Risk of Amyotrophic Lateral Sclerosis in Patients With Diabetes: A Nationwide Population-Based Cohort Study.

BACKGROUND: Glucose intolerance in patients with amyotrophic lateral sclerosis (ALS) has been inconsistently reported. Evidence for the association of ALS and diabetes mellitus is limited. We aimed to assess the overall and age- and sex-specific risks of ALS among patients with diabetes in Taiwan. METHODS: The study cohort included 615 492 diabetic patients and 614 835 age- and sex-matched subjects as a comparison cohort, followed from 2000 to 2008. We estimated the incidence densities of ALS and calculated the relative hazard ratios (HRs) of ALS (ICD-9-CM 335.20) in relation to diabetes using a Cox proportional hazard regression model, with adjustment for potential confounders, including sex, age, geographic area, urbanization status, Charlson Comorbidity Index, frequency of medical visit, and histories of hypertension, hyperlipidemia, and chronic obstructive pulmonary disease. RESULTS: Over a 9-year period, 255 diabetic and 201 non-diabetic subjects developed ALS, corresponding to incidence densities of 7.42 and 5.06 per 100 000 person-years, respectively. After adjustment for potential confounders, patients with diabetes experienced a significantly elevated HR of 1.35 (95% confidence interval [CI], 1.10-1.67). A higher covariate adjusted HR was noted in men (HR 1.48; 95% CI, 1.13-1.94) than in women (HR 1.17; 95% CI, 0.84-1.64), while men aged ≤65 years showed the most increased HR of 1.67 (95% CI, 1.18-2.36). CONCLUSIONS: This study demonstrated a moderate but significant association of diabetes with ALS onset, and such association is not confounded by socio-demographic characteristics or certain ALS-related co-morbidities. Further studies are warranted to examine whether the findings observed in our study can be replicated.

[Hospice palliative care policy in Taiwan: past developments and future perspectives].

The duty of medical personnel is to save lives, cure diseases, relieve suffering, and promote health. Medical personnel care for their patients from birth to death. At the end of terminal care, medical personnel should maintain a religious / holistic commitment to their patients to "remove their suffering and provide happiness" as much as possible. Mackay Hospital opened the first hospice in Taiwan in 1990. Financial coverage of hospice care by the National Health Insurance, the enactment of the Hospice Palliative Act, the attention of Hospital Accreditation to hospice care, and the establishment of the system of clinical chaplaincy have all contributed to the development of hospice palliative care in Taiwan. Application of the Taiwan Coma Scale has been shown to decrease the use of futile life sustaining treatments in the ICU. The author hopes that nurses may further expand community hospice care services to help facilitate the peaceful dying of terminal patients at home.

Risk of stroke with thiazolidinediones: a ten-year nationwide population-based cohort study.

BACKGROUND: Thiazolidinediones (TZDs) - rosiglitazone and pioglitazone - a class of insulin sensitizer for treating type 2 diabetes, have been reported to exhibit neuroprotective effects in preclinical studies and have good effects in the control of blood sugar for diabetic patients with insulin resistance. However, clinical trials and observational studies have raised the possibility of higher stroke risk in patients treated with rosiglitazone. Whether pioglitazone poses similar stroke risk remains uncertain. Most of the studies on cardiovascular effects of TZDs were based on studies in the USA and Europe. The present study aimed to compare the stroke risk among diabetic patients on TZD to those on non-TZD medications in an Asian population. METHODS: The study cohort included 15,981 patients with a diagnosis of diabetes without prior stroke, acute myocardial infarction (AMI) or heart failure who were followed from 2001 to 2010. Patients were classified by their prescriptions into rosiglitazone, pioglitazone and non-TZD groups. The study end points included ischemic and hemorrhagic stroke. In view of the reported association of heart failure and AMI with rosiglitazone, these 2 end points were also included in the present study. Cox hazard proportional models were used to estimate the risk of developing the end points. Likelihood ratio test was used to examine the age-drug interactions. Dose-response effects were evaluated by comparing the incidence rates among patients with different cumulative exposures to TZD. RESULTS: During the 10-year follow-up, the rosiglitazone group showed significantly higher risk of ischemic stroke (multivariate adjusted hazard ratio, HR = 1.39; 95% confidence interval, CI = 1.16-1.66) and heart failure (HR = 1.59; 95% CI = 1.18-2.14) than the non-TZD group. The pioglitazone group did not show significant difference from the non-TZD group in ischemic stroke (HR = 0.97; 95% CI = 0.75-1.26) and heart failure (HR = 0.94; 95% CI = 0.59-1.50). The results also showed a significant dose-dependent effect of higher risk of ischemic stroke with increasing dosage of rosiglitazone, while there was no increased risk at any level of pioglitazone dosage. CONCLUSIONS: This population-based cohort study shows that rosiglitazone imposes a higher risk of developing stroke or heart failure in this Asian patient population, suggesting the adverse side effects of rosiglitazone across ethnic boundaries. Pioglitazone, on the other hand, does not increase cardiovascular or stroke risk compared to the non-TZD group among diabetic patients without a history of macrovascular disease.

Madelung's disease associated with polyneuropathy and symptomatic hypokalemia.

Madelung's disease (multiple symmetric lipomatosis) is a rare disease characterized by abnormal diffuse lipomatosis in proximal upper limbs and neck. Previous reports have shown that this disease is associated with alcoholism, polyneuropathy, mitochondrial disease, and glucose intolerance. Here, we describe a 46-year-old man having Madelung's disease associated with polyneuropathy and symptomatic hypokalemia. He presented with insidious-onset weakness and numbness in lower limbs for 7 years and recent deterioration of symptoms. Proximal weakness improved with potassium supplement. Our observation may extend the phenotype of Madelung's disease to hypokalemic periodic paralysis.

Prediction of infarct growth and neurologic deterioration in patients with positive perfusion-diffusion mismatch.

BACKGROUND: To assess the value of baseline clinical severity and perfusion-diffusion mismatch as predictors for further infarct growth and clinical outcome. METHODS: Patients with acute ischemic stroke and initial perfusion-diffusion mismatch within 72 h were enrolled. Baseline perfusion defects on time-to-peak (TTP) and cerebral blood volume (CBV) maps were measured. Infarct volume and stroke severity were assessed by diffusion-weighted image (DWI) and NIHSS, and were repeatedly assessed 7 days later. The predictive value of baseline NIHSS and perfusion defects on further infarct growth and neurologic deterioration was determined. RESULTS: Fifty-two patients (mean age 68.3±12.8 years, 42% women) were enrolled. CBV defects were significantly associated with infarct growth (CBV, p=0.02). Initial stroke severity, but not TTP and CBV mismatch (p=0.65 and 0.76, respectively), significantly inversely correlated with neurologic deterioration (p=0.001). CONCLUSIONS: In patients with mismatch, those with severe symptoms initially are more likely to have infarct growth, while those with minor symptoms tend to suffer from larger extent of neurologic deterioration within 1 week. CBV is associated with further infarct growth but not clinical deterioration.

Lack of association between total serum homocysteine and extracranial cerebral flow.

BACKGROUND/PURPOSE: High homocysteine (Hcy) concentration is associated with slow coronary flow. This study examined the association between Hcy and hemodynamic status in the extracranial cerebral arteries in healthy individuals. METHODS: A total of 535 healthy adults underwent physical examination and duplex ultrasonography of the extracranial carotid and vertebral arteries, and blood laboratory tests, including biochemistry and serum total Hcy. Flow hemodynamic parameters including velocity, resistance, and volume of the carotid and vertebral arteries were measured. Multiple regression analysis was performed to examine the association between Hcy and the flow parameters. RESULTS: Participants with higher Hcy were more likely to have a lower systolic velocity of the internal carotid artery (p = 0.01) and vertebral artery (p < 0.001), and lower resistance of the vertebral artery (p = 0.004). However, the multiple-adjusted means of the flow velocity, resistance, and flow volume of the carotid or vertebral artery were not significantly different across quartiles of Hcy. When Hcy was treated as a continuous variable, there was still no significant relationship between Hcy levels and the aforementioned hemodynamic status. CONCLUSION: Our results did not support the hypothesis that the levels of Hcy are associated with the flow velocity, resistance, and volume of the extracranial cerebral artery in healthy individuals.

Different prevalence rates of Parkinson's disease in urban and rural areas: a population-based study in Taiwan.

BACKGROUND: Rural living has long been debated as a risk factor for idiopathic Parkinson's disease (IPD). But few community-based studies compared this difference between urban and rural areas. METHODS: Population-based surveys by neurologists using a standardized diagnostic protocol were conducted in the urban areas of Keelung City and compared the prevalence rates of IPD with those we had previously determined in the rural area of Ilan County, Taiwan. Subjects were diagnosed with IPD when at least 2 of the 4 cardinal signs of parkinsonism were present and by exclusion of secondary parkinsonism. Gender-specific age-standardized prevalence rates of IPD by using the 1970 and 2000 US censuses were calculated for comparison. RESULTS: The participation rate was 84.9%. The crude prevalence rate of IPD in persons aged 40 years and over was 706 (95% CI: 551-864) per 100,000 population. The age-adjusted prevalence rates by using the 1970 US census were 633 (95% CI: 620-646) for people aged 40 and over and 230 (95% CI: 227-234) for all ages. Our results were similar to those obtained in Sicily, Rotterdam, and 3 communities in China. Moreover, the prevalence rates of IPD in Keelung, the urban area studied, were twice as high as those in Ilan, the rural area studied (p < 0.001). CONCLUSIONS: Our results suggest that urban living is more important as a risk factor for IPD development than rural living in Taiwan.

Mortality of Parkinson's disease by Hoehn-Yahr stage from community-based and clinic series [Keelung Community-based Integrated Screening (KCIS) no. 17)].

PURPOSE: We aimed to quantify the mortality reduction by which the early detection of Parkinson's disease (PD) within a community-based study could reduce the number of advanced cases. METHODS: Data used in this study were derived from two community-based surveys and from a clinical series of PD cases identified from a medical centre. The cumulative survival by Hoehn-Yahr (H-Y) scale was estimated and the mortality reduction derived from a community-based survey was predicted. RESULTS: A total of 117 PD patients were detected through two community-based approaches. By comparing the H-Y stage distribution of screen-detected cases with those from the clinical series, a 22.5% excess in the number of early PD (H-Y stage I and stage II) were identified with screening. The risk ratios of being H-Y stage III or severe for community-based detected cases versus clinical series were 0.49 (95% confidence interval: 0.30-0.78). The total death rate adjusted by H-Y stage distribution was 21% and 28% for cases from community and clinical series, respectively. CONCLUSIONS: The present study revealed that early detection of PD through a community-based survey may reduce 51% incidence of stage III or more severe PD at diagnosis, leading to a 25% reduction in mortality.

Patient characteristics predict occurrence and outcome of complaints against physicians: a study from a medical center in central Taiwan.

BACKGROUND/PURPOSE: A better understanding of the risk factors for medical malpractice is essential for implementing long-term prevention strategies. Certain physician characteristics have been reported to be associated with malpractice litigation. However, patient characteristics have not been fully investigated. METHODS: We conducted a hospital-based case-control study. We reviewed a total of 147 cases in the inpatient risk management file (RMF) and 44,045 inpatient controls. The RMF was opened if the patient's complaint may have led to legal action. We compared demographic data of RMF cases and controls to investigate the risk factors for filing a complaint. Outcomes of the RMF cases were classified as resolution, compensation, and lawsuit. RESULTS: RMF cases were associated with admission via the emergency room (odds ratio [OR]=1.62, p=0.005), surgical specialty (OR=1.86, p=0.001) and living in an urban area (OR=1.93, p<0.001). Once RMF cases were filed, living in an urban area was the only independent factor for filing a lawsuit (OR=4.10, p=0.007). RMF cases with medical injury were more likely to reach compensation (OR=10.51, p<0.001) and to receive significantly higher compensation (p=0.007). The severity of medical injury was correlated positively with the likelihood of reaching compensation and the amount of compensation. Only 15.0% of RMF cases entered the litigation phase. CONCLUSION: Patients with certain characteristics tend to file complaints, receive compensation, or bring a case to court. Understanding of patient characteristics may be useful for predicting occurrence and outcome of complaints against physicians.

Natural history and effectiveness of early detection of Parkinson's disease: results from two community-based programmes in Taiwan (KCIS no. 11).

OBJECTIVES: The natural course of Parkinson's disease (PD), as measured on the Hoehn-Yahr (H-Y) scale, and the impact that early detection would have on prognosis for those with the disease, has barely been addressed since the introduction of L-dopa. This study aimed to elucidate the natural history of PD and effectiveness of early detection in reducing advanced disability and mortality. METHOD: A total of 21 362 participants aged 40 years or older were invited to two community-based programmes for the early detection of PD. The step-by-step annual progression rates from H-Y stage I to stage IV or V, and cumulative survival rates, by the H-Y scale, were estimated and applied to simulated data to assess the impact of different screening intervals upon stage at diagnosis and subsequent survival. RESULTS: The average duration in stages I, II and III was estimated as 2.83, 6.62 and 1.41 years, respectively. The average delay time before deteriorating into H-Y stage III was 9.45 year. Application of these parameters to simulated model predicted a 36% (95% CI: 28-39%), 26% (95% CI: 20-32%) and 19% (95% CI: 13-24%) reduction in death for annual, 5-yearly and 10-yearly screening programmes, respectively. CONCLUSION: The present study recommended a 5-yearly screening programme, with 74% of PD cases prevented from progressing to H-Y stage III or worse within 10 years of diagnosis, and leading to a corresponding 26% reduction in mortality.

Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients.

BACKGROUND: Elevated serum homocysteine levels have been associated with the development of Alzheimer's dementia (AD). The combined use of a mecobalamin capsule preparation, which contains vitamin B12 0.5 mg with an active methyl base, and an over-the-counter nutritional supplement that contains folic acid 1 mg and pyridoxine hyperchloride 5 mg may be effective as a homocysteine-lowering vitamin regimen. OBJECTIVE: The aim of this study was to determine whether oral multivitamin supplementation containing vitamins B6 and B12 and folic acid would improve cognitive function and reduce serum homocysteine levels in patients with mild to moderate AD. METHODS: This randomized, double-blind, placebocontrolled trial was conducted at En Chu Kong Hospital, Taipei, Taiwan. Male and female patients aged >50 years with mild to moderate AD and normal folic acid and vitamin B12 concentrations were enrolled. All patients received treatment with an acetylcholinesterase inhibitor and were randomized to receive add-on mecobalamin (B12) 500 mg + multivitamin supplement, or placebos, PO QD for 26 weeks. The multivitamin contained pyridoxine (B6) 5 mg, folic acid 1 mg, and other vitamins and iron. Serum homocysteine level was measured and cognitive tests were conducted at baseline and after 26 weeks. The primary efficacy outcome was change in cognition, measured as the change in score from baseline to week 26 on the Alzheimer's Disease Assessment Scale 11-item Cognition subscale. Secondary efficacy outcomes included changes in function in performance of activities of daily living (ADLs) and concentrations of homocysteine, B12, and folic acid. Tolerability was assessed by comparing the 2 study groups with respect to physical examination findings, including changes in vital signs, laboratory test abnormalities, concomitant medication use, and compliance of study medication was assessed using an interview with the patient's caregiver, as well as the monitoring of adverse events (AEs) throughout the study. RESULTS: Eighty-nine patients (45 men, 44 women; all Taiwanese; mean [SD] age, 75 [7.3] years) were enrolled and randomized. Overall, there were no significant differences in cognition or ADL function scores between the 2 groups. At week 26, the mean (SD) between-group difference in serum homocysteine concentration versus placebo was -2.25 (2.85) micromol/L (P = 0.008), and the mean serum concentrations of vitamin B12 and folic acid were significantly higher (but within normal range) in the multivitamin group compared with placebo (., +536.9 [694.4] pg/mL [P < 0.001] and +13.84 ng/mL [11.17] [P = 0.012] at 26 weeks, respectively). The 2 most common AEs were muscle pain (11.1% and 6.8%) and insomnia (8.9% and 9.1%) in the multivitamin and placebo groups, respectively. CONCLUSIONS: In this population of patients with mild to moderate AD in Taiwan, a multivitamin supplement containing vitamins B(6) and B(12) and folic acid for 26 weeks decreased homocysteine concentrations. No statistically significant beneficial effects on cognition or ADL function were found between multivitamin and placebo at 26 weeks.

Institution type-dependent high prevalence of dementia in long-term care units.

BACKGROUND/AIMS: It is estimated that there are 90,000 patients with dementia in the 23 million habitants of Taiwan, with a few institutions specialized in dementia care. To assess the need of institutional care for dementia, we investigated the institution prevalence of dementia. METHODS: We performed stratified randomized sampling of elder residents from different types of institutions in different regions of Taiwan. A 2-stage survey with screening and clinical confirmation was carried out in 2004. RESULTS: In total, 1,525 residents aged 65 years and over in 60 institutions participated in the study in which 1,308 elders completed the 2-stage survey. Among these, 631 elders were diagnosed as having dementia. The dementia prevalence was 26.8% in the residential houses, 61.8% in the assisted living facilities and 64.5% in the nursing homes. Vascular dementia was the leading cause of dementia in the institutions. Old age, diabetes mellitus and family history of dementia increased risks for both Alzheimer's disease and vascular dementia. CONCLUSION: The investigation showed that the prevalence of dementia in the long-term care units of Taiwan was much higher than those from community studies and the high prevalence in the institutions depended on the type of the long-term care unit.

Botulinum toxin type a in the prophylactic treatment of transformed migraine in Taiwanese patients: a review of 30 consecutive cases.

BACKGROUND: Botulinum toxin type A (BoNT-A) for the treatment of patients with various forms of migraine has been studied, but there is a paucity of data regarding the use of BoNT-A in Asian headache patients. Our study was designed to evaluate the efficacy of BoNT-A in the treatment of transformed migraine (TM) in a population of Taiwanese patients. METHODS: We retrospectively analyzed 30 patients who underwent BoNT-A treatment for TM from July 2003 to May 2004. Of 30 patients, 14 had palpable muscle tenderness (or tender points) in the pericranial region and 16 did not. All patients received injections into the corrugator, procerus, frontalis, and temporalis muscles (a total of 30 U), while a subset of TM patients with tender points (6 of 14 patients) also received injections to additional muscles based on a follow-the-tenderness approach (mean dose, 45 U). RESULTS: Twenty-seven of the 30 patients (90%) surveyed reported effective relief of their symptoms with BoNT-A treatment (at least a 50% reduction in the number of headache days or in headache intensity). The greatest reduction in headache days per month and headache intensity was found in TM patients with tender points who received a mean dose of 45 U compared to those who received fixed-site dosing of 30 U. CONCLUSION: Our results suggest that BoNT-A may be an effective prophylactic treatment for TM in Taiwanese patients. Interestingly, similar efficacy was demonstrated in TM patients with tender points compared to those without tender points when an additional dose of BoNT-A was injected into the tender muscles in the former.

Population-based survey on prevalence of adult patients with epilepsy in Taiwan (Keelung community-based integrated screening no. 12).

PURPOSE: To determine the prevalence rate and patterns of adult patients with epilepsy in Taiwan, we conducted a community-based neuroepidemiological survey. METHODS: Epilepsy was detected by neurologists using one-stage method. It was integrated into a community health screening service and performed from 1 January 2001 to 31 December 2001 in Keelung, a northern city in Taiwan. A total of 13,663 subjects aged 30 years or older participated in this survey. RESULTS: There were 52 patients with epilepsy in this study. Among them, 37 were patients with active epilepsy. The age-adjusted prevalence rate of active epilepsy above 30 years old was 2.77/1000 (to the 1980 US population) with the highest rate in subjects aged 40-49 years (4.0/1000). There was a trend of higher prevalence rate in male than in female. The most common seizure type was complex partial seizure (46.0%). Using one-stage detection method, we found nine (24.3%) patients with active epilepsy who had never been diagnosed before. Among the patients with active epilepsy, 35.1% were symptomatic cases. Head injury (13.5%) is the leading cause, followed by CNS infection (8.1%), stroke (5.4%) and perinatal insult (5.4%). The lifetime prevalence rate of epilepsy (including active epilepsy and epilepsy in remission) was 3.14/1000 for age above 30 years. CONCLUSIONS: Comparing to previous epilepsy survey in 1993, our results showed that the prevalence rate of epilepsy was rather stable over the past decade in northern Taiwan. Head injury is the leading cause responsible for active epilepsy. Improving public safety is an important public health issue which may help to reduce occurrence of epilepsy.

Mortality in adult patients with epilepsy in Taiwan.

To investigate mortality in adult patients with epilepsy in Taiwan, a total of 263 patients with epilepsy aged > or = 17 years, referred to the outpatient epilepsy clinic between 1 Jan and 31 December 1991, were prospectively enrolled and followed up until 31 December 2000. A total of 32 deaths were reported. Overall case-fatality rate was 12.2%. The age-adjusted standard mortality ratio (SMR) was calculated to compare the risk of death in patients with epilepsy to the general population. Patients with epilepsy had a 3.5-fold higher risk of death as compared with the general population (SMR: 3.47, 95% CI: 2.46-4.91). The Cox proportional hazards regression model was used to assess relevant clinical contributions to death. Patients with an age-at-onset > or = 40 years had a 4-fold higher risk of death as compared with those with an earlier onset. The multivariate analysis revealed that age-at-onset between 40 and 59 years, tumor etiology, and being male increased the risk of death in epilepsy. One-third of the deaths in patients with age-at-onset between 40-59 years died of liver cirrhosis and hepatoma. Hepatitis B virus infection is endemic in Taiwan, and this is closely associated with liver cirrhosis and hepatoma. Whether anticonvulsants contributed to the hepatotoxicity that led to fatal liver disease in this group needs further investigation.

Health related quality of life in adult patients with epilepsy compared with a general reference population in Taiwan.

To compare the health-related quality of life (HRQL) for patients with epilepsy and health subjects, we collected the clinical and demographic data and information on health states by using the Taiwan version of World Health Organization quality of life (WHOQOL)-BREF questionnaire in 296 patients (aged 19-73 years) with confirmed active epilepsy visiting the clinic of National Taiwan University Hospital, and 296 age-, gender-, municipal- and education-matched Taiwanese healthy subjects sampled from a national health interview survey. Multiple regression analyses with stepwise selection strategy were conducted to study risk factors for impairment of HRQL. Patients with epilepsy have poorer HRQL than the healthy population in physical, psychological and social domains but not in environment domain (p<0.005). Patients with less than 4 attacks during the previous 1 month had a better score in the availability and quality of health and social care in environment domain than healthy subjects (p<0.05). After controlling other determinants, seizure frequency, and comobid with other diseases are the important factors in predicting HRQL for epilepsy patients. Patients with employment and married had a significantly better HRQL. Effective control of seizure frequency and thoughtful promotion of positive attitudes in community are essential to improve the HRQL of epilepsy patients.

Carotid atherosclerosis, intima media thickness and risk factors--an analysis of 1781 asymptomatic subjects in Taiwan.

The aim of this study was to investigate the association of intima media thickness (IMT) and plaque with risk factors for atherosclerosis in asymptomatic subjects in Taiwan. Between 1998 and 2001, the study recruited 1781 asymptomatic subjects (1131 men and 650 women [mean age, 49 years; range 18-85 years]). These were examined by B-mode ultrasound to measure the IMT at the far wall of the common carotid artery (CCA) and the extent of plaque formation. A wide range of vascular risk factors including age, gender, smoking, body mass index, blood chemistry, and previous history were surveyed. The mean (+/-S.D.) IMT observed was 0.68 (+/-0.12) and 0.66 (+/-0.11) mm for men and women, respectively, (P=0.0008). The mean (S.D.) IMT of the CCA was 0.66 (+/-0.12) mm on the right side and 0.68 (+/-0.12) mm on the left side (P=0.0004). IMT increased with aging, according to the equation IMT=(0.005xage in years)+0.403 [corrected]. Higher IMT was associated with male gender, and IMT was greater in the left CCA. About 36.9% of subjects had carotid plaques. The percentage of plaque increased with aging. The plaque prevalence was positively associated with IMT. The value of IMT over the cut point of 0.68 mm correlated with obviously increased risk of carotid atherosclerosis. Age, systolic blood pressure and fasting blood sugar were independent risk factors related to both carotid atherosclerosis and thick IMT.