Assessment of Utilization and Cost-Effectiveness of Telemedicine Program in Western Regions of China: A 12-Year Study of 249 Hospitals Across 112 Cities.

BACKGROUND: The imbalance in healthcare between urban and rural areas is still a problem in China. In recent decades, China has aimed to develop telemedicine. We assessed the implementation, utilization, and cost-effectiveness of a large telemedicine program across western China. MATERIALS AND METHODS: In 2002-2013, a government-sponsored major telemedicine program was established by West China Hospital of Sichuan University (hub), covering 249 spoke hospitals in 112 cities throughout western China and in 40 medical expertise areas. We analyzed the cross-sectional data from 11,987 consultations conducted at West China Hospital using the telemedicine network over a 12-year period. The types of diseases as well as the diagnosis and treatment changes were assessed. We also performed a cost-savings analysis and a one-way sensitivity analysis. RESULTS: Of the 11,987 teleconsultations, we noted that neoplasms (19.4%), injuries (13.9%), and circulatory diseases (10.3%) were the three most common diagnoses. Teleconsultations resulted in a change of diagnosis in 4,772 (39.8%) patients, and 3,707 (77.7%) of them underwent major diagnosis changes. Moreover, it led to a change of treatment in 6,591 (55.0%) patients, including 3,677 (55.8%) changes not linked to diagnosis changes. The telemedicine network resulted in an estimated net saving of $2,364,525 (if the patients traveled to the hub) or $3,759,014 (if the specialists traveled to the spoke hospitals). CONCLUSIONS: The introduction of telemedicine in China, linking highly specialized major hospitals (hub) with hundreds of small rural hospitals (spoke), can greatly improve the quality, efficiency, and cost-effectiveness of healthcare delivery and utilization. This new Internet-based healthcare model should be utilized more widely in developing countries.

Genetic predictors of Stevens-Johnson syndrome and toxic epidermal necrolysis induced by aromatic antiepileptic drugs among the Chinese Han population.

BACKGROUND: Previous studies suggested that one or more HLA alleles participate in the pathogenesis of AED-induced SJS/TEN, but most of these studies focused only on the HLA-B alleles. PURPOSE: The aim of this study was to investigate the pathogenesis of AED-induced SJS/TEN across a broader spectrum of HLA alleles, including the HLA-A, -B and -DRB1 alleles, to further explore the association between each HLA allele and SJS/TEN induced by aromatic AEDs. METHODS: A total of 27 patients exhibiting AED-induced SJS/TEN (16 CBZ-SJS/TEN, seven LTG-SJS/TEN, two PHT-SJS/TEN, and two PB-SJS/TEN patients) and 64 patients who exhibited tolerance to AEDs were recruited. High-resolution HLA genotyping was performed to estimate the prevalence of the HLA-A, -B and -DRB1 alleles for each subject. RESULTS: Fifteen subjects in the SJS/TEN group (12 exhibiting CBZ-SJS/TEN, two exhibiting LTG-SJS, and one exhibiting PB-SJS) carried the HLA-B*15:02 allele, whereas only 4/64 subjects in the AED-tolerant group carried this allele; the carrier rate of HLA-B*15:02 was significantly different between the groups (P<0.001). Nine patients in the SJS/TEN group carried the HLA-DRB1*15:01 allele, while 12/64 subjects in the tolerant group carried this allele; considering that two patients in the SJS/TEN group (one exhibiting LTG-SJS and one exhibiting PB-SJS) were homozygous for this allele, the prevalence of HLA-DRB1*15:01 expression between the two groups was significantly different (P=0.041). Furthermore, the carrier rates of HLA-A*33:03, HLA-B*58:01, and HLA-DRB1*03:01 were lower in the SJS/TEN group compared with the AED-tolerant group. The carrier rates of these alleles between the two groups were significantly different (P=0.009, 0.016, and 0.009, respectively). CONCLUSIONS: The HLA-DRB1*15:01 allele may represent a risk factor for AED-induced SJS/TEN among Han Chinese. The HLA-A*33:03, HLA-B*58:01, and HLA-DRB1*03:01 alleles may be "protectors" against AED-induced SJS/TEN, especially CBZ-SJS/TEN.

MOG antibody disease with ovarian teratoma: A case report and review of the literature.

Myelin oligodendrocyte glycoprotein (MOG) antibody disease is a rare inflammatory disease of the central nervous system. There are a variety of clinical and imaging manifestations of MOG antibody disease (MOG-AD). At present, there is no report on related cases of MOG antibody positivity complicated with teratoma in China, and one case admitted to our hospital is reported. By reviewing relevant literature to increase the study of MOG-AD.

Clinical features of psychogenic nonepileptic seizures: a study of 64 cases in southwest China.

This article describes the clinical features of psychogenic nonepileptic seizures (PNES) in people in southwest China. Patients with a confirmed diagnosis of pure PNES by video/EEG monitoring were retrospectively reviewed. A total of 64 patients with PNES were included, 32 (50%) of whom were male. Twenty (31.3%) patients had previously been misdiagnosed and treated for epilepsy. Psychological trauma and head injuries were considered antecedent traumatic factors. A history of abuse was rare. The PNES cases were divided into three subtypes: psychogenic minor motor seizures, psychogenic major motor seizures, and unresponsive seizures. Age at onset was identified as a predictor of prognosis. The results of this study demonstrated a higher prevalence of PNES in males compared with previous studies. The semiology of PNES in China is similar to that in Western countries. Classification of semiology may be helpful in the differential diagnosis of PNES.

Levetiracetam-induced cutaneous adverse drug reactions were not associated with HLA genes in a small sample of Chinese patients with epilepsy.

PURPOSE: This study aimed to evaluate the clinical characteristics of levetiracetam (LEV)-induced cutaneous adverse drug reactions (cADRs) and to explore its possible genetic association with the human leukocyte antigen (HLA) genes. METHODS: Nine cases with LEV-induced cADRs were recruited. Demographic and clinical information of these cases was summarized. Additionally, cases were matched with LEV-tolerant controls (1:4). High-resolution HLA class I and class II genotyping was performed for each participant. The allele frequencies between the cases and controls were compared. RESULTS: All LEV-induced cADRs were mild skin rashes which occurred within 28 days of LEV exposure. The mean latency from LEV exposure to skin rash was (15.67±5.41) days (ranging 6-27). The carrier rates of the two alleles, HLA-DRB1*0405 and HLA-DQB1*0401, were higher in cases compared with controls (the same P=0.036, OR=13.875, 95% CI: 1.273-151.230). The association between the HLA-C*0304 allele and LEV-induced cADRs was boundary (P=0.05, OR=5.2, 95% CI: 1.086-24.897). However, the above-mentioned HLA alleles didn't reach statistical significance after multiple comparisons. CONCLUSIONS: Safety monitoring was necessary within four weeks after the initiation of LEV treatment, although it has been regarded as a safe antiepileptic drug. Our study failed to show any potential link between HLA alleles and LEV-induced cADRs in Han Chinese. Further studies are needed to clarify the genetic and immunological mechanisms of LEV-induced cADRs.

Efficacy of low to moderate doses of oxcarbazepine in adult patients with newly diagnosed partial epilepsy.

PURPOSE: The objective of this study was to explore the efficacy of low dose of oxcarbazepine (OXC) in adult patients with newly diagnosed partial epilepsy in an actual clinical setting. The associated factors influencing the poor control of seizures were also evaluated. METHODS: The epilepsy database (2010-2014) from the Epilepsy Clinic of West China Hospital was retrospectively reviewed. RESULTS: A total of 102 adult patients with newly diagnosed, previously untreated partial epilepsy initially treated with OXC were included, and divided into good response group (64) and poor response group (38) according to whether they were seizure-free for at least 12 months. There were 27 (26.5%) patients becoming seizure-free with OXC 600 mg/day monotherapy. The remaining 75 patients had doses of either increasing OXC to 900 mg/day (n = 59) or the addition of another antiepileptic drug (AED) (n = 16), with another 20 (19.6%) and six (5.9%) patients becoming seizure-free, respectively (P = 0.788). In addition, two (2.0%) and nine (8.8%) patients became seizure-free with OXC > 900 mg/day monotherapy and OXC ≥ 900 mg/day combination therapy, respectively. Multivariate binary logistic regression analysis revealed that the time from onset of epilepsy to treatment initiation is significantly associated with seizure control (P = 0.02). CONCLUSION: Our results indicated that OXC at low to moderate doses is effective for the treatment of Chinese adult patients with newly diagnosed, previously untreated partial epilepsy, and a longer time interval from the onset of epilepsy to the start of treatment significantly predicts poor seizure control.

Genetic susceptibility to the cross-reactivity of aromatic antiepileptic drugs-induced cutaneous adverse reactions.

BACKGROUND: The cross-allergic reactions among aromatic antiepileptic drugs (AEDs) are common, but little is known about the genetic mechanisms. PURPOSE: The aim of this study was to investigate the genetic associations of the human leukocyte antigen (HLA) genes with the cross-reactivity of cutaneous adverse drug reactions (cADRs) induced by different aromatic AEDs. METHODS: We reviewed 60 Chinese patients with a history of cADRs induced by an aromatic AED, and which re-challenged other aromatic AEDs as an alternative to the causative AED owing to some particular reasons. According to whether developing another episode of cADRs, these patients were automatically divided into the cross-reactivity group and tolerant control group. High-resolution HLA-A, -B, -DRB1 genotyping were performed for each patient. RESULTS: One out of 10 patients (10%, 1/10) carried the HLA-A*2402 allele in the cross-reactivity group. However, 23 patients (46%, 23/50) carried this allele in the tolerant control group. The difference of the HLA-A*2402 allele between the two groups is statistically significant (P=0.040, OR=0.130, 95% CI: 0.015-1.108). In addition, the frequency differences of other HLA alleles between the two groups, including the HLA-B*1502 allele, did not reach statistical significance (P>0.05). CONCLUSIONS: The HLA genes contribute to the genetic susceptibility of the cross-reactivity of cADRs among aromatic AEDs. Our results suggest that HLA-B*1502 is not a major responsible allele for the cross-reactivity of cADRs to aromatic AEDs, but the HLA-A*2402 allele may be a protective marker for the cross-allergic reactions among aromatic AEDs in Han Chinese. Further studies are warranted to test the potential predictive value of the HLA-A*2402 allele in future.

Prospective study on the withdrawal and reinstitution of antiepileptic drugs among seizure-free patients in west China.

This study explored the relapse rates and risk factors for seizure recurrence after discontinuing antiepileptic drug (AED) therapy among seizure-free patients in west China, and explored whether to reinstitute AED immediately after a single seizure after AED withdrawal. Patients with epilepsy who were seizure-free for at least 2 years and decided to gradually stop AED therapy were followed up every 3 months for seizure relapse. Patients who experienced their first seizure after drug withdrawal were divided into two groups according to their willingness to reinstitute AED therapy, and were followed up until their second seizure. In the mean 29.35 months of follow-up, 37 patients (37/162, 22.8%) suffered at least one seizure after withdrawal. The cumulative probability of seizure recurrence was 16% at 12 months and 20.2% at 24 months. AED response time >1 year and multiple types of seizure were identified as risk factors for seizure recurrence. Eight patients (8/32, 25%) suffered a second seizure within 1 year after the first whether or not they reinstituted AED immediately. There were no significant demographic or clinical differences between patients who reinstituted AED therapy and those who did not. The epilepsy recurrence rate after AED withdrawal is relatively low, with a relatively slow tapering process. Patients with long AED response times and/or multiple types of seizures have a higher risk of seizure recurrence. The first seizure after drug withdrawal is not an indication for immediate AED reinstitution, but may be recommended after a second seizure.

Effectiveness of levetiracetam use following resective surgery in patients with refractory epilepsy: a prospective observational study.

PURPOSE: This study aimed to evaluate the effectiveness of levetiracetam (LEV) use for seizure control in patients who had undergone resective surgery for intractable epilepsy in routine clinical practice. METHODS: This was a prospective, observational study. Refractory epilepsy patients who underwent epilepsy surgery from January 2008 to December 2011 in the Department of Neurosurgery, West China Hospital were prospectively analyzed. Patients were divided into two groups according to antiepileptic drug (AED) treatment used immediately after epilepsy surgery (group A: therapy with LEV; group B: therapy without LEV). AED regimens were compared with regard to seizure-outcome for a period of more than 2 years. The International League Against Epilepsy (ILAE) classification was used to categorize seizure outcome. RESULTS: A total of 319 patients (184 male and 135 female patients; mean age 28.2±13.4 years) were studied. The mean postoperative follow-up period was 3.9±1.2 years. The two groups showed was no significant difference in preoperative baseline data. At the 6-month follow-up, the proportion of patients with seizure freedom was significantly higher in group A than in group B (78.8% vs. 67.5%, p=0.03). Seizure outcomes after 2 years were assessed using the ILAE classification. The proportion of patients under ILAE seizure-outcome classification I (seizure freedom) was significantly higher in group A than in group B (74.3% vs. 60.7%, p=0.01). Seizure recurrence rates at the final assessment, after planned reduction or withdrawal, were 26.3% for group A and 40.6% for group B (p=0.04). CONCLUSIONS: AED strategy after resective surgery may be a potentially modifiable prognostic indicator influencing seizure outcome in patients with intractable epilepsy. Compared to other AEDs, LEV appears to be more effective in controlling postoperative seizures in our long-term follow-up, and the advantage can be seen in early stage after surgery.

Predictive markers for carbamazepine and lamotrigine-induced maculopapular exanthema in Han Chinese.

The aims of this study were to clarify the possible associations of carbamazepine (CBZ)- and lamotrigine (LTG)-induced maculopapular exanthema (MPE) with the human leukocyte antigen (HLA) alleles in Chinese patients. A total of 249 subjects, including 40 patients with CBZ-induced MPE (CBZ-MPE), 43 patients with LTG-induced MPE (LTG-MPE), 52 CBZ-tolerant controls, 42 LTG-tolerant controls and 72 healthy controls, were included in this study. High-resolution HLA genotyping was performed by a specific kit. Differences in the allele frequencies among the groups were assessed. The allele frequencies of HLA-A*0201 and HLA-DRB1*1405 were significantly higher (P=0.033 and P=0.003, respectively), but those of HLA-B*5801 and HLA-DRB1*0301 (P=0.037 and P=0.024, respectively) were lower in the CBZ-MPE patients when compared with the CBZ-tolerant group. We also observed two significantly increased alleles of HLA-A*3001 and HLA-B*1302 (P=0.013 and P=0.013, respectively) and a decreased allele of HLA-A*3303 (P=0.048) in the LTG-MPE patients when compared with those in the LTG-tolerant group. Our results support the hypothesis that these HLA alleles contribute to the genetic susceptibility to CBZ/LTG-MPE and may be valuable as potential biomarkers for CBZ/LTG-MPE in Han Chinese.

Evaluation of different antiepileptic drug strategies in medically refractory epilepsy patients following epilepsy surgery.

PURPOSE: This study aimed to explore the most appropriate antiepileptic drug strategies after successful epilepsy surgery. METHODS: A total of 131 refractory epilepsy patients who underwent epilepsy surgery from January 2005 to December 2008 in the Department of Neurosurgery, West China Hospital, were retrospectively reviewed. Patients were divided into three groups (monotherapy, duotherapy, and polytherapy) according to drug combinations used immediately after epilepsy surgery. Seizure outcomes were followed up for more than 2 years. Engel classification was used to evaluate seizure outcomes. RESULTS: The mean postoperative follow-up period was 3.7±1.0 years. Preoperative baseline data among the three groups were comparable. Seizure recurrence rate in monotherapy was obviously higher than in other groups (34.1% vs. 15.1%, 7.1%) at 6-month follow-up, which showed a statistically significant difference (p=0.02). Seizure outcomes for 2 years were assessed using Engel classification. In the duotherapy group, the rate of Engel class I was definitely higher than in the other two groups (69.9% vs. 47.7%, 57.1%, p=0.02). Seizure relapse rates at the 2-year follow-up, after planned reduction or withdrawal, were 46.4% for monotherapy, 16.9% for duotherapy, and 25.0% for polytherapy (p=0.01). CONCLUSIONS: Monotherapy may be not sufficient enough to control seizures completely. It appears to have a higher risk for seizure relapse when considering drug reduction. It suggests that duotherapy may be more effective and safer than monotherapy. Even after successful epilepsy surgery, duotherapy seems preferable to monotherapy or polytherapy for control of residual seizures.

Etiologic features of newly diagnosed epilepsy: hospital-based study of 892 consecutive patients in West China.

PURPOSE: We evaluated data from a large cohort of newly diagnosed epilepsy patients from the biggest epilepsy center in West China. The aim was to determine the most prevalent etiologic factors in this region. METHODS: From May 2008 to May 2010, the clinical data of patients with newly diagnosed epilepsy were consecutively, systematically and prospectively recorded in a database. The data were analyzed according to sex, age, seizure type, etiology, and other factors. RESULTS: The present study examined 892 patients with newly diagnosed epilepsy. Among these patients, 346 (38.8%) were confirmed as symptomatic, with the largest constituent ratio among the elderly (63.2%). In this symptomatic group, central nervous system (CNS) infections and traumatic brain injuries (TBI) were the two most common etiologies. When analyzed according to age bracket, cortical dysplasia, mesial temporal sclerosis, and CNS infection were the most frequent causes among young patients (<18 years). On the other hand, CNS infection and TBI were the two most common causes in patients between 18 and 60 years. Stroke was the most common cause of newly diagnosed symptomatic epilepsy in the elderly (>60 years). CONCLUSIONS: More than 30% of newly diagnosed epilepsy cases were shown to be symptomatic by medical history as well as careful clinical and laboratory examination. Detailed epilepsy assessments are essential to formulate a therapeutic plan and to improve prognosis. The etiology spectrum found in this large cohort forms a comparative baseline for future studies.

Phenytoin-induced Stevens-Johnson syndrome with negative HLA-B*1502 allele in mainland China: two cases.

Antiepileptic drugs-induced Stevens-Johnson syndrome (SJS) is a life-threatening severe cutaneous adverse reaction. Recent studies in Thailand and Taiwan showed a significant association between phenytoin (PHT)-induced SJS and human leucocyte antigen HLA-B*1502 allele. Although the US FDA had issued an alert to clinicians, insufficient information is available to recommend testing for HLA-B*1502 in Asian patients in line for PHT treatment. Therefore, extended studies are necessary to further evaluate the potential association between PHT-induced SJS and HLA-B*1502 allele in various populations. To date, no similar data exist in mainland China. Here, we describe two Chinese Han cases of PHT-induced SJS with negative HLA-B*1502 allele, in which HLA high-resolution genotyping showed two heterozygous HLA-B*4601/B*5102 and HLA-B*3701/B*4601 allele, respectively. Our findings provide evidence to support that other genetic markers or nongenetic factors could contribute to the susceptibility of PHT-induced SJS, except for HLA-B*1502 allele. Further studies are encouraged to investigate the genetic link with PHT-induced serious skin reactions in future.

Pilot association study of oxcarbazepine-induced mild cutaneous adverse reactions with HLA-B*1502 allele in Chinese Han population.

BACKGROUND: Recent study demonstrated that HLA-B*1502 was a common risk allele in aromatic antiepileptic drugs (AEDs) induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. However, the association of AEDs-induced mild maculopapular eruption (MPE) with HLA-B*1502 remains unclear until recently. In the present study, we conducted a pilot study to detect a possible association of oxcarbazepine (OXC)-induced MPE with HLA-B*1502 allele in Chinese Han population. METHODS: We enrolled 90 subjects involving 9 patients with OXC-induced MPE and two groups of controls, 9 OXC-tolerant and 72 normal controls. High-resolution HLA genotyping was performed by specific kit. The results of HLA genotyping are expressed as positive or negative for HLA-B*1502 allele. Differences in genotype frequencies between groups were assessed by the Fisher's exact test. RESULTS: Four cases were detected as positive for HLA-B*1502 amongst 9 patients. However, only 1 subject was positive amongst 9 tolerant controls, and 6 subjects were positive amongst 72 normal controls. The difference in HLA-B*1502 allele frequencies between the MPE group and normal controls was statistically significant (OR: 8.8; 95% CI: 1.853-41.790; P=0.011). In addition, we also observed an increased frequency of HLA-B*1502 allele in patients (44.44%) compared with tolerant controls (11.11%), although it failed to reach statistical significance (P=0.294). CONCLUSIONS: Our findings indicate that HLA-B*1502 allele may contribute to the genetic susceptibility to OXC-induced MPE in Chinese Han population. In order to safer AEDs use, we recommend that HLA-B*1502 allele should be tested for patients with OXC-induced MPE before changing to other AEDs, and AEDs with similar chemical structure should be avoided in individuals who test positive for HLA-B*1502 allele. It should be pointed out that, however, our results may well be just by chance owing to the small sample size and should be further confirmed in future studies.

Association study of lamotrigine-induced cutaneous adverse reactions and HLA-B*1502 in a Han Chinese population.

Antiepileptic drugs including lamotrigine (LTG) and carbamazepine (CBZ) are among the most common causes of cutaneous adverse reactions (cADRs). Human leukocyte antigen (HLA)-B*1502 has been strongly associated with CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). To investigate this relationship, we performed high-resolution HLA genotyping on LTG-tolerant controls, healthy volunteers, and patients affected by LTG-induced cADRs, ranging from maculopapular exanthema (MPE) to SJS/TEN. Patients with LTG-induced cADRs (n=25, including three with SJS/TEN and 22 with MPE), 21 LTG-tolerant controls, and 71 healthy volunteers were enrolled. The differences in the starting dosage of LTG among the SJS/TEN, MPE, and LTG-tolerant control groups were not statistically significant. HLA-B*1502 frequency was 33.3% (1/3; LTG-induced SJS/TEN group), 9.1% (2/22; LTG-induced MPE group), 4.8% (1/21; LTG-tolerant group), and 8.5% (6/71; healthy volunteers). There was no significant difference in the frequency of subjects with the HLA-B*1502 allele between the SJS/TEN group and LTG-tolerant group (p=0.239, OR=10.0, 95% CI 0.44-228.7), and healthy volunteers (p=0.26, OR=5.42, 95% CI 0.43-68.8), MPE and LTG-tolerant groups (p=1.0, OR=1.08, 95% CI 0.20-5.8), and healthy volunteers (p=1.0, OR=2.0, 95% CI 0.17-23.9). None of the HLA alleles detected were associated with LTG-induced cADRs. In conclusion, HLA-B*1502 and other HLA alleles are not directly associated with LTG-induced MPE. The possibility that HLA-B*1502 is associated with an increased risk of LTG-induced SJS/TEN could not be excluded.