Effective Interventions and Decline of Antituberculosis Drug Resistance in Eastern Taiwan, 2004–2008

BACKGROUND: The Taiwan health authority recently launched several tuberculosis (TB) control interventions, which may have an impact on the epidemic of drug-resistant TB. We conducted a population-based antituberculosis drug resistance surveillance program in Eastern Taiwan to measure the proportions of notified TB patients with anti-TB drug resistance and the trend from 2004 to 2008. METHODS AND FINDINGS: All culture-positive TB patients were enrolled. Drug susceptibility testing results of the first isolate of each TB patient in each treatment course were analyzed. In total, 2688 patients were included, of which 2176 (81.0%) were new TB cases and 512 (19.0%) were previously treated cases. Among the 2176 new TB cases, 97 (4.5%) were retreated after the first episode of TB treatment within the study period. The proportion of new patients with any resistance, isoniazid resistance but not multidrug-resistant TB (resistant to at least isoniazid and rifampin, MDR-TB), and MDR-TB was 16.4%, 7.5%, and 4.0%, respectively, and that among previously treated cases was 30.9%, 7.9%, and 17.6%, respectively. The combined proportion of any resistance decreased from 23.3% in 2004 to 14.3% in 2008, and that of MDR-TB from 11.5% to 2.4%. CONCLUSIONS: The proportion of TB patients with drug-resistant TB in Eastern Taiwan remains substantial. However, an effective TB control program has successfully driven the proportion of drug resistance among TB patients downward

Down-regulation of PKCζ in renal cell carcinoma and its clinicopathological implications

<p>Abstract</p> <p>Background</p> <p>Metastatic renal cell carcinoma (RCC) is highly resistant to systemic chemotherapy. Unfortunately, nearly all patients die of the metastatic and chemoresistant RCC. Recent studies have shown the atypical PKCζ is an important regulator of tumorigenesis. However, the correlation between PKC<b>ζ </b>expression and the clinical outcome in RCC patients is unclear. We examined the level of PKCζ expression in human RCC.</p> <p>Methods</p> <p>PKCζ mRNA and protein expressions were examined by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) respectively in RCC tissues of 144 patients. Cellular cytotoxicity and proliferation were assessed by MTT.</p> <p>Results</p> <p>PKCζ expression was significantly higher in normal than in cancerous tissues (<it>P </it>< 0.0001) by real-time PCR and IHC. Similarly, PKCζ expression was down-regulated in four renal cancer cell lines compared to immortalized benign renal tubular cells. Interestingly, an increase of PKCζ expression was associated with the elevated tumor grade (<it>P </it>= 0.04), but no such association was found in TNM stage (<it>P </it>= 0.13). Tumors with higher PKCζ expression were associated with tumor size (<it>P </it>= 0.048). Expression of higher PKCζ found a poor survival in patients with high tumor grade. Down-regulation of PKCζ showed the significant chemoresistance in RCC cell lines. Inactivation of PKCζ expression enhanced cellular resistance to cisplatin and paclitaxel, and proliferation in HK-2 cells by specific PKC<b>ζ </b>siRNA and inhibitor.</p> <p>Conclusions</p> <p>PKCζ expression was associated with tumorigenesis and chemoresistance in RCC.</p

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019

Background: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. Methods: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). Findings: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1–38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78–0·91) per female living with HIV in 2019, 0·99 male infections (0·91–1·10) for every female infection, and 1·02 male deaths (0·95–1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58–35·43, and a 39·66% decrease in deaths, 36·49–42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05–0·06) and the global incidence-to-mortality ratio was 1·94 (1·76–2·12). No regions met suggested thresholds for progress. Interpretation: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. Funding: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Stress on caregivers providing prolonged mechanical ventilation patient care in different facilities: A cross-sectional study.

PurposeTaiwan has implemented an integrated prospective payment program (IPP) for prolonged mechanical ventilation (PMV) patients that consists of four stages of care: intensive care unit (ICU), respiratory care center (RCC), respiratory care ward (RCW), and respiratory home care (RHC). We aimed to investigate the life impact on family caregivers of PMV patients opting for a payment program and compared different care units.MethodA total of 610 questionnaires were recalled. Statistical analyses were conducted by using the chi-square test and multivariate logistic regression model.ResultsThe results indicated no associations between caregivers' stress levels and opting for a payment program. Participants in the non-IPP group spent less time with friends and family owing to caregiver responsibilities. The results of the family domain show that the RHC group (OR = 2.54) had worsened family relationships compared with the ICU group; however, there was less psychological stress in the RCC (OR = 0.54) and RCW (OR = 0.16) groups than in the ICU group. In the social domain, RHC interviewees experienced reduced friend and family interactivity (OR = 2.18) and community or religious activities (OR = 2.06) than the ICU group. The RCW group felt that leisure and work time had less effect (OR = 0.37 and 0.41) than the ICU group. Furthermore, RCW interviewees (OR = 0.43) were less influenced by the reduced family income than the ICU group in the economic domain.ConclusionsRHC family caregivers had the highest level of stress, whereas family caregivers in the RCW group had the lowest level of stress

Short-term Results of Vagus Nerve Stimulation in Pediatric Patients with Refractory Epilepsy

Vagus nerve stimulation (VNS), an alternative method to manage patients with medically intractable epilepsy, has shown favorable results in reducing seizure relapse and improvements in quality of life. In 1997, the U.S. Food and Drug Administration approved the use of this device as an adjunctive therapy for intractable seizure in adults and adolescents older than 12 years of age. Methods: We present a preliminary study of pediatric patients, who suffered from medically intractable seizure and underwent VNS implantation after observation of the baseline seizure frequency. Classification of epileptic syndrome, seizure patterns, age of onset, seizure frequency reduction and adverse effects were recorded. Results: Patients who underwent VNS implantation included four adolescents and four children. The follow-up duration ranged from 9–33 months. All the patients were responders after the beginning of the stimulation. Five of the eight patients responded to VNS with a seizure frequency reduction rate > 50%, and four of the eight patients experienced a ≥ 90% seizure reduction. No significant adverse effects were noted in all patients during the observation period. Conclusion: The effective management of medically intractable seizure remains challenging to most clinical physicians. In addition to ketogenic diet and epilepsy surgery, VNS provides an alternative way to manage this issue. Our results suggest that VNS is well tolerated in pediatric patients, and is a favorable and safe method of treating intractable seizure in common clinical practice

Prevalence of resistance to first line anti-tuberculosis drugs in Eastern Taiwan, 2004–2008, by type of case.

a<p>Multidrug resistance, defined as resistance to at least isoniazid and rifampicin.</p

Demographic profiles of the population in Eastern Taiwan, 2004–2008.

a<p>HIV, human immunodeficiency virus.</p

Trend of resistance to first-line anti-tuberculosis drugs among previously treated cases (n = 609) in Eastern Taiwan, 2004–2008.

a<p>INH = isoniazid; RMP = rifampin; EMB = ethambutol; SM = streptomycin; MDR = resistance to at least INH and RMP.</p