Search

Summary Background Mortality in patients with COVID-19 pneumonia and systemic hyperinflammation is high. We aimed to examine whether mavrilimumab, an anti-granulocyte–macrophage colony-stimulating factor receptor-α monoclonal antibody, added to standard management, improves clinical outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation. Methods This single-centre prospective cohort study included patients aged 18 years or older who were admitted to San Raffaele Hospital (Milan, Italy) with severe COVID-19 pneumonia, hypoxia, and systemic hyperinflammation. Patients received a single intravenous dose (6 mg/kg) of mavrilimumab added to standard care given by the hospital at the time. The control group consisted of contemporaneous patients with similar baseline characteristics who received standard care at the same hospital. The main outcome was time to clinical improvement (defined as improvement of two or more points on the seven-point ordinal scale of clinical status). Other outcomes included proportion of patients achieving clinical improvement, survival, mechanical ventilation-free survival, and time to fever resolution. Adverse events were monitored daily. Findings Between March 17 and April 15, 2020, 13 non-mechanically ventilated patients (median age 57 years [IQR 52–58], 12 [92%] men) received mavrilimumab and 26 patients (median age 60 [IQR 53–67], 17 [65%] men) in the control group received standard care. During the 28-day follow-up, no patients in the mavrilimumab group died, and seven (27%) patients in the control group died (p=0·086). At day 28, all patients in the mavrilimumab group and 17 (65%) patients in the control group showed clinical improvement (p=0·030), with earlier improvement in the mavrilimumab than in the control group (mean time to improvement 8 days [IQR 5 to 11] vs 19 days [11 to >28], p=0·0001). By day 28, one (8%) patient in the mavrilimumab group progressed to mechanical ventilation compared with nine (35%) patients in the control group who progressed to mechanical ventilation or died (p=0·14). By day 14, fever resolved in ten (91%) of 11 febrile patients in the mavrilimumab group, compared with 11 (61%) of 18 febrile patients in the control group (p=0·18); fever resolution was faster in mavrilimumab recipients versus controls (median time to resolution 1 day [IQR 1 to 2] vs 7 days [3 to >14], p=0·0093). Mavrilimumab was well tolerated, with no infusion reactions. Three (12%) patients in the control group developed infectious complications. Interpretation Mavrilimumab treatment was associated with improved clinical outcomes compared with standard care in non-mechanically ventilated patients with severe COVID-19 pneumonia and systemic hyperinflammation. Treatment was well tolerated. Confirmation of efficacy requires controlled testing. Funding IRCCS San Raffaele Scientific Institute.

Summary Background Mortality of patients with coronavirus disease 2019 (COVID-19), acute respiratory distress syndrome (ARDS), and systemic inflammation is high. In areas of pandemic outbreak, the number of patients can exceed maximum capacity of intensive care units (ICUs), and, thus, these individuals often receive non-invasive ventilation outside of the ICU. Effective treatments for this population are needed urgently. Anakinra is a recombinant interleukin-1 receptor antagonist that might be beneficial in this patient population. Methods We conducted a retrospective cohort study at the San Raffaele Hospital in Milan, Italy. We included consecutive patients (aged ≥18 years) with COVID-19, moderate-to-severe ARDS, and hyperinflammation (defined as serum C-reactive protein ≥100 mg/L, ferritin ≥900 ng/mL, or both) who were managed with non-invasive ventilation outside of the ICU and who received standard treatment of 200 mg hydroxychloroquine twice a day orally and 400 mg lopinavir with 100 mg ritonavir twice a day orally. We compared survival, mechanical ventilation-free survival, changes in C-reactive protein, respiratory function, and clinical status in a cohort of patients who received additional treatment with anakinra (either 5 mg/kg twice a day intravenously [high dose] or 100 mg twice a day subcutaneously [low dose]) with a retrospective cohort of patients who did not receive anakinra (referred to as the standard treatment group). All outcomes were assessed at 21 days. This study is part of the COVID-19 Biobank study, which is registered with ClinicalTrials.gov , NCT04318366 . Findings Between March 17 and March 27, 2020, 29 patients received high-dose intravenous anakinra, non-invasive ventilation, and standard treatment. Between March 10 and March 17, 2020, 16 patients received non-invasive ventilation and standard treatment only and comprised the comparison group for this study. A further seven patients received low-dose subcutaneous anakinra in addition to non-invasive ventilation and standard treatment; however, anakinra treatment was interrupted after 7 days because of a paucity of effects on serum C-reactive protein and clinical status. At 21 days, treatment with high-dose anakinra was associated with reductions in serum C-reactive protein and progressive improvements in respiratory function in 21 (72%) of 29 patients; five (17%) patients were on mechanical ventilation and three (10%) died. In the standard treatment group, eight (50%) of 16 patients showed respiratory improvement at 21 days; one (6%) patient was on mechanical ventilation and seven (44%) died. At 21 days, survival was 90% in the high-dose anakinra group and 56% in the standard treatment group (p=0·009). Mechanical ventilation-free survival was 72% in the anakinra group versus 50% in the standard treatment group (p=0·15). Bacteraemia occurred in four (14%) of 29 patients receiving high-dose anakinra and two (13%) of 16 patients receiving standard treatment. Discontinuation of anakinra was not followed by inflammatory relapses. Interpretation In this retrospective cohort study of patients with COVID-19 and ARDS managed with non-invasive ventilation outside of the ICU, treatment with high-dose anakinra was safe and associated with clinical improvement in 72% of patients. Confirmation of efficacy will require controlled trials. Funding None.

The A-ADS is one the first validated measures of attitudes of dementia in adolescents, though further validation is needed. 630 adolescents were recruited from secondary schools in England. A Principal Component Analysis was completed (n=230) followed by a Confirmatory Factor Analysis (n=400). Reducing the A-ADS into a single factor, 13-item measure (Brief A-ADS) improved the model fit of the measure (χ2 =182.75, DF=65, CMIN/DF= 2.81, p

Background: Tinnitus is believed to cause significant psychological distress leading to impairment in quality of life (QOL). Purpose: To assess the negative impact of tinnitus on patient’s QOL and discuss the management approach of tinnitus patient. Method: A cross-sectional study was conducted within one year duration on 88 patients who experienced tinnitus. Patients from Otorhinolaryngology clinic, Universiti Kebangsaan Malaysia Medical Centre (UKMMC) were evaluated based on socio-demographic data, clinical data and QOL. QOL was assessed using Tinnitus Handicap Inventory (THI), a self-report questionnaire measuring 3 domains of QOL: functional, emotional and catastrophic scales. Result: Respondents consisted of 35 males (39.8%) and 53 females (60.2%), with mean age of 57.9±13.9 years old. Pure tone audiometry should be done at least once during the follow up period. Patients with persistent tinnitus had significantly higher mean THI total scores (p=0.042) and emotional subscale score (p=0.037) compared to patients with intermittent tinnitus. However, there were no significant associations between gender, duration of tinnitus and laterality of tinnitus with patient’s THI score. Discussion: All patients should have good history taking, proper physical examination and investigation. Those without the primary cause of tinnitus would be given tinnitus activity treatment by good counselling on tinnitus. Patient with vascular disorder would be given conservative treatment. Conclusion: Magnetic resonance imaging was indicated in asymmetrical hearing loss with tinnitus. Computed tomography scan with contrast was indicated when there is pulsatile tinnitus with/without abnormal ear finding. Patients with high grades THI questionnaire would be referred to psychiatrist for further assessment. ABSTRAK Latar belakang: Tinitus diyakini dapat menyebabkan stress psikologi yang signifikan sehingga mengakibatkan penurunan kualitas hidup seseorang ( Quality of Life / QOL). Tujuan: Menilai dampak negatif tinitus pada kualitas hidup penderita dan merencanakan penatalaksanaannya. Metode: Penelitian ini merupakan studi potong lintang pada 88 penderita tinitus selama satu tahun. Penderita yang datang ke unit rawat jalan Telinga Hidung Tenggorok Bedah Kepala dan Leher (THT-KL), Universiti Kebangsaan Malaysia Medical Centre (UKMMC) dilakukan evaluasi berdasarkan data demografi, data klinis dan QOL. Quality of life dinilai menggunakan Tinnitus Handicap Inventory (THI), kuesioner tentang penderita yang mengukur 3 domain QOL: skala fungsional, emosional dan katastropik. Hasil: Responden terdiri dari 35 laki-laki (39,8%) dan 53 perempuan (60,2%), dengan rerata usia 57.9±13.9 tahun. Audiometri nada murni perlu dilakukan minimal satu kali selama periode penelitian. Penderita dengan tinitus persisten secara signifikan memiliki nilai rata-rata THI yang lebih tinggi (p=0.042) dan nilai emotional subscale (p=0.037) dibandingkan dengan penderita tinitus intermiten. Tidak ada hubungan yang signifikan antara jenis kelamin, durasi tinitus dan lateralisasi tinitus dengan nilai THI penderita. Diskusi: Semua penderita diperlukan anamnesis yang baik dan pemeriksaan fisik yang menyeluruh. Penderita tanpa penyebab primer dari tinitusnya akan diberikan terapi konseling tinitus yang baik. Penderita dengan gangguan pembuluh darah akan diberikan pengobatan konservatif. Kesimpulan: Magnetic resonance imaging perlu dilakukan pada gangguan pendengaran satu sisi dengan tinitus. Computed tomography scan dengan kontras dilakukan pada tinitus pulsatil dengan atau tanpa kelainan pada telinga. Pada pendertita dengan nilai kuesioner THI yang tinggi akan dirujuk ke psikiater untuk penilaian lebih lanjut.

Objective\ud \ud To produce a strategic roadmap for supporting the development of dementia research in Pakistan.\ud \ud \ud \ud Background\ud \ud While global research strategies for dementia research already exist, none is tailored to the specific needs and challenges of low- and middle-income countries (LMIC) like Pakistan.\ud \ud \ud \ud Methods\ud \ud We undertook an iterative consensus process with lay and professional experts to develop a Theory of Change-based strategy for dementia research in Pakistan. This included Expert Reference Groups (ERGs), strategic planning techniques, a “research question” priority survey, and consultations with Key Opinion Leaders.\ud \ud \ud \ud Results\ud \ud We agreed on ten principles to guide dementia research in Pakistan, emphasizing pragmatic, resource sparing, real-world approaches to support people with dementia, both locally and internationally. Goals included capacity/capability building. Priority research topics included raising awareness and understanding of dementia, and improving quality of life.\ud \ud \ud \ud Conclusion\ud \ud This roadmap may be a model for other LMIC health ecosystems with emerging dementia research cultures.