OBJECTIVE: To perform a systematic review and meta-analysis to determine the prevalence, risk factors for contracting COVID-19, and complications of COVID-19, in children with CLD.
METHODS: This systematic review was based on articles published between January 1, 2020 and July 25, 2022. Children under 18 years old, with any CLD and infected with COVID-19 were included.
RESULTS: Ten articles involving children with asthma and four involving children with cystic fibrosis (CF) were included in the analyses. The prevalence of COVID-19 in children with asthma varied between 0.14% and 19.1%. The use of inhaled corticosteroids (ICS) was associated with reduced risk for COVID-19 (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.40-0.90). Uncontrolled asthma, younger age, AND moderate-severe asthma were not significant risk factors for contracting COVID-19. Children with asthma had an increased risk for hospitalization (RR: 1.62, 95% CI: 1.07-2.45) but were not more likely to require assisted ventilation (RR: 0.51, 95% CI: 0.14-1.90). The risk of COVID-19 infection among children with CF was <1%. Posttransplant and cystic fibrosis-related diabetes mellitus (CFRDM) patients were at an increased risk for hospitalization and intensive care treatment.
CONCLUSION: Hospitalizations were higher in children with asthma with COVID-19 infection. However, using ICS reduced the risk of COVID-19 infection. As for CF, postlung transplantation and CFRDM were risk factors for severe disease.
METHODS: Electronic databases and country-specific healthcare databases were searched to identify relevant studies/reports. The quality assessment of individual studies was conducted using the Newcastle-Ottawa Scale. Country-specific proportion of individuals with COVID-19 who developed ARDS and reported death were combined in a random-effect meta-analysis to give a pooled mortality estimate of ARDS.
RESULTS: The overall pooled mortality estimate among 10,815 ARDS cases in COVID-19 patients was 39% (95% CI: 23-56%). The pooled mortality estimate for China was 69% (95% CI: 67-72%). In Europe, the highest mortality estimate among COVID-19 patients with ARDS was reported in Poland (73%; 95% CI: 58-86%) while Germany had the lowest mortality estimate (13%; 95% CI: 2-29%) among COVID-19 patients with ARDS. The median crude mortality rate of COVID-19 patients with reported corticosteroid use was 28.0% (lower quartile: 13.9%; upper quartile: 53.6%).
CONCLUSIONS: The high mortality in COVID-19 associated ARDS necessitates a prompt and aggressive treatment strategy which includes corticosteroids. Most of the studies included no information on the dosing regimen of corticosteroid therapy, however, low-dose corticosteroid therapy or pulse corticosteroid therapy appears to have a beneficial role in the management of severely ill COVID-19 patients.
METHODS: The translation of the English version of the valid 10-item TAI questionnaire into BM was followed by subjecting it to a series of tests establishing factorial, concurrent and known group validities. Concurrent validity was assessed through Spearman's rank correlation coefficient against pharmacy refill-based adherence scores. Known group validity was assessed by cross-tabulation against asthma symptom control and using chi-square test. The internal consistency of the test scale was determined by a test-retest method using Cronbach's alpha (α) value and intraclass correlation coefficients.
RESULTS: A total of 120 adult asthma patients participated in the study. A 2-factor structure was obtained and confirmed with acceptable fit indices; CFI, NFI, IFI, TLI >0.9 and, RMSEA was 0.08. The reliability of the scale was 0.871. The test-retest reliability coefficient for the total sum score was 0.832 (p 85%.
CONCLUSIONS: The scale successfully translated into BM and validated. The 10-item TAI-BM appears fit for use in testing inhaler adherence of Malaysian patients with asthma.
CLINICAL QUESTION: What is the role of drugs in the treatment of patients with covid-19?
CONTEXT: The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and underway. Emerging SARS-CoV-2 variants and subvariants are changing the role of therapeutics.
WHAT IS NEW?: The guideline development group (GDG) defined 1.5% as a new threshold for an important reduction in risk of hospitalisation in patients with non-severe covid-19. Combined with updated baseline risk estimates, this resulted in stratification into patients at low, moderate, and high risk for hospitalisation. New recommendations were added for moderate risk of hospitalisation for nirmatrelvir/ritonavir, and for moderate and low risk of hospitalisation for molnupiravir and remdesivir. New pharmacokinetic evidence was included for nirmatrelvir/ritonavir and molnupiravir, supporting existing recommendations for patients at high risk of hospitalisation. The recommendation for ivermectin in patients with non-severe illness was updated in light of additional trial evidence which reduced the high degree of uncertainty informing previous guidance. A new recommendation was made against the antiviral agent VV116 for patients with non-severe and with severe or critical illness outside of randomised clinical trials based on one RCT comparing the drug with nirmatrelvir/ritonavir. The structure of the guideline publication has also been changed; recommendations are now ordered by severity of covid-19.
ABOUT THIS GUIDELINE: This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF on the WHO website, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact.
FUTURE RECOMMENDATIONS: Recommendations on anticoagulation are planned for the next update to this guideline. Updated data regarding systemic corticosteroids, azithromycin, favipiravir and umefenovir for non-severe illness, and convalescent plasma and statin therapy for severe or critical illness, are planned for review in upcoming guideline iterations.
METHODS: This is a systematic review and a meta-analysis evaluating the evidence from clinical trials on the effect of colchicine and corticosteroids against COVID-19. In this review, we have systematically searched five databases [(PubMed, Embase, clinicaltrials.gov, ICTRP, CINAHL (EBSCO)]. Cochrane's data extraction sheet was used to collect the required information, and RevMan-5.4.1 was used to conduct the meta-analysis and to assess the risk of bias. The review was registered in Prospero (CRD42022299718).
RESULTS: The total number of included studies was 17, with 18,956 participants; the majority were male 12,001. Out of which, 8772 participants were on colchicine, 569 took methylprednisolone, and 64 patients received prednisolone. The meta-analysis has shown that colchicine had no significant effect on reducing the mortality rate among COVID-19 patients [OR 0.98(95% CI 0.90-1.08), p = .70), I2:1%)], corticosteroids have significantly reduced the mortality rates [OR 0.55 (95% CI 0.33-0.91), p = .02, I2:40]. Colchicine did not reduce the incidence of ICU admissions [OR 0.74 (95% CI 0.39-1.40), p = .35, I2:0%], while steroidal drugs significantly reduced the ICU admissions [OR 0.42 (95% CI 0.23-0.78), p = .005, I2:0%]. Unlike steroidal drugs [OR 0.53 (95% CI 0.30-0.95), p = .03, I2:61%], colchicine failed to reduce the need for mechanical ventilation [OR 0.73 (95% CI 0.48-1.10), p = .13, I2:76%]. Steroidal drugs significantly reduced the duration of hospitalization among COVID-19 patients [OR -0.50 (95% CI -0.79-0.21), p = .0007, I2:36%].
CONCLUSIONS: The use of colchicine did not significantly reduce the mortality rate, ICU admissions, and mechanical ventilation among COVID-19 patients. Conversely, corticosteroids significantly reduced the mortality rate, ICU admissions, mechanical ventilation, and hospitalization duration among COVID-19 patients.
METHODS: Seven licensed practicing community pharmacists (from the Klang Valley, Malaysia) were interviewed between 23rd September to 14th November 2021. These were CPs participating in the questionnaire study who agreed to be interviewed. NVIVO 11 software was used for data analysis. Codes and themes were generated and agreed on by the researchers.
RESULTS: The major themes identified related to the process mentioned of providing information to patients, the issues addressed by CPs during the counselling (including steroid phobia, overuse of TCS, patients asking for a specific preparation by name), less counselling support material, language barriers, lesser knowledge about certain conditions, information sources used by CPs (material provided by Ministry of Health and Malaysian Pharmacists Association, MIMS) and suggestions to strengthen the quality of counselling (specialization in skin diseases, webinars, shared care models). For patients requesting a particular preparation by name, the pharmacist will decide whether the preparation requested is suitable or suggest an alternative. Steroid phobia was seen more commonly among parents of young children and young patients. MIMS was available as a smartphone application making it easier to use. Advanced training for CPs in the management of skin conditions like that provided for diabetes mellitus can be considered.
CONCLUSIONS: Counselling was conducted while dispensing TCS in the open area of the pharmacy. Challenges to counselling were lack of time, limited counselling materials, and language barriers. Steroid phobia requires attention. Initiatives to strengthen counselling were mentioned by respondents and appear feasible. Further research covering the entire country is required.
METHODS: Patients enrolled in the PROGRESS registry were evaluated for use of vasopressor and LDC (equivalent or lesser potency to hydrocortisone 50 mg six-hourly plus 50 microg 9-alpha-fludrocortisone) for treatment of severe sepsis at any time in intensive care units (ICUs). Baseline characteristics and hospital mortality were analyzed, and logistic regression techniques used to develop propensity score and outcome models adjusted for baseline imbalances between groups.
RESULTS: A total of 8,968 patients with severe sepsis and sufficient data for analysis were studied. A total of 79.8% (7,160/8,968) of patients received vasopressors, and 34.0% (3,051/8,968) of patients received LDC. Regional use of LDC was highest in Europe (51.1%) and lowest in Asia (21.6%). Country use was highest in Brazil (62.9%) and lowest in Malaysia (9.0%). A total of 14.2% of patients on LDC were not receiving any vasopressor therapy. LDC patients were older, had more co-morbidities and higher disease severity scores. Patients receiving LDC spent longer in ICU than patients who did not (median of 12 versus 8 days; P <0.001). Overall hospital mortality rates were greater in the LDC than in the non-LDC group (58.0% versus 43.0%; P <0.001). After adjusting for baseline imbalances, in all mortality models (with vasopressor use), a consistent association remained between LDC and hospital mortality (odds ratios varying from 1.30 to 1.47).
CONCLUSIONS: Widespread use of LDC for the treatment of severe sepsis with significant regional and country variation exists. In this study, 14.2% of patients received LDC despite the absence of evidence of shock. Hospital mortality was higher in the LDC group and remained higher after adjustment for key determinates of mortality.