Malignant thyroid teratoma: an integrated analysis of case series/case reports.

Malignant thyroid teratoma (MTT) is a very rare thyroid malignancy. These neoplasms have been reported only in case reports and small-sized case series so far. In this study, we searched for MTTs in the Surveillance, Epidemiology, and End Result (SEER) program during 1975-2016. Subsequently, we incorporated the SEER data with published MTT cases in the literature to analyze the characteristics and prognostic factors of MTTs. Integrated data were analyzed using chi-square or Fisher's exact test for categorical covariates, and t-test or Mann-Whitney test for continuous variables. We included 28 studies with 36 MTT cases and found additional 8 cases from the SEER program for final analyses. Our results showed that MTT is typically seen in adult females. These neoplasms were associated with an aggressive clinical course with high rates of extrathyroidal extension (80%) and nodal involvement (62%). During follow-up, the development of recurrence and metastases were common (42% and 46%, respectively), and one-third of patients died at the last follow-up. Large tumor size (P = 0.022) and the presence of metastases during follow-up (P = 0.008) were associated with a higher mortality rate. In conclusion, our study demonstrated the characteristic features of MTT patients and outlined some parameters associated with a negative outcome which could help clinicians better predict the clinical course of these neoplasms.

Collaborative data familiarisation and quality assessment: Reflections from use of a national dataset to investigate palliative care for Indigenous Australians.

BACKGROUND: Data quality is fundamental to the integrity of quantitative research. The role of external researchers in data quality assessment (DQA) remains ill-defined in the context of secondary use for research of large, centrally curated health datasets. In order to investigate equity of palliative care provided to Indigenous Australian patients, researchers accessed a now-historical version of a national palliative care dataset developed primarily for the purpose of continuous quality improvement. OBJECTIVES: (i) To apply a generic DQA framework to the dataset and (ii) to report the process and results of this assessment and examine the consequences for conducting the research. METHOD: The data were systematically examined for completeness, consistency and credibility. Data quality issues relevant to the Indigenous identifier and framing of research questions were of particular interest. RESULTS: The dataset comprised 477,518 records of 144,951 patients (Indigenous N = 1515; missing Indigenous identifier N = 4998) collected from participating specialist palliative care services during a period (1 January 2010-30 June 2015) in which data-checking systems underwent substantial upgrades. Progressive improvement in completeness of data over the study period was evident. The data were error-free with respect to many credibility and consistency checks, with anomalies detected reported to data managers. As the proportion of missing values remained substantial for some clinical care variables, multiple imputation procedures were used in subsequent analyses. CONCLUSION AND IMPLICATIONS: In secondary use of large curated datasets, DQA by external researchers may both influence proposed analytical methods and contribute to improvement of data curation processes through feedback to data managers.

Symptom-Related Distress among Indigenous Australians in Specialist End-of-Life Care: Findings from the Multi-Jurisdictional Palliative Care Outcomes Collaboration Data.

Symptom relief is fundamental to palliative care. Aboriginal and Torres Strait Islander (Indigenous) Australians are known to experience inequities in health care delivery and outcomes, but large-scale studies of end-of-life symptoms in this population are lacking. We compared symptom-related distress among Indigenous and non-Indigenous Australian patients in specialist palliative care using the multi-jurisdictional Palliative Care Outcomes Collaboration dataset. Based on patient-reported rating scale responses, adjusted relative risks (aRRs) stratified by care setting were calculated for occurrence of (i) symptom-related moderate-to-severe distress and worsening distress during a first episode of care and (ii) symptom-related moderate-to-severe distress at the final pre-death assessment. The p-value significance threshold was corrected for multiple comparisons. First-episode frequencies of symptom-related distress were similar among Indigenous (n = 1180) and non-Indigenous (n = 107,952) patients in both inpatient and community settings. In final pre-death assessments (681 Indigenous and 67,339 non-Indigenous patients), both groups had similar occurrence of moderate-to-severe distress when care was provided in hospital. In community settings, Indigenous compared with non-Indigenous patients had lower pre-death risks of moderate-to-severe distress from overall symptom occurrence (aRR 0.78; p = 0.001; confidence interval [CI] 0.67-0.91). These findings provide reassurance of reasonable equivalence of end-of-life outcomes for Indigenous patients who have been accepted for specialist palliative care.

Indigenous compared with non-Indigenous Australian patients at entry to specialist palliative care: Cross-sectional findings from a multi-jurisdictional dataset.

BACKGROUND: There are few quantitative studies on palliative care provision to Indigenous Australians, a population known to experience distinctive barriers to quality healthcare and to have poorer health outcomes than other Australians. OBJECTIVES: To investigate equity of specialist palliative care service provision through characterising and comparing Indigenous and non-Indigenous patients at entry to care. METHODS: Using data (01/01/2010-30/06/2015) from all services participating in the multi-jurisdictional Palliative Care Outcomes Collaboration, Indigenous and non-Indigenous patients entering palliative care were compared on proportions vis-à-vis those expected from national statutory datasets, demographic characteristics, and entry-to-care status across fourteen 'problem' domains (e.g., pain, functional impairment) after matching by age, sex, and specific diagnosis. RESULTS: Of 140,267 patients, 1,465 (1.0%, much lower than expected from statutory data) were Indigenous, 133,987 (95.5%) non-Indigenous, and 4,905 (3.5%) had a missing identifier. The proportion of patients with a missing identifier diminished markedly over the study period, without a corresponding increase in the proportion identified as Indigenous. Indigenous compared with non-Indigenous patients were younger (mean 62.8 versus 73.0 years, p<0.001), a higher proportion were female (51.5% versus 46.3%; p<0.001) or resided outside major cities (44.2% versus 21.5%, p<0.001). Across all domains, Indigenous compared with matched non-Indigenous patients had lower or equal risk of status requiring prompt intervention. CONCLUSIONS: Indigenous patients (especially those residing outside major cities) are substantially under-represented in care by services participating in the nationwide specialist palliative care Collaboration, likely reflecting widespread access barriers. However, the similarity of status indicators among Indigenous and non-Indigenous patients at entry to care suggests that Indigenous patients who are able to access these services do not disproportionately experience clinically important impediments to care initiation.

Self-perceptions and actual employment patterns amongst recent Australian dental graduates.

INTRODUCTION: With nine dental schools across Australia graduating over 500 dental students each year, in addition to nearly 200 overseas-qualified dentists entering the workforce, dental students are anecdotally advised that they are joining a profession ubiquitous with workforce oversupply. The aim of this study was to shed light on the employment patterns of recent dental graduates from Australian universities and their self-perceptions of the job market. MATERIALS AND METHODS: This cross-sectional pilot study involved an online survey conducted in 2017 on recent dental graduates from all Australian dental schools. Graduates' demographics, their perception of the dental employment prospects, their employment-related behaviours and employment outcomes, and the relationships between these variables were explored. RESULTS: Data on seventy-one survey respondents (approximately 12% of the total sampling frame) were analysed. They suggested that recent Australian dental graduates are seeking work (73.2%) and undertaking work experience (54.9%) prior to graduation, successfully finding employment within the first-year post-graduation (97%), yet not always in their perceived ideal workplace environment (42.2%). Relationships between age, perception of market competitiveness and job searching patterns were revealed. Graduates expressed a desire for more workplace mentorship. The small sample size of this study limits the generalisability of the results, indicating that further research is required. CONCLUSIONS: The dental employment landscape appears to have adequate employment opportunities for recent dental graduates, yet not always in their perceived ideal workplace environment. Graduates are seeking more mentorship in the workplace.

Delay in commencement of palliative care service episodes provided to Indigenous and non-Indigenous patients: cross-sectional analysis of an Australian multi-jurisdictional dataset.

BACKGROUND: Rapid effective responsiveness to patient needs is pivotal to high quality palliative care. Aboriginal and Torres Strait Islander (Indigenous) people are susceptible to life-limiting illnesses at younger ages than other Australians and experience inequity of health service provision. The Palliative Care Outcomes Collaboration collects Australia-wide health service data on patient care, and has established performance benchmarks for specialist palliative care services. We investigated whether the benchmark for timely commencement of palliative care episodes (occurrence of delay >1 day after being designated 'ready for care' in <10% instances) is being met for Indigenous Australians in participating services. Additionally, we investigated the association between identification as Indigenous and delay. METHODS: Using multi-jurisdictional Palliative Care Outcomes Collaboration data, this cross-sectional analytical study investigated all episodes of care (n = 84,238) provided to patients ≥18 years (n = 61,073: Indigenous n = 645) in hospital and community settings commenced and completed during the period 01/07/2013-30/06/2015. Proportions of episodes resulting in delay were determined. Crude and adjusted odds of delay among Indigenous compared with non-Indigenous patients were investigated using multiple logistic regression, with missing data handled by multiple imputation. RESULTS: The benchmark was met for both Indigenous and non-Indigenous patients (delay in 8.3 and 8.4% episodes respectively). However, the likelihood of delay was modestly higher in episodes provided to Indigenous than non-Indigenous patients (adjusted odds ratio [aOR], 1.41; 95% confidence interval [CI] 1.07-1.86). Excess delay among Indigenous patients was accentuated in first episodes (aOR, 1.53; 95% CI 1.14-2.06), in patients aged < 65 years (aOR, 1.66; 95% CI 1.14-2.41), and among those residing in Inner Regional areas (aOR, 1.97; 95% CI 1.19-3.28), and also approached significance among those in outer regional, remote and very remote areas collectively (aOR, 1.72; CI 0.97-3.05). CONCLUSIONS: Although the timeliness benchmark is being met for Indigenous Australians in palliative care, they may experience delayed initiation of care episodes, particularly if younger, and especially at first encounter with a service. Qualitative research is required to explore determinants of delay in initiating palliative care episodes. The timeliness of initial referral for specialist palliative care in this population remains to be determined.

Clinical significance of RET and RAS mutations in sporadic medullary thyroid carcinoma: a meta-analysis.

There are ongoing debates with respect to the prognostic roles of molecular biomarkers in sporadic medullary thyroid carcinoma (MTC). In this study, we aimed at investigating the prognostic value of RET and RAS mutations - the two most common mutations in sporadic MTCs. A search was conducted in four electronic databases. Relevant data were extracted and pooled into odds ratios (OR), mean differences (MD) and corresponding 95% confidence intervals (CI) using the random-effect model. We used Egger's regression test and visual of funnel plots to assess the publication bias. From 2581 studies, we included 23 studies with 964 MTCs for meta-analysis. Overall, the presence of RET mutation was associated with an elevated risk for lymph node metastasis (OR = 3.61; 95% CI = 2.33-5.60), distant metastasis (OR = 2.85; 95% CI = 1.64-4.94), advanced tumor stage (OR = 3.25; 95% CI = 2.02-5.25), tumor recurrence (OR = 3.01; 95% CI = 1.65-5.48) and patient mortality (OR = 2.43; 95% CI = 1.06-5.57). RAS mutation had no significant prognostic value in predicting tumor aggressiveness. To summarize, our results affirmed that RET mutation is a reliable molecular biomarker to identify a group of highly aggressive sporadic MTCs. It can help clinicians better assess patient prognosis and select appropriate treatment decisions.

BRAF Mutation is Associated with an Improved Survival in Glioma-a Systematic Review and Meta-analysis.

Newly emerged molecular markers in gliomas provide prognostic values beyond the capabilities of histologic classification. BRAF mutation, especially BRAF V600E, is common in a subset of gliomas and may represent a potential prognostic marker. The aim of our study is to investigate the potential use of BRAF mutations on prognosis of glioma patients. Four electronic databases were searched for potential articles, including PubMed, Scopus, ISI Web of Science, and Virtual Health Library (VHL). Data of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were directly obtained from original papers or indirectly estimated from Kaplan Meier curve (KMC). A random effect model weighted by inverse variance method was used to calculate the pooled HR. From 705 articles, we finally included 11 articles with 1308 glioma patients for the final analysis. The overall estimates showed that BRAF V600E was associated with an improved overall survival (OS) in glioma patients (HR = 0.60; 95% CI = 0.44-0.80). Results for progression-free survival (PFS), however, were not statistically significant (HR = 1.39; 95% CI = 0.82-2.34). In subgroup analyses, BRAF V600E showed its effect in improving survival in pediatric and young adult gliomas (under 35 years) but did not have prognostic value in old adult. Additionally, BRAF V600E was only associated with a favorable prognosis in lower grade glioma. Our meta-analysis provides evidence that BRAF mutation has a favorable prognostic impact in gliomas and its prognostic value might be dependent on patient age and tumor grade. This mutation can be used as a prognostic factor in glioma but additional studies are required to clarify its prognostic value taking into account other confounding factors.

TERT promoter mutation and its interaction with IDH mutations in glioma: Combined TERT promoter and IDH mutations stratifies lower-grade glioma into distinct survival subgroups-A meta-analysis of aggregate data.

The clinical significance of telomerase reverse transcriptase (TERT) promoter mutation in glioma remains unclear. The aim of our meta-analysis is to investigate the prognostic impact TERT promoter mutation in glioma patients and its interaction with other molecular markers, particularly Isocitrate Dehydrogenase (IDH) mutation from aggregate level data. Relevant articles were searched in four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library. Pooled HRs were calculated using random effect model weighted by inverse variance method. From 1010 studies, we finally included 28 studies with 11519 patients for meta-analyses. TERT mutation is significantly associated with compromised overall survival (OS) (HR=1.38; 95% CI=1.15-1.67) and progression-free survival (PFS) (HR=1.31; 95% CI=1.06-1.63) in glioma patients. In studying its reaction with IDH, TERT promoter mutation was associated with reduced OS in both IDH-mutant (IDH-mut) and IDH-wild type (IDH-wt) glioblastomas but shown to have inverse effects on IDH-mut and IDH-wt grade II/III tumors. Our analysis categorized WHO grade II/III glioma patients into four distinct survival subgroups with descending survival as follow: TERT-mut/IDH-mut≫TERT-wt/IDH-mut≫TERT-wt/IDH-wt≫TERT-mut/IDH-wt. Prognostic value of TERT promoter mutations in gliomas is dependent on tumor grade and the IDH mutational status. With the same tumor grade in WHO grade II and III tumors and the same IDH mutation status, TERT-mut is a prognostic factor.

A meta-analysis of prognostic roles of molecular markers in papillary thyroid carcinoma.

The prognostic role of molecular markers in papillary thyroid carcinoma (PTC) is a matter of ongoing debate. The aim of our study is to investigate the impact of RAS, BRAF, TERT promoter mutations and RET/PTC rearrangements on the prognosis of PTC patients. We performed a search in four electronic databases: PubMed, Scopus, Web of Science and Virtual Health Library (VHL). Data of hazard ratio (HR) and its 95% confidence interval (CI) for disease-specific survival (DSS) and disease-free survival (DFS) were directly obtained from original papers or indirectly estimated from Kaplan-Meier curve (KMC). Pooled HRs were calculated using random-effect model weighted by inverse variance method. Publication bias was assessed by using Egger's regression test and visual inspection of funnel plots. From 2630 studies, we finally included 35 studies with 17,732 patients for meta-analyses. TERT promoter mutation was significantly associated with unfavorable DSS (HR = 7.64; 95% CI = 4.00-14.61) and DFS (HR = 2.98; 95% CI = 2.27-3.92). BRAF mutations significantly increased the risk for recurrence (HR = 1.63; 95% CI = 1.27-2.10) but not for cancer mortality (HR = 1.41; 95% CI = 0.90-2.23). In subgroup analyses, BRAF mutation only showed its prognostic value in short-/medium-term follow-up. Data regarding RAS mutations and RET/PTC fusions were insufficient for meta-analyses. TERT promoter mutation can be used as an independent and reliable marker for risk stratification and predicting patient's outcomes. The use of BRAF mutation to assess patient prognosis should be carefully considered.

Hospital psychiatric comorbidity and its role in heroin dependence treatment outcomes using naltrexone implant or methadone maintenance.

Our objectives were to (i) estimate lifetime prevalence of psychiatric comorbidity in heroin users and (ii) evaluate psychiatric comorbidity as a predictor of drug-related hospitalization following either (a) methadone maintenance or (b) naltrexone implant treatment. Our method consisted of retrospective, longitudinal follow-up using prospectively collected, state-wide hospital data on two cohorts of heroin-dependent persons (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), first time treated with naltrexone implant (n = 317) or methadone (n = 521) between January 2001 and December 2002. Outcome measures were: (i) prevalence of comorbidity and (ii) changes in risk for drug-related hospitalization - categorized as 'opioid drugs', 'non-opioid drugs', and 'any drug' - to 3.5 years post-treatment. Nearly 32% had psychiatric comorbidity. In both cohorts, comorbid patients generally had significantly greater odds of drug-related hospitalization pre-treatment compared with non-comorbid counterparts. These differences generally reduced in magnitude post-treatment. Comorbid naltrexone-treated patients had less 'opioid' and 'any drug' related hospitalizations post-treatment. Similarly, comorbid methadone-treated patients had reduced hospitalization risk for 'non-opioid' and 'any drug' related hospitalization post-treatment. Treatment of persons without depression, anxiety, or personality disorder with naltrexone implant was associated with increased risk of 'non-opioid' drug-related hospitalization, while methadone treatment was associated with increased risk of 'opioid' drug-related hospitalization. Although comorbid heroin users entered treatment with significantly higher risk of drug-related hospitalization than non-comorbid users, substantial reductions in drug-related hospitalization were generally observed post-treatment. This challenges the view that comorbidity predicts poor drug treatment outcomes. Differences in research methodology were noted; recommendation for rigorous analytical methodology in future research on assessing treatment outcomes was accordingly offered.

Risk factors for craving and relapse in heroin users treated with oral or implant naltrexone.

BACKGROUND: Oral naltrexone effectively antagonizes heroin, but patient noncompliance limits its utility; sustained-release preparations may overcome this. Few data are available on optimal blood naltrexone levels for preventing craving and/or return to heroin use. This study assesses various risk factors, including blood naltrexone level, for heroin craving and relapse to illicit opioids. METHODS: Heroin-dependent persons from a randomized controlled trial of oral versus implant naltrexone were followed up for 6 months. Thirty-four participants received 50 mg oral naltrexone daily, plus placebo implant; thirty-five participants received a single dose of 2.3 g naltrexone implant, plus daily oral placebo tablets. RESULTS: Compared to oral naltrexone patients, implant naltrexone patients were significantly less likely to use any opioids and had one-fifth the risk of using heroin > or = weekly. Risk of > or = weekly heroin use increased by 2.5 times at blood naltrexone concentration < .5 ng/mL compared with > or = .5 ng/mL, with 3 ng/mL associated with very low risk of use. Craving remained near "floor" levels for implant patients but rebounded to higher levels among oral patients. Lower craving scores (< or = 20/70) predicted lower relapse risk. Noncompliance with daily oral formula, higher baseline craving, longer history of use, and being younger predicted higher craving at follow-up. CONCLUSIONS: Implant naltrexone was better associated with reduced heroin craving and relapse than oral naltrexone. Effective treatment was achieved at blood naltrexone levels of 1 ng/mL to 3 ng/mL, with higher levels associated with greater efficacy. Craving assessment may be valuable in predicting relapse risk allowing timely intervention.

Comparing drug-related hospital morbidity following heroin dependence treatment with methadone maintenance or naltrexone implantation.

CONTEXT: Most research on heroin dependence treatments assesses short-term changes in patients' self-reported drug use. To our knowledge, long-term sustainability of changes in patients' drug use and associated hospital morbidity posttreatment have not been studied. OBJECTIVES: To evaluate drug-related hospital morbidity in heroin users at 6 months and 3 1/2 years after receiving naltrexone implant treatment and to compare these results with outcomes from a similar cohort treated with methadone maintenance treatment. DESIGN: Retrospective longitudinal follow-up, using data prospectively collected via a state hospital (public and private) reporting system. SETTING: Perth, Western Australia. Methadone maintenance dosage was generally dispensed daily by registered community pharmacies. Naltrexone implant treatment was performed as a day procedure at a community clinic. PARTICIPANTS: A total of 522 and 314 heroin-dependent persons (according to DSM-IV), first time treated with methadone maintenance or a naltrexone implant, respectively, between January 1, 2001, and December 30, 2002, were identified, using health record linkage. MAIN OUTCOME MEASURES: Planned outcomes included crude hospital admission rates, adjusted changes in risks (odds ratio [OR]), and rates (rate ratio) of "overdose-related" and "non-overdose-related" hospital morbidity associated with opioid vs nonopioid drugs 6 months and 3 1/2 years posttreatment. RESULTS: Following naltrexone implant treatment, opioid-related risk decreased for overdose (OR, 0.23; 95% confidence interval [CI], 0.11-0.48) and nonoverdose (OR, 0.64; 95% CI, 0.46-0.89) conditions at 3 1/2 years. Such reductions were not observed after methadone treatment. Overdose on nonopioid drugs increased in older patients to 6 months: OR of 16.31 (95% CI, 3.07-86.53) for naltrexone and OR of 5.03 (95% CI, 1.18-21.54) for methadone. Nonoverdose (eg, dependence and withdrawal) associated with nonopioid drugs also increased for patients receiving the naltrexone implant: OR of 1.52 (95% CI, 1.04-2.23) at 3 1/2 years. In addition, there were 6 drug-related deaths: 5 after methadone maintenance and 1 after naltrexone implantation. CONCLUSIONS: Naltrexone implants, but not methadone maintenance, has long-term benefits in reducing opioid-related hospital morbidity. However, long-lasting and increased nonopioid drug-related morbidity following naltrexone implantation is particularly concerning. Similar studies are required to confirm these findings.

Biodegradability of naltrexone-poly(DL) lactide implants in vivo assessed under ultrasound in humans.

Ultrasound was used to assess the in vivo biodegradability of a sustained release poly(DL)lactide naltrexone implant in 71 persons previously treated for heroin dependence. We assessed 139 implant sites ranging from 2 to 1808 days post implant. Ultrasound assessment showed that implant tablets were initially well demarcated from each other and from the surrounding tissues. Biodegradation resulted in less demarcated tablets followed by clumping into a single mass-like structure. This mass subsequently dispersed by approximately 1201 days post implant with no implant material visualized by ultrasound. The biodegradation was also assessed by visual clinical examination and palpation of the implant site as well as patient self-report. These measures were generally well correlated with ultrasound results. Clinical assessment of the biodegradation process concluded that the implant changed from 'firm' to 'less firm' and from 'initial square edge' to 'rounded edge' tablets. Collectively, these data provide direct evidence of the in vivo absorption of the Go Medical implant over time, and its biodegradability in humans.

Mental health outcomes following naltrexone implant treatment for heroin-dependence.

BACKGROUND: Oral naltrexone is an approved treatment for opioid dependence. However, the impact of sustained release naltrexone on the mental health of treated opioid users has not been studied. AIMS: To assess if naltrexone via implant treatment was associated with any change in (i) risk, (ii) rate, and (iii) duration for hospital morbidity related to several categories of mental disorders among treated heroin users. METHOD: A cohort of 359 heroin users treated with sustained release naltrexone via implants in Western Australia was retrospectively followed up for mental health related outcomes via a health record linkage system over an average period of 1.78 years post-treatment. RESULTS: Individual patient's risk for hospital mental diagnoses was not altered after naltrexone implant. On a population cohort level, hospital admission rates related to all mental health problems, except mood disorders, declined significantly post-treatment; however, length of hospital stay did not improve. Overall, young, female patients or those with pre-existing mental illness were more likely than other patients to require hospital care for mental health issues following treatment. Longer period of heroin use was associated with poorer mood outcomes. CONCLUSIONS: Naltrexone implants were not associated with an increased risk for hospitalisation due to mental illness, and in most cases, were associated with a decrease in mental related hospital admission rate.