Fecal microbiota transplantation for treatment of refractory or recurrent Clostridioides difficile infection in Taiwan: a cost-effectiveness analysis.

Background: Compared to antibiotic treatment, fecal microbiota transplantation (FMT) is a more effective treatment for refractory or recurrent CDI (rCDI). Patients with inflammatory bowel disease (IBD) have a higher incidence of CDI and worse outcomes. There has been no study from Asia to evaluate the cost-effectiveness of FMT for overall rCDI patients and rCDI patients with IBD. Methods: We applied a Markov model with deterministic and probabilistic sensitivity analyses to evaluate the cost and effectiveness of different treatments for rCDI patients with a time horizon of 1 year from the payer's perspective. We compared the cost and clinical outcomes of FMT through colonoscopy to two antibiotics (vancomycin and fidaxomicin) using data from Chang Gung Memorial Hospital, Taoyuan, Taiwan. Results: Compared to vancomycin, FMT was cost-effective in overall rCDI patients as well as IBD patients with rCDI [USD 39356 (NT$1,101,971.98)/quality-adjusted life year (QALY) gained in overall patients; USD65490 (NT$1,833,719.14)/QALY gained in IBD patients]. Compared to fidaxomicin, FMT was only cost-effective in overall rCDI patients [USD20255 (NT$567,133.45)/QALY gained] but slightly increased QALY (0.0018 QALY gained) in IBD patients with rCDI. Conclusion: FMT is cost-effective, compared to vancomycin or fidaxomicin, for the treatment of rCDI in most scenarios from the payers' perspective in Taiwan.

Budget Impact Analysis of Comprehensive Genomic Profiling in Advanced Non-Small Cell Lung Cancer in Taiwan.

OBJECTIVES: The concept of precision oncology using genetic testing has become popular for cancer treatment in recent years. This research aimed to evaluate the financial impact of comprehensive genomic profiling (CGP) in patients with advanced non-small cell lung cancer before receiving any systemic treatments, compared with current practice using single-gene testing, in the hope that the findings can inform the National Health Insurance Administration the decision regarding CGP reimbursement. METHODS: A budget impact analysis model was developed comparing the sum of gene testing costs, the first-line and subsequent systemic treatment costs, and other medical costs between the current practice of traditional molecular testing and the new test strategy of CGP. The evaluation time horizon is 5 years from the perspective of the National Health Insurance Administration. Outcome endpoints were incremental budget impact and life-year gained. RESULTS: This research indicated CGP reimbursement would benefit 1072 to 1318 more patients receiving target therapies than the current practice and consequently had incremental 232 to 1844 life-years gained from 2022 to 2026. The new test strategy also led to higher gene testing cost and systemic treatment cost. Nevertheless, less medical resource utilization and better patient outcome were demonstrated. The incremental budget impact ranged from US dollar 19 to US dollar 27 million in the 5-year period. CONCLUSION: This research shows that CGP could pave the way for personalized healthcare with moderate increase of National Health Insurance budget.

Association between hepatic angiosarcoma and end-stage renal disease: nationwide population-based evidence and enriched mutational signature of aristolochic acid exposure.

Hepatic angiosarcoma (HAS) is an aggressive mesenchymal malignancy that remains underexplored with respect to its etiology and mutational landscapes. To clarify the association between HAS and end-stage renal disease (ESRD), we used nationwide data of the National Health Insurance Research Database (NHIRD) in Taiwan, covering ~99% of the population, from 2001 to 2016. To investigate molecular signatures, we performed whole-exome sequencing (WES) in 27 surgical specimens, including nine ESRD-associated cases. The NHIRD analysis demonstrated that HAS ranked second among all angiosarcomas in Taiwan, with the incidence rates of HAS being 0.08, 2.49, and 5.71 per 100,000 person-years in the general population, chronic kidney disease (CKD), and ESRD patients, respectively. The standardized incidence ratios of HAS in CKD and ESRD patients were 29.99 and 68.77, respectively. In comparison with nonhepatic angiosarcoma, the multivariate regression analysis of our institutional cohort confirmed CKD/ESRD as an independent risk factor for HAS (odds ratio: 9.521, 95% confidence interval: 2.995-30.261, p < 0.001). WES identified a high tumor mutation burden (TMB; median: 8.66 variants per megabase) and dominant A:T-to-T:A transversion in HAS with frequent TP53 (81%) and ATRX (41%) mutations, KDR amplifications/gains (56%), and CDKN2A/B deletions (48%). Notably, ESRD-associated HAS had a significantly higher TMB (17.62 variants per megabase, p = 0.01) and enriched mutational signatures of aristolochic acid exposure (COSMIC SBS22, p < 0.001). In summary, a significant proportion of HAS in Taiwan is associated with ESRD and harbors a distinctive mutational signature, which concomitantly links nephrotoxicity and mutagenesis resulting from exposure to aristolochic acid or related compounds. A high TMB may support the eligibility for immunotherapy in treating ESRD-associated HAS. © 2023 The Pathological Society of Great Britain and Ireland.

Economic Burden of Cervical and Head and Neck Cancer in Taiwan from a Societal Perspective.

BACKGROUND: Head and neck cancers (HNC) are increasingly recognized as important human papillomavirus (HPV)-related malignancies in addition to cervical cancer (CC). However, data on the socioeconomic impact of HNC and CC in Taiwan are limited. METHODS: A retrospective cohort study was conducted to estimate the total direct medical cost and indirect productivity loss from CC and HNC between 2014 and 2015. Patient data from the Taiwan National Cancer Registry were analyzed, with matched non-cancer controls from the Taiwan National Healthcare Reimbursement Database. Indirect costs due to premature deaths were calculated using public data from Taiwanese government reports. RESULTS: In the direct cost analysis, 2083 patients with newly diagnosed CC and 11,078 with newly diagnosed HNC (10,036 males) were identified between 2014 and 2015 and followed up through the end of 2016 or until death. The total direct medical costs incurred in 2014 and 2015 due to HNC were 11.54 times higher in males than in females, and 4.55 times higher than CC. Indirect cost analysis showed the total annual productivity loss was New Taiwan Dollar (NTD) $12 billion in 2019, and 79.99% was attributed to male HNC. CONCLUSION: In Taiwan, the socioeconomic burden associated with male HNC is high and greater than that seen with CC. While not all HNCs are attributable to HPV infection, prevention of HNC through HPV vaccination should be considered for both sexes.

The Clinical and Economic Impact of a Nonavalent Versus Bivalent Human Papillomavirus National Vaccination Program in Taiwan.

OBJECTIVES: This study aimed to estimate the epidemiologic and economic impact of a nonavalent human papillomavirus (HPV) vaccination program for 13- to 14-year-old females compared with that of the bivalent vaccine in Taiwan. METHODS: A previously developed dynamic transmission model for the nonavalent HPV vaccine was adapted to the Taiwan setting. The natural history of cervical cancer and genital warts was simulated by the HPV model assuming an 80% vaccination coverage rate in girls aged 13 to 14 years of age with a 2-dose schedule for the nonavalent and bivalent HPV vaccines. A lifetime duration of vaccine protection was assumed for the HPV vaccine types. RESULTS: The model estimated that the nonavalent HPV vaccine would prevent an additional 15 951 cervical cancer cases, 6600 cervical cancer-related deaths, 176 702 grade 2 or grade 3 cervical intraepithelial neoplasia cases, 103 959 grade 1 cervical intraepithelial neoplasia cases, and 1 115 317 genital warts cases compared with the bivalent HPV vaccine. The nonavalent HPV vaccination program was projected to cost an additional New Taiwan dollars (NTD) 675.21 per person and to produce an additional 0.00271 quality-adjusted life-year per person over 100 years compared with the bivalent HPV vaccine. Thus, the incremental cost-effectiveness ratio of the nonavalent HPV vaccine versus the bivalent HPV vaccine was NTD 249 462/quality-adjusted life-year. CONCLUSIONS: A nonavalent HPV vaccination program for 13- to 14-year-old girls would have additional public health and economic impacts and would be highly cost-effective compared with the bivalent HPV vaccine, relative to per capita gross domestic product, which is estimated at NTD 746 526 for Taiwan.

The impact of depression on survival of head and neck cancer patients: A population-based cohort study.

Background: Depression is common among patients with head and neck cancer, thereby affecting their survival rate. However, whether close monitoring of depression affects the survival outcomes of these patients is unknown. Therefore, this study aimed to determine whether depression treatment continuity after the diagnosis of cancer affects the survival of these patients. Methods: A total of 55,069 patients diagnosed with head and neck cancer in the Cancer Registration System database in Taiwan were enrolled. This cohort was followed from January 1, 2007 to December 31, 2017. Furthermore, the patients were divided into four groups, namely, "no depression," "pre-cancer only," "post-cancer only," and "both before and after cancer," on the basis of the diagnosis of depression and the duration of the follow-up period in the psychiatric clinic. Further, the Cox proportional hazard model was applied to estimate the hazard of death for the four groups. Results: A total of 6,345 (11.52%) patients were diagnosed with depression in this cohort. The "pre-cancer only" group had a lower overall survival (HR = 1.18; 95% CI = 1.11-1.25) compared with the "no depression" group. Moreover, the "post-cancer only" group had better overall survival (HR = 0.88; 95% CI = 0.83-0.94) compared with the "no depression" group, especially in advanced-stage patients. Patients who were diagnosed with depression before cancer and had continuous depression treatments after the cancer diagnosis had better overall survival (HR = 0.78; 95% CI = 0.71-0.86) compared with patients who had treatment interruptions. Conclusion: Patients with pre-cancer depression had poorer survival outcomes, especially those who did not receive psychiatric clinic visits after their cancer diagnosis. Nonetheless, in patients with advanced-stage cancer, depression treatment may improve overall survival.

Survival, treatment regimens and medical costs of women newly diagnosed with metastatic triple-negative breast cancer.

Individuals diagnosed with metastatic triple-negative breast cancer (mTNBC) suffer worse survival rates than their metastatic non-TNBC counterparts. There is little information on survival, treatment patterns, and medical costs of mTNBC patients in Asia. Therefore, this study aimed to examine 5-year survival, regimens of first-line systemic therapy, and healthcare costs of mTNBC patients in Taiwan. Adult females newly diagnosed with TNBC and non-TNBC as well as their survival data, treatment regimens and costs of health services were identified and retrieved from the Cancer Registry database, Death Registry database, and National Health Insurance (NHI) claims database. A total of 9691 (19.27%) women were identified as TNBC among overall BC. The 5-year overall survival rate of TNBC and non-TNBC was 81.28% and 86.50%, respectively, and that of mTNBC and metastatic non-TNBC was 10.81% and 33.46%, respectively. The majority of mTNBC patients received combination therapy as their first-line treatment (78.14%). The 5-year total cost in patients with metastatic non-TNBC and with mTNBC was NTD1,808,693 and NTD803,445, respectively. Higher CCI scores were associated with an increased risk of death and lower probability of receiving combination chemotherapy. Older age was associated with lower 5-year medical costs. In sum, mTNBC patients suffered from poorer survival and incurred lower medical costs than their metastatic non-TNBC counterparts. Future research will be needed when there are more treatment options available for mTNBC patients.

Risk Factors of Carpal Tunnel Syndrome in Taiwan: A Population-Based Cohort Study.

BACKGROUND: Carpal tunnel syndrome (CTS), 1 of the most common peripheral neuropathies of the upper extremity, has been studied for decades regarding its epidemiology and associated medical conditions. We conducted a large-scale, age- and gender-matched study from an Asian population database to investigate the relationship between the incidence and the demographic characteristics. METHODS: A retrospective cohort study using data of National Health Insurance Research Database was conducted. One million enrollees in Taiwan was used to identify 9442 patients with CTS and 37,768 randomly selected controls, in a control-case ratio of 4:1. Diagnoses of CTS were ascertained from January 1, 2003, to December 31, 2012. Sociodemographic and medical characteristics were evaluated to assess the correlation with CTS. RESULTS: Annual incidence of CTS was approximately 0.4% during the 10-year-period in Taiwan, with higher incidence rate in female sex and middle age of group (50-59 years). Among the medical conditions, previous wrist injuries, obesity, gout, and rheumatoid arthritis were associated with CTS most significantly. CONCLUSIONS: Carpal tunnel syndrome has presented a relatively constant incidence in Taiwan. Female gender with middle age seemed to have the highest incident rate during a 10-year period from 2003 to 2012. Among the risk factors of CTS, previous wrist injuries, obesity, gout, and rheumatoid arthritis were demonstrated to be the most significantly correlated comorbidities.

Association Between Obstructive Sleep Apnea and Diabetic Macular Edema in Patients with Type 2 Diabetes.

PURPOSE: To evaluate the relationship between obstructive sleep apnea (OSA) and diabetic macular edema (DME) and the effect of OSA on refractory DME in patients with type 2 diabetes (T2DM). DESIGN: Retrospective clinical cohort study. METHODS: A population-based study was conducted at Chang Gung Memorial Hospital from March 1, 2009, to March 1, 2020. Among 14,152 patients who had undergone polysomnography (PSG) and whose data were registered on the sleep center's PSG database, 121 patients (242 eyes) with T2DM were enrolled according to the International Classification of Diseases, Ninth Revision (ICD-9) code 3620 for diabetic retinopathy (DR). Patients with a secondary cause of macular edema and those lacking medical records were excluded. All patients with T2DM enrolled in our study received both optical coherence tomography (OCT) and PSG. The prevalence of severe (apnea-hypopnea index [AHI] ≥30) and nonsevere (AHI <30) OSA was compared between patients with and without DME and refractory DME. RESULTS: In total, 102 eyes (54 patients) were divided into groups of 40 eyes with DME or 62 eyes without DME. Severe OSA (odds ratio, 7.36; 95% confidence interval [CI]: 1.32-40.96; P = .023) was significantly associated with DME. Refractory DME was significantly more frequent in patients with severe OSA (27%) than in those with nonsevere OSA (0%; P = .009). Cox proportional hazards regression analysis revealed that OSA (hazard ratio, 2.97; CI, 1.08-8.16; P = .034) independently increased the DME risk after adjustment for age, sex, glycohemoglobin level, hypertension, and hypercholesterolemia. CONCLUSIONS: Severe OSA is a risk factor for DME and is associated with having refractory DME.

The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes.

The clinicopathological significance of altered SWI/SNF complex has not been well evaluated in gastric cancer (GC). We examined SMARCA2, SMARCA4, SMARCB1 and ARID1A expression by immunohistochemistry in 1224 surgically resected GCs with subtyping into Epstein-Barr virus (EBV), microsatellite instability (MSI) and non-EBV/MSI Lauren histotypes. SWI/SNF mutations were investigated using the GC dataset of the TCGA Pan-Cancer Atlas. Clinicopathological association was assessed by statistical analysis. There were 427 cases (35%) of SWI/SNF-attenuated GC, including 344 SMARCA2 (28%), 28 SMARCA4 (2%), 11 SMARCB1 (1%) and 197 ARID1A (16%) cases. Simultaneous alterations of multiple subunits were observed. Compared to SWI/SNF-retained cases, SWI/SNF-attenuated GC exhibited a significant predilection to older ages, EBV and MSI genotypes, higher lymphatic invasion and less hematogenous recurrence (P < 0.05). SWI/SNF attenuation was an independent risk factor for short overall survival (P = 0.001, hazard ratio 1.360, 95% confidence interval 1.138-1.625). The survival impact stemmed from SMARCA2-attenuated GCs in stage III and non-EBV/MSI diffuse/mixed subtypes (P = 0.019 and < 0.001, respectively). ARID1A-lost/heterogeneous GCs were more aggressive in the EBV genotype (P = 0.016). SMARCB1 or SMARCA4 loss was not restricted to rhabdoid/undifferentiated carcinoma. In the TCGA dataset, 223 of 434 GCs (52%) harbored deleterious SWI/SNF mutations, including ARID1A (27%), SMARCA2 (9%), ARID2 (9%), ARID1B (8%), PBRM1 (7%), and SMARCA4 (7%). SWI/SNF-mutated GCs displayed a favorable outcome owing to the high percentage with the MSI genotype. In conclusion, SWI/SNF-altered GCs are common and the clinicopathological significance is related to the genotype.

Outcome and cost analysis of primary total knee arthroplasty in end-stage renal disease patients: A nationwide population-based study.

BACKGROUND: A number of patients with end-stage renal disease (ESRD) undergo total knee arthroplasty (TKA) due to advanced knee joint osteoarthritis. There are few studies describing the incidence, morbidities, mortality rate, and cost analysis regarding ESRD patients receiving TKA. METHODS: We retrospectively retrieved patient data from National Health Insurance Research Database in Taiwan during 2005-2011, and evaluated the outcomes of TKA in patients with (ESRD group) and without ESRD (non-ESRD group). Patients' demographic data, comorbidities, mortality, and in-hospital cost were recorded. RESULTS: A total of 578 TKAs and 110,895 TKAs were identified in the ESRD and non-ESRD group, respectively. The incidence of patients receiving TKA was higher in the ESRD than in non-ESRD group by at least 2 folds. The ESRD group showed significantly more medical complications (pneumonia, peptic ulcer disease, and acute myocardial infarction) after surgery. In prosthesis-related complications, the ESRD group also had more periprosthetic joint infections, and prosthetic loosenings by one year. The one-year mortality rate was more than 6 times higher in the ESRD than in the non-ESRD group. The ESRD group had higher in-hospital medical expense than the non-ESRD group, especially when there were complications, even when the dialysis-related costs were exempted. CONCLUSION: The complication rate, mortality rate, and cost were higher in the ESRD patients receiving TKA. When considering TKA in ESRD patients, it is crucial to weigh the risks against benefits of TKA, and have a thorough discussion with the patients.

Detecting Lesional Granulysin Levels for Rapid Diagnosis of Cytotoxic T lymphocyte-Mediated Bullous Skin Disorders.

BACKGROUND: Bullous skin disorders are induced by different pathomechanisms and several are emergent, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Rapid diagnostic methods for SJS/TEN or cytotoxic T-lymphocyte (CTL)-mediated bullous disorders are crucial for early treatment. Granulysin, primarily expressed by CTLs, is a specific cytotoxic protein responsible for SJS/TEN and similar skin reactions. OBJECTIVE: To assess granulysin levels in blister fluids to differentiate SJS/TEN and similar CTL-mediated bullous reactions from other autoimmune bullous disorders. METHODS: Using ELISA, we measured granulysin in blister fluids from patients with bullous skin disorders, including SJS/TEN, erythema multiforme major, bullous fixed-drug eruption, bullous lupus erythematosus, paraneoplastic pemphigus, pemphigus vulgaris, bullous pemphigoid, purpura fulminans-related bullae, and hand-foot syndrome/hand-foot-skin reactions. We compared serum and blister granulysin levels in patients with SJS/TEN presenting varying severity, monitoring serial granulysin levels from acute to late stages. RESULTS: Overall, 144 patients presenting with bullous skin disorders were enrolled. Blister granulysin levels (mean ± SD) in CTL-mediated disorders, including TEN (n = 28; 3938.7 ± 3475.7), SJS-TEN overlapping (n = 22; 1440.4 ± 1179.6), SJS (n = 14; 542.0 ± 503.2), erythema multiforme major (n = 7; 766.3 ± 1073.7), generalized bullous fixed-drug eruption (n = 10; 720.4 ± 858.3), and localized bullous fixed-drug eruption (n = 16; 69.0 ± 56.4), were significantly higher than in non-CTL-mediated bullous disorders (P < .0001), including bullous lupus erythematosus (n = 3; 22.7 ± 20.1), paraneoplastic pemphigus (n = 3; 20.3 ± 8.6), pemphigus vulgaris (n = 3; 4.4 ± 2.8), bullous pemphigoid (n = 18; 4.0 ± 2.7), purpura fulminans (n = 4; 5.9 ± 5.5), and hand-foot syndrome/hand-foot-skin reactions (n = 6; 4.6 ± 3.5). Blister granulysin levels correlated with clinical severity of SJS/TEN (P < .0001). CONCLUSIONS: Determination of blister granulysin levels is a noninvasive and useful tool for rapid differential diagnosis of SJS/TEN and other similar CTL-mediated bullous skin disorders for treatment selection.

National trends in incidence, mortality, hospitalizations, and expenditures for pemphigus in Taiwan.

BACKGROUND: Data on trends in epidemiological characteristics and economic burden of pemphigus are scarce. OBJECTIVE: To describe national trends in pemphigus' incidence, mortality, hospitalizations, and expenditures between 2003 and 2015 in Taiwan. METHODS: This nationwide study used the Taiwan National Health Insurance Research Database to identify pemphigus patients from 2003 to 2015. Annual incidence, prevalence, healthcare utilization, and expenditure trends were calculated and analyzed. RESULTS: Pemphigus' incidence increased significantly from 3.19 to 4.70 per million person-years in 2003-2010 but fluctuated in 2011-2015. Pemphigus patients had higher mortality and care costs. Medical utilization and expenditure declined for pemphigus inpatients and outpatients. Systemic corticosteroid use decreased, but mortality remained stable. CONCLUSION: The health expense reduction for pemphigus was mainly attributed to decreased utilization, length of stay, and inpatient costs. The persistently elevated mortality rate highlights an unmet need in pemphigus therapy.

Increased incidence, morbidity, and mortality in cirrhotic patients with hip fractures: A nationwide population-based study.

OBJECTIVES: Hip fractures mostly require surgical treatment and are associated with increased health-care costs and mortality rates. Patients with cirrhosis have low bone marrow density and inferior immune status which contribute to a higher fracture rate and higher surgical complication rate. This population-based study evaluated the prevalence, complication, and mortality rates due to hip fractures in cirrhotic patients. METHODS: Taiwan National Health Insurance Research Database data were used. The study group included 117,129 patients with hip fractures diagnosed from 2004 to 2010, including 4048 patients with cirrhosis. The overall prevalence, morbidity, and mortality rates of the cirrhosis group with hip fractures were compared with the rates of a general group with hip fractures. RESULTS: The cirrhosis group patients were younger than the general group patients (71.2 vs. 73.96 years, p < 0.001). The annual incidence of hip fractures in the cirrhosis and general groups was 46-54 and 7-7.5 per 10,000 person-years, respectively, with an incidence rate ratio of 6.95 (95% confidence interval 6.74-7.18). The rates of infection, urinary tract infection, and peptic ulcer disease were higher in the cirrhosis group (3.46% vs. 1.91%, 9.56% vs. 9.11%, and 8.05% vs. 3.55%, respectively; all p < 0.001). The mortality rate after hip fracture was also higher in the cirrhosis group than in the general group (within 3 months: 8.76-12.64% vs. 4.96-5.30% and within 1 year: 29.72-37.99% vs. 12.84-14.57%). Conclusion: Cirrhotic patients with hip fractures were relatively younger; had a seven times higher annual hip fracture incidence; had higher complication rates of infection, urinary tract infection, and peptic ulcer disease; and had two to three times higher a mortality rate at 3 months and 1 year. Clinicians should pay particular attention to the possibility of osteoporosis and hip fractures in patients with liver cirrhosis. LEVEL OF EVIDENCE: Level III, case-control study.

Increased periprosthetic hip and knee infection projected from 2014 to 2035 in Taiwan.

BACKGROUND: Periprosthetic joint infection (PJI) is a disastrous complication associated with hip and knee arthroplasty. The literature suggests that the economic consequences associated with treating PJI are substantial. Our study aimed to investigate the past trends of PJI rates, and to estimate the projected number of PJI cases, consequent bed-day requirements, and medical expenses in Taiwan up to year 2035. METHODS: A nationwide epidemiological study was conducted using the inpatient database of the Bureau of National Health Insurance from 2004 through 2013. Patients with the International Classification of Disease-Clinical Modification, ninth revision (ICD9-CM) code 99,666 (PJI) who had received surgical treatment including debridement, removal of hip or knee prosthesis, or revision of total hip/knee arthroplasty (THA/TKA) were identified. Projections were performed with Poisson regression on historical incidence rates in combination with projections of arthroplasty numbers from 2014 to 2035. RESULTS: A total of 4935 hip (1871) and knee (3064) PJIs were identified between 2004 and 2013. The rates of PJI were 2.46% for hip arthroplasty and 1.63% for knee arthroplasty. The number of PJIs was expected to increase markedly with time from 728 in 2013 to 3542 in 2035 (a 4.87-fold increase). The bed-day requirements for treating PJI was 17,205 in 2013 and is expected to be 82,509 bed-days in 2035 (a 4.79-fold increase). The total hospitalization cost will increase 4.86-fold by 2035. CONCLUSIONS: The number of PJI cases is increasing rapidly due to the increasing numbers of arthroplasty surgery and the cumulative number of latent infection. This may place a large economic burden on the health care system.

Severe OSA associated with higher risk of mortality in stage III and IV lung cancer.

STUDY OBJECTIVES: OSA has been associated with increased cancer incidence and mortality. The aim of this study was to investigate cancer-related mortality, overall survival, and progression-free survival in patients with suspected OSA and lung cancer. METHODS: This was a case series analysis of lung cancer from a sleep cohort with suspected OSA between 2009 and 2014. The AHI, hypoxia index, and survival outcome were recorded. Immunohistochemistry was used to analyze hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor expression in tumor pathology. RESULTS: In the sleep cohort comprising 8,261 patients, a total of 23 patients had lung cancer. The incidence of lung cancer was significantly higher in the sleep cohort than in the entire adult population in Taiwan (crude incidence rate: 242.1 vs 51.5 per 105 persons, P < .01). The 3-year cancer-related mortality was 25% in AHI < 15 events/h, 50% in AHI 15-29 events/h, and 80% in AHI ≥ 30 events/h (χ² test for trend, P = .03). In Kaplan-Meier survival analysis, patients with stage III-IV lung cancer and AHI < 30 events/h exhibited significantly better overall survival (P = .02) and progression-free survival (P = .02) than patients with severe OSA. Overexpression of HIF-1α and vascular endothelial growth factor was shown in 63% and 45% of lung tumor samples. Overexpression of HIF-1α was positively associated with AHI (P = .04). CONCLUSIONS: In this preliminary case series, severe OSA is associated with an increased risk of cancer mortality in patients with stage III-IV lung cancer. AHI was significantly associated with HIF-1α overexpression.

Severe Obstructive Sleep Apnea Associated With Higher Risk of Mortality in Stage III and IV Lung Cancer.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been associated with increased cancer incidence and mortality. The aim of this study was to investigate cancer-related mortality, overall survival and progression free survival in patients with suspected OSA and lung cancer. METHODS: This was a case series analysis of lung cancer from a sleep cohort with suspected OSA between 2009 and 2014. The apnea- hypopnea index (AHI), Tsat90% (hypoxia index) and survival outcome were recorded. Immunohistochemistry was used to analyze HIF-1α and VEGF expression in tumor pathology. RESULTS: In the sleep cohort comprising 8261 patients, a total of 23 patients had lung cancer. The incidence of lung cancer was significantly higher in the sleep cohort than in the entire adult population in Taiwan (242.1 vs 51.5 per 105 persons, P< 0.01). The 3-year cancer-related mortality was 25% in AHI < 15, 50% in AHI 15 to 29 and 80% in AHI ≥ 30 (chi-squared test for trend P =0.03). In Kaplan-Meier survival analysis, patients with stage III-IV lung cancer and AHI< 30 exhibited significantly better overall survival (P = 0.02) and progression free survival (P = 0.02) than patients with severe OSA. Overexpression of HIF-1α and VEGF was shown in 63 % and 45 % of lung tumor samples. Overexpression of HIF-1α was positively associated with AHI (P = 0.04). CONCLUSIONS: In this preliminary case series, severe OSA is associated with an increased risk of cancer mortality in patients with stage III-IV lung cancer. AHI was significantly associated with HIF-1α overexpression.

Incidence and Risk of Carpal Tunnel Syndrome in End-Stage Renal Disease Patients on Dialysis: A Nationwide Population-Based Matched Cohort Study.

Carpal tunnel syndrome (CTS) is a common cause of compression neuropathy of the upper extremities. This retrospective nationwide matched cohort study was conducted using the data from the Taiwan National Health Insurance Research Database between January 2003 and December 2012. The incidence rate of CTS was 975.84 and 544.12/100,000 person-years, respectively, yielding an incidence rate ratio of 1.79 (95% confidence interval, 1.68-1.91, P < 0.0001). CTS patients with End-stage renal disease (ESRD) in the dialysis group were more likely to receive surgical intervention than those the control group (62.41% vs 12.89%, P < 0.0001). The risk of CTS was significantly higher in the ESRD on dialysis cohort (10-year cumulative incidence, 8.0%) than in the control cohort (5.1%), which yielded an adjusted hazard ratio of 13.95 (95% confidence interval, 10.95-17.76, P < 0.0001). The high risk of CTS in ESRD patients on dialysis suggests that timely referral to hand surgeons with appropriate treatment should prevent permanent median nerve damage by CTS and may possibly improve patients' quality of life.

Maintenance of pegylated liposomal doxorubicin/carboplatin in patients with advanced ovarian cancer: randomized study of an Asian Gynecologic Oncology Group.

OBJECTIVES: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. METHODS: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m², n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. RESULTS: Enrollment was slow, accrual was closed when 7+ years had passed. With a median follow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19-0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCA/non-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11-1.18; p=0.091). CONCLUSIONS: Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.

Nomogram predicting extrahepatic metastasis of hepatocellular carcinoma based on commonly available clinical data.

BACKGROUND AND AIM: Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) leads to a worse prognosis. We aimed to develop a nomogram based on noninvasive pretreatment clinical data to predict EHM of HCC sooner. METHODS: Three cohorts containing 1820, 479, and 988 HCC patients were enrolled from three hospitals in different regions in Taiwan and served as the training and validation cohorts. Pretreatment clinical data were analyzed by Cox regression modeling for independent risk factors of EHM. RESULTS: Platelet count ≥ 200 × 103/µL, serum alfa-fetoprotein ≥ 100 ng/dL, tumor size ≥ 3 cm, tumor number > 1, and macrovascular invasion were independent risk factors for EHM and were used to develop a nomogram. This nomogram had concordance indices of 0.733 (95% confidence interval [CI]: 0.688-0.778) and 0.739 (95% CI: 0.692-0.787) for the prediction of EHM during a 5-year follow-up duration in the training and validation cohorts, respectively. A nomogram score > 61 implied a high risk of EHM (hazard ratio [HR] = 3.83; 95% CI: 2.77-5.31, P < 0.001). CONCLUSION: We have developed a nomogram that could accurately predict EHM of HCC and be readily available for formulating individualized treatment for all individual HCC patients to improve therapeutic efficacy.