Convalescent plasma transfusion in severe COVID-19 patients: Clinical and laboratory outcomes.

INTRODUCTION: The objective of this study was to investigate the effect of convalescent plasma (CP) transfusion on clinical and serial laboratory parameters in severe COVID-19 patients. The Coronavirus Disease 2019 (COVID-19) pandemic presents a challenge to the healthcare system worldwide due to the limited treatment options available. The body of evidence reported that CP containing anti- COVID-19 antibodies could be effective against the infection. MATERIALS AND METHODS: This was a cross-sectional study that involved retrospective data collection of severe COVID-19 adult patients who received CP transfusion along with the best-of-care (CP group, n: 53) and best-of-care only (control group, n: 53). An age, gender, and comorbidity were manually matched approximately at a 1:1 ratio. RESULTS: The prevalence of adverse transfusion reactions was 5.7%. A shorter duration of oxygen support (median: 12 days vs 14 days, P=0.030) and a shorter duration of mechanical ventilation (median: 6 days vs 10 days, P=0.048) were found in the CP group. The laboratory parameters were also improved. However, there was no significant difference in the mechanical ventilation rate, length of hospital stay, length of intensive care unit (ICU) stay, and mortality rate across both groups (P = 0.492, 0.614, 0.793, 0.374). CONCLUSION: CP transfusion is safe and effective in the treatment of severe COVID-19 patients. However, a revision of our approaches such as early CP transfusion and use of a high-titre anti-COVID-19 neutralising antibody (nAb) unit is necessary to unlock the full potential benefits of CP transfusion among COVID-19 patients.

Convalescent plasma as an adjunctive therapy for COVID-19: A single centre experience in Malaysia.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic posed a significant and urgent threat to global health and economy. Currently, there is no effective treatment known to alter the course of COVID-19. Convalescent plasma (CP) has been used previously to treat several types of infections during pandemics. The aim of our study is to evaluate the efficacy of CP in the treatment of severe COVID-19 infections at Hospital Sultanah Bahiyah, Kedah, Malaysia. MATERIALS AND METHODS: A retrospective cross-sectional study of all severe COVID-19 patients who received CP treatment from 1st August 2020 until 31st December 2020 was conducted. Clinical outcomes were compared before and after CP transfusion. RESULTS: Thirty-four patients were enrolled and received CP transfusion during the study period. The most common presenting complaints were fever (64.7%) and cough (58.8%). Fourteen patients showed improvement in oxygen support after CP transfusion. Several laboratory parameters also improved such as increased lymphocyte count (1.48 vs 1.98, p=0.008) and decreased C-reactive protein levels (28.1 vs 10.6, p=0.004), and these were statistically significant. Median time from symptoms onset to CP transfusion was 6 days (range 1-11) while median time from PCR diagnosis to CP transfusion was 5 days (range 1-11). One patient developed urticaria after CP transfusion and no severe adverse events were observed. Two of our patients passed away due to secondary causes. CONCLUSION: This study showed CP treatment was well tolerated and could potentially prevent progression of COVID-19 to a severe disease if administered early during the viraemic phase. Further evaluation with randomized control trial should be conducted to help ascertain the optimal dose and effectiveness of CP treatment, in correlation with the IgG titer of the donated CP.

Emergency Laparotomy in a COVID-19 patient with acute abdomen.

We describe here the first laparotomy involving a COVID-19 patient in Malaysia. A 60-year-old man screened positive for SARS-CoV-2 in March 2020 and developed acute abdomen in the ward in Hospital Sultanah Bahiyah, Kedah. He underwent laparotomy and cholecystectomy for gangrenous cholecystitis. All personnel adhered to infectious control precautions, donning full personal protective equipment (PPE) throughout the surgery. Post-operatively, due to raised septic parameters, he was carefully diagnosed with and treated empirically for superimposed bacterial sepsis instead of cytokine release syndrome, with confirmed blood culture of Klebsiella pneumoniae. Patient was discharged well later. None of the staff involved in his care developed COVID-19 infection.

Collaboration between a tertiary pain centre and community teams during the pandemic.

People with chronic pain faced potential treatment disruption during the COVID-19 pandemic in Singapore, as the focus of healthcare shifted. A model of rapid integration of a pain centre with community healthcare teams was implemented to care for vulnerable older patients with chronic pain and multiple comorbidities. Telemedicine and home visits by community nurses were used, with risk-mitigation measures, ensuring comprehensive assessment and treatment compliance. Medications from pain physicians were delivered at home through a hospital pharmacy. A secure national electronic health records system used by all teams ensured seamless access and documentation. Potential emergency department visits, admissions and delayed discharges were thus avoided. Integration of community teams with chronic pain management services can be recommended to ensure pandemic preparedness.

Methicillin-resistant Staphylococcus aureus colonisation: epidemiological and molecular characteristics in an acute-care tertiary hospital in Singapore.

Current knowledge of methicillin-resistant Staphylococcus aureus (MRSA) colonisation in relation to epidemiological characteristics is incomplete. We conducted a cross-sectional study at an acute-care tertiary infectious diseases hospital of MRSA isolates identified through routine surveillance from January 2009 to December 2011. We randomly selected 205 MRSA isolates (119 inpatients) from 798 isolates (427 inpatients) for molecular profiling using multilocus sequence typing. Multilevel multinomial logistic regression was used to estimate odds ratio (OR) assessing the predilection of MRSA strains for anatomic sites, and associations of strains with human immunodeficiency virus (HIV) infection. The most frequent sequence types (STs) were 239, 22 and 45. The proportion of ST22 increased over the sampling period, replacing ST239 as the dominant lineage. However, ST239 remained the most prevalent among HIV-seropositive individuals who were six times more likely to be colonised with this strain than non-HIV patients (adjusted OR (aOR) 6.44, 95% confidence interval (CI) 1.94-21.36). ST45 was >24 times more likely to be associated with perianal colonisation than in the nares, axillae and groin sites (aOR 24.20, 95% CI 1.45-403.26). This study underlines the clonal replacement of MRSA in Singapore as previously reported but revealed, in addition, key strain differences between HIV-infected and non-infected individuals hospitalised in the same environment.

A phase Ib study of selumetinib (AZD6244, ARRY-142886) in combination with sorafenib in advanced hepatocellular carcinoma (HCC).

BACKGROUND: Treatment with sorafenib, although associated with inhibition of tumour growth and angiogenesis in in vivo studies, leads to up-regulation of pERK. The addition of MEK inhibition could potentially abrogate this effect and potentiate anti-tumour activity. This phase I study investigated the maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK) and biomarker correlates of selumetinib combined with sorafenib in patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients with Child-Pugh (CP) score ≤7 were treated with 400 mg twice daily of sorafenib with escalating doses of selumetinib in a 3 + 3 study design. The dose-limiting toxicity (DLT) evaluation period was 28 days. PK of selumetinib was determined. Angiogenic effect was evaluated with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). RESULTS: Twenty-seven patients of Asian ethnicity were enrolled. The MTD was selumetinib 75 mg daily with sorafenib 400 mg twice daily. DLT included grade 3 transaminitis, diarrhoea and fatigue. Most common treatment-related adverse events at MTD (all grades) were diarrhoea (85%), rash (59%), hypertension (44%), fatigue (30%), anorexia (22%) and hand-foot syndrome (22%). Four patients (15%) had PR and 13 (48%) had SD. PR or SD was observed for ≥6 months in seven patients. The median overall survival was 14.4 months. Selumetinib exposures in combination with sorafenib were comparable to other monotherapy studies. A reduction in permeability-surface area product noted in DCE-MRI with treatment correlated with worse survival outcomes. CONCLUSION: The MTD of selumetinib was 75 mg daily when combined with sorafenib 400 mg twice a day in CP ≤7 HCC. Acceptable adverse events and encouraging anti-tumour activity warrant further evaluation. DCE-MRI findings deserve prospective evaluation. CLINICALTRIALSGOV IDENTIFIER: NCT01029418.

A forgotten clinical sign making a comeback.

We report a case of Staphylococcus aureus infective endocarditis in a patient presenting with fever and rare cutaneous manifestations of Osler Nodes and Janeway Lesions. There had not been any distinct risk factors. His echocardiography subsequently revealed vegetation at the anterior mitral valve leaflet. As Staphylococcus aureus infective endocarditis is of utmost significance in morbidity and mortality, a sharp clinical acumen and follow up investigations is required alongside a prolonged course of antibiotics. Our patient was then started on intravenous cloxacillin for 28 days and gentamicin for 5 days to which he made good progress and recovery.

Fostering social health of people with dementia: evaluation of the Razem przed siebie dementia awareness campaign in Poland.

Background: Due to the need to increase social awareness about dementia and the needs of patients living with dementia in Poland, the Razem przed siebie (eng. Forward with Dementia) campaign was created. The aim of the study was to evaluate its effectiveness. Methods: To disseminate key campaign messages to the target audiences (people with dementia, carers, health and social care professionals [HSCP] and general public) a website, social and traditional media promotions, webinars and social activities were created. The campaign ran between September 2021 and April 2022. Mixed methods (online survey, reach estimates and interviews) were used to evaluate the campaign. Results: Almost 1,300 people visited the website during the campaign period. Of these, 55 carers and HSCP responded to the online survey. The most read section of the website was Understanding the diagnosis (carers [56% of 25] and HSCP [80% out of 30]). The website was mostly accessed by carers (68%) and HSCP (66.7%) through word-of-mouth recommendations. 80% carers and 90% HSCP found the website very or extremely helpful. Over 90% of carers and HSCP expressed an intention to revisit the website. Based on 31 interviews, campaign effects, change mechanisms and limitations were identified. Campaign events elicited positive emotions among people with dementia, providing them with a feeling of belonging and engagement. Esteeming personal interactions over informational campaign materials, those with dementia felt acknowledged and empowered by the events. Carers also reported positive experiences and increased interest and knowledge, though they expressed disappointment with the lack of respite care, an issue beyond the campaign's scope. HSCP perceived the campaign events positively and identified significant gaps in the dementia care system. Conclusion: Evaluation of the Razem przed siebie campaign revealed successes and limitations. While effectively incorporating anti-stigma campaign recommendations and enhancing social health for individuals with dementia, the campaign clearly showed the pressing need for systemic solutions. Despite positive perception of the campaign, there is a need for a better diagnostic and post-diagnostic support for people with dementia and their carers.

Autosomal recessive chronic granulomatous disease presenting with cutaneous dermatoses and ocular infection.

Dermatoses such as eczematous dermatitis and cutaneous infection are recognized presentations of primary immunodeficiency (PID). However, atopic dermatitis affects approximately 10% of infants, and cutaneous infections are not uncommon in children, therefore the challenge for the dermatologist is to distinguish the few patients that have PID from the many that do not. We report on a 6-year-old girl who was ultimately diagnosed with autosomal recessive chronic granulomatous disease (AR-CGD) after presenting to various hospitals with dermatitis, scalp plaques recalcitrant to treatment, and recurrent infections over a 3-year period, and describe some aspects of her diagnosis and management. This report highlights the importance of considering rare disorders such as AR-CGD in the differential diagnosis of recurrent or recalcitrant dermatological infections in children.

Evaluation of the utility of hospital databases to provide data in assessing the quality of strabismus surgery.

AIMS AND BACKGROUND: Rates of re-operation, which may be related to an unsatisfactory surgical outcome, can provide a long-term index of the quality of strabismus surgery. This study aims to evaluate the utility of the Scottish Morbidity Records (SMR1) in determining nature and rates of re-operation for strabismus at the Royal Hospital for Sick Children (RHSC), Glasgow. METHODS: SMR1 data on strabismus surgery performed on children aged between 0 and 17 years at the RHSC, Glasgow, between January 2000 and March 2009 were analysed. RESULTS: In total, 1376 strabismus procedures were carried out on 1274 individuals. The median time between first and subsequent procedures was 19 months; the commonest reasons being under-correction or recurrence. The Kaplan-Meier rate of undergoing re-operation was 7.4% after 9 years with a 95% confidence interval of 5.4-9.9%. CONCLUSIONS: The SMR1 is a useful source of hospital-based and population data. With supplementation from parallel databases, routine administrative databases like the SMR1 can provide better quality data to inform practice.

Impact of the COVID-19 pandemic on the research activities of UK ophthalmologists.

BACKGROUND: The COVID-19 pandemic has impacted negatively on many areas of biomedical research and there is concern that academic recovery will take several years. This survey aimed to define the impact of the COVID-19 pandemic on UK ophthalmologists' research activities and understand the implications for recovery. METHODS: An online survey comprising multiple choice and free-text questions was designed, piloted and then distributed to Royal College of Ophthalmologists (RCOphth) members in January 2021. Respondent characteristics, research expectations and experiences through the pandemic were captured. Descriptive and comparative statistics were applied to quantitative data alongside content analysis of qualitative data. RESULTS: In total, 148 respondents (3.7% of RCOphth membership) comprised 46 trainees (31.1%), 97 consultants (65.5%) and 5 SAS doctors (3.4%); 54 had clinical-academic roles (36.5%) and 65/94 (69.1%) ophthalmologists with fully clinical posts identified as research-active. Of 114 research-active respondents, 104 (91.2%) reported an impact on their research from COVID-19; negative impacts included loss of research time (n = 69), research delays (n = 96) and funding shortfalls (n = 63). Content analysis identified five common themes; type of research activity, clinical demands, institutional challenges, COVID-19 alignment and work-life balance. CONCLUSIONS: UK ophthalmology research has been adversely impacted by the pandemic. A substantial proportion of UK ophthalmologists are research active, but 20.4% of those surveyed felt that the pandemic had made research less attractive. Strategic steps must be taken to nurture UK ophthalmologists' engagement with research, especially for those who currently do no research, if the profession is to align itself with the Government vision of 'Research for All'.

Pubic bone injuries in primiparous women: magnetic resonance imaging in detection and differential diagnosis of structural injury.

OBJECTIVE: To evaluate the utility of magnetic resonance imaging (MRI) in diagnosing structural injury in primiparous women at risk for pelvic floor injury. METHODS: This was an observational study of 77 women who underwent 3T MRI after delivery. Women were operationally defined as high risk (n = 45) for levator ani muscle tears (risk factors: second-stage labor > 150 min or < 30 min, anal sphincter tear, forceps, maternal age > 35 years and birth weight > 4000 g) or low risk (n = 32): vaginally delivered without these risk factors (n = 12); delivered by Cesarean section after second-stage labor > 150 min (n = 14) or delivered by Cesarean section without labor (n = 6). All women were imaged using fluid-sensitive MRI sequences. Two musculoskeletal radiologists reviewed images for bone marrow edema, fracture, pubic symphysis measurements and levator ani tear. RESULTS: MRI showed pubic bone fractures in 38% of women at high risk for pelvic floor injury and in 13% of women at low risk for pelvic floor injury (χ(2) (3) = 9.27, P = 0.03). Levator ani muscle tears were present in 44% of the high-risk women and in 9% of the low-risk women (χ(2) (3) = 11.57, P = 0.010). Bone marrow edema in the pubic bones was present in 61% of women studied across delivery categories. Complex patterns of injury included combinations of bone marrow edema, fractures, levator ani tears and pubic symphysis injuries. No MRI-documented injuries were present in 18% of women at high risk and 44% at low risk for pelvic floor injury (χ(2) (1) = 6.2, P = 0.013). CONCLUSIONS: Criteria identifying primiparous women at risk for pelvic floor injury can predict increased risk of bone and soft tissue changes at the pubic symphysis. Fluid-sensitive MRI has utility for differential diagnosis of structural injury in postpartum women.

Amlodipine-induced linear IgA disease.

A 58-year-old woman presented with a 3-week history of a pruritic rash, which had started a week after commencing treatment with amlodipine. On physical examination, large, well-demarcated erythematous plaques, surrounded by small clusters of clear vesicles, were seen on the patient's torso. Subepidermal blisters with neutrophils and eosinophils were seen in a skin biopsy, and direct immunofluorescence showed deposition of IgA along the basement membrane, in keeping with a diagnosis of linear IgA dermatosis (LAD). Amlodipine was discontinued, and the patient was started on prednisolone 30 mg, supplemented shortly afterwards by dapsone, which resulted in prompt resolution of the rash. Only a few cases of drug-induced LAD have been reported, mostly in association with vancomycin. To our knowledge, this is the first reported case precipitated by amlodipine.

Women's Knowledge of Bladder Health: What We Have Learned in the Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium.

Purpose of Review: The goal of this manuscript is to review the current literature on bladder health education, summarize Prevention of Lower Urinary Tract Symptoms (PLUS) [50] findings on environmental factors that influence knowledge and beliefs about toileting and bladder function, and describe how PLUS work will contribute to improved understanding of women's bladder-related knowledge and inform prevention intervention strategies. Recent Findings: Analysis of focus group transcripts revealed the various ways women view, experience, and describe bladder function. In the absence of formal bladder health educational platforms, women appear to develop knowledge of normal and abnormal bladder function from a variety of social processes including environmental cues and interpersonal sources. Importantly, focus group participants expressed frustration with the absence of structured bladder education to inform knowledge and practices. Summary: There is a lack of bladder health educational programming in the USA, and it is unknown to what degree women's knowledge, attitudes, and beliefs influence their risk of developing lower urinary tract symptoms (LUTS). The PLUS Consortium RISE FOR HEALTH study will estimate the prevalence of bladder health in adult women and assess risk and protective factors. A Knowledge, Attitudes, and Beliefs (KAB) questionnaire will be administered to determine KAB around bladder function, toileting, and bladder-related behaviors, and examine the relationship of KAB to bladder health and LUTS. The data generated from PLUS studies will identify opportunities for educational strategies to improve bladder health promotion and well-being across the life course.

Post-traumatic stress disorder, child abuse history, birthweight and gestational age: a prospective cohort study.

OBJECTIVE: To determine the extent to which prenatal post-traumatic stress disorder (PTSD) is associated with lower birthweight and shorter gestation, and to explore the effects of childhood maltreatment as the antecedent trauma exposure. DESIGN: Prospective three-cohort study. SETTING: Ann Arbor and Detroit, Michigan, United States. SAMPLE: In all, 839 diverse nulliparas in PTSD-positive (n = 255), trauma-exposed, resilient (n = 307) and non-exposed to trauma (n = 277) cohorts. METHODS: Standardised telephone interview before 28 weeks of gestation to ascertain trauma history, PTSD, depression, substance use, mental health treatment history and sociodemographics, with chart abstraction to obtain chronic condition history, antepartum complications and prenatal care data, as well as outcomes. MAIN OUTCOME MEASURES: Infant birthweight and gestational age per delivery record. RESULTS: Infants born to women with PTSD during pregnancy had a mean birthweight 283 g less than infants of trauma-exposed, resilient women and 221 g less than infants of non-exposed women (F(3,835) = 5.4, P = 0.001). PTSD was also associated with shorter gestation in multivariate models that took childhood abuse history into account. Stratified models indicated that PTSD subsequent to child abuse trauma exposure was most strongly associated with adverse outcomes. PTSD was a stronger predictor than African American race of shorter gestation and a nearly equal predictor of birthweight. Prenatal care was not associated with better outcomes among women abused in childhood. CONCLUSIONS: Abuse-related PTSD may be an additional or alternative explanation for adverse perinatal outcomes associated with low socio-economic status and African American race in the USA. Biological and interventions research is warranted along with replication studies in other nations.

Serum is not required for ex vivo IFN-gamma ELISPOT: a collaborative study of different protocols from the European CIMT Immunoguiding Program.

The Cancer Immunotherapy Immunoguiding Program has conducted an IFN-gamma ELISPOT proficiency panel to examine the influence of serum supplementation of test media on assay performance. Sixteen European laboratories analyzed the same PBMC samples using different locally established protocols. Participants generated two simultaneous data sets-one using medium supplemented with serum and one without serum. Performances of the two test conditions were compared by quantifying: (1) the number of viable cells, (2) background spot formation induced in the medium only control and (3) the ability to detect antigen-specific T cell responses. The study demonstrated that the number of viable cells recovered and the overall background spot production were not significantly different between the two conditions. Furthermore, overall laboratory performance was equivalent for the two test conditions; 11 out of 16 laboratories reported equal or greater detection rates using serum-free medium, while 5 laboratories reported decreased detections rates under serum-free conditions. These results show that good performance of the IFN-gamma ELISPOT assay can be achieved under serum-free conditions. Optimization of the protocol for serum-free conditions should result in excellent detection rates and eliminate the requirement of serum batch and stability testing, allowing further harmonization of the assay.