Characterization of hypersensitivity reactions reported among Andrographis paniculata users in Thailand using Health Product Vigilance Center (HPVC) database

Background: Andrographis paniculata (andrographis) is one of the herbal products that are widely used for various indications. Hypersensitivity reactions have been reported among subjects receiving Andrographis paniculata in Thailand. Understanding of characteristics of patients, adverse events, and clinical outcomes is essential for ensuring population safety. This study aimed to describe the characteristics of hypersensitivity reactions reported in patients receiving andrographis containing products in Thailand using national pharmacovigilance database. Methods: Thai Vigibase data from February 2001 to December 2012 involving andrographis products were used. This database includes the reports submitted through the spontaneous reporting system and intensive monitoring programmes. The database contained patient characteristic, adverse events associated with andrographis products, and details on seriousness, causality, and clinical outcomes. Case reports were included for final analysis if they met the inclusion criteria; 1) reports with andrographis being the only suspected cause, 2) reports with terms consistent with the constellation of hypersensitivity reactions, and 3) reports with terms considered critical terms according to WHO criteria. Descriptive statistics were used. Results: A total of 248 case reports of andrographis-associated adverse events were identified. Only 106 case reports specified andrographis herbal product as the only suspected drug and reported at least one term consistent with constellation of hypersensitivity reactions. Most case reports (89%) came from spontaneous reporting system with no previously documented history of drug allergy (88%). Of these, 18 case reports were classified as serious with 16 cases requiring hospitalization. For final assessment, the case reports with terms consistent with constellation of hypersensitivity reactions and critical terms were included. Thirteen case reports met such criteria including anaphylactic shock (n = 5), anaphylactic reaction (n = 4) and angioedema (n = 4). Time to development of symptoms ranged from 5 minutes to 1 day. The doses of andrographis used varied from 352 mg to 1,750 mg. Causality assessment of 13 case reports were certain (n = 3), probable (n = 8) and possible (n = 2). Conclusions: Our findings suggested that hypersensitivity reactions have been reported among patients receiving Andrographis paniculata. Healthcare professionals should be aware of this potential risk. Further investigation of the causal relationship is needed; meanwhile including hypersensitivity reactions for andrographis product labeling should be considered

To Switch or Not to Switch Payment Scheme? Determinants and Effects in a Bargaining Game

The incentive scheme selected in a laboratory experiment might trigger different type of behavior in participants. This paper is an attempt to screen the strategies adopted by agents in a bargaining game when buyer and seller have partly conflicting interests and are asymmetrically informed. We allow participants to choose the incentive scheme through which they will be paid at the end of the experiment controlling for past experience and individual characteristics. It is well known that payment method is highly correlated to the risk preferences shown by individuals, but little research is devoted to the analysis of the behavior induced by Random Lottery Incentive scheme (RLI for short) and Cumulative Scheme payment (CS for short) both on individual and social results. This paper aims to fill the gap

Hearing loss screening tool (COBRA score) for newborns in primary care setting

PurposeTo develop and evaluate a simple screening tool to assess hearing loss in newborns. A derived score was compared with the standard clinical practice tool.MethodsThis cohort study was designed to screen the hearing of newborns using transiently evoked otoacoustic emission and auditory brain stem response, and to determine the risk factors associated with hearing loss of newborns in 3 tertiary hospitals in Northern Thailand. Data were prospectively collected from November 1, 2010 to May 31, 2012. To develop the risk score, clinical-risk indicators were measured by Poisson risk regression. The regression coefficients were transformed into item scores dividing each regression-coefficient with the smallest coefficient in the model, rounding the number to its nearest integer, and adding up to a total score.ResultsFive clinical risk factors (Craniofacial anomaly, Ototoxicity, Birth weight, family history [Relative] of congenital sensorineural hearing loss, and Apgar score) were included in our COBRA score. The screening tool detected, by area under the receiver operating characteristic curve, more than 80% of existing hearing loss. The positive-likelihood ratio of hearing loss in patients with scores of 4, 6, and 8 were 25.21 (95% confidence interval [CI], 14.69–43.26), 58.52 (95% CI, 36.26–94.44), and 51.56 (95% CI, 33.74–78.82), respectively. This result was similar to the standard tool (The Joint Committee on Infant Hearing) of 26.72 (95% CI, 20.59–34.66).ConclusionA simple screening tool of five predictors provides good prediction indices for newborn hearing loss, which may motivate parents to bring children for further appropriate testing and investigations

Smoking and risk of negative outcomes among COVID-19 patients: A systematic review and meta-analysis

INTRODUCTION: COVID-19 has major effects on the clinical, humanistic and economic outcomes among patients, producing severe symptoms and death. Smoking has been reported as one of the factors that increases severity and mortality rate among COVID-19 patients. However, the effect of smoking on such medical outcomes is still controversial. This study conducted a comprehensive systematic review and meta-analysis (SR/MA) on the association between smoking and negative outcomes among COVID-19 patients. METHODS: Electronic databases, including PubMed, EMBASE, Cochrane Library, Science Direct, Google Scholar, were systematically searched from the initiation of the database until 12 December 2020. All relevant studies about smoking and COVID-19 were screened using a set of inclusion and exclusion criteria. The Newcastle-Ottawa Scale was used to assess the methodological quality of eligible articles. Random meta-analyses were conducted to estimate odds ratios (ORs) with 95% confidence interval (CIs). Publication bias was assessed using the funnel plot, Begg's test and Egger's test. RESULTS: A total of 1248 studies were retrieved and reviewed. A total of 40 studies were finally included for meta-analysis. Both current smoking and former smoking significantly increase the risk of disease severity (OR=1.58; 95% CI: 1.16-2.15, p=0.004; and OR=2.48; 95% CI: 1.64-3.77, p<0.001; respectively) with moderate appearance of heterogeneity. Similarly, current smoking and former smoking also significantly increase the risk of death (OR=1.35; 95% CI: 1.12-1.62, p=0.002; and OR=2.58; 95% CI: 2.15-3.09, p<0.001; respectively) with moderate appearance of heterogeneity. There was no evidence of publication bias, which was tested by the funnel plot, Begg's test and Egger's test. CONCLUSIONS: Smoking, even current smoking or former smoking, significantly increases the risk of COVID-19 severity and death. Further causational studies on this association and ascertianing the underlying mechanisms of this relation is warranted

Real-world effectiveness of pneumococcal vaccination in older adults: Cohort study using the UK Clinical Practice Research Datalink

Background: The 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for UK older adults, but how age moderates effectiveness is unclear. Methods: Three annual cohorts of primary-care patients aged≥65y from the Clinical Practice Research Datalink selected from 2003–5 created a natural experiment (n = 324,804), reflecting the staged introduction of the vaccine. The outcome was symptoms consistent with community-acquired pneumococcal pneumonia (CAP) requiring antibiotics or hospitalisation. We used the prior event rate ratio (PERR) approach to address bias from unmeasured confounders. Results: Vaccinated patients had higher rates of CAP in the year before vaccination than their controls, indicating the potential for confounding bias. After adjustment for confounding using the prior event rate ratio (PERR) method, PPV23 was estimated to be effective against CAP for two years after vaccination in all age sub-groups with hazard ratios (95% confidence intervals) of 0.86 (0.80 to 0.93), 0.74 (0.65 to 0.85) and 0.65 (0.57 to 0.74) in patients aged 65–74, 75–79 and 80+ respectively in the 2005 cohort. Age moderated the effect of vaccination with predicted risk reductions of 8% at 65y and 29% at 80y. Conclusions: PPV23 is moderately effective at reducing CAP among UK patients aged≥65y, in the two years after vaccination. Vaccine effectiveness is maintained, and may increase, in the oldest age groups in step with increasing susceptibility to CAP

Association of HLA-B*5801 allele and allopurinol-induced stevens johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis

Background: Despite some studies suggesting a possible association between human leukocyte antigen, HLA-B*5801 and allopurinol induced Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), the evidence of association and its magnitude remain inconclusive. This study aims to systematically review and meta-analyze the association between HLA-B*5801 allele and allopurinol-induced SJS/TEN.Methods: A comprehensive search was performed in databases including MEDLINE, Pre-MEDLINE, Cochrane Library, EMBASE, International Pharmaceutical Abstracts (IPA), CINAHL, PsychInfo, the WHO International, Clinical Trial Registry, and ClinicalTrial.gov from their inceptions to June 2011. Only studies investigating association between HLA-B*5801 with allopurinol-induced SJS/TEN were included. All studies were extracted by two independent authors. The primary analysis was the carrier frequency of HLA-B*5801 comparison between allopurinol-induced SJS/TEN cases and each comparative group. The pooled odds ratios were calculated using a random effect model.Results: A total of 4 studies with 55 SJS/TEN cases and 678 matched-controls (allopurinol-tolerant control) was identified, while 5 studies with 69 SJS/TEN cases and 3378 population-controls (general population) were found. SJS/TEN cases were found to be significantly associated with HLA-B*5801 allele in both groups of studies with matched-control (OR 96.60, 95%CI 24.49-381.00, p < 0.001) and population-control (OR 79.28, 95%CI 41.51-151.35, p < 0.001). Subgroup analysis for Asian and Non-Asian population yielded similar findings.Conclusion: We found a strong and significant association between HLA-B*5801 and allopurinol-induced SJS/TEN. Therefore, HLA-B*5801 allele screening may be considered in patients who will be treated with allopurinol

Effect of Air Pollution on Obesity in Children: A Systematic Review and Meta-Analysis

Air pollution exposure has been identified as being associated with childhood obesity. Nevertheless, strong evidence of such an association is still lacking. To analyze whether air pollution exposure affects childhood obesity, we conducted a systematic review and meta-analysis utilizing the PRISMA guidelines. Of 7343 studies identified, eight studies that investigated the effects of air pollutant characteristics, including PM2.5, PM10, PMcoarse, PMabsorbance, NOx, and NO2, on childhood obesity were included. The polled effects showed that air pollution is correlated with a substantially increased risk of childhood obesity. PM2.5 was found to be associated with a significantly increased risk (6%) of childhood obesity (OR 1.06, 95% CI 1.02–1.10, p = 0.003). In addition, PM10, PM2.5absorbance, and NO2 appeared to significantly increase the risk of obesity in children (OR 1.07, 95% CI 1.04–1.10, p &lt; 0.00; OR 1.23, 95% CI 1.06–1.43, p = 0.07; and OR 1.10, 95% CI 1.04–1.16, p &lt; 0.001, respectively). PMcoarse and NOx also showed trends towards being associated with an increased risk of childhood obesity (OR 1.07, 95% CI 0.95–1.20, p = 0.291, and OR 1.00, 95% CI 0.99–1.02, p = 0.571, respectively). Strong evidence was found to support the theory that air pollution exposure is one of the factors that increases the risk of childhood obesity

Cost-effectiveness analysis of HLA-B*5801 testing in preventing allopurinol-induced SJS/TEN in Thai population

Background: Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), caused by allopurinol therapy, are strongly associated with the human leukocyte antigen (HLA), HLA-B 5801. Identification of HLA-B 5801 genotype before prescribing allopurinol offers the possibility of avoiding allopurinol-induced SJS/TEN. As there is a paucity of evidence about economic value of such testing, this study aims to determine the cost-effectiveness of HLA-B 5801 testing compared with usual care (no genetic testing) before allopurinol administration in Thailand. Methods and Finding: A decision analytical and Markov model was used to estimate life time costs and outcomes represented as quality adjusted life years (QALYs) gained. The model was populated with relevant information of the association between gene and allopurinol-induced SJS/TEN, test characteristics, costs, and epidemiologic data for Thailand from a societal perspective. Input data were obtained from the literature and a retrospective database analysis. The results were expressed as incremental cost per QALY gained. A base-case analysis was performed for patients at age 30. A series of sensitivity analyses including scenario, one-way, and probabilistic sensitivity analyses were constructed to explore the robustness of the findings. Based on a hypothetical cohort of 1,000 patients, the incremental total cost was 923,919 THB (USD 29,804) and incremental QALY was 5.89 with an ICER of 156,937.04 THB (USD 5,062) per QALY gained. The cost of gout management, incidence of SJS/TEN, case fatality rate of SJS/TEN, and cost of genetic testing are considered very influential parameters on the cost-effectiveness value of HLA-B 5801 testing. Conclusions: The genetic testing for HLA-B 5801 before allopurinol administration is considered a highly potential costeffective intervention in Thailand. The findings are sensitive to a number of factors. In addition to cost-effectiveness findings, consideration of other factors including ethical, legal, and social implications is needed for an informed policy decision making