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1.
J Clin Oncol ; : JCO1901395, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31794323

RESUMO

PURPOSE: Urothelial cancers (UCs) have a substantial hereditary component, but, other than their association with Lynch syndrome, the contribution of genetic risk factors to UC pathogenesis has not been systematically defined. We sought to determine the prevalence of pathogenic/likely pathogenic (P/LP) germline variants in patients with UC and identify associated clinical factors. PATIENTS AND METHODS: Overall, 586 patients with UC underwent prospective, matched tumor-normal DNA sequencing. Seventy-seven genes associated with cancer predisposition were analyzed; allele frequencies were compared with publicly available database. RESULTS: P/LP germline variants were identified in 80 (14%) of 586 individuals with UC. The most common P/LP variants in high- or moderate-penetrance genes were BRCA2 (n = 9; 1.5%), MSH2 (n = 8; 1.4%), BRCA1 (n = 8; 1.4%), CHEK2 (n = 6; 1.0%), ERCC3 (n = 4; 0.7%), and NBN and RAD50 (n = 3; 0.5% each). Sixty-six patients (83%) had germline P/LP variants in DNA-damage repair (DDR) genes, of which 28 (42%) had biallelic inactivation. Patients with P/LP variants were more commonly diagnosed at an early age (22% v 6% in those without variants; P = .01). BRCA2 and MSH2 were significantly associated with an increased risk for UC (odds ratio, 3.7 [P = .004] and 4.6 [P = .001], respectively). Current clinical guidelines for referral for genetic testing failed to identify 6 (26%) patients with high-penetrance variants. CONCLUSION: Clinically significant P/LP germline variants in DDR genes frequently are present in patients with advanced UC. The presence of DDR germline variants could guide cancer screening for patients and their families and serve as predictive biomarkers of response to targeted or immunotherapies. Family history-based criteria to identify patients with hereditary UC susceptibility are insensitive. Broader germline testing in UC, particularly in those of young ages, should be considered.

2.
Nat Med ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31768065

RESUMO

Histiocytoses are clonal hematopoietic disorders frequently driven by mutations mapping to the BRAF and MEK1 and MEK2 kinases. Currently, however, the developmental origins of histiocytoses in patients are not well understood, and clinically meaningful therapeutic targets outside of BRAF and MEK are undefined. In this study, we uncovered activating mutations in CSF1R and rearrangements in RET and ALK that conferred dramatic responses to selective inhibition of RET (selpercatinib) and crizotinib, respectively, in patients with histiocytosis.

3.
Int J Epidemiol ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740967

RESUMO

BACKGROUND: Anthropogenic pressure in biodiversity hotspots is increasingly recognized as a major driver of the spillover and expansion of zoonotic disease. In the Western Ghats region of India, a devastating tick-borne zoonosis, Kyasanur Forest disease (KFD), has been expanding rapidly beyond its endemic range in recent decades. It has been suggested that anthropogenic pressure in the form of land use changes that lead to the loss of native forest may be directly contributing to the expanding range of KFD, but clear evidence has not yet established the association between forest loss and KFD risk. METHODS: The current study sought to investigate the relationship between KFD landscape suitability and both forest loss and mammalian species richness, to inform its epidemiology and infection ecology. A total of 47 outbreaks of KFD between 1 January 2012 and 30 June 2019 were modelled as an inhomogeneous Poisson process. RESULTS: Both forest loss [relative risk (RR) = 1.83; 95% confidence interval (CI) 1.33-2.51] and mammalian species richness (RR = 1.29; 95% CI 1.16-1.42) were strongly associated with increased risk of KFD and dominated its landscape suitability. CONCLUSIONS: These results provide the first evidence of a clear association between increasing forest loss and risk for KFD. Moreover, the findings also highlight the importance of forest loss in areas of high biodiversity. Therefore, this evidence provides strong support for integrative approaches to public health which incorporate conservation strategies simultaneously protective of humans, animals and the environment.

4.
ANZ J Surg ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31674151

RESUMO

BACKGROUND: Surgical treatment of gastric cancer in New Zealand is challenging because of a low annual incidence of 400 patients and population dispersal over a wide area with little data on regional treatment trends and outcomes. This investigation was undertaken to evaluate the surgical outcomes of gastric cancer patients presenting to a single upper gastrointestinal centre (WDHB, Waitemata District Health Board) and to compare these to national and international standards. METHODS: Data on 135 patients with histologically proven gastric adenocarcinoma presenting between January 2010 and December 2014 were reviewed and compared with nationally available procedural volume data. RESULTS: Sixty of 135 patients were resected (resection rate 44%) and 75 patients were managed with palliative chemotherapy/symptomatic care alone. Twenty-six patients (43%) received adjuvant or neoadjuvant chemotherapy and only two patients (3%) underwent laparoscopic resection. In resected patients, 90-day mortality was 1.6%, and 11 patients (18%) developed complications ≥ Clavien-Dindo grade 3. Fifty-two patients (87%) had ≥15 lymph nodes resected and 54 patients (90%) had a histological R0 resection. At median follow-up of 49 months, 30 patients remain alive and disease-free with 20 true 5-year disease-free survivors. National data between 2010 and 2014 showed WDHB performed 20% (338/1710) of gastric resections for all indications in New Zealand. CONCLUSION: While WDHB is an internationally low volume centre for gastric cancer, surgical outcomes benchmark satisfactorily to international standards. New Zealand's national treatment standards should set aspirational goals for gastric cancer treatment and have a clear strategy to address issues of surgical volume and national service provision.

5.
Plast Reconstr Surg ; 144(5): 1238-1245, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31688772

RESUMO

BACKGROUND: The fragility index has been proposed as a metric to evaluate the robustness of statistically significant findings in randomized controlled trials. It measures the number of events that a trial result relies on to maintain statistical significance. This study examines the robustness of statistically significant results from randomized controlled trials in the plastic surgery literature. METHODS: A systematic literature search of the 15 highest impact plastic surgery journals was conducted to identify randomized controlled trials published between 2000 and 2017 that reported a statistically significant dichotomous outcome (p < 0.05). The fragility index of each study was calculated using Fisher's exact test. Multiple linear regression was used to determine trial characteristics associated with the fragility index. RESULTS: The 90 eligible randomized controlled trials had a median sample size of 73.5 patients (25th to 75th percentile, 50 to 115) and a median of 20 events (25th to 75th percentile, 11 to 33.5) for the chosen outcome. The median fragility index was 1 (25th to 75th percentile, 0 to 4), indicating that statistical significance would be lost in half of the randomized controlled trials if a single patient had a change in event status. The fragility index was 0 in 24 of 90 (27 percent) randomized controlled trials, meaning the outcome immediately lost statistical significance on recalculation of the p value using Fisher's exact test. CONCLUSIONS: The results of randomized controlled trials in plastic surgery demonstrate substantial fragility, as statistically significant results were found to hinge on a small number of events. The fragility index offers an intuitive and simple metric to complement the p value and determine the confidence in the results of randomized controlled trials.

6.
Blood Adv ; 3(20): 2962-2979, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31648317

RESUMO

Standardized variant curation is essential for clinical care recommendations for patients with inherited disorders. Clinical Genome Resource (ClinGen) variant curation expert panels are developing disease-associated gene specifications using the 2015 American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines to reduce curation discrepancies. The ClinGen Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP) was created collaboratively between the American Society of Hematology and ClinGen to perform gene- and disease-specific modifications for inherited myeloid malignancies. The MM-VCEP began optimizing ACMG/AMP rules for RUNX1 because many germline variants have been described in patients with familial platelet disorder with a predisposition to acute myeloid leukemia, characterized by thrombocytopenia, platelet functional/ultrastructural defects, and a predisposition to hematologic malignancies. The 28 ACMG/AMP codes were tailored for RUNX1 variants by modifying gene/disease specifications, incorporating strength adjustments of existing rules, or both. Key specifications included calculation of minor allele frequency thresholds, formulating a semi-quantitative approach to counting multiple independent variant occurrences, identifying functional domains and mutational hotspots, establishing functional assay thresholds, and characterizing phenotype-specific guidelines. Preliminary rules were tested by using a pilot set of 52 variants; among these, 50 were previously classified as benign/likely benign, pathogenic/likely pathogenic, variant of unknown significance (VUS), or conflicting interpretations (CONF) in ClinVar. The application of RUNX1-specific criteria resulted in a reduction in CONF and VUS variants by 33%, emphasizing the benefit of gene-specific criteria and sharing internal laboratory data.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31645348

RESUMO

Recurrent somatic missense mutations in histone H3 genes have been identified in subsets of pediatric cancers. H3K36 histone mutations have recently been recognized as oncogenic drivers in rare subsets of malignant soft tissue sarcomas but have not been reported in histiocytic neoplasms. Currently, the histological and molecular spectrum, as well as the clinical behavior of H3K36-mutant soft tissue malignancies, is largely unknown. We describe a pediatric patient with a HIST1H3B K36I-mutant histiocytic tumor arising in the skull. After the failure of upfront therapy for histiocytosis and development of widely disseminated metastatic disease, the patient had an exceptional response to empiric chemotherapy and remains in complete disease remission for more than 5 years. Our report expands the histological spectrum of H3K36M/I-mutant soft tissue malignancies to histiocytic neoplasms and indicates that multiagent sarcoma-like chemotherapy can be highly effective even in the setting of widely disseminated metastatic disease.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31618944

RESUMO

Traditional languages are a key element of Indigenous peoples' identity, cultural expression, autonomy, spiritual and intellectual sovereignty, and wellbeing. While the links between Indigenous language loss and poor mental health have been demonstrated in several settings, little research has sought to identify the potential psychological benefits that may derive from language reclamation. The revival of the Barngarla language on the Eyre Peninsula, South Australia, offers a unique opportunity to examine whether improvements in mental health and social and emotional wellbeing can occur during and following the language reclamation process. This paper presents findings from 16 semi-structured interviews conducted with Barngarla community members describing their own experienced or observed mental health and wellbeing impacts of language reclamation activities. Aligning with a social and emotional wellbeing framework from an Aboriginal and Torres Strait Islander perspective, key themes included connection to spirituality and ancestors; connection to Country; connection to culture; connection to community; connection to family and kinship; connection to mind and emotions; and impacts upon identity and cultural pride at an individual level. These themes will form the foundation of assessment of the impacts of language reclamation in future stages of the project.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31495887

RESUMO

BACKGROUND: Whether the survival benefit of ß-blockers in congestive heart failure (CHF) from randomized trials extends to patients with advanced chronic kidney disease (CKD) [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 but not receiving dialysis] is uncertain. METHODS: This was a retrospective cohort study using administrative datasets. Older adults from Ontario, Canada, with incident CHF (median age 79 years) from April 2002 to March 2014 were included. We matched new users of ß-blockers to nonusers on age, sex, eGFR categories (>60, 30-60, <30), CHF diagnosis date and a high-dimensional propensity score. Using Cox proportional hazards models, we examined the association of ß-blocker use versus nonuse with all-cause mortality. RESULTS: We matched 5862 incident ß-blocker users (eGFR >60, n = 3136; eGFR 30-60, n = 2368; eGFR <30, n = 358). There were 2361 mortality events during follow-up. ß-Blocker use was associated with reduced all-cause mortality [adjusted hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.54-0.64]. This result was consistent across all eGFR categories (>60: adjusted HR 0.55, 95% CI 0.49-0.62; 30-60: adjusted HR 0.63, 95% CI 0.55-0.71; <30: adjusted HR 0.55, 95% CI 0.41-0.73; interaction term, P = 0.30). The results were consistent in an intention-to-treat analysis and with ß-blocker use treated as a time-varying exposure. CONCLUSIONS: ß-Blocker use is associated with reduced all-cause mortality in elderly patients with CHF and CKD, including those with an eGFR <30. Randomized trials that examine ß-blockers in patients with CHF and advanced CKD are needed.

10.
Int J Numer Method Biomed Eng ; : e3259, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31483945

RESUMO

Areas of disturbed shear that develop following arteriovenous fistula (AVF) creation are believed to trigger the onset of intimal hyperplasia (IH), leading to AVF dysfunction. The presence of helical flow can suppress the flow disturbances that lead to disturbed shear in other areas of the vasculature. However, the relationship between helical flow and disturbed shear remains unevaluated in AVF. In this study, computational fluid dynamics (CFD) is used to evaluate the relationship between geometry, helical flow, and disturbed shear in parameterised models of an AVF characterised by four different anastomosis angles. The AVF models with a small anastomosis angle demonstrate the lowest distribution of low/oscillating shear and are characterised by a high helical intensity coupled with a strong balance between helical structures. Contrastingly, the models with a large anastomosis angle experience the least amount of high shear, multidirectional shear, as well as spatial and temporal gradients of shear. Furthermore, the intensity of helical flow correlates strongly with curvature (r = 0.73, P < .001), whereas it is strongly and inversely associated with taper (r = -0.87, P < .001). In summary, a flow field dominated by a high helical intensity coupled with a strong balance between helical structures can suppress exposure to low/oscillating shear but is ineffective when it comes to other types of shear. This highlights the clinical potential of helical flow as a diagnostic marker of exposure to low/oscillating shear, as helical flow can be identified in vivo with the use of ultrasound imaging.

11.
Hum Mutat ; 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31444830

RESUMO

Fumarate hydratase (FH) mutations underpin the autosomal recessive syndrome. FH deficiency and the autosomal dominant syndrome hereditary leiomyomatosis and renal cell carcinoma (HLRCC). The FH c.1431_1433dupAAA (p.Lys477dup) genomic alteration has been conclusively shown to contribute to FH deficiency when occurring with another FH germline alteration. However, a sufficiently large dataset has been lacking to conclusively determine its clinical significance to cancer predisposition in the heterozygous state. We reviewed a series of 7,571 patients with cancer who received germline results through MSK-IMPACT testing at the Memorial Sloan Kettering Cancer Center. The FH c.1431_1433dupAAA (p.Lys477dup) variant was detected in 24 individuals, none of whom was affected with renal cancer. Eleven of the 372 patients with renal cancer were identified to carried pathogenic FH variants associated with HLRCC. None of these 372 patients with renal cancer carried the FH c.1431_1433dupAAA variant. Our data indicate the FH c.1431_1433dupAAA is not associated with cancer including renal cell carcinoma.

12.
Cytopathology ; 30(6): 614-619, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31390089

RESUMO

OBJECTIVE: To evaluate the utility of claudin-4 as a pan-carcinoma marker in cell-blocks of effusion specimens and compare results with Ber-Ep4 staining. METHODS: Effusion cell-blocks (n = 284) were stained for claudin-4 and results compared with Ber-Ep4. Cases included 172 metastatic malignancies (137 adenocarcinomas, 20 small cell lung tumours, eight metastatic melanoma, four squamous cell carcinoma, three urothelial cell carcinoma), 49 benign reactive cases and 63 mesotheliomas. RESULTS: All 49 benign effusions were negative. Only 1/63 (1.6%) mesotheliomas was positive for claudin-4. Claudin-4 staining was positive in 131/137 (95.6%) adenocarcinoma cases. Cases negative for claudin-4 included single cases of metastases from breast, colon, stomach, prostate, kidney and ovary. Claudin-4 outperformed Ber-Ep4. Sensitivity (95.6% vs 85.4%), specificity (99.1% vs 86.6%), negative predictive value (94.9% vs 82.9%) and positive predictive value (99.2% vs 88.6%) were all higher for claudin-4 compared with Ber-Ep4, respectively. Only two cases were claudin-4-/Ber-Ep4+. Significantly (P < .0064) more cases of metastatic adenocarcinoma stained positive for claudin-4 (131/137; 95.6%) than Ber-Ep4 (117/137; 86.2%). Claudin-4 staining was present in 15/20 (75%) of neuroendocrine carcinomas, 3/4 (75%) squamous cell carcinoma and 3/3 (100%) urothelial cell carcinoma. All eight cases of melanoma were negative for both claudin-4 and Ber-Ep4. CONCLUSIONS: Claudin-4 staining is a useful addition to IHC panels for effusions specimens with superior performance to Ber-Ep4.

13.
Acta Biomater ; 99: 479-494, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31449928

RESUMO

Biodegradable stents show promise to revolutionize coronary artery disease treatment. Its successful implementation in the global market remains limited due to the constraints of current generation biodegradable materials. Cold gas dynamic spraying (CGDS) has been proposed as a manufacturing approach to fabricate a metallic biodegradable amalgamate for stent application. Iron and 316L stainless steel powders are combined in a 4:1 ratio to create a novel biomaterial through cold spray. Cold spray processing however, produces a coating in a work hardened state, with limited ductility, which is a critical mechanical property in stent design. To this end, the influence of annealing temperature on the mechanical and corrosion performances of the proposed Fe-316L amalgamate is investigated. It was found that annealing at 1300 °C yielded a complex material microstructure, with an ultimate tensile strength of approximately 280 MPa and ductility of 23%. The static corrosion rate determined at this annealing temperature was equal to 0.22 mg cm-2 day-1, with multiple corrosion species identified within the degradation layers. Precipitates were observed throughout the microstructure, which appeared to accelerate the overall corrosion behaviour. It was shown that cold-sprayed Fe-316L has significant potential to be implemented in a clinical setting. STATEMENT OF SIGNIFICANCE: Biodegradable stents have potential to significantly improve treatment of coronary artery disease by decreasing or potentially eliminating late-term complications, including stent fracture and in-stent restenosis. Current generation polymer biodegradable stents have led to poorer patient outcomes in comparison to drug-eluting stents, however, and it is evident that metallic biomaterials are required, which have increased strength. To this end, a novel iron and stainless steel 316L biomaterial is proposed, fabricated through cold-gas dynamic spraying. This study analyses the effect of annealing on the Fe-316L biomaterial through corrosion, mechanical, and microstructural investigations. The quantitative data presented in this work suggests that Fe-316L, in its annealed condition, has the mechanical and corrosion properties necessary for biodegradable stent application.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31420501

RESUMO

A model was developed that can be used to predict how hydrogen peroxide (H2O2) transfers into a liquid drug product that is exposed to Vapor Phase Hydrogen Peroxide (VPHP). This model accounts for fluid flow in both the gas and liquid phases as well as the diffusion and convection mechanisms of mass transfer using first principles of engineering to predict the amount of hydrogen peroxide that will transfer from the gas to liquid phase considering a given geometrical system and surrounding conditions. The model was used to investigate how much space you need in a given container to eliminate convective mass transfer and create a balance between mass transfer and air / liquid interface for oxidation sensitive products in cartridges or vials being filled in an isolator. Experimental results compare well with model predictions. A no-slip boundary condition between the gas and liquid phases was used for the model, which was especially important for the full syringes where convective mass transport predominated. This model may be used to evaluate isolator designs for filling oxidation-sensitive products utilizing the correlation between spiking studies and VPHP uptake to minimize the uptake studies required. It could also be used to inform the design of containers to be used that would minimize potential for VPHP uptake. For the geometry tested here, it was demonstrated that convection only occurs near the top few millimeters of the container. If the fill level is lower, as it would be for a syringe, the diffusion mechanism of transfer predominates and the rate of transfer of H2O2 is much slower. The balance between mass transfer by convection and diffusion should be a consideration in the design of the system to be filled.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31415463

RESUMO

STUDY DESIGN: Cadaveric study on fresh unprocessed, non- preserved, undyed specimens which has not previously been reported. OBJECTIVES: We aimed to perform surgically relevant exposures of the anterior cervical spine with particular attention to observing the potential vulnerabilities of the RLN on right and left. SUMMARY OF BACKGROUND DATA: Vulnerability of the RLN in the anterior cervical spine approach on the right versus left is the subject of ongoing debate. Whilst most cadaveric studies focus on course variations, structural relations of RLN, they have been done in preserved (fixed) cadavers without relevance to the needs of spinal exposure. METHODS: Twelve fresh undyed cadavers had extensive layer by layer dissections by 2 surgeons (one with extensive experience as anatomy dissector). Both sides were explored for vulnerability during cervical spinal procedures. Each dissection was carried out in a phased approach and deliberately explored beyond what can be afforded in live surgery to allow the reader to conceptualize a better view of the structures. RESULTS: In all specimens, we consistently demonstrated that the right surgical corridor involved manipulation of the nerve and its branches especially below C5 in order to achieve optimum midline access: In the right corridor, the RLN is on its oblique course to the tracheoesophageal groove. On the left RLN is already in the tracheoesophageal groove and out of the surgical field involving minimal direct mobilization of the nerve. CONCLUSIONS: RLN surgical anatomy photographed here is novel in using fresh unprocessed cadaveric specimens which has previously not been reported.Right surgical corridor, below C5, involves retraction/manipulation of RLN for achieving optimum spinal midline access, highlighting potential surgical vulnerability of right RLN. LEVEL OF EVIDENCE: 3.

17.
J Am Vet Med Assoc ; 255(2): 224-230, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31260400

RESUMO

OBJECTIVE To identify factors associated with keratopathy in captive pinnipeds and to provide guidance for preventive measures. ANIMALS 319 captive pinnipeds (229 otariids [sea lions and fur seals], 74 phocids [true seals], and 16 odobenids [walrus]) from 25 facilities. PROCEDURES Descriptive data collected from questionnaires completed by facilities and from medical records and physical examinations of pinnipeds were compiled and evaluated. Variables were assessed with χ2 tests of homogeneity to determine potential association with keratopathy, and variables with values of P ≤ 0.25 were inserted into the multivariable logistic regression model. RESULTS Results indicated that variables associated with significantly increased odds of keratopathy in captive pinnipeds included lighter or reflective pool color (OR, 2.11; 95% confidence interval [CI], 1.20 to 3.97), pool water salinity < 29 g/L (OR, 3.48; 95% CI, 1.89 to 6.56), and history of eye disease (OR, 3.30; 95% CI, 1.85 to 5.98), trauma (OR, 3.80; 95% CI, 1.72 to 8.89), and having been tested for leptospirosis (OR, 3.83; 95% CI, 1.54 to 10.26). However, odds of keratopathy decreased with UV index ≤ 6 (OR, 0.39; 95% CI, 0.2 to 0.72) and age < 20 years (OR, 0.32; 95% CI, 0.15 to 0.66). CONCLUSIONS AND CLINICAL RELEVANCE Findings indicated that odds of keratopathy in pinnipeds could be reduced by maintenance of pool water salinity ≥ 29 g/L and reduction of UV radiation exposure (eg, with adequate shade structures and use of darker, natural colors). Because UV radiation exposure is cumulative, even small attempts to reduce lifetime exposure to it could help control keratopathy in pinnipeds.

19.
Drug Alcohol Depend ; 202: 156-161, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31352304

RESUMO

AIM: To measure outcomes in Quality of Life in alcohol dependent patients' following a medicated withdrawal from alcohol. METHODS: 79 patients that were admitted to a detoxification unit in Auckland, New Zealand between March 2016 and September 2016 were assessed for severity of alcohol dependence using the Alcohol Use Disorders Identification Test (AUDIT) and Severity of Alcohol Dependency Questionnaire (SADQ) and Quality of Life (QOL) using the World Health Organisation Quality of Life-abbreviated version of the WHOQOL 100 New Zealand version (WHOQOL-BREF NZ). Patients were followed up at three months and 12 months and an estimate of drinking behavior and the WHO-QOL BREF NZ were completed via telephone interview. QOL domain scores were assessed from baseline to three months and baseline to 12 months in both relapse and abstinent groups. At three months, a single question was asked in order to collect qualitative data. RESULTS: At baseline, the study population had statistically significantly lower mean QOL domain scores than scores reported from the general population. QOL improved in patients following detoxification at three months and 12 months in both the relapse and abstinent groups; however, the change in scores from baseline was greater in the abstinent group compared to the relapse group. The majority of patients reported that the admission had been a positive experience. CONCLUSION: QOL improves in individuals following a medicated withdrawal from alcohol regardless of whether individual's relapse; however, those that remain abstinent have greater improvements in quality of life.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31303579

RESUMO

BACKGROUND: The Agatston Calcium Score is a predictor of major adverse cardiovascular events but it is unable to identify high-risk lesions. Recent research suggests that examining calcification phenotype could be more indicative of plaque stability. OBJECTIVE: To examine the Agatston score's ability to determine atherosclerotic calcification phenotype. METHODS: Micro-Computed Tomography was performed on 20 carotid and 20 peripheral lower limb lesions. ImageJ pixel histogram analysis quantified the non-calcified (≥30HU, <130HU) and calcified (≥130HU) tissue volumes. ImageJ '3D Objects Counter' plugin determined the calcified particle count, volumes and maximum attenuation density of each particle. Image stacks were subsequently downsampled to a resolution of 0.7 × 0.7 × 3 mm and an approximation for the Extra-Coronary Calcium Scores (ECCS) were calculated. Spearman's correlation examined the relationships between ECCS approximations and calcification parameters. RESULTS: ECCS has a strong positive correlation with the Calcified Volume Fraction (CVF) (rs = 0.865, p < 0.0005), weak positive correlations with Calcified Particle Fraction (CPF) (rs = 0.422, p = 0.007) and Microcalcification Fraction (micro-CF) (rs = 0.361, p = 0.022). There is no correlation evident between ECCS and Calcified Particle Index (CPI) (rs = -0.162, p = 0.318). It is apparent that there is a high prevalence of microcalcifications in both carotid and peripheral lower limb lesions. Additionally, an inverse relationship exists between calcified particle volume and maximum-recorded attenuation density. CONCLUSION: The density-weighted Agatston calcium scoring methodology needs to be reviewed. Calcium scoring which differentiates between critical calcification morphologies, rather than presenting a density-weighted score, is required to direct high-risk plaques towards tailored treatment.

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