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1.
Eur J Phys Rehabil Med ; 58(1): 137-143, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1754135

ABSTRACT

BACKGROUND: Millions of human beings have suffered in the epidemic of Coronavirus disease 2019 (COVID-19), but until now the effective treatment methods have been limited. AIM: This study aimed to evaluate the efficacy and safety of short-wave diathermy (SWD) treatment for moderate COVID-19 patients. DESIGN: A prospective, double-blind, randomized controlled clinical study. SETTING: Inpatients Unit of a COVID-19 specialized hospital. POPULATION: Forty-two patients with moderate COVID-19 were randomly allocated at a 2:1 ratio to two groups: the SWD group and the control group. METHODS: Participants of the SWD group received SWD treatment, and participants of the control group received placebo SWD treatment for one session per day, 10 minutes per session, for no more than 14 days. Both groups were given standard care treatment. Primary outcome was the rate of clinical improvement according to a seven-category ordinal scale. Secondary outcomes included the rate of computed tomography (CT) improvement and the rate of potential adverse events. RESULTS: Clinical improvement occurred in 92.6% of patients in the SWD group by day 14 compared with 69.2% of patients in the control group (P=0.001). The Cox model indicated that the SWD group had a higher clinical improvement probability than the control group (hazard ratio: 3.045; 95% CI: 1.391-6.666; P=0.005). Similarly, CT improvement occurred in 85.2% of patients in the SWD group and 46.2% of patients in the control group respectively by day 14 (P=0.001). The Cox model indicated SWD group had a higher CT improvement probability than control group (hazard ratio: 3.720; 95% CI: 1.486-9.311; P=0.005). There was no significant difference in adverse events between the SWD group and the control group (2 of 27 [7.4%] SWD vs. 1 of 13 [7.7%] control, P=1.000), the most frequent of which were headache (1 of 27 [3.7%] SWD vs. 1 of 13 [7.7%] control patients) and dizziness (1 of 27 [3.7%] SWD vs. 0 of 13 [0%] control patients). CONCLUSIONS: SWD is a valid and reliable adjuvant therapy with a favorable safety profile for moderate COVID-19 patients. CLINICAL REHABILITATION IMPACT: Clinically relevant information is lacking regarding the efficacy and safety of SWD for patients with COVID-19. This study provides the first evidence that SWD is a promising adjuvant therapy for COVID-19.


Subject(s)
COVID-19 , Diathermy , Double-Blind Method , Humans , Prospective Studies , SARS-CoV-2 , Treatment Outcome
2.
Clin Infect Dis ; 74(4): 715-718, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1702854

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins were measured in longitudinal plasma samples collected from 13 participants who received two doses of mRNA-1273 vaccine. Eleven of 13 participants showed detectable levels of SARS-CoV-2 protein as early as day 1 after first vaccine injection. Clearance of detectable SARS-CoV-2 protein correlated with production of immunoglobulin G (IgG) and immunoglobulin A (IgA).


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunoglobulin A , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/blood , Spike Glycoprotein, Coronavirus/genetics
3.
Eur Arch Otorhinolaryngol ; 279(2): 759-764, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1661677

ABSTRACT

PURPOSE: The aim of this study was to reveal the effect of N95 and surgical masks on mucociliary clearance function and sinonasal complaints. METHODS: Sixty participants were enrolled in this study, including 30 people in N95 mask group and 30 people in surgical mask group. Two interviews, three days apart, were performed with all participants. The participants were asked not to use any mask before the first interview while they were asked to use the determined mask just before the second interview for 8 h. In both interviews, the mucociliary clearance times (MCTs) were measured and participants were asked to score ten distinct sinonasal complaints using visual analog scale (VAS). Data obtained from first interview were named pre-mask data, data obtained from second interview were called after-mask data. In both groups, pre-mask MCTs and VAS scores were compared with after-mask MCTs and VAS scores. RESULTS: After-mask MCTs (mean = 13.03 ± 6.05 min) were significantly longer than pre-mask MCTs (mean = 10.19 ± 4.21 min) in N95 mask group (p = 0.002). No significant difference was found between after-mask and pre-mask MCTs (mean = 12.05 ± 5.21 min, mean = 11.00 ± 5.44 min, respectively) in surgical mask group (p = 0.234). When after-mask VAS scores were compared with pre-mask VAS scores, it was found that N95 mask use increased nasal blockage and postnasal discharge, surgical mask usage increased nasal blockage. CONCLUSION: While the use of N95 mask leads to nasal blockage and postnasal discharge, surgical mask use results in nasal blockage. N95 masks cause impairment in mucociliary clearance function. But all these effects are mild. Surgical masks have not been found to have any effect on mucociliary clearance function.


Subject(s)
COVID-19 , Masks , Humans , Mucociliary Clearance , N95 Respirators , SARS-CoV-2
4.
Lancet ; 397(10285): 1637-1645, 2021 May 01.
Article in English | MEDLINE | ID: covidwho-1655260

ABSTRACT

BACKGROUND: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. METHODS: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg-800 mg (depending on weight) given intravenously. A second dose could be given 12-24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76-0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12-1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77-0·92; p<0·0001). INTERPRETATION: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. FUNDING: UK Research and Innovation (Medical Research Council) and National Institute of Health Research.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19/drug therapy , COVID-19/therapy , Hypoxia/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , Female , Hospital Mortality , Hospitalization , Humans , Hypoxia/diagnosis , Hypoxia/virology , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , SARS-CoV-2/isolation & purification , Severity of Illness Index , Treatment Outcome , Young Adult
5.
Lancet Infect Dis ; 21(10): 1383-1394, 2021 10.
Article in English | MEDLINE | ID: covidwho-1621119

ABSTRACT

BACKGROUND: Given the scale of the ongoing COVID-19 pandemic, the development of vaccines based on different platforms is essential, particularly in light of emerging viral variants, the absence of information on vaccine-induced immune durability, and potential paediatric use. We aimed to assess the safety and immunogenicity of an MF59-adjuvanted subunit vaccine for COVID-19 based on recombinant SARS-CoV-2 spike glycoprotein stabilised in a pre-fusion conformation by a novel molecular clamp (spike glycoprotein-clamp [sclamp]). METHODS: We did a phase 1, double-blind, placebo-controlled, block-randomised trial of the sclamp subunit vaccine in a single clinical trial site in Brisbane, QLD, Australia. Healthy adults (aged ≥18 to ≤55 years) who had tested negative for SARS-CoV-2, reported no close contact with anyone with active or previous SARS-CoV-2 infection, and tested negative for pre-existing SARS-CoV-2 immunity were included. Participants were randomly assigned to one of five treatment groups and received two doses via intramuscular injection 28 days apart of either placebo, sclamp vaccine at 5 µg, 15 µg, or 45 µg, or one dose of sclamp vaccine at 45 µg followed by placebo. Participants and study personnel, except the dose administration personnel, were masked to treatment. The primary safety endpoints included solicited local and systemic adverse events in the 7 days after each dose and unsolicited adverse events up to 12 months after dosing. Here, data are reported up until day 57. Primary immunogenicity endpoints were antigen-specific IgG ELISA and SARS-CoV-2 microneutralisation assays assessed at 28 days after each dose. The study is ongoing and registered with ClinicalTrials.gov, NCT04495933. FINDINGS: Between June 23, 2020, and Aug 17, 2020, of 314 healthy volunteers screened, 120 were randomly assigned (n=24 per group), and 114 (95%) completed the study up to day 57 (mean age 32·5 years [SD 10·4], 65 [54%] male, 55 [46%] female). Severe solicited reactions were infrequent and occurred at similar rates in participants receiving placebo (two [8%] of 24) and the SARS-CoV-2 sclamp vaccine at any dose (three [3%] of 96). Both solicited reactions and unsolicited adverse events occurred at a similar frequency in participants receiving placebo and the SARS-CoV-2 sclamp vaccine. Solicited reactions occurred in 19 (79%) of 24 participants receiving placebo and 86 (90%) of 96 receiving the SARS-CoV-2 sclamp vaccine at any dose. Unsolicited adverse events occurred in seven (29%) of 24 participants receiving placebo and 35 (36%) of 96 participants receiving the SARS-CoV-2 sclamp vaccine at any dose. Vaccination with SARS-CoV-2 sclamp elicited a similar antigen-specific response irrespective of dose: 4 weeks after the initial dose (day 29) with 5 µg dose (geometric mean titre [GMT] 6400, 95% CI 3683-11 122), with 15 µg dose (7492, 4959-11 319), and the two 45 µg dose cohorts (8770, 5526-13 920 in the two-dose 45 µg cohort; 8793, 5570-13 881 in the single-dose 45 µg cohort); 4 weeks after the second dose (day 57) with two 5 µg doses (102 400, 64 857-161 676), with two 15 µg doses (74 725, 51 300-108 847), with two 45 µg doses (79 586, 55 430-114 268), only a single 45 µg dose (4795, 2858-8043). At day 57, 67 (99%) of 68 participants who received two doses of sclamp vaccine at any concentration produced a neutralising immune response, compared with six (25%) of 24 who received a single 45 µg dose and none of 22 who received placebo. Participants receiving two doses of sclamp vaccine elicited similar neutralisation titres, irrespective of dose: two 5 µg doses (GMT 228, 95% CI 146-356), two 15 µg doses (230, 170-312), and two 45 µg doses (239, 187-307). INTERPRETATION: This first-in-human trial shows that a subunit vaccine comprising mammalian cell culture-derived, MF59-adjuvanted, molecular clamp-stabilised recombinant spike protein elicits strong immune responses with a promising safety profile. However, the glycoprotein 41 peptide present in the clamp created HIV diagnostic assay interference, a possible barrier to widespread use highlighting the criticality of potential non-spike directed immunogenicity during vaccine development. Studies are ongoing with alternative molecular clamp trimerisation domains to ameliorate this response. FUNDING: Coalition for Epidemic Preparedness Innovations, National Health and Medical Research Council, Queensland Government, and further philanthropic sources listed in the acknowledgments.


Subject(s)
Adjuvants, Immunologic/pharmacology , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Squalene/immunology , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Australia , Female , Healthy Volunteers , Humans , Male , Pandemics/prevention & control , Polysorbates , Vaccination/adverse effects , Young Adult
6.
Female Pelvic Med Reconstr Surg ; 27(12): 719-725, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1526238

ABSTRACT

OBJECTIVE: Preoperative counseling can affect postoperative outcomes and satisfaction. We hypothesized that patient preparedness would be equivalent after preoperative counseling phone calls versus preoperative counseling office visits before prolapse surgery. METHODS: This was an equivalence randomized controlled trial of women undergoing pelvic organ prolapse surgery. Participants were randomized to receive standardized counseling via a preoperative phone call or office visit. The primary outcome was patient preparedness measured on a 5-point Likert scale by the Patient Preparedness Questionnaire at the postoperative visit. A predetermined equivalence margin of 20% was used. Two 1-sided tests for equivalence were used for the primary outcome. RESULTS: We randomized 120 women. The study was concluded early because of COVID-19 and subsequent surgery cancellations. There were 85 participants with primary outcome data (43 offices, 42 phones). Mean age was 62.0 years (±1.0) and 64 (75.3%) had stage III or stage IV prolapse. The primary outcome, patient preparedness measured at the postoperative visit, was equivalent between groups (office, n = 43 [97.7%]; phone, n = 42 [97.6%], P < 0.001). Most women reported they would have preferred a phone call (n = 66, 65.5%) with more women in the phone group expressing this preference than the office group (office 40.5% vs phone 90.5%, P < 0.001). Ultimately, nearly all women (96.5%) were satisfied with their method of counseling. CONCLUSIONS: Preoperative counseling phone calls were equivalent to office visits for patient preparedness for pelvic organ prolapse surgery. This study demonstrates patient acceptance of phone calls for preoperative counseling. Telehealth modalities should be considered as an option for preoperative patient counseling.


Subject(s)
Counseling/methods , Office Visits , Patient Education as Topic/methods , Pelvic Organ Prolapse/surgery , Telephone , Early Termination of Clinical Trials , Female , Humans , Middle Aged , Patient Preference , Patient Satisfaction , Preoperative Care
7.
Clin Infect Dis ; 73(10): 1927-1939, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1522145

ABSTRACT

Large-scale deployment of safe and durably effective vaccines can curtail the coronavirus disease-2019 (COVID-19) pandemic. However, the high vaccine efficacy (VE) reported by ongoing phase 3 placebo-controlled clinical trials is based on a median follow-up time of only about 2 months, and thus does not pertain to long-term efficacy. To evaluate the duration of protection while allowing trial participants timely access to efficacious vaccine, investigators can sequentially cross participants over from the placebo arm to the vaccine arm. Here, we show how to estimate potentially time-varying placebo-controlled VE in this type of staggered vaccination of participants. In addition, we compare the performance of blinded and unblinded crossover designs in estimating long-term VE.


Subject(s)
COVID-19 , Vaccines , COVID-19 Vaccines , Humans , Pandemics , SARS-CoV-2
8.
Pain Rep ; 6(1): e891, 2021.
Article in English | MEDLINE | ID: covidwho-1501238

ABSTRACT

INTRODUCTION: Multimodal treatment is recognized as the optimal paradigm for the management of chronic pain (CP). Careful balance between pharmacological and physical/psychological approaches is thus desirable but can be easily disrupted. OBJECTIVES: This study aimed at exploring the impact of the COVID-19 pandemic on pharmacological and physical/psychological treatments of CP. METHODS: A Pan-Canadian cross-sectional web-based study was conducted between April 16th and May 31st 2020 among adults living with CP when the country was in the ascending slope of the first COVID-19 pandemic wave. RESULTS: A total of 2864 participants shared their treatment experience (mean age: 49.7 years and women: 83.5%). Among medication users (n = 2533), 38.3% reported changes in their pharmacological pain treatment. The main reasons were as follows: (1) changes in pain symptoms, (2) lack of access to prescribers/cancellation of medical appointments, and (3) increased medication intake in compensation for stopping physical/psychological treatments because of the pandemic. Among participants who used physical/psychological pain management approaches before the pandemic (n = 2467), 68.3% had to modify their treatments or self-management strategies. Common reasons were lack of access to clinics/exercise facilities and the need to compensate for having to stop another type of physical/psychological treatment because of the pandemic-related public health safety measures. CONCLUSIONS: Our study underlines the negative impact of the COVID-19 pandemic on access to pain relief, which is considered a fundamental human right. Results will help to justify resource allocation and inform the development of interventions to be better prepared for waves to come and future health crises.

9.
J Am Soc Nephrol ; 32(3): 708-722, 2021 03.
Article in English | MEDLINE | ID: covidwho-1496675

ABSTRACT

BACKGROUND: Late antibody-mediated rejection (ABMR) is a leading cause of transplant failure. Blocking IL-6 has been proposed as a promising therapeutic strategy. METHODS: We performed a phase 2 randomized pilot trial to evaluate the safety (primary endpoint) and efficacy (secondary endpoint analysis) of the anti-IL-6 antibody clazakizumab in late ABMR. The trial included 20 kidney transplant recipients with donor-specific, antibody-positive ABMR ≥365 days post-transplantation. Patients were randomized 1:1 to receive 25 mg clazakizumab or placebo (4-weekly subcutaneous injections) for 12 weeks (part A), followed by a 40-week open-label extension (part B), during which time all participants received clazakizumab. RESULTS: Five (25%) patients under active treatment developed serious infectious events, and two (10%) developed diverticular disease complications, leading to trial withdrawal. Those receiving clazakizumab displayed significantly decreased donor-specific antibodies and, on prolonged treatment, modulated rejection-related gene-expression patterns. In 18 patients, allograft biopsies after 51 weeks revealed a negative molecular ABMR score in seven (38.9%), disappearance of capillary C4d deposits in five (27.8%), and resolution of morphologic ABMR activity in four (22.2%). Although proteinuria remained stable, the mean eGFR decline during part A was slower with clazakizumab compared with placebo (-0.96; 95% confidence interval [95% CI], -1.96 to 0.03 versus -2.43; 95% CI, -3.40 to -1.46 ml/min per 1.73 m2 per month, respectively, P=0.04). During part B, the slope of eGFR decline for patients who were switched from placebo to clazakizumab improved and no longer differed significantly from patients initially allocated to clazakizumab. CONCLUSIONS: Although safety data indicate the need for careful patient selection and monitoring, our preliminary efficacy results suggest a potentially beneficial effect of clazakizumab on ABMR activity and progression.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Graft Rejection/therapy , Interleukin-6/antagonists & inhibitors , Kidney Transplantation/adverse effects , Adult , Allografts , Antibodies, Monoclonal, Humanized/adverse effects , Double-Blind Method , Female , Glomerular Filtration Rate , Graft Rejection/immunology , Graft Rejection/physiopathology , Humans , Infections/etiology , Interleukin-6/immunology , Isoantibodies/blood , Male , Middle Aged , Tissue Donors , Treatment Outcome , Young Adult
10.
BMJ ; 369: m1849, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-1495142

ABSTRACT

OBJECTIVE: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). DESIGN: Multicentre, open label, randomised controlled trial. SETTING: 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. PARTICIPANTS: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). INTERVENTIONS: Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). MAIN OUTCOME MEASURE: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone. RESULTS: Of 150 patients, 148 had mild to moderate disease and two had severe disease. The mean duration from symptom onset to randomisation was 16.6 (SD 10.5; range 3-41) days. A total of 109 (73%) patients (56 standard of care; 53 standard of care plus hydroxychloroquine) had negative conversion well before 28 days, and the remaining 41 (27%) patients (19 standard of care; 22 standard of care plus hydroxychloroquine) were censored as they did not reach negative conversion of virus. The probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), similar to that in the standard of care group (81.3%, 71.2% to 89.6%). The difference between groups was 4.1% (95% confidence interval -10.3% to 18.5%). In the safety population, adverse events were recorded in 7/80 (9%) hydroxychloroquine non-recipients and in 21/70 (30%) hydroxychloroquine recipients. The most common adverse event in the hydroxychloroquine recipients was diarrhoea, reported in 7/70 (10%) patients. Two hydroxychloroquine recipients reported serious adverse events. CONCLUSIONS: Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients. TRIAL REGISTRATION: ChiCTR2000029868.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Adult , COVID-19 , China , Female , Humans , Male , Middle Aged , Pandemics , Treatment Outcome
11.
Eur Geriatr Med ; 12(5): 1045-1055, 2021 10.
Article in English | MEDLINE | ID: covidwho-1474202

ABSTRACT

AIMS: To evaluate the efficacy of multi-component interventions for prevention of hospital-acquired pneumonia in older patients hospitalized in geriatric wards. METHODS: A randomized, parallel-group, controlled trial was undertaken in patients aged 65 and above who were admitted to a tertiary hospital geriatric unit from January 1, 2016 to June 30, 2018 for an acute non-respiratory illness. Participants were randomized by to receive either a multi-component intervention (consisting of reverse Trendelenburg position, dysphagia screening, oral care and vaccinations), or usual care. The outcome measures were the proportion of patients who developed hospital-acquired pneumonia during hospitalisation, and mean time from randomization to the next hospitalisation due to respiratory infections in 1 year. RESULTS: A total of 123 participants (median age, 85; 43.1% male) were randomized, (n = 59) to intervention group and (n = 64) to control group. The multi-component interventions did not significantly reduce the incidence of hospital-acquired pneumonia but did increase the mean time to next hospitalisation due to respiratory infection (11.5 months vs. 9.5 months; P = 0.049), and reduced the risk of hospitalisation in 1 year (18.6% vs. 34.4%; P = 0.049). Implementation of multi-component interventions increased diagnoses of oropharyngeal dysphagia (35.6% vs. 20.3%; P < 0.001) and improved the influenza (54.5% vs 17.2%; P < 0.001) and pneumococcal vaccination rates (52.5% vs. 20.3%; P < 0.001). CONCLUSIONS: The nosocomial pneumonia multi-component intervention did not significantly reduce the incidence of hospital-acquired pneumonia during hospitalisation but reduce subsequent hospitalisations for respiratory infections. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov, NCT04347395.


Subject(s)
COVID-19 , Cross Infection , Healthcare-Associated Pneumonia , Aged , Aged, 80 and over , Cross Infection/epidemiology , Female , Healthcare-Associated Pneumonia/epidemiology , Humans , Male , SARS-CoV-2 , Treatment Outcome
12.
BMJ Open ; 11(6): e048109, 2021 06 08.
Article in English | MEDLINE | ID: covidwho-1462955

ABSTRACT

OBJECTIVES: We integrated an established participant-centred active vaccine safety surveillance system with a cloud-based pharmacy immunisation-recording program in order to measure adverse events following immunisation (AEFI) reported via the new surveillance system in pharmacies, compared with AEFI reported via an existing surveillance system in non-pharmacy sites (general practice and other clinics). DESIGN: A prospective cohort study. PARTICIPANTS AND SETTING: Individuals >10 years receiving influenza immunisations from 22 pharmacies and 90 non-pharmacy (general practice and other clinic) sites between March and October 2020 in Western Australia. Active vaccine safety surveillance was conducted using short message service and smartphone technology, via an opt-out system. OUTCOME MEASURES: Multivariable logistic regression was used to assess the primary outcome: differences in proportions of AEFI between participants immunised in pharmacies compared with non-pharmacy sites, adjusting for confounders of age, sex and influenza vaccine brand. A subgroup analysis of participants over 65 years was also performed. RESULTS: Of 101 440 participants (6992 from pharmacies; 94 448 from non-pharmacy sites), 77 498 (76.4%) responded; 96.1% (n=74 448) within 24 hours. Overall, 4.8% (n=247) pharmacy participants reported any AEFI, compared with 6% (n=4356) non-pharmacy participants (adjusted OR: 0.87; 95% CI: 0.76 to 0.99; p=0.039). Similar proportions of AEFIs were reported in pharmacy (5.8%; n=31) and non-pharmacy participants (6; n=1617) aged over 65 years (adjusted OR: 0.94; 95% CI: 0.65 to 1.35; p=0.725). The most common AEFIs in pharmacy were: pain (2%; n=104), tiredness (1.9%; n=95) and headache (1.7%; n=88); and in non-pharmacy sites: pain (2.3%; n=1660), tiredness (1.9%; n=1362) and swelling (1.5%; n=1121). CONCLUSIONS: High and rapid response rates demonstrate good participant engagement with active surveillance in both pharmacy and non-pharmacy participants. Significantly fewer AEFIs reported after pharmacist immunisations compared with non-pharmacy immunisations, with no difference in older adults, may suggest different cohorts attend pharmacy versus non-pharmacy immunisers. The integrated pharmacy system is rapidly scalable across Australia with global potential.


Subject(s)
Influenza Vaccines , Influenza, Human , Pharmacies , Adverse Drug Reaction Reporting Systems , Aged , Australia/epidemiology , Humans , Influenza Vaccines/adverse effects , Influenza, Human/prevention & control , Prospective Studies , Seasons , Vaccination , Western Australia/epidemiology
13.
BMJ Qual Saf ; 30(1): 17-26, 2021 01.
Article in English | MEDLINE | ID: covidwho-1430192

ABSTRACT

BACKGROUND: User-testing and subsequent modification of clinical guidelines increases health professionals' information retrieval and comprehension. No study has investigated whether this results in safer care. OBJECTIVE: To compare the frequency of medication errors when administering an intravenous medicine using the current National Health Service Injectable Medicines Guide (IMG) versus an IMG version revised with user-testing. METHOD: Single-blind, randomised parallel group in situ simulation. Participants were on-duty nurses/midwives who regularly prepared intravenous medicines. Using a training manikin in their clinical area, participants administered a voriconazole infusion, a high-risk medicine requiring several steps to prepare. They were randomised to use current IMG guidelines or IMG guidelines revised with user-testing. Direct observation was used to time the simulation and identify errors. Participant confidence was measured using a validated instrument. The primary outcome was the percentage of simulations with at least one moderate-severe IMG-related error, with error severity classified by an expert panel. RESULTS: In total, 133 participants were randomised to current guidelines and 140 to user-tested guidelines. Fewer moderate-severe IMG-related errors occurred with the user-tested guidelines (n=68, 49%) compared with current guidelines (n=79, 59%), but this difference was not statistically significant (risk ratio: 0.82; 95% CI 0.66 to 1.02). Significantly more simulations were completed without any IMG-related errors with the user-tested guidelines (n=67, 48%) compared with current guidelines (n=26, 20%) (risk ratio: 2.46; 95% CI 1.68 to 3.60). Median simulation completion time was 1.6 min (95% CI 0.2 to 3.0) less with the user-tested guidelines. Participants who used user-tested guidelines reported greater confidence. CONCLUSION: User-testing injectable medicines guidelines reduces the number of errors and the time taken to prepare and administer intravenous medicines, while increasing staff confidence. TRIAL REGISTRATION NUMBER: researchregistry5275.


Subject(s)
State Medicine , Adult , COVID-19 , Female , Humans , Infusions, Intravenous , Male , SARS-CoV-2 , Single-Blind Method
14.
Adv Ther ; 38(6): 3066-3076, 2021 06.
Article in English | MEDLINE | ID: covidwho-1384648

ABSTRACT

INTRODUCTION: Ophthalmologists are inevitably exposed to tears and ocular discharge during ophthalmologic examinations and are at high risk for SARS-CoV-2 infection. To understand the role of aerosols in disease transmission, we adopted a prospective cross-sectional study design and investigated the count and size distribution of aerosols generated by a non-contact tonometer and its correlation with individual tear film characteristics. METHODS: This study constituted two parts. The study population included outpatients who underwent an intraocular pressure examination in an intraocular pressure examination room (Part I) and 20 participants who underwent an intraocular pressure examination in a laboratory (Part II). The following main outcomes were measured: aerosol counts at 0, 50, 100, 150, and 200 cm from the non-contact tonometer (Part I); aerosol counts after each participant underwent non-contact tonometry, and lipid layer thickness score and tear film break-up time (Part II). RESULTS: The aerosol count decreased with increasing distance from the tonometer. The aerosol count at 0 cm had the highest value compared to that at other distances. For aerosols of diameters 0.25-0.5 µm and 0.5-1.0 µm, the count decreased at 50 cm and remained stable at further distances. For aerosols of diameters 1.0-2.5 µm and ≥ 2.5 µm, the count dropped progressively at all five distances. The aerosol count from each tonometer correlated positively with the lipid layer thickness score (r = 0.490, P = 0.028), whereas the aerosol count correlated negatively with the tear film break-up time (r = - 0.675, P = 0.001). CONCLUSIONS: Aerosols tended to coagulate during diffusion. A 50-cm distance from the tonometer could confer safety from aerosols with < 1.0-µm diameter. Aerosols generated during non-contact tonometry could contain a lipid layer component. Moreover, tear film stability could affect aerosol generation. Protective eyewear is recommended for reducing infection risk from aerosols. Individual tear film characteristics should be considered during non-contact tonometry.


Subject(s)
COVID-19 , Aerosols , Cross-Sectional Studies , Humans , Manometry , Prospective Studies , SARS-CoV-2 , Tears , Tonometry, Ocular
15.
Eur J Dermatol ; 31(2): 199-204, 2021 Apr 01.
Article in English | MEDLINE | ID: covidwho-1352754

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, wearing face masks is mandatory not only for health care workers (HCWs) but also for the general population in many countries around the globe. OBJECTIVES: The aim of the study was to investigate the onset of adverse facial skin reactions due to compulsory face masks during the COVID-19 pandemic in HCWs and non-HCWs, and draw awareness of this new dermatological condition and its preventive measures. MATERIALS & METHODS: A questionnaire was distributed to 550 patients and HCWs from the Department of Dermatology and Allergy of the University Hospital Munich (LMU), Germany. Participants were surveyed regarding mask type, duration of usage and adverse facial skin reactions. Information on symptoms and the use of skin care products and topical drugs were retrieved. RESULTS: The duration of wearing masks showed a significant impact on the prevalence of symptoms (p < 0.001). Type IV hypersensitivity was significantly more likely in participants with symptoms compared to those without symptoms (p = 0.001), whereas no increase in symptoms was observed in participants with atopic diathesis. HCWs used facial skin care products significantly more often than non-HCWs (p = 0.001). CONCLUSION: Preventive and therapeutic measures should be established in order to avoid "face mask dermatitis", especially for people with underlying risk factors.


Subject(s)
COVID-19/prevention & control , Dermatitis, Contact/etiology , Dermatitis, Occupational/etiology , Facial Dermatoses/etiology , Health Personnel , Masks/adverse effects , Dermatitis, Contact/epidemiology , Dermatitis, Occupational/epidemiology , Facial Dermatoses/epidemiology , Germany/epidemiology , Humans
16.
Chin Med J (Engl) ; 134(11): 1289-1298, 2021 Apr 28.
Article in English | MEDLINE | ID: covidwho-1343718

ABSTRACT

BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 µg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 µg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-µg vaccine (n = 24), 10-µg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-µg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-µg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-µg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-µg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-µg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , COVID-19 Vaccines , Double-Blind Method , Humans , Vaccines, Inactivated/adverse effects
17.
Int J Drug Policy ; 93: 102904, 2021 07.
Article in English | MEDLINE | ID: covidwho-1343192

ABSTRACT

BACKGROUND: The popularity of virtual raves and happy hours has increased during the COVID-19 pandemic. While nightlife settings are often associated with drug use, it is unknown whether virtual events are associated with use. METHODS: Electronic dance music (EDM) partygoers who live in New York and reported recent drug use were recruited online and screened for eligibility throughout April and May 2020. Eligible adults (n = 128) were asked about virtual rave and happy hour attendance during the COVID-19 crisis. We examined prevalence and correlates of drug use during such events. RESULTS: 55.5% of participants attended virtual raves and 69.5% attended virtual happy hours. 40.9% used illegal drugs during virtual raves and the most frequently used drugs were cannabis (29.6%), ecstasy/MDMA/Molly (8.5%), LSD (7.0%), and cocaine (4.2%). 33.7% used illegal drugs during virtual happy hours and the most frequently used drugs were cannabis (29.2%), cocaine (3.4%), and ketamine (3.4%). Older participants were more likely to use illegal drugs during virtual raves, and those reporting past-year use of more drugs were more likely to use drugs during virtual raves and/or happy hours (ps<0.05). CONCLUSIONS: EDM partygoers are at risk for using drugs during virtual events. Results can inform prevention and harm reduction efforts.


Subject(s)
COVID-19 , Dancing , Illicit Drugs , Music , N-Methyl-3,4-methylenedioxyamphetamine , Substance-Related Disorders , Adult , Electronics , Humans , New York , Pandemics , SARS-CoV-2 , Substance-Related Disorders/epidemiology
18.
Lancet ; 396(10259): 1345-1352, 2020 10 24.
Article in English | MEDLINE | ID: covidwho-1337017

ABSTRACT

BACKGROUND: Lopinavir-ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies. Here, we report the results of a randomised trial to assess whether lopinavir-ritonavir improves outcomes in patients admitted to hospital with COVID-19. METHODS: In this randomised, controlled, open-label, platform trial, a range of possible treatments was compared with usual care in patients admitted to hospital with COVID-19. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus lopinavir-ritonavir (400 mg and 100 mg, respectively) by mouth for 10 days or until discharge (or one of the other RECOVERY treatment groups: hydroxychloroquine, dexamethasone, or azithromycin) using web-based simple (unstratified) randomisation with allocation concealment. Randomisation to usual care was twice that of any of the active treatment groups (eg, 2:1 in favour of usual care if the patient was eligible for only one active group, 2:1:1 if the patient was eligible for two active groups). The primary outcome was 28-day all-cause mortality. Analyses were done on an intention-to-treat basis in all randomly assigned participants. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. FINDINGS: Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive lopinavir-ritonavir and 3424 patients to receive usual care. Overall, 374 (23%) patients allocated to lopinavir-ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1·03, 95% CI 0·91-1·17; p=0·60). Results were consistent across all prespecified subgroups of patients. We observed no significant difference in time until discharge alive from hospital (median 11 days [IQR 5 to >28] in both groups) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 0·98, 95% CI 0·91-1·05; p=0·53). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1·09, 95% CI 0·99-1·20; p=0·092). INTERPRETATION: In patients admitted to hospital with COVID-19, lopinavir-ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. These findings do not support the use of lopinavir-ritonavir for treatment of patients admitted to hospital with COVID-19. FUNDING: Medical Research Council and National Institute for Health Research.


Subject(s)
COVID-19/drug therapy , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Aged , Aged, 80 and over , Drug Combinations , Female , Hospitalization , Humans , Male , Treatment Outcome
19.
Trials ; 21(1): 544, 2020 Jun 19.
Article in English | MEDLINE | ID: covidwho-1331953

ABSTRACT

OBJECTIVES: Phase I - To determine the optimal dose of each candidate (or combination of candidates) entered into the platform. Phase II - To determine the efficacy and safety of each candidate entered into the platform, compared to the current Standard of Care (SoC), and recommend whether it should be evaluated further in a later phase II & III platforms. TRIAL DESIGN: AGILE-ACCORD is a Bayesian multicentre, multi-arm, multi-dose, multi-stage open-label, adaptive, seamless phase I/II randomised platform trial to determine the optimal dose, activity and safety of multiple candidate agents for the treatment of COVID-19. Designed as a master protocol with each candidate being evaluated within its own sub-protocol (Candidate Specific Trial (CST) protocol), randomising between candidate and SoC with 2:1 allocation in favour of the candidate (N.B the first candidate has gone through regulatory approval and is expected to open to recruitment early summer 2020). Each dose will be assessed for safety sequentially in cohorts of 6 patients. Once a phase II dose has been identified we will assess efficacy by seamlessly expanding into a larger cohort. PARTICIPANTS: Patient populations can vary between CSTs, but the main eligibility criteria include adult patients (≥18 years) who have laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We will include both severe and mild-moderate patients defined as follows: Group A (severe disease) - patients with WHO Working Group on the Clinical Characteristics of COVID-19 infection 9-point ordinal scale of Grades 4 (hospitalised, oxygen by mask or nasal prongs), 5 (hospitalised, non-invasive ventilation or high flow oxygen), 6 (hospitalised, intubation and mechanical ventilation) or 7 (hospitalised, ventilation and additional organ support); Group B (mild-moderate disease) - ambulant or hospitalised patients with peripheral capillary oxygen saturation (SpO2) >94% RA. If any CSTs are included in the community setting, the CST protocol will clarify whether patients with suspected SARS-CoV-2 infection are also eligible. Participants will be recruited from England, North Ireland, Wales and Scotland. INTERVENTION AND COMPARATOR: Comparator is the current standard of care (SoC), in some CSTs plus placebo. Candidates that prevent uncontrolled cytokine release, prevention of viral replication, and other anti-viral treatment strategies are at various stages of development for inclusion into AGILE-ACCORD. Other CSTs will be added over time. There is not a set limit on the number of CSTs we can include within the AGILE-ACCORD Master protocol and we will upload each CST into this publication as each opens to recruitment. MAIN OUTCOMES: Phase I: Dose limiting toxicities using Common Terminology Criteria for Adverse Events v5 Grade ≥3 adverse events. Phase II: Agreed on a CST basis depending on mechanism of action of the candidate and patient population. But may include; time to clinical improvement of at least 2 points on the WHO 9-point category ordinal scale [measured up to 29 days from randomisation], progression of disease (oxygen saturation (SaO2) <92%) or hospitalization or death, or change in time-weighted viral load [measured up to 29 days from randomisation]. RANDOMISATION: Varies with CST, but default is 2:1 allocation in favour of the candidate to maximise early safety data. BLINDING (MASKING): For the safety phase open-label although for some CSTs may include placebo or SoC for the efficacy phase. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Varies between CSTs. However simulations have shown that around 16 participants are necessary to determine futility or promise of a candidate at a given dose (in efficacy evaluation alone) and between 32 and 40 participants are required across the dose-finding and efficacy evaluation when capping the maximum number of participants contributing to the evaluation of a treatment at 40. TRIAL STATUS: Master protocol version number v5 07 May 2020, trial is in setup with full regulatory approval and utilises several digital technology solutions, including Medidata's Rave EDC [electronic data capture], RTSM for randomisation and patient eConsent on iPads via Rave Patient Cloud. The recruitment dates will vary between CSTs but at the time of writing no CSTs are yet open for recruitment. TRIAL REGISTRATION: EudraCT 2020-001860-27 14th March 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Randomized Controlled Trials as Topic , Antiviral Agents/adverse effects , COVID-19 , Humans , Pandemics , SARS-CoV-2
20.
JAMA ; 326(1): 35-45, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1318655

ABSTRACT

Importance: Although effective vaccines against COVID-19 have been developed, additional vaccines are still needed. Objective: To evaluate the efficacy and adverse events of 2 inactivated COVID-19 vaccines. Design, Setting, and Participants: Prespecified interim analysis of an ongoing randomized, double-blind, phase 3 trial in the United Arab Emirates and Bahrain among adults 18 years and older without known history of COVID-19. Study enrollment began on July 16, 2020. Data sets used for the interim analysis of efficacy and adverse events were locked on December 20, 2020, and December 31, 2020, respectively. Interventions: Participants were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 (5 µg/dose; n = 13 459) and HB02 (4 µg/dose; n = 13 465) strains or an aluminum hydroxide (alum)-only control (n = 13 458); they received 2 intramuscular injections 21 days apart. Main Outcomes and Measures: The primary outcome was efficacy against laboratory-confirmed symptomatic COVID-19 14 days following a second vaccine dose among participants who had no virologic evidence of SARS-CoV-2 infection at randomization. The secondary outcome was efficacy against severe COVID-19. Incidence of adverse events and reactions was collected among participants who received at least 1 dose. Results: Among 40 382 participants randomized to receive at least 1 dose of the 2 vaccines or alum-only control (mean age, 36.1 years; 32 261 [84.4%] men), 38 206 (94.6%) who received 2 doses, contributed at least 1 follow-up measure after day 14 following the second dose, and had negative reverse transcriptase-polymerase chain reaction test results at enrollment were included in the primary efficacy analysis. During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 [95% CI, 8.3-17.8] per 1000 person-years), 21 in the HB02 group (9.8 [95% CI, 6.4-15.0] per 1000 person-years), and 95 in the alum-only group (44.7 [95% CI, 36.6-54.6] per 1000 person-years), resulting in a vaccine efficacy, compared with alum-only, of 72.8% (95% CI, 58.1%-82.4%) for WIV04 and 78.1% (95% CI, 64.8%-86.3%) for HB02 (P < .001 for both). Two severe cases of COVID-19 occurred in the alum-only group and none occurred in the vaccine groups. Adverse reactions 7 days after each injection occurred in 41.7% to 46.5% of participants in the 3 groups; serious adverse events were rare and similar in the 3 groups (WIV04: 64 [0.5%]; HB02: 59 [0.4%]; alum-only: 78 [0.6%]). Conclusions and Relevance: In this prespecified interim analysis of a randomized clinical trial, treatment of adults with either of 2 inactivated SARS-CoV-2 vaccines significantly reduced the risk of symptomatic COVID-19, and serious adverse events were rare. Data collection for final analysis is pending. Trial Registration: ClinicalTrials.gov Identifier: NCT04510207; Chinese Clinical Trial Registry: ChiCTR2000034780.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , Adult , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Datasets as Topic , Double-Blind Method , Female , Humans , Injections, Intramuscular , Male , Middle Aged , Middle East , Vaccines, Inactivated/immunology
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