Philippine guidelines on periodic health examination: Pediatric immunization

Executive Summary@#This Clinical Practice Guideline for the Periodic Health Examination (Pediatric Immunization) is an output from the joint undertaking of the Department of Health and National Institutes of Health-Institute of Clinical Epidemiology. This clinical practice guideline is a systematic synthesis of scientific evidence on immunization for the prevention of human papilloma virus (HPV) infection, influenza, typhoid fever, Japanese encephalitis, poliomyelitis, meningococcal infection, and Hepatitis A in the pediatric population. The CPG provides nine (9) recommendations on prioritized questions regarding the relevant vaccines for preventing these seven (7) diseases. Recommendations are based on the appraisal of the best available evidence on each of the eight identified clinical questions. The CPG is intended to be used by general practitioners and specialists in the primary care setting, policy makers, employers and administrators, allied health practitioners and even patients. The guideline development process followed the widely accepted Grading of Recommendations, Assessment, Development, and Evaluation or the GRADE approach including GRADE Adolopment, a systematic process of adapting evidence summaries and the GRADE Evidence to Decision (EtD) framework. 1,2 It includes 1) identification of critical questions and critical outcomes, 2) retrieval of current evidence, 3) assessment and synthesis of the evidence base for these critical questions, 4) formulation of draft recommendations, 5) convening of a multi-sectoral stakeholder panel to discuss values and preferences and assess the strength of the recommendations, and 6) planning for dissemination, implementation, impact evaluation and updating. The recommendations in this CPG shall hold and will be updated after 3 years or when new evidence arise.

Clinical characteristics and patient symptoms associated with poor outcomes among children with COVID-19: A rapid review

Objective@#To identify specific clinical characteristics and patient signs and symptoms that increase the risk of developing severe/critical COVID-19 disease or death in the pediatric population, and identify strength of these associations @*Methodology@#A systematic search was done in PubMed, Science Direct, Cochrane Library and grey literature databases focusing on severe and critical COVID-19 disease in the zero to eighteen year old age group until August 26, 2020. Data regarding patient characteristics, signs and symptoms on admission and disease severity were extracted. Outcomes measured were severe or critical COVID-19, Multisystem Inflammatory Syndrome in Children (MIS-C) or death. Results were pooled and meta-analyzed. @*Results@#Four eligible studies with a total of 292 pediatric patients with COVID-19 were examined. Older children (MD=6.62, 95%CI=4.23 to 9.00, p-value<0.00001, I2=33%) significantly present with a higher percentage of severe disease. Shortness of breath (OR=8.14, 95%CI=2.33 to 28.47, p-value=0.001, I2=42%) was also found to be associated with severe COVID-19 disease. The presence of a pre-existing medical condition (OR=4.02, 95%CI=1.55 to 10.43, p-value=0.004, I2=0%), especially cardiac disease (OR=6.40, 95%CI=1.45 to 28.38, p-value=0.01, I 2=13%) and diabetes (OR=7.01, 95%CI=1.54 to 31.95, p-value=0.01, I2=0%) was noted to be a risk factor for severe disease. @*Conclusion@#Based on poor quality observational studies, older age group, shortness of breath, and a pre-existing medical condition, especially cardiac disease or diabetes were found to be associated with poor outcomes in children with COVID-19.

Assessing quality of systematic reviews in dermatology from the Philippines using AMSTAR 2 Part 1: Methodologic quality of dermatological systematic reviews from the Philippines

@#BACKGROUND: Quality systematic reviews (SRs) are essential in the practice of evidence-based dermatology. We assessed the methodologic quality of SRs in dermatology from the Philippines. METHODS: We searched databases (MEDLINE, CDSR, PROSPERO, HERDIN; from inception until June 30, 2019), and secondary sources. We included SRs, authored by Filipino primary authors, which included clinical trials on any intervention for the treatment or prevention of a dermatologic disease or for maintenance of healthy skin, hair or nails. Two reviewers independently extracted data and appraised the methodological quality of each included SR using the AMSTAR 2. The 16-item AMSTAR 2 has 7 critical items and 9 non-critical items. The number of critical items mainly determine the overall confidence in the results of the review. Descriptive analysis using means and standard deviation for continuous data, and frequency and percentage distribution for categorical data were employed. RESULTS: Twenty SRs were included in this review, and were mostly published in the 2010s. Majority of SRs had three authors, who belonged to a single institution, with at least one dermatologist. The most common topic was infections and both oral and topical interventions were used. Majority had 5 included studies in the SRs, with a median number of 425 participants. The median number of critical flaws in the included SRs was 4.5, and non-critical flaws, 5. Overall confidence was critically low in majority (19/20 ) of included reviews, with only one review rated as low. CONCLUSION: The methodologic quality of the dermatology SRs from the Philippines based on the AMSTAR 2 tool was poor with a rating of critically low in majority. There is a need to improve quality of conduct and reporting through dissemination of the reporting guidelines such as the PRISMA

Assessment of quality of systematic reviews in dermatology using AMSTAR 2 Part 2 of 2. Validity and reliability testing of AMSTAR 2 (UP-PGH)

@#BACKGROUND AMSTAR 2 enables a more detailed assessment of systematic reviews and includes non-randomised studies of healthcare interventions, compared to its earlier version, AMSTAR. We validated AMSTAR 2 in a group of systematic reviews in dermatology in the Philippines. METHODS We used a cohort of systematic reviews (SRs) in dermatology from the Philippine that were previously described in Part 1 of this 2-part series. The SRs included clinical trials on any intervention for the treatment or prevention of a dermatologic disease or for maintenance of healthy skin, hair or nails. Two reviewers independently extracted data and used AMSTAR 2 to appraise the methodological quality of each included SR. We determined construct validity by comparing the number of critical flaws between a set of non-Cochrane and matched Cochrane reviews, using Wilcoxon rank sum test. We tested for interrater reliability of the AMSTAR 2 tool using Gwet’s AC1 statistic. RESULTS: We included 20 non-Cochrane systematic reviews in dermatology by Philippine-based authors, and a set of 20 reviews from the Cochrane skin group, matched by year and randomly chosen. Construct validity testing showed a significantly greater number of AMSTAR 2 critical flaws (median 4.5 vs 0.0; z=3.64; P=0.000) and non-critical weaknesses (5 vs 2.0; z-score=3.10; P-value=0.001) by non-Cochrane reviews compared to a matched set of Cochrane skin group reviews. There was good interrater reliability (average Gwet’s AC1 statistic = 0.87) with the lowest agreement (0.62) for discussion of heterogeneity (item 14), and the highest agreement (0.97) for study selection criteria (item 3). CONCLUSION The AMSTAR 2 was a valid and reliable tool for assessing systematic reviews using a cohort of reviews by dermatology reviews, both non-Cochrane and Cochrane. Further validation of the AMSTAR 2 is needed to determine if it can be applied to a wide variety of systematic reviews.

The diagnostic accuracy of SARS-CoV-2 rapid antibody tests among asymptomatic employees returning to work during General Community Quarantine Period (June 1 to July 31, 2020)

Objectives@#The study was done to determine the diagnostic accuracy of rapid antibody tests (RATs) in detecting SARS-CoV-2 infection among asymptomatic employees returning to work. The study also aimed to determine the prevalence of asymptomatic RT-PCR-confirmed COVID-19 infection among these workers. @*Methods@#The study was a retrospective cohort of asymptomatic employees involved in the manufacturing, marketing, and sales of pharmaceutical, consumer, and animal products in the Philippines. They underwent screening for COVID-19 using both rapid antibody and RT-PCR tests as part of the return-to-work company policy from June 1 to July 31, 2020. The sensitivity and specificity of the RATs were computed using RT-PCR as the reference standard. The prevalence of RT-PCR positive COVID-19 infections among asymptomatic returning workers was also determined. @*Results@#Asymptomatic workers (n=5,585) were simultaneously tested for COVID-19 using RAT and RT-PCR. The sensitivity of a positive IgG and IgM was 23.9 (95% CI: 22.8 – 25.0), while the specificity was 93.3 (95% CI: 92.6 - 93.9). The prevalence of RT-PCR identified COVID-19 infection among asymptomatic workers was 4.9% (95% CI: 4.4 – 5.5). @*Conclusion@#The utility of RATs as a screening tool to detect asymptomatic COVID-19 individuals is limited due to its low sensitivity compared to RT-PCR.

Should Lopinavir/Ritonavir combination be used in the treatment of COVID-19?

Background@#Lopinavir/Ritonavir is an oral combination agent being used to treat Human Immunodeficiency Virus. It was demonstrated to have clinical and in vitro activity against coronaviruses. There are no specific anti viral preparation or biologic agents currently recommended to treat Severe Acute Respiratory Syndrome Corona Virus 2(SARS-CoV-2) infection. There are no in-vitro studies published as well, for Lopinavir/ritonavir against SARS- CoV-2. However, recent case series and cohort studies showed earlier clinical improvement and shorter duration of viral shedding were noted especially if the combination drug is administered early in the course of the disease. @*Objective@#The objective of this review is to search, retrieve, appraise and summarize existing studies and clinical trials regarding the efficacy and safety of Lopinavir/Ritonavir combination in the treatment of SARS Cov-2 infection. The evidenced based recommendations may be used as a guide by clinicians and practitioners in their current practice.@*Methods@#Electronic databases were searched for evidences (Medline, CENTRAL, ISRCTN registry, ClinicalTrial. gov and Chinese Clinical Trial Registry) and articles were selected based on a pre-defined criteria according to population, intervention, outcome and study designs.@*Results@#Two randomized controlled trials were included in this review. Lopinavir/ritonavir treatment did not significantly accelerate clinical improvement, reduce mortality, or shoten the viral RNA detectability in patients with serious COVID-19.@*Conclusion@#There is little evidence to conclude on the effectiveness of lopinavir/ritonavir in patients with COVID-19. More high-quality randomized controlled trials are needed.

Should Colchicine be used in the treatment of COVID-19?

Key Findings@#There is currently insufficient evidence on the use of colchicine in the treatment of COVID-19 patients, but there are 4 ongoing trials awaiting completion this 2020. Colchicine is an anti-inflammatory agent currently being used for a variety of inflammatory conditions such as gout, familial Mediterranean fever, Behcet’s syndrome and pericarditis. Its powerful anti-inflammatory properties may have the potential to prevent the development of COVID-19 complications. There are currently no evidence for its use on COVID-19 patients, but there are 4 ongoing studies that may be released from the period of May 2020 to September 2020. Common adverse events include gastrointestinal effects such as diarrhea but does not exhibit serious and life-threatening adverse events. There is no mention of colchicine in the WHO Interim Guidance, US CDC Clinical Interim Guidelines and Chinese Clinical Guidance for COVID-19 management.

Should vitamin C/Ascorbic acid infusion be used in the treatment of COVID-19?

Key Findings@#There is no direct evidence available as of this point for efficacy of intravenous vitamin C as an adjunctive treatment in preventing mortality or shortening disease course among adults suspected of, or positive for COVID-19. • Vitamin C is currently not mentioned in the treatment guidelines for COVID. • Currently, there are 3 ongoing trials registered in clinicaltrials.gov studying intravenous vitamin C in COVID-19. No other ongoing or planned trials were registered in the other trial registries. • Most of the available data are from studies on disease populations which may be considered as COVID-19 suspects:  Conflicting results on mortality from indirect evidence among patients with sepsis with or without ARDS with significant reduction in mortality found in only a small subset of patients (n-40) with severe sepsis given high dose Vitamin C infusion.  Strong evidence supporting no mortality benefit from 5 meta-analyses on critically ill patients due to conditions other than or in combination with sepsis who were given Vit C infusion alone or in combinations with other medications. One meta-analysis showed benefit in decreasing duration of ICU stay and mechanical ventilation but sample size is small. Most showed no benefit on and other key endpoints such as acute kidney injury, duration of hospital stay/ ICU stay/ duration of vasopressor use or duration of mechanical ventilation. • The use of Vit C infusion is not mentioned in the treatment guidelines for COVID-19 or ARDS. • The risks or adverse events with short term use of Vitamin C infusion in the general population is negligible or minimal. It should be avoided in patients with G6PD insufficiency. The dose should be carefully adjusted for patients with renal insufficiency.

What are the effective methods of decontaminating N95 mask for reuse?

KEY FINDINGS@# Based on laboratory-based studies, ultraviolet germicidal irradiation (UVGI), microwave generated steam, warm moist heat, and hydrogen peroxide vapor (HPV) were able to reduce the load of influenza viruses (A/H5N1, H1N1) or G. stearothermophilus and at the same time maintain the integrity of N95 respirators. • Considering the current pandemic, there is a potential for shortage of N95 facepiece filtering respirator (FFR) for healthcare workers. • No studies in humans were found comparing effectiveness of N95 post-decontamination. • Laboratory based studies done on influenza virus (A/H5N1, H1N1) have shown that ultraviolet germicidal irradiation, microwave generated steam, or warm moist heat was able to reduce the viral load by as much as 4 log and at the same time maintain respirator performance by keeping the percent penetration below 5% and the pressure drop within standards. • While UVGI was able to maintain integrity of FFRs up to 3 cycles, microwave generated steam may melt the metallic components of certain N95 masks. • Hydrogen peroxide vapor (HPV) had minimal effect on respirator performance and structural integrity up to 20 cycles and was also effective in eradicating G. stearothermophilus and aerosolized bacteriophages. • Bleach, ethanol and isopropanol all affected the mean penetration of the mask beyond the 5% limit. • The Centers for Disease Control (CDC) does not recommend decontamination then reuse of FFRs as standard care but decontamination with UVGI, HPV or moist heat may be considered as an option in FFR shortages.

Rapid evidence reviews for the Philippine COVID-19 crisis

@#One of the consequences of the COVID-19 pandemic is an avalanche of information that is unprecedented in magnitude. In the past 2 months, healthcare providers, policy-makers and the general public have been overwhelmed by this phenomenon. Aside from usual news from TV, radio, newspapers and medical journals, people from all walks of life have had to process kilometric threads on viber, facebook and twitter, as well as hundreds of issuances from all government agencies - from the Office of the President down to the barangays. The information from these various sources are often inconsistent or conflicting, and are always rapidly evolving. New information emerges as outdated information is just beginning to circulate. To aggravate the situation, the chaos is taken advantage of by perpetrators of false information. Clearly, this “informageddon” has led to “information overload” – the inability to process facts because of volume or pace. The manifestation is the widespread panic we are witnessing from all sectors of society. The consequence is impaired decision making – by individuals, families, communities and policy makers. Ultimately, this may lead to a prolonged, uncontrolled pandemic characterized by avoidable deaths, disability, and huge social and economic costs. Even healthcare providers are affected. Because of fear, many feel pressured to do tests and give treatments for COVID-19, that are poorly tested for effectiveness and safety. To help manage the information for policy-makers, healthcare workers and the general public, a group of 70 clinical epidemiologists and health professionals gathered together from the Institute of Clinical Epidemiology, National Institutes of Health-UP Manila and the Asia-Pacific Center for Evidence Based Healthcare Inc. The group conducted voluntary rapid evidence reviews and referred to themselves as “The Rappers”. The reviews were graciously shared by Philippine Society of Microbiology and Infectious Diseases through their website (PSMID.org). The online version allowed regular and rapid updates as evidence accrued.