receive medical treatment. However, the optimal antithrombotic strategy is still unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to define risk/benefit profile of anticoagulation compared with antiplatelet treatment in PFO-related stroke. Systematic review protocol was registered in PROSPERO (CRD42019117559). Following PRISMA guidelines, we searched MEDLINE, EMBASE, and Cochrane CENTRAL database (2000–2019) for RCTs randomly allocating patients with cryptogenic stroke and PFO to medical treatment. Risk of bias was assessed with Cochrane RoB tool. Main outcomes were stroke recurrence and major bleeding. RoPE score-dependent analysis was implemented to define a possible role for patient selection. Five RCTs met inclusion criteria (3 high-, 1 fair-, 1 poor-quality RCTs). Overall, meta-analysis included 1565 patients (mean age 55.5 years), 753 (48.1%) receiving anticoagulation. Compared with antiplatelet treatment, anticoagulation conveyed no net benefit in prevention of recurrent stroke (OR = 0.66, 95% CI 0.41–1.07, pheterogeneity = 0.46), and associated with a non-significant higher risk of major bleeding (OR = 1.64, 95% CI 0.79–3.43, pheterogeneity = 0.57). In patients with high RoPE score, anticoagulation significantly reduced the risk of recurrent stroke (OR = 0.22, 95% CI 0.06–0.8, pheterogeneity = 0.88). Our meta-analysis shows that anticoagulation confers no net benefit in recurrent stroke prevention over antiplatelets in patients with PFO-related stroke. RoPE score might help in selecting patients benefiting from anticoagulation, but further trials are needed to delineate risk/benefit profile of anticoagulation.

In this study, we sought for a cerebrospinal fluid (CSF) metabolomic fingerprint in Alzheimer's disease (AD) patients characterized, according to the clinical picture and CSF AD core biomarkers (Aβ42, p-tau, and t-tau), both at pre-dementia (mild cognitive impairment due to AD, MCI-AD) and dementia stages (ADdem) and in a group of patients with a normal CSF biomarker profile (non-AD) using untargeted 1H nuclear magnetic resonance (NMR) spectroscopy-based metabolomics. This is a retrospective study based on two independent cohorts: a Dutch cohort, which comprises 20 ADdem, 20 MCI-AD, and 20 non-AD patients, and an Italian cohort, constituted by 14 ADdem and 12 non-AD patients. 1H NMR CSF spectra were analyzed using OPLS-DA. Metabolomic fingerprinting in the Dutch cohort provides a significant discrimination (86.1% accuracy) between ADdem and non-AD. MCI-AD patients show a good discrimination with respect to ADdem (70.0% accuracy) but only slight differences when compared with non-AD (59.6% accuracy). Acetate, valine, and 3-hydroxyisovalerate result to be altered in ADdem patients. Valine correlates with cognitive decline at follow-up (R = 0.53, P = 0.0011). The discrimination between ADdem and non-AD was confirmed in the Italian cohort. The CSF metabolomic fingerprinting shows a signature characteristic of ADdem patients with respect to MCI-AD and non-AD patients.

Purpose Critical care units, such as heart failure units, house inpatients with a compromised general health status that requires rigorous prevention of further complications. Oral health infections that gain access through the bloodstream or airway might represent such potential complications (eg, endocarditis pneumonia). Avoiding these critical occurrences requires that adequate oral health care be provided by nursing personnel. Here we assessed the knowledge of oral health care practices by nurses working in three Italian heart failure units in Umbria, Italy. Design This was a cross-sectional study. Methods Forty-four nurses were interviewed using a six-item modified Adams' questionnaire on the topic of oral health care. A multidisciplinary panel of experts established the criteria for answer correctness based on the most relevant dentistry literature evidence and judged each reply. The expected percentage of correctly replying nurses was 75%, and significant differences from this expected probability were calculated with one-sided binomial probability tests. Cronbach's α method was used to establish the questionnaire's internal consistency (reliability). Results For five out of six questionnaire items, the percentage of nurses who correctly answered was significantly lower than the expected value of probability. Lack of knowledge was found for usefulness of checking the patients' mouths (p=0.003), the most relevant lesions affecting the mouth (p=0.0001), the tools/solutions for cleaning the mouth and dentures (p= 0.0416), and drugs that affect the mouth and their side effects (p Conclusion In this study, few nurses working in heart failure units showed both an adequate willingness to check inpatients and a good knowledge of oral health care (significantly lower than the expected 75%). Further studies that use validated questionnaires and include more participants should be conducted to confirm and elaborate on our preliminary data.

Background The aim of our study was to identify independent predictors of functional decline in older nursing home (NH) residents, taking into account both resident and facility characteristics. Methods Longitudinal observational study involving 1,760 older (≥65 y) residents of NH participating in the SHELTER* study (57 NH in eight countries). All residents underwent a comprehensive geriatric assessment using the interRAI LTCF. Functional decline was defined as an increase of at least one point in the MDS Long Form ADL scale during a 1 year follow-up. Facility and country effects were taken into account. Results During the study period 891 (50.6%), NH residents experienced ADL decline. Residents experiencing ADL decline were older, had lower disability at baseline, were more frequently affected by severe dementia and by urinary incontinence, and used more antipsychotics. In the mixed-effect logistic regression model, factors independently associated with a higher risk of functional decline were dementia and urinary incontinence, whereas the presence of a geriatrician was a protective factor. Conclusions Both resident and facility characteristics are associated with the risk of functional decline in NH residents. Increasing the quality of healthcare by involving a geriatrician in residents’ care might be an important strategy to improve the outcome of this vulnerable population.

We have been experiencing a global pandemic with baleful consequences for mankind, since the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first identified in Wuhan of China, in December 2019. So far, several potential risk factors for SARS-CoV-2 infection have been identified. Among them, the role of ABO blood group polymorphisms has been studied with results that are still unclear. The aim of this study was to collect and meta-analyze available studies on the relationship between SARS-CoV-2 infection and different blood groups, as well as Rhesus state. We performed a systematic search on PubMed/MEDLINE and Scopus databases for published articles and preprints. Twenty-two studies, after the removal of duplicates, met the inclusion criteria for meta-analysis with ten of them also including information on Rhesus factor. The odds ratios (OR) and 95% confidence intervals (CI) were calculated for the extracted data. Random-effects models were used to obtain the overall pooled ORs. Publication bias and sensitivity analysis were also performed. Our results indicate that blood groups A, B and AB have a higher risk for COVID-19 infection compared to blood group O, which appears to have a protective effect: (i) A group vs O (OR = 1.29, 95% Confidence Interval: 1.15 to 1.44), (ii) B vs O (OR = 1.15, 95% CI 1.06 to 1.25), and (iii) AB vs. O (OR = 1.32, 95% CI 1.10 to 1.57). An association between Rhesus state and COVID-19 infection could not be established (Rh+ vs Rh- OR = 0.97, 95% CI 0.83 to 1.13).

We have been experiencing a global pandemic with baleful consequences for mankind, since the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first identified in Wuhan of China, in December 2019. So far, several potential risk factors for SARS-CoV-2 infection have been identified. Among them, the role of ABO blood group polymorphisms has been studied with results that are still unclear. The aim of this study was to collect and meta-analyze available studies on the relationship between SARS-CoV-2 infection and different blood groups, as well as Rhesus state. We performed a systematic search on PubMed/MEDLINE and Scopus databases for published articles and preprints. Twenty-two studies, after the removal of duplicates, met the inclusion criteria for meta-analysis with ten of them also including information on Rhesus factor. The odds ratios (OR) and 95% confidence intervals (CI) were calculated for the extracted data. Random-effects models were used to obtain the overall pooled ORs. Publication bias and sensitivity analysis were also performed. Our results indicate that blood groups A, B and AB have a higher risk for COVID-19 infection compared to blood group O, which appears to have a protective effect. An association between Rhesus state and COVID-19 infection could not be estabished.

The objective of this work was to estimate the diagnostic accuracy of RT-PCR and Lateral flow immunoassay tests (LFIA) for COVID-19, depending on the time post symptom onset. Based on the cross-classified results of RT-PCR and LFIA, we used Bayesian latent class models (BLCMs), which do not require a gold standard for the evaluation of diagnostics. Data were extracted from studies that evaluated LFIA (IgG and/or IgM) assays using RT-PCR as the reference method. The cross-classified results of LFIA and RT-PCR were analysed separately for the first, second and third week post symptom onset. The SeRT-PCR was 0.695 (95% probability intervals: 0.563; 0.837) for the first week and remained similar for the second and the third week. The SeIgG/M was 0.318 (0.229; 0.416) for the first week and increased steadily. It was 0.755 (0.673; 0.829) and 0.927 (0.881; 0.965) for the second and third week, respectively. Both tests had a high to absolute Sp, with point median estimates for SpRT-PCR being consistently higher. SpRT-PCR was 0.990 (0.980; 0.998) for the first week. The corresponding value for SpIgG/M was 0.962 (0.905; 0.998). Further, Sp estimates for each test did not differ between weeks. BLCMs provide a valid and efficient alternative for evaluating the rapidly evolving diagnostics for COVID-19, under various clinical settings and for different risk profiles.

Background HIV/AIDS remains a threat to global development and human security. Sub-Saharan Africa is the worst affected, with an estimated 25.7 million people living with HIV as at 2018 and the youth accounting for 33% of new infections. Despite the high proportion, there is paucity of data on testing and counselling among the youth and which factors influence their decision are largely unknown. This study assessed factors influencing uptake of HIV testing and counselling among the youth aged 15 to 24 years in Kintampo South District in Ghana. Methods This was a cross-sectional study involving the youth who have lived in the Kintampo South District for not less than 6 months. A total of 309 respondents aged 15 to 24 years were drawn from four sub-districts of the six administrative sub-districts by simple random sampling. Simple proportions and logistic regression analyses were performed to elucidate factors influencing uptake of HIV testing and counselling. The level of acceptable statistical significance used was p

Background Seroprevalence of SARS Cov-2 provides a good indication of the extent of exposure and spread in the population, as well as those likely to benefit from a vaccine candidate. To date, there is no published or ongoing systematic review on the seroprevalence of COVID-19 in Low- and Middle-Income Countries (LMICs). This systematic review and meta-analysis will estimate SARS Cov-2 seroprevalence and the risk factors for SARS Cov-2 infection in LMICs.Methods We will search PubMed, EMBASE, WHO COVID-19 Global research database, Google Scholar, the African Journals Online, LILAC, HINARI, medRxiv, bioRxiv and Cochrane Library for potentially useful studies on seroprevalence of COVID-19 in LMICs from December 2019 to December 2020 without language restriction. Two authors will independently screen all the articles, select studies based on pre-specified eligibility criteria and extract data using a pre-tested data extraction form. Any disagreements will be resolved through discussion between the authors. The pooled seroprevalence of SARS CoV-2 for people from LMICs will be calculated. Random effects model will be used in case of substantial heterogeneity in the included studies, otherwise fixed-effect model will be used. A planned subgroup, sensitivity and meta-regression analyses will be performed. For comparative studies, the analyses will be performed using Review Manager v 5.4; otherwise, STATA 16 will be used. All effect estimates will be presented with their confidence intervals.Discussion The study will explore and systematically review empirical evidence on SARS Cov-2 seroprevalence in LMICs, and to assess the risk factors for SARS Cov-2 infection in Low Middle Income Countries in the context of rolling out vaccines in these countries. Finally, explore risk classifications to help with the rolling out of vaccines in LMICs.Systematic review registration: The protocol for this review has been registered in PROSPERO (CRD422020221548).

In the management of Parkinson's disease, reliable diagnostic and prognostic biomarkers are urgently needed. The diagnosis of Parkinson's disease mostly relies on clinical symptoms, which hampers the detection of the earliest phases of the disease-the time at which treatment with forthcoming disease-modifying drugs could have the greatest therapeutic effect. Reliable prognostic markers could help in predicting the response to treatments. Evidence suggests potential diagnostic and prognostic value of CSF and blood biomarkers closely reflecting the pathophysiology of Parkinson's disease, such as α-synuclein species, lysosomal enzymes, markers of amyloid and tau pathology, and neurofilament light chain. A combination of multiple CSF biomarkers has emerged as an accurate diagnostic and prognostic model. With respect to early diagnosis, the measurement of CSF α-synuclein aggregates is providing encouraging preliminary results. Blood α-synuclein species and neurofilament light chain are also under investigation because they would provide a non-invasive tool, both for early and differential diagnosis of Parkinson's disease versus atypical parkinsonian disorders, and for disease monitoring. In view of adopting CSF and blood biomarkers for improving Parkinson's disease diagnostic and prognostic accuracy, further validation in large independent cohorts is needed.

Cognitive impairment (CI) is a disabling symptom of multiple sclerosis (MS). Axonal damage disrupts neural circuits and may play a role in determining CI, but its detection and monitoring are not routinely performed. Cerebrospinal fluid (CSF) neurofilament light chain (NfL) is a promising marker of axonal damage in MS. To retrospectively examine the relationship between CSF NfL and CI in MS patients. CSF NfL concentration was measured in 28 consecutive newly diagnosed MS patients who underwent a neuropsychological evaluation with the Brief Repeatable Battery of Neuropsychological tests (BRBN). CSF NfL was higher in patients with overall CI (947.8 ± 400.7 vs 518.4 ± 424.7 pg/mL, p

To create an objective rating tool for hemifacial spasm (HFS) and validate it on a cohort of patients. A panel of movement disorders specialists elaborated, through the Delphi method, the Hemifacial Spasm Grading Scale (HSGS). The validity of the scale was tested in a longitudinal, prospective observational study, with standardized video recording protocol before and after botulinum neurotoxin (BoNT) treatment. The video recordings obtained from each patient were then independently assessed with HSGS by three blinded raters. The scale was compared to patient-reported HFS-7 scale and to the clinical grading of spasm intensity scale. Intra-rater reproducibility ranged between ICC 0.73 (95% CI = 0.54–0.86) and 0.83 (0.68–0.92) and inter-rater reproducibility between 0.62 (95% CI = 0.44–0.77) and 0.82 (0.69–0.90). HSGS scores correlated with clinical grading of spasm intensity scale scores, but not with HFS-7. HSGS confirmed BoNT efficacy, with scores lowering at 1 month from treatment. HSGS represents an objective, quick and reliable scale for the assessment of HFS, and might be useful to monitor BoNT treatment efficacy over time.

Objectives To evaluate whether early tracheostomy is associated with better outcomes in mechanical ventilation–dependent patients after cardiac surgery compared with a late tracheostomy. Design Retrospective, observational study. Setting Cardiac surgical intensive care unit (ICU) of a tertiary care center. Participants All patients who underwent tracheostomy after cardiac surgery between 2004 and 2015 were subdivided into the following 2 groups according to the timing of tracheostomy: “early” if the tracheostomy was performed before the 14th postoperative day and “late” from the 14th postoperative day onward. Interventions Early versus late tracheostomy. Measurements and Main Results During the study period, 112 of 5,148 patients (2.2%) underwent tracheostomy after cardiac surgery. Early tracheostomy was performed in 62 patients, and 50 patients underwent late tracheostomy. Both groups of patients were similar in terms of preoperative and intraoperative characteristics, perioperative risk, and postoperative complications. Patients in the early group had a significantly shorter ventilation time (31.3 ± 23.6 v 39.4 ± 22.4 d; p = 0.034), shorter ICU stay (37.7 ± 21.7 v 46.4 ± 25 d; p = 0.025), and a shorter hospital stay (53.4 ± 29.3 v 66.8 ± 38.5 d; p = 0.020). There were no intergroup differences in weaning rates and in-hospital, 3-month, and 1- and 2-year mortality. Conclusions In this study, early tracheostomy after cardiac surgery in patients requiring prolonged mechanical ventilation was associated with a shorter ventilation time and ICU and hospital stay, but did not result in a lower in-hospital and long-term mortality rate.

Background Alzheimer’s disease (AD) pathology begins several years before the clinical onset. The long preclinical phase is composed of three stages according to the 2011National Institute on Aging and Alzheimer’s Association (NIA-AA) criteria, followed by mild cognitive impairment (MCI), a featured clinical entity defined as “due to AD”, or “prodromal AD”, when pathophysiological biomarkers (i.e., cerebrospinal fluid or positron emission tomography with amyloid tracer) are positive. In the clinical setting, there is a clear need to detect the earliest symptoms not yet fulfilling MCI criteria, in order to proceed to biomarker assessment for diagnostic definition, thus offering treatment with disease-modifying drugs to patients as early as possible. According to the available evidence, we thus estimated the prevalence and risk of progression at each preclinical AD stage, with special interest in Stage 3. Methods Cross-sectional and longitudinal studies published from April 2008 to May 2018 were obtained through MEDLINE-PubMed, screened, and systematically reviewed by four independent reviewers. Data from included studies were meta-analyzed using random-effects models. Heterogeneity was assessed by I2 statistics. Results Estimated overall prevalence of preclinical AD was 22% (95% CI = 18–26%). Rate of biomarker positivity overlapped in cognitively normal individuals and people with subjective cognitive decline. The risk of progression increases across preclinical AD stages, with individuals classified as NIA-AA Stage 3 showing the highest risk (73%, 95% CI = 40–92%) compared to those in Stage 2 (38%, 95% CI = 21–59%) and Stage 1 (20%, 95% CI = 10–34%). Conclusion Available data consistently show that risk of progression increases across the preclinical AD stages, where Stage 3 shows a risk of progression comparable to MCI due to AD. Accordingly, an effort should be made to also operationalize the diagnostic work-up in subjects with subtle cognitive deficits not yet fulfilling MCI criteria. The possibility to define, in the clinical routine, a patient as “pre-MCI due to AD” could offer these subjects the opportunity to use disease-modifying drugs at best. Electronic supplementary material The online version of this article (10.1186/s13195-018-0459-7) contains supplementary material, which is available to authorized users.

Although amyloid pathology plays a role in epilepsy, little is known about the relationship between beta amyloid and progression to Alzheimer's disease (AD) among patients with late-onset epilepsy of unknown origin (LOEU). This multicenter, observational, prospective study enrolled 40 consecutive nondemented adults diagnosed with LOEU, together with 43 age- and sex-matched healthy controls. All patients completed neuropsychological tests, core CSF AD biomarkers assessment (Aβ1-42, total tau, and phosphorylated tau), and follow-up for a mean of 3 years to verify cognitive decline. Despite age and baseline cognitive performance were similar to healthy controls, patients with LOEU had significant prevalence of CSF pathological Aβ1-42 (

Background. This paper presents, for the first time, the Epidemic Volatility Index (EVI), a conceptually simple, early warning tool for emerging epidemic waves. Methods. EVI is based on the volatility of the newly reported cases per unit of time, ideally per day, and issues an early warning when the rate of the volatility change exceeds a threshold. Results. Results from the COVID-19 epidemic in Italy and New York are presented here, while daily updated predictions for all world countries and each of the United States are available online. Interpretation. EVI’s application to data from the current COVID-19 pandemic revealed a consistent and stable performance in terms of detecting oncoming waves. The application of EVI to other epidemics and syndromic surveillance tasks in combination with existing early warning systems will enhance our ability to act fast and optimize containment of outbreaks.

BackgroundThe WHO-recommended prevalence thresholds for deciding schistosomiasis mass drug administration (MDA) are based on anecdotal evidence and may mislead. This study systematically synthesized evidence to generate a single optimal ‘global’ prevalence threshold that should guide schistosomiasis MDA programmes worldwide.MethodsWe searched several databases from 1978 to 31st October 2021 without language restriction. Two reviewers selected studies, extracted data, and assessed risk of bias using relevant risk of bias tools, and resolved disagreements through discussion. The review followed best practices protocols and guidelines. Data were analysed and presented as prevalence reduction (PR) and relative risk (RR) for dichotomous outcomes or mean difference for continuous outcomes, each presented with their 95% confidence intervals (CI). Meta-regression of observations on prevalence rates and intensity of infection were performed to assess the effect of repeat MDA over time. Sensitivity analysis was performed to test the robustness of the results to the risk of bias components. The overall level of evidence was graded using GRADE.FindingsOf the 1,232 studies retrieved, 38 met our inclusion criteria and 34 were included in the meta-analysis. No direct relation was observed between prevalence and intensity of infection. Praziquantel reduced prevalence of S. mansoni in school age children (SAC) at 12 months (RR 0.56, 95% CI 0.46 to 0.69; 14 studies, n=86,073); 24 months (RR 0.46; 95% CI 0.32 to 0.66; 14 studies; n=83,721); 36 months (RR 0.44, 95% CI 0.33 to 0.58; 7 studies, n=70,933) and 48 months (RR 0.25, 95% CI 0.11 to 0.59; 5 studies; n=27,483). Similarly for S. haematobium, there were reductions in prevalence in school age children (SAC) at 12 months (RR 0.38, 95% CI 0.28 to 0.52; 8 studies, n=37,868); at 24 months (RR 0.30; 95% CI 0.30─0.52; 7 studies; n=37,107); and 36 months (RR 0.39, 95% CI 0.21 to 0.71; 5 studies, n=28,146). There was no significant reduction in prevalence at 48 months (2 studies, n=10,954). Further analyses were performed from a series of prevalence thresholds created from the data at 5%, 10%, 15%, 20%, 30% and ≥40% and the results showed differences in the effect of MDA when each threshold was applied in the regression model. For annual MDA involving SAC, school-based treatment (SBT) appeared to perform better than community-wide treatment (CWT) in terms of prevalence reduction; but this could be subject to the frequency of treatment and retreatment applied in SAC compared to CWT. Using the optimal prevalence threshold of 10%, the model suggested it will take over 10 years to bring the prevalence of schistosomiasis to 1% for S. haematobium and up to 15 years for S. mansoni with repeated annual MDA.InterpretationThis systematic review and meta-analysis provides evidence that 10% prevalence is the optimum that should be used as the ‘standard global threshold’ for implementing MDA in endemic countries.FundingThis work was commissioned and supported by the World Health Organization, Geneva, Switzerland as part of evidence-based schistosomiasis guideline development.Research in contextEvidence before this studyCurrently, the prevalence thresholds used in implementing mass drug administration within the preventive chemotherapy strategy for schistosomiasis control are based on anecdotal evidence and unreliable. We identified relevant studies regardless of language or publication status (published, unpublished, in press, and ongoing). We searched PubMed, CINAHL and LILACS from 1978 to 31st October 2021 without language restriction. We also searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2021), mRCT, Hinari, the WHO Library Database, Africa Journals Online and Google Scholar. Experts in the field of schistosomiasis were contacted, preprint repositories were searched and the reference lists of articles were reviewed for additional or unpublished data. This study was commissioned by the WHO to provide systematically synthesized evidence to inform on a single global prevalence threshold that should be applied by endemic countries when deciding MDA campaigns for the prevention and control of schistosomiasis.Added value of this studyThis is the first systematic review and meta-analysis commissioned by the WHO to determine a single prevalence threshold that should be employed by endemic countries for the implementation of global schistosomiasis mass drug administration. This study pooled data involving thousands of participants across thousands of villages from all endemic settings, making it unique in terms of statistical power and generalizability of the main findings and conclusions. The study used PICOS (P-population, I-intervention, C-comparator, O-outcomes and S-study) to formulate an appropriate review question, clear objectives, stringent inclusion and exclusion criteria as well as rigorous quality assessment and data synthesis, following strictly best practices for preparing and reporting systematic reviews. The search has been very comprehensive including all relevant electronic databases and non-electronic sources, done in close collaboration with experienced information specialist. The review process ensured meticulous attention to details, making the necessary effort to minimize bias, carrying out aspects of the review independently by the reviewers and addressing disagreements through discussions between the reviewers. Given the geographical variations, and differences in the levels of baseline endemicities, diagnostic criteria, age groups treated and follow-up times across studies, this necessitated robust sub-group analyses to detect any sub-group effects. We ran meta-regression analyses to identify any potentially useful trends, and tested the robustness of effect estimates from sensitivity analyses. We have assembled world-class experts from diverse backgrounds and geographical locations, including epidemiologists, evidence synthesis specialists, economists, allied health professionals, statisticians, biomedical scientists, clinicians and non-medical experts to produce this innovative, demand-driven, policy- and context-relevant systematic review and meta-analysis that will help guide policy and practice in the global control of schistosomiasis.Implications of all the available evidenceOur review provides evidence that 10% baseline prevalence is the minimum optimal threshold that should be used to decide the implementation of MDA programmes in schistosomiasis endemic countries. Praziquantel is effective in reducing the prevalence of schistosomiasis at 12 months, but incremental benefit of repeated annual treatment appears to be minimal after 12 months. Effectiveness depends on several factors, which are difficult to disentangle, however, the rate at which prevalence decreases does not appear to be influenced by baseline intensity of infection and treatment approach (whether whole community or school-based). From exploratory analysis, intensity of infection appears to be more stable than prevalence for assessing outcome of MDA. Therefore, further research is needed to determine an optimal intensity threshold and compare it with prevalence threshold. In terms of policy, the difficulty in achieving elimination with mass drug administration alone means that integration of non-pharmacological interventions such access to clean water, improved sanitation, hygiene education (WASH) and snail control to complement MDA if elimination is to be achieved.This systematic review was registered in PROSPERO ̶ CRD422020221548.

BACKGROUND AND PURPOSE A reduction of retinal thickness and an alteration of retinal perfusion have been found in Alzheimer disease (AD). Nowadays, retinal layers and retinal perfusion can be evaluated by means of noninvasive imaging techniques, namely, optical coherence tomography (OCT) and OCT-angiography (OCT-A). Here, we have compared the retinal thickness and the perfusion index, measured by means of OCT and OCT-A, in patients with mild cognitive impairment due to AD (MCI-AD) and in age- and sex-matched cognitively healthy controls. METHODS Twenty-four MCI-AD patients and 13 control subjects were enrolled. MCI-AD patients underwent lumbar puncture; all of them showed a cerebrospinal fluid (CSF) profile compatible with AD. OCT was used for evaluating retinal volumes and thicknesses, whereas with OCT-A we measured fractal dimension (FD), vascular perfusion density (VPD), and vessel length density (VLD) of superficial capillary plexus (SCP), intermediate capillary plexus (ICP), deep capillary plexus (DCP), and choriocapillaris. The comparisons between groups were made after adjustment for age, diabetes, and hypertension. RESULTS A significant reduction of SCP-VLD (p = 0.012), ICP-VPD (p = 0.015), ICP-VLD (p = 0.004), DCP-VPD (p = 0.012), and DCP-VLD (p = 0.009) was found in MCI-AD patients compared to controls. Conversely, FD was higher in MCI-AD than in controls (p = 0.044). CSF Aβ42/total tau negatively correlated with FD (r = -0.51, p = 0.010). CONCLUSIONS OCT-A might have a potential role in detecting new noninvasive biomarkers for early AD detection. Retinal VPD might identify amyloid angiopathy-related chronic injury, and FD could show early vessel recruitment as a compensative mechanism at disease onset. Further studies will be needed to confirm these findings.

Impaired olfactory function is one of the main features of Parkinson’s disease. However, how peripheral olfactory structures are involved remains unclear. Using diffusion tensor imaging fiber tracking, we investigated for MRI microstructural changes in the parkinsonian peripheral olfactory system and particularly the olfactory tract, in order to seek a better understanding of the structural alternations underlying hyposmia in Parkinson’s disease. All patients were assessed utilizing by the Italian Olfactory Identification Test for olfactory function and the Unified Parkinson’s Disease Rating Scale-III part as well as Hoehn and Yahr rating scale for motor disability. Imaging was performed on a 3 T Clinical MR scanner. MRI data pre-processing was carried out by DTIPrep, diffusion tensor imaging reconstruction, and fiber tracking using Diffusion Toolkit and tractography analysis by TrackVis. The following parameters were used for groupwise comparison: fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity, and tract volume. Overall 23 patients with Parkinson’s disease (mean age 63.6 ± 9.3 years, UPDRS-III 24.5 ± 12.3, H&Y 1.9 ± 0.5) and 18 controls (mean age 56.3 ± 13.7 years) were recruited. All patients had been diagnosed hyposmic. Diffusion tensor imaging analysis of the olfactory tract showed significant fractional anisotropy, and tract volume decreases for the Parkinson’s disease group compared with controls (P < 0.05). Fractional anisotropy and age, in the control group, were significant for multiple correlations (r = − 0.36, P < 0.05, Spearman’s rank correlation). Fiber tracking diffusion tensor imaging analysis of olfactory tract was feasible, and it could be helpful for characterizing hyposmia in Parkinson’s disease.