General characteristics, economic burden, causative drugs and medical errors associated with medical damage litigation involving severe cutaneous adverse drug reactions in China.

WHAT IS KNOWN AND OBJECTIVE: To investigate the general characteristics, economic burden, causative drugs and medical errors associated with litigation involving severe cutaneous adverse drug reactions (SCADRs) in China, with the aims of improving rational medication use and reducing the extent of damage from SCADRs. METHODS: This study analysed 150 lawsuit judgements involving SCADRs from 2005 to 2019, collected from China Judgments Online. RESULTS AND DISCUSSION: In total, 50% of lawsuits stemmed from SCADRs occurring in general hospitals. The average time elapsed from the date of occurrence of the SCADRs to the end of litigation procedures was 1055 days. Of the patients involved, 51% were female and more than two thirds (69%) were under 60 years old. The most common outcome of SCADRs was death (39%), followed by disabilities (30%). The average responsibility of the medical provider was 48 ± 29%. The average amount of compensation was $43 424. Of the cases studied, 51% of SCADRs were Stevens-Johnson syndrome or toxic epidermal necrolysis, which together accounted for 75% of cases with known clinical subtype. The overall average economic burden of SCADRs was $99 178, of which indirect costs made up the largest proportion (more than 60%). The most common causative drug groups were antimicrobial drugs (49%), Chinese patent medicine and Chinese herbal medicine (17%), and antipyretic analgesics (16%). Finally, 61% of medical errors were found to stem from violation of duty of care, 20% from violation of informed consent and 18% from violations related to the medical record writing and management system. WHAT IS NEW AND CONCLUSION: Severe cutaneous adverse drug reactions not only severely affect patient survival and quality of life, but also impose a heavy economic burden in terms of health care and societal costs. Medical providers should be better educated on strategies to reduce risk to patients and establish mechanisms of risk sharing and management.

Predictors of 30-day readmission in Stevens-Johnson syndrome and toxic epidermal necrolysis: A cross-sectional database study.

BACKGROUND: The predictors of readmission in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have not been characterized. OBJECTIVE: To determine the variables predictive of 30-day readmission after SJS/TEN hospitalization. METHODS: We performed a cross-sectional study of the 2010-2014 Nationwide Readmissions Database. Bivariate and multivariable logistic regression was used to evaluate associations of patient demographics, comorbidities, and hospital characteristics with readmission. Aggregate and per-readmission costs were calculated. RESULTS: There were 8837 index admissions with SJS/TEN reported; of these, 910 (10.3%) were readmitted, with diagnoses including systemic infection (22.0%), SJS/TEN (20.6%), and cutaneous infection (9.1%). Associated characteristics included age 45 to 64 years (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.43-2.49), Medicaid insurance (OR, 1.83; 95% CI, 1.48-2.27), and nonmetropolitan hospital admission (OR, 1.67; 95% CI, 1.31-2.13). Associated comorbidities included HIV/AIDS (OR, 2.48; 95% CI, 1.63-3.75), collagen vascular disease (OR, 2.38; 95% CI, 1.88-3.00), and metastatic cancer (OR, 2.16; 95% CI, 1.35-3.46). The median per-readmission cost was $10,019 (interquartile range, $4,788-$16,485). LIMITATIONS: The Nationwide Readmissions Database lacks the ability to track the same patient across calendar years. The diagnostic code lacks specificity for hospitalizations <3 days. CONCLUSIONS: Thirty-day readmissions after SJS/TEN hospitalizations are common. Dedicated efforts to identify at-risk patients may improve peridischarge continuity.

Cost-effectiveness analysis of HLA-B*58: 01 genetic testing before initiation of allopurinol therapy to prevent allopurinol-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in a Malaysian population.

OBJECTIVE: Studies found a strong association between allopurinol-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and the HLA-B*58:01 allele. HLA-B*58:01 screening-guided therapy may mitigate the risk of allopurinol-induced SJS/TEN. This study aimed to evaluate the cost-effectiveness of HLA-B*58:01 screening before allopurinol therapy initiation compared with the current practice of no screening for Malaysian patients with chronic gout in whom a hypouricemic agent is indicated. METHODS: This cost-effectiveness analysis adopted a societal perspective with a lifetime horizon. A decision tree model coupled with Markov models were developed to estimate the costs and outcomes, represented by quality-adjusted life years (QALYs) gained, of three treatment strategies: (a) current practice (allopurinol initiation without HLA-B*58:01 screening); (b) HLA-B*58:01 screening before allopurinol initiation; and (c) alternative treatment (probenecid) without HLA-B*58:01 screening. The model was populated with data from literature review, meta-analysis, and published government documents. Cost values were adjusted for the year 2016, with costs and health outcomes discounted at 3% per annum. A series of sensitivity analysis including probabilistic sensitivity analysis were carried out to determine the robustness of the findings. RESULTS: Both HLA-B*58:01 screening and probenecid prescribing were dominated by current practice. Compared with current practice, HLA-B*58:01 screening resulted in 0.252 QALYs loss per patient at an additional cost of USD 322, whereas probenecid prescribing resulted in 1.928 QALYs loss per patient at an additional cost of USD 2203. One SJS/TEN case would be avoided for every 556 patients screened. At the cost-effectiveness threshold of USD 8695 per QALY, the probability of current practice being the best choice is 99.9%, in contrast with 0.1 and 0% in HLA-B*58:01 screening and probenecid prescribing, respectively. This is because of the low incidence of allopurinol-induced SJS/TEN in Malaysia and the lower efficacy of probenecid compared with allopurinol in gout control. CONCLUSION: This analysis showed that HLA-B*58:01 genetic testing before allopurinol initiation is unlikely to be a cost-effective intervention in Malaysia.

Pediatric Stevens-Johnson syndrome and toxic epidermal necrolysis in the United States.

BACKGROUND: Little is known about the epidemiology of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in children. OBJECTIVE: We sought to determine the morbidity, mortality, and comorbid health conditions of SJS and TEN in US children. METHODS: This was a cross-sectional study of the 2009 to 2012 Nationwide Inpatient Sample, which contains a representative 20% sample of all US hospitalizations. Sociodemographics, inflation-adjusted cost, length of stay, comorbidities, and mortality were analyzed using descriptive statistics and multivariate regression analyses. RESULTS: The incidences of SJS, SJS-TEN, and TEN were a mean 5.3, 0.8, and 0.4 cases per million children per year in the US, respectively. Prolonged length of stay and higher costs of care (SJS: 9.4 ± 0.6 days, $24,947 ± $3171; SJS-TEN: 15.7 ± 1.5 days, $63,787 ± $8014; TEN: 20.4 ± 6.3 days, $102,243 ± $37,588) were observed compared with all other admissions (4.6 ± 0.1 days, $10,496 ± $424). Mortality was 0% for SJS, 4% for SJS-TEN, and 16% for TEN. In regression models, predictors of mortality included renal failure (adjusted OR [aOR] 300.28, 95% confidence interval [CI] 48.59->999.99), malignancy (aOR 54.33, 95% CI 9.40-314.22), septicemia (aOR 30.45, 95% CI 7.91-117.19), bacterial infection (aOR 20.38, 95% CI 5.44-76.36), and epilepsy (aOR 5.56, 95% CI 1.37-26.2). LIMITATIONS: Data regarding treatment were not available. Date of diagnosis of comorbidities was not present, precluding temporal analysis. CONCLUSIONS: Pediatric SJS/TEN poses a substantial health burden in the United States.

Is universal HLA-B*15:02 screening a cost-effective option in an ethnically diverse population? A case study of Malaysia.

BACKGROUND: A strong association has been documented between HLA-B*15:02 and carbamazepine-induced severe cutaneous adverse reactions (SCARs) in Asians. Human leucocyte antigen testing is potentially valuable in many countries to facilitate early recognition of patient susceptibility to SCARs. OBJECTIVES: To determine the cost-effectiveness of universal HLA-B*15:02 screening in preventing carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in an ethnically diverse Malaysian population. METHODS: A hybrid model of a decision tree and Markov model was developed to evaluate three strategies for treating newly diagnosed epilepsy among adults: (i) carbamazepine initiation without HLA-B*15:02 screening (current practice); (ii) universal HLA-B*15:02 screening prior to carbamazepine initiation; and (iii) alternative treatment [sodium valproate (VPA)] prescribing without HLA-B*15:02 screening. Base-case analysis and sensitivity analyses were performed over a lifetime time horizon. Incremental cost-effectiveness ratios were calculated. RESULTS: Both universal HLA-B*15:02 screening and VPA prescribing were dominated by current practice. Compared with current practice, universal HLA-B*15:02 screening resulted in a loss of 0·0255 quality-adjusted life years (QALYs) at an additional cost of 707 U.S. dollars (USD); VPA prescribing resulted in a loss of 0·2622 QALYs at an additional cost of USD 4127, owing to estimated differences in antiepileptic treatment efficacy. CONCLUSIONS: Universal HLA-B*15:02 screening is unlikely to be a cost-effective intervention in Malaysia. However, with the emergence of an ethnically diverse population in many other countries, this may render HLA-B*15:02 screening a viable intervention when an increasing proportion of the population is at risk and an equally effective yet safer antiepileptic drug is available.

Incidence of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Nationwide Population-Based Study Using National Health Insurance Database in Korea.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases; however, it is hard to estimate their incidence due to the rarity of these diseases. We evaluated the incidence of SJS and TEN using a nationwide administrative database. METHODS: We used a national medical insurance review system (Health Insurance Review and Assessment) database which contained the claim data of the entire nation from 2009 to 2013 to estimate the accurate incidence of SJS and TEN in Korea. The diagnostic codes of L511 (SJS) or L512 (TEN) from the International Classification of Diseases-10th revision were used to define the target study population. We also retrospectively followed up a 2011 SJS and TEN cohort for 24 months in order to assess the in-hospital mortality, related complications and total claims cost due to SJS and TEN. RESULTS: A total of 1,167 (938 SJS and 229 TEN) cases were newly diagnosed from 2010 to 2013. The age- and sex-standardized annual incidences estimated in this study were 3.96 to 5.03 in SJS and 0.94 to 1.45 in TEN per million. There was no significant change in annual incidence throughout the study periods. When analyzed by 10-year age groups, the annual incidence was the lowest in group 20-29 years and the highest in group 70 for both SJS and TEN. Based on the 2011 cohort analysis, the in-hospital mortality were 5.7 and 15.1% for SJS and TEN, respectively. The mortality increased with age, particularly, after 40 years of age. Among the complications related with SJS or TEN, ocular sequelae was the most common (43.1 and 43.4% of SJS and TEN patients, respectively) followed by urethral sequelae (5.7 and 9.4% of SJS and TEN patients, respectively). CONCLUSION: Overall, our data suggest that SJS, and TEN are infrequent but constantly arise throughout the years.

Morbidity and Mortality of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in United States Adults.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening disorders. Our study objective was to describe the incidence, costs of care, length of stay, comorbidities, and mortality of SJS and TEN in US adults. The Nationwide Inpatient Sample 2009-2012, containing a 20% sample of all US hospitalizations, was analyzed. We used a validated approach involving International Classification of Disease, 9th edition, Clinical Modification codes to identify SJS, SJS/TEN, and TEN (n = 2,591, n = 502, and n = 564, respectively). The mean estimated incidences of SJS, SJS/TEN, and TEN were 9.2, 1.6, and 1.9 per million adults per year, respectively. SJS/TEN was associated with nonwhite race, particularly Asians (odds ratio = 3.27, 95% confidence interval = 3.02-3.54) and blacks (odds ratio = 2.01, 95% confidence interval = 1.92-2.10). Significantly prolonged length of stay and higher costs of care (SJS: 9.8 ± 0.3 days, $21,437 ± $807; SJS/TEN: 16.5 ± 1.0 days, $58,954 ± $5,238; TEN: 16.2 ± 1.0 days, $53,695 ± $4,037) were observed compared with all other admissions (4.7 ± 0.02 days, $11,281 ± $98). Mean adjusted mortality was 4.8% for SJS, 19.4% for SJS/TEN, and 14.8% for TEN. SJS, SJS/TEN, and TEN pose a substantial health care burden. Predictors of mortality included increasing age, increasing number of chronic conditions, infection (septicemia, pneumonia, tuberculosis), hematological malignancy (non-Hodgkin's lymphoma, leukemia), and renal failure (P ≤ 0.03 for all). Further studies are needed to confirm mortality findings to improve prognostication of SJS/TEN.

Real-world efficiency of pharmacogenetic screening for carbamazepine-induced severe cutaneous adverse reactions.

OBJECTIVES: We evaluated the cost and efficiency of routine HLA-B*15 ∶ 02 screening to prevent carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (CBZ-SJS/TEN) in Hong Kong. METHODS: Data were extracted from patients who commenced CBZ as the first-ever AED treatment or tested for HLA-B*15 ∶ 02 allele in three years before policy implementation (pre-policy: 16 September 2005 to 15 September 2008) and three years after (post-policy: 16 September 2008 to 15 September 2011). Using published unit costs, we estimated the cost of screening by comparing the costs to prevent and treat CBZ-SJS/TEN. We compared the number of person-tests needed and the cost to prevent resultant death with cancer screening programs. RESULTS: The number of screening tests needed to prevent one case of CBZ-SJS/TEN was 442, and to prevent one resultant death was 1,474 to 8,840. The screening cost was $332 per person, of which 42% was attributed to an additional consultation to review result and prescribe appropriate medication. HLA-B*15 ∶ 02 screening expended $146,749 to prevent a case of CBZ-SJS/TEN, and $489,386- $2,934,986 to prevent a resultant death. The corresponding numbers of tests and costs for mammography and Pap smear to prevent death due to breast and cervical cancers were 7,150 and 7,000, and $614,900 and $273,000, respectively. Comparing to the SJS/TEN treatment cost, HLA-B*15 ∶ 02 screening would become cost saving if a point-of-care test of less than $37 was available. CONCLUSIONS: HLA-B*15 ∶ 02 screening is as efficient as mammography and Pap smear in preventing death. Development of point-of-care testing will vastly improve efficiency.

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 cost-effective 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.

Cost-effectiveness of osteo-odonto keratoprosthesis in Singapore.

PURPOSE: To determine the long-term cost-effectiveness of osteo-odonto keratoprosthesis (OOKP) relative to no treatment among patients with end-stage corneal and ocular surface diseases in Singapore. DESIGN: Cost-effectiveness analysis based on data from a retrospective cohort study. METHODS: From a health system perspective, we calculated the incremental cost-effectiveness ratio of OOKP treatment relative to no treatment over a 30-year horizon, based on data from a cohort of 23 patients who underwent OOKP surgery between 2004 and 2009 at Singapore National Eye Centre. Preoperative and postoperative vision-related quality-of-life values were estimated from patients' visual outcomes and were used to calculate the gain in quality-adjusted life years (QALYs) resulting from OOKP treatment. Unsubsidized costs for surgery, consultations, examinations, medications, follow-up visits, and treatments for complications were retrieved from patients' bills to estimate the total costs associated with OOKP treatment. Sensitivity analyses were conducted to test the robustness of the model. RESULTS: Over a 30-year period, OOKP treatment, compared with no treatment, improved QALYs by 3.991 among patients with end-stage corneal and ocular surface diseases at an additional cost of S$67 840 (US$55 150), resulting in an incremental cost-effectiveness ratio of S$17 000/QALY (US$13 820/QALY). CONCLUSIONS: Based on commonly cited cost-effectiveness benchmarks, the OOKP is a cost-effective treatment for patients with end-stage corneal and ocular surface diseases.

Cost of medications in patients admitted to a burn center.

BACKGROUND: Few studies have examined the cost associated with burn patients, and those which have been conducted have generally focused on overall hospitalization costs associated with these patients. No studies to date have examined the overall drug utilization and costs of medications used in the treatment of burn patients. OBJECTIVE: To describe the pattern of drug utilization and associated costs for the treatment of patients admitted to the Ross Tilley Burn Centre at Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada. METHODS: A retrospective chart review was conducted based on the medical records of 30 adult patients (>18 years old) consecutively admitted to the burn center between 1 August 1999 and 30 September 1999. Charts were examined to determine drugs administered, doses and duration of use. Medications administered in the operating room were excluded from the analysis. Drug costs were calculated using hospital acquisition costs (1999 Canadian dollars [$Can]) and medications were categorized by pharmacological class according to the American Hospital Formulary Service. Demographic information for the patients was extracted from the burn center's database. The economic analysis was performed from the perspective of the hospital burn center. A descriptive statistical analysis was completed for all variables; the Pearson correlation coefficient was used to examine the relationship between certain variables. A sensitivity analysis was conducted to examine the impact of patient subgroups on certain variables RESULTS: Of the 28 patients included in the analysis, 19 were admitted with acute burn injuries, two with toxic epidermal necrolysis and seven for post-burn reconstructive surgery. Patients admitted for acute burns or toxic epidermal necrolysis had the highest associated drug costs. On average, patients received 13 different drugs representing four different pharmacological categories. The mean daily drug cost per patient was $Can18.39 and the mean expenditure per admission was $Can792.97. Opioid analgesics and sedatives accounted for the largest expenditure (50.9%), followed by anti-infective agents (23.4%). For patients admitted with acute burns, there was a good correlation between daily drug costs and mortality risk (r = 0.82, p < 0.001). The findings from this study group were used to extrapolate annual expenses for medications in the burn center and these were estimated to exceed $Can280 300 in 2003. CONCLUSION: The findings of this retrospective analysis serve to elucidate the patterns of drug utilization within a population of burn patients and confirm the significant impact of a burn center on an institution's drug expenditure.