Incidence of Stevens-Johnson syndrome following combination drug use of allopurinol, carbamazepine and phenytoin in Taiwan: A case-control study.

The goal of our study was to investigate the incidence of Stevens-Johnson syndrome (SJS), the frequency of SJS diagnosis, and the association between SJS and prior use of allopurinol, carbamazepine or phenytoin. This case-control study utilized data from the National Health Insurance Research Database (NHIRD) of Taiwan. Controls visited the emergency department of the same hospital for trauma or fractures (excluding burns) and used allopurinol, carbamazepine or phenytoin during the past 3 months. We determined whether patients were prescribed a combination of drugs in addition to allopurinol, carbamazepine or phenytoin within the last 3 months. We identified 1 853 985 controls and 7327 SJS-diagnosed patients using the Taiwan NHIRD records for 2000-2008. Higher use of allopurinol (49.8%), carbamazepine (39.1%) or phenytoin (21.3%) was observed among patients (n = 3131) than among controls (n = 2858). The overall SJS incidence rate was 3.6/1 000 000. Drug combinations were uncommon (<10%) in patients or controls taking allopurinol. However, combination drug use exceeded 10% in patients taking carbamazepine or phenytoin. Logistic regression analysis of recent combination drug use revealed that phenobarbital, valproate, non-steroidal anti-inflammatory drugs (NSAIDs) including piroxicam and tenoxicam, and antibiotics including amoxicillin and cephalexin were strongly associated with SJS. Patients with gout or epilepsy taking allopurinol, carbamazepine or phenytoin should be evaluated carefully by physicians. Concurrent use of piroxicam, tenoxicam, phenobarbital, valproate, amoxicillin or cephalexin, in addition to carbamazepine or phenytoin, may increase the incidence of SJS.

Correlation between drug-drug interaction-induced Stevens-Johnson syndrome and related deaths in Taiwan.

Concomitant use of some drugs can lead to interactions between them resulting in severe adverse effects. To date, there are few reports of incidences of Stevens-Johnson syndrome (SJS) associated with combination drug administration. Therefore, we studied the relationship between drug combinations and SJS-related mortality, with the hope that a retrospective study of this nature would provide information crucial for the prevention of future drug-drug interaction related deaths attributable to SJS. This retrospective longitudinal study used mortality cases from 1999 to 2008 that were diagnosed as erythema multiforme (International Classification of Diseases, Ninth Revision, Clinical Modification 695.1) from the National Health Insurance database in Taiwan. Statistical comparisons of the results were performed using analysis of variance (ANOVA), independent sample t-tests, and odds ratio (OR). In this way, the relationship between combinations of SJS-inducing drugs and mortality could be determined. A total of 111 patients who had died, including 63 males and 48 females (66.0 ± 20 and 70.0 ± 17.7 years, respectively), were suspected of having experienced drug-drug interaction-related adverse effects. The associated drug combinations included allopurinol and ampicillin (p = 0.049), carbamazepine and sulfamethoxazole/trimethoprim (TMP) (p < 0.0001), carbamazepine and phenytoin (p < 0.0001), sulfamethoxazole/TMP and phenytoin (p = 0.015), sulfadoxine and piroxicam (p = 0.045), phenobarbital and cephalexin (p < 0.0001), ampicillin and erythromycin (p < 0.0001), erythromycin and minocycline (p < 0.0001), and vancomycin and ethambutol (p < 0.0001) administered 1 month before the patients' deaths. Caution should be exercised when administering any drugs that may possibly induce SJS. In addition, attention should be paid to ensure prompt identification of possible drug-drug interactions, and patients should be closely monitored. Furthermore, medications should be immediately discontinued at the first sign or symptom suggesting the occurrence of drug-related SJS, and then prompt, adequate supportive care should be provided.

NHI-PharmaCloud in Taiwan--A preliminary evaluation using the RE-AIM framework and lessons learned.

OBJECTIVES: The aim of this article is to present the preliminary impact of a medication monitoring program, PharmaCloud, in Taiwan and analyze the embedded factors that have contributed to the performance thereof. This article also compared PharmaCloud with similar international programs in order to draw lessons learned. METHODS: The five domains of the RE-AIM framework - reach, effectiveness, adoption, implementation, and maintenance - were examined using qualitative and quantitative data. A difference-in-differences model was applied to analyze the quantitative impact of PharmaCloud on drug utilization and drug expenses. The qualitative impact was evaluated by document analysis based on field reports from the participating medical institutions. RESULTS: Reach and adoption: although all of the major hospitals adopted PharmaCloud and some of the hospitals had high inquiry rates, more time and incentives are needed to raise the overall inquiry rate. Effectiveness: during the study period of 3 months, the number of medications per prescription declined in the intervention group was 0.15 more than that of the general population, and the drug expense per person declined in the intervention group was NT $567 (US $18.9) more than that of the general population. The potential savings could be between 2% and 5% of the total pharmaceutical expenditure. Medication duplication was found to have decreased more in the intervention group. IMPLEMENTATION: a variety of innovations in care delivery are being developed in which the pharmacists play a more significant role. Maintenance: the embedded National Health Insurance would lend strong support for PharmaCloud to grow and thrive. CONCLUSION: PharmaCloud owes its effectiveness to the embedded National Health Insurance (NHI) program, which is universal and provides a comprehensive benefit package including more than 16,000 prescription drugs. An effective medication program is one that operates under the principle of universality and comprehensiveness, facilitates innovations, and has a substantial level of interoperability with the intra-hospital health information systems.

Repeated vertebral augmentation for new vertebral compression fractures of postvertebral augmentation patients: a nationwide cohort study.

PURPOSE: Postvertebral augmentation vertebral compression fractures are common; repeated vertebral augmentation is usually performed for prompt pain relief. This study aimed to evaluate the incidence and risk factors of repeat vertebral augmentation. METHODS: We performed a retrospective, nationwide, population-based longitudinal observation study, using the National Health Insurance Research Database (NHIRD) of Taiwan. All patients who received vertebral augmentation for vertebral compression fractures were evaluated. The collected data included patient characteristics (demographics, comorbidities, and medication exposure) and repeat vertebral augmentation. Kaplan-Meier and stratified Cox proportional hazard regressions were performed for analyses. RESULTS: The overall incidence of repeat vertebral augmentation was 11.3% during the follow-up until 2010. Patients with the following characteristics were at greater risk for repeat vertebral augmentation: female sex (AOR=1.24; 95% confidence interval [CI]: 1.10-2.36), advanced age (AOR=1.60; 95% CI: 1.32-2.08), diabetes mellitus (AOR=4.31; 95% CI: 4.05-5.88), cerebrovascular disease (AOR=4.09; 95% CI: 3.44-5.76), dementia (AOR=1.97; 95% CI: 1.69-2.33), blindness or low vision (AOR=3.72; 95% CI: 2.32-3.95), hypertension (AOR=2.58; 95% CI: 2.35-3.47), and hyperlipidemia (AOR=2.09; 95% CI: 1.67-2.22). Patients taking calcium/vitamin D (AOR=2.98; 95% CI: 1.83-3.93), bisphosphonates (AOR=2.11; 95% CI: 1.26-2.61), or calcitonin (AOR=4.59; 95% CI: 3.40-5.77) were less likely to undergo repeat vertebral augmentation; however, those taking steroids (AOR=7.28; 95% CI: 6.32-8.08), acetaminophen (AOR=3.54; 95% CI: 2.75-4.83), or nonsteroidal anti-inflammatory drugs (NSAIDs) (AOR=6.14; 95% CI: 5.08-7.41) were more likely to undergo repeat vertebral augmentation. CONCLUSION: We conclude that the incidence of repeat vertebral augmentation is rather high. An understanding of risk factors predicting repeat vertebral augmentation provides valuable basis to improve health care for geriatric populations.

Modified fluoroscopy-guided sacroiliac joint injection: a technical report.

BACKGROUND AND OBJECTIVE: Sacroiliac joint (SIJ) injection can occasionally be challenging. We describe our experience in using conventional technique, and we developed an adjustment to overcome difficulties incurred. METHODS: Conventional technique required superimposition of the posterior and anterior SIJ lines. If this technique failed to provide entry into the joint, fluoroscopy was slightly adjusted to obtain an oblique view. RESULTS: Of 50 SIJ injections, 29 (58%; 44-72%) were successfully performed using conventional technique. In another 21 procedures, 18 (85.7%; 64-99%) were subsequently completed using oblique view technique. The medial joint line, viewed from this angle, corresponded to the posterior joint line in 17 cases. The lateral joint line corresponded to the posterior joint line in one case. CONCLUSIONS: Oblique view technique can improve the success rate of SIJ injection.

Deterioration of cutaneous microcirculatory status of Kawasaki disease.

Kawasaki disease (KD) is associated with generalized vasculitis with a predilection for coronary artery leading to ectasia and aneurysm in some cases. The aim of this study was to noninvasively assess the cutaneous microcirculation and correlate it with the coronary artery diameter in these patients. Laser Doppler flowmetry and dynamic capillaroscopy were performed at the nailbeds to assess total cutaneous blood flow and microcirculation in children with KD, both in the afebrile phase (after the resolution of fever) and convalescent phases, in comparison to controls. The 100 subjects analyzed in this study included 64 patients with KD (33 in afebrile phase and 31 in convalescent phase) and 36 normal controls. In KD, the capillary morphology was abnormal when compared to controls, with a larger diameter of the arterial and venous limbs, a higher intercapillary distance and a decrease in the loop numbers. Significantly decreased capillary blood cell velocity was noted in afebrile phase but not in convalescent phase. In the afebrile phase, a decreased capillary blood cell velocity significantly correlated with an increased coronary artery diameter. In conclusion, KD patients, both in the afebrile and convalescent phases, exhibited morphologic alterations in the microcirculation when compared to the controls. The results indicate the potential role of dynamic capillaroscopy for the noninvasive survey of microcirculation abnormalities in patients with KD.

Acute-phase reactants and a supplemental diagnostic aid for Kawasaki disease.

The diagnosis of acute Kawasaki disease (KD) is based on characteristic clinical signs and not on a specific diagnostic test. The authors performed a comprehensive evaluation of acute-phase reactants in KD to determine which of the acute-phase reactants would most accurately distinguish KD from other febrile illnesses. Blood was collected from 218 cases of febrile children with KD (64 cases); bacterial pneumonia (74 cases); hand, foot, and mouth disease (31 cases); and upper respiratory tract infection (49 cases) in acute-stage illness before any therapy. The demographics, body temperature, and laboratory markers including white blood cell count, red blood cell count, and levels of hemoglobin, platelets, C-reactive protein, haptoglobin, apolipoprotein A-I, and apolipoprotein B were evaluated. Using post hoc analysis, the platelet count (10(3)/µl) and haptoglobin/apolipoprotein A-I ratio were significantly higher for the KD patients (404.64 ± 161.68, P = 0.004; 4.74 ± 2.73, P < 0.001) than for the other groups including patients with pneumonia (272.76 ± 115.07, 2.03 ± 1.88); hand, foot, and mouth disease (274 ± 105.9, 2.24 ± 1.19); and upper respiratory tract infection (282.06 ± 107.72, 1.4 ± 0.98). The best cutoff value of the haptoglobin/apolipoprotein A-I ratio obtained from receiver operating characteristics (ROC) curves for KD was 2 (area under the ROC curve, 0.88; 95% confidence interval, 0.801-0.955), with a sensitivity of 89.7% and a specificity of 85.6% for detecting KD. Our data indicate that the serum haptoglobin/apolipoprotein A-I ratio could be a useful supplemental laboratory marker for the acute phase of KD.