Schizophrenia is one of the top 25 leading causes of disability worldwide in 2013. Despite its low prevalence, its health, social, and economic burden has been tremendous, not only for patients but ...also for families, caregivers, and the wider society. The magnitude of disease burden investigated in an economic burden study is an important source to policymakers in decision making. This study aims to systematically identify studies focusing on the economic burden of schizophrenia, describe the methods and data sources used, and summarize the findings of economic burden of schizophrenia.
A systematic review was performed for economic burden studies in schizophrenia using four electronic databases (Medline, EMBASE, PsycINFO, and EconLit) from inception to August 31, 2014.
A total of 56 articles were included in this review. More than 80% of the studies were conducted in high-income countries. Most studies had undertaken a retrospective- and prevalence-based study design. The bottom-up approach was commonly employed to determine cost, while human capital method was used for indirect cost estimation. Database and literature were the most commonly used data sources in cost estimation in high-income countries, while chart review and interview were the main data sources in low and middle-income countries. Annual costs for the schizophrenia population in the country ranged from US$94 million to US$102 billion. Indirect costs contributed to 50%-85% of the total costs associated with schizophrenia. The economic burden of schizophrenia was estimated to range from 0.02% to 1.65% of the gross domestic product.
The enormous economic burden in schizophrenia is suggestive of the inadequate provision of health care services to these patients. An informed decision is achievable with the increasing recognition among public and policymakers that schizophrenia is burdensome. This results in better resource allocation and the development of policy-oriented research for this highly disabling yet under-recognized mental health disease.
A systematic review and network‐meta analysis (NMA) were performed to test significance of the galactagogue effect of fenugreek administrated to lactating women versus other comparators (i.e., ...placebo/control/other galactagogues). A pairwise comparison for the treatment effect was carried out to generate the forest plot for the NMA. League tables were generated using treatment effect, weighted mean difference (WMD; 95% confidence interval, CI) for all pairwise comparisons, where WMD > 0 favors the column‐defining treatment. Five studies were identified with 122 participants receiving treatment with fenugreek. The NMA results of 4 studies indicated that consumption of fenugreek significantly increased amount of the produced breast milk 11.11, CI 95% 6.77, 15.46 versus placebo. The pairwise comparison revealed that fenugreek was effective as a galactagogue compared to placebo, control, and reference groups WMD 17.79 CI 11.71, 23.88. However, the effect of fenugreek was substantially inferior to Coleus amboinicus Lour and palm date. The NMA using pairwise comparison demonstrated the effect of C. amboinicus and palm date in the stimulation of the breast milk production was comparable and superior to all comparators.
Accurate prognostication may aid in the selection of patients who will benefit from surgery at recurrent WHO grade 4 glioma. This study aimed to evaluate the role of serial tumour volumetric ...measurements for prognostication at first tumour recurrence.
We retrospectively analyzed patients with histologically-diagnosed WHO grade 4 glioma at initial and at first tumour recurrence at a tertiary hospital between May 2000 and September 2018. We performed auto-segmentation using ITK-SNAP software, followed by manual adjustment to measure serial contrast-enhanced T1W (CE-T1W) and T2W lesional volume changes on all MRI images performed between initial resection and repeat surgery.
Thirty patients met inclusion criteria; the median overall survival using Kaplan-Meier analysis from second surgery was 10.5 months. Seventeen (56.7%) patients received treatment post second surgery. Univariate cox regression analysis showed that greater rate of increase in lesional volume on CE-T1W (HR = 2.57; 95% CI 1.18, 5.57; p = 0.02) in the last 2 MRI scans leading up to the second surgery was associated with a higher mortality likelihood. Patients with higher Karnofsky Performance Score (KPS) (HR = 0.97; 95% CI 0.95, 0.99; p = 0.01) and who received further treatment following second surgery (HR = 0.43; 95% CI 0.19, 0.98; p = 0.04) were shown to have a better survival.
Higher rate of CE-T1W lesional growth on the last 2 MRI images prior to surgery at recurrence was associated with increase mortality risk. A larger prospective study is required to determine and validate the threshold to distinguish rapidly progressive tumour with poor prognosis.
Recent studies have demonstrated that discriminatory salivary biomarkers can be readily detected upon the development of systemic diseases such as pancreatic cancer, breast cancer, lung cancer, and ...ovarian cancer. However, the utility of salivary biomarkers for the detection of systemic diseases has been undermined due to the absence of the biological and mechanistic rationale as to why distal diseases from the oral cavity would lead to the development of discriminatory biomarkers in saliva. Here, we examine the hypothesis that pancreatic tumor-derived exosomes are mechanistically involved in the development of pancreatic cancer-discriminatory salivary transcriptomic biomarkers. We first developed a pancreatic cancer mouse model that yielded discriminatory salivary biomarkers by implanting the mouse pancreatic cancer cell line Panc02 into the pancreas of the syngeneic host C57BL/6. The role of pancreatic cancer-derived exosomes in the development of discriminatory salivary biomarkers was then tested by engineering a Panc02 cell line that is suppressed for exosome biogenesis, implanting into the C56BL/6 mouse, and examining whether the discriminatory salivary biomarker profile was ablated or disrupted. Suppression of exosome biogenesis results in the ablation of discriminatory salivary biomarker development. This study supports that tumor-derived exosomes provide a mechanism in the development of discriminatory biomarkers in saliva and distal systemic diseases.
Background: Salivary biomarkers for systemic diseases have been undermined due to lack of mechanistic and biological rationale.
Results: Suppression of exosome biogenesis leads to ablation of salivary biomarkers.
Conclusion: Tumor-derived exosomes provide a mechanism for discriminatory biomarkers in saliva.
Significance: Tumor-derived exosomes provide the scientific rationale that connects pancreatic tumors and the oral cavity leading to salivary biomarkers.
Background & Aims Lack of detection technology for early pancreatic cancer invariably leads to a typical clinical presentation of incurable disease at initial diagnosis. New strategies and biomarkers ...for early detection are sorely needed. In this study, we have conducted a prospective sample collection and retrospective blinded validation to evaluate the performance and translational utilities of salivary transcriptomic biomarkers for the noninvasive detection of resectable pancreatic cancer. Methods The Affymetrix HG U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA) was used to profile transcriptomes and discover altered gene expression in saliva supernatant. Biomarkers discovered from the microarray study were subjected to clinical validation using an independent sample set of 30 pancreatic cancer patients, 30 chronic pancreatitis patients, and 30 healthy controls. Results Twelve messenger RNA biomarkers were discovered and validated. The logistic regression model with the combination of 4 messenger RNA biomarkers ( KRAS , MBD3L2 , ACRV1 , and DPM1 ) could differentiate pancreatic cancer patients from noncancer subjects (chronic pancreatitis and healthy control), yielding a receiver operating characteristic plot, area under the curve value of 0.971 with 90.0% sensitivity and 95.0% specificity. Conclusions The salivary biomarkers possess discriminatory power for the detection of resectable pancreatic cancer, with high specificity and sensitivity. This report provides the proof of concept of salivary biomarkers for the noninvasive detection of a systemic cancer and paves the way for prediction model validation study followed by pivotal clinical validation.
Background and purpose: Several recent randomized controlled trials
(RCTs) in non-metastatic castration resistant prostate cancer
(nmCRPC) have demonstrated a significant improvement in ...metastasis-free survival
(MFS); however, an improvement in overall survival (OS) is not
reported yet. Since the surrogacy of MFS to OS has not been formally investigated in nmCRPC in
Japan, this study evaluated the correlation between MFS and OS among a nmCRPC population in
Japan.
Methods: This is a retrospective longitudinal observational cohort study in
patients with nmCRPC using the Japanese Medical Data Vision (MDV) database
covering over 20 million patients. A total of 1236 patients with CRPC who had no prior medical
history of cancer except prostate cancer and no distant metastasis, and who fulfilled PCWG2
criteria, were identified. Following the identification of nmCRPC, patients' medical
records were investigated for subsequent events of metastasis and death.
Results: The median follow-up time was 24 months. Median MFS was
28 months (95% CI: 24.0 to 33.0 months) and median OS could
not be estimated (95% CI: not estimated). There was a statistically
significant correlation between MFS and OS (Pearson's correlation
coefficient = 0.62; 95% CI: 0.58-0.65;
p < .0001, Spearman's correlation
coefficient = 0.62; 95% CI: 0.58-0.65;
p < .0001 and Kendall's τ
statistic = 0.53; 95% CI: 0.49-0.56;
p < .0001).
Conclusions: The results of this study indicate a significant correlation
between MFS and OS. It may justify the usefulness of MFS as surrogate for OS in nmCRPC.
Trial registration:
ClinicalTrials.gov identifier: NCT01946204.
Trial registration:
ClinicalTrials.gov identifier: NCT02200614.
A sensitive assay to identify biomarkers using non-invasively collected clinical specimens is ideal for breast cancer detection. While there are other studies showing disease biomarkers in saliva for ...breast cancer, our study tests the hypothesis that there are breast cancer discriminatory biomarkers in saliva using de novo discovery and validation approaches. This is the first study of this kind and no other study has engaged a de novo biomarker discovery approach in saliva for breast cancer detection. In this study, a case-control discovery and independent preclinical validations were conducted to evaluate the performance and translational utilities of salivary transcriptomic and proteomic biomarkers for breast cancer detection.
Salivary transcriptomes and proteomes of 10 breast cancer patients and 10 matched controls were profiled using Affymetrix HG-U133-Plus-2.0 Array and two-dimensional difference gel electrophoresis (2D-DIGE), respectively. Preclinical validations were performed to evaluate the discovered biomarkers in an independent sample cohort of 30 breast cancer patients and 63 controls using RT-qPCR (transcriptomic biomarkers) and quantitative protein immunoblot (proteomic biomarkers). Transcriptomic and proteomic profiling revealed significant variations in salivary molecular biomarkers between breast cancer patients and matched controls. Eight mRNA biomarkers and one protein biomarker, which were not affected by the confounding factors, were pre-validated, yielding an accuracy of 92% (83% sensitive, 97% specific) on the preclinical validation sample set.
Our findings support that transcriptomic and proteomic signatures in saliva can serve as biomarkers for the non-invasive detection of breast cancer. The salivary biomarkers possess discriminatory power for the detection of breast cancer, with high specificity and sensitivity, which paves the way for prediction model validation study followed by pivotal clinical validation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cancer cells exhibit alterations in histone modification patterns at individual genes and globally at the level of single nuclei in individual cells. We demonstrated previously that lower ...global/cellular levels of histone H3 lysine 4 dimethylation (H3K4me2) and H3K18 acetylation (ac) predict a higher risk of prostate cancer recurrence. Here we show that the cellular levels of both H3K4me2 and H3K18ac also predict clinical outcome in both lung and kidney cancer patients, with lower levels predicting significantly poorer survival probabilities in both cancer groups. We also show that lower cellular levels of H3K9me2, a modification associated with both gene activity and repression, is also prognostic of poorer outcome for individuals with either prostate or kidney cancers. The predictive power of these histone modifications was independent of tissue-specific clinicopathological variables, the proliferation marker Ki-67, or a p53 tumor suppressor mutation. Chromatin immunoprecipitation experiments indicated that the lower cellular levels of histone modifications in more aggressive cancer cell lines correlated with lower levels of modifications at DNA repetitive elements but not with gene promoters across the genome. Our results suggest that lower global levels of histone modifications are predictive of a more aggressive cancer phenotype, revealing a surprising commonality in prognostic epigenetic patterns of adenocarcinomas of different tissue origins.
A cochlear implant is a small electronic device that provides a sense of sound for the user, which can be used unilaterally or bilaterally. Although there is advocacy for the benefits of binaural ...hearing, the high cost of cochlear implant raises the question of whether its additional benefits over the use of an acoustic hearing aid in the contralateral ear outweigh its costs. This cost-effectiveness analysis aimed to separately assess the cost-effectiveness of simultaneous and sequential bilateral cochlear implantations compared to bimodal hearing (use of unilateral cochlear implant combined with an acoustic hearing aid in the contralateral ear) in children with severe-to-profound sensorineural hearing loss in both ears from the Singapore healthcare payer perspective. Incremental quality-adjusted life year (QALYs) gained and costs associated with bilateral cochlear implants over the lifetime horizon were estimated based on a four-state Markov model. The analysis results showed that, at the 2017 mean cost, compared to bimodal hearing, patients receiving bilateral cochlear implants experienced more QALYs but incurred higher costs, resulting in an incremental cost-effectiveness ratio (ICER) of USD$60,607 per QALY gained for simultaneous bilateral cochlear implantation, and USD$81,782 per QALY gained for sequential bilateral cochlear implantation. The cost-effectiveness of bilateral cochlear implants is most sensitive to utility gain associated with second cochlear implant, and cost of bilateral cochlear implants. ICERs increased when the utility gain from bilateral cochlear implants decreased; ICERs exceeded USD$120,000 per QALY gained when the utility gain was halved from 0.03 to 0.015 in both simultaneous and sequential bilateral cochlear implantations. The choice of incremental utility gain associated with the second cochlear implant is an area of considerable uncertainty.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Plasma levels of fibulin-3 reliably distinguish patients with pleural mesothelioma from patients with other types of pleural effusions and asbestos-exposed persons.
Despite advances in chemotherapy, ...radiation therapy, and surgical management for malignant pleural mesothelioma, the median survival remains 12 months.
1
Early detection is limited by the long latency period, an inability of imaging to detect the disease at an early stage even when it is used as a screening strategy, and the lack of sensitive and specific blood-based markers.
2
Moreover, in patients with undiagnosed pleural effusion, the ability to diagnose mesothelioma is delayed by failure to include the disease in the differential diagnosis and by the lack of noninvasive mesothelioma-specific blood-based markers. Soluble mesothelin-related protein, the most extensively studied blood-based mesothelioma . . .
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