Esophageal sphincter device for gastroesophageal reflux disease

BACKGROUND Patients with gastroesophageal reflux disease who have a partial response to proton-pump inhibitors often seek alternative therapy. We evaluated the safety and effectiveness of a new magnetic device to augment the lower esophageal sphincter. METHODS We prospectively assessed 100 patients with gastroesophageal reflux disease before and after sphincter augmentation. The study did not include a concurrent control group. The primary outcome measure was normalization of esophageal acid exposure or a 50% or greater reduction in exposure at 1 year. Secondary outcomes were 50% or greater improvement in quality of life related to gastroesophageal reflux disease and a 50% or greater reduction in the use of proton-pump inhibitors at 1 year. For each outcome, the prespecified definition of successful treatment was achievement of the outcome in at least 60% of the patients. The 3-year results of a 5-year study are reported. RESULTS The primary outcome was achieved in 64% of patients (95% confidence interval [CI], 54 to 73). For the secondary outcomes, a reduction of 50% or more in the use of proton-pump inhibitors occurred in 93% of patients, and there was improvement of 50% or more in quality-of-life scores in 92%, as compared with scores for patients assessed at baseline while they were not taking proton-pump inhibitors. The most frequent adverse event was dysphagia (in 68% of patients postoperatively, in 11% at 1 year, and in 4% at 3 years). Serious adverse events occurred in six patients, and in six patients the device was removed. CONCLUSIONS In this single-group evaluation of 100 patients before and after sphincter augmentation with a magnetic device, exposure to esophageal acid decreased, reflux symptoms improved, and use of proton-pump inhibitors decreased. Follow-up studies are needed to assess long-term safety. (Funded by Torax Medical; ClinicalTrials.gov number, NCT00776997.

Burying the 'refuse revolution': the rise of controlled tipping in Britain 1920-1960

The definitive, peer-reviewed and edited version of this article is published in Environment and Planning A, 42, 5, 1033-1048, 2010, 10.1068/a42120.This paper investigates the emergence of ‘controlled tipping’ as the dominant method of municipal waste disposal in Britain between 1920 and 1960. The triumph of controlled tipping, despite the availability of alternative disposal technologies, needs to be understood in the context of the contested meanings of ‘waste’ and ‘wasteland’, which helped to determine attitudes and approaches to disposal. Following the conclusion of the First World War there was an urgent requirement for a cheap means of disposing of increasing amounts of urban municipal waste. The obvious choice was tipping. Before the war, however, refuse tipping had been rejected as insanitary by the emerging waste disposal profession. Public cleansing professionals therefore had to recuperate tipping as a medically and environmentally benign mode of disposal that was reconcilable with the needs of sanitary science and landscape preservation. Controlled tipping, with its combined claims to scientific progress and the revalorization of refuse, enabled dumping to be successfully re-produced as the dominant mode of municipal refuse disposal in Britain. However, tipping faced further challenges after 1945 from changing popular understandings of the value of ‘derelict’ landscapes and from the politics of amenity. The ‘refuse revolution’ was a work in progress

Exposure to a firefighting overhaul environment without respiratory protection increases immune dysregulation and lung disease risk

Firefighting activities appear to increase the risk of acute and chronic lung disease, including malignancy. While self-contained breathing apparatuses (SCBA) mitigate exposures to inhalable asphyxiates and carcinogens, firefighters frequently remove SCBA during overhaul when the firegrounds appear clear of visible smoke. Using a mouse model of overhaul without airway protection, the impact of fireground environment exposure on lung gene expression was assessed to identify transcripts potentially critical to firefighter-related chronic pulmonary illnesses. Lung tissue was collected 2 hrs post-overhaul and evaluated via whole genome transcriptomics by RNA-seq. Although gas metering showed that the fireground overhaul levels of carbon monoxide (CO), carbon dioxide (CO2), hydrogen cyanine (HCN), hydrogen sulfide (H2S) and oxygen (O2) were within NIOSH ceiling recommendations, 3852 lung genes were differentially expressed when mice exposed to overhaul were compared to mice on the fireground but outside the overhaul environment. Importantly, overhaul exposure was associated with an up/down-regulation of 86 genes with a fold change of 1.5 or greater (p<0.5) including the immunomodulatory-linked genes S100a8 and Tnfsf9 (downregulation) and the cancer-linked genes, Capn11 and Rorc (upregulation). Taken together these findings indicate that, without respiratory protection, exposure to the fireground overhaul environment is associated with transcriptional changes impacting proteins potentially related to inflammation-associated lung disease and cancer.This work was supported by the Department of Homeland Security Fire Prevention and Safety Grant #EMW-2013-FP-00766 to G.H. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ope

Excellent outcomes of laparoscopic esophagomyotomy for achalasia in patients older than 60 years of age

The effectiveness of an esophagomyotomy for dysphagia in elderly patients with achalasia has been questioned. This study was designed to provide an answer. A total of 162 consecutive patients with achalasia who had a laparoscopic myotomy and Dor fundoplication and who were available for follow-up interview were divided by age: &lt;60 years (range, 14–59; 118 patients), and ≥60 years (range, 60–93; 44 patients). Primary outcome measures were severity of dysphagia, regurgitation, heartburn, and chest pain before and after the operation as assessed on a four-point Likert scale, and the need for postoperative dilatation or revisional surgery. Follow-up averaged 64 months. Older patients had less dysphagia (mean score 3.6 vs. 3.9; P &lt; 0.01) and less chest pain (1.0 vs. 1.8; P &lt; 0.01). Regurgitation (3.0 vs. 3.2; P = not significant (NS)) and heartburn (1.6 vs. 2.0, P = NS) were similar. Older patients were no different in degree of esophageal dilation, manometric findings, number of previous pneumatic dilatations, or previous botulinum toxin therapy. None of the older patients had previously had an esophagomyotomy, whereas 14% of younger patients had (P &lt; 0.01). After laparoscopic myotomy, older patients had better relief of dysphagia (mean score 1.0 vs 1.6; P &lt; 0.01), less heartburn (0.8 vs. 1.1; P = 0.03), and less chest pain (0.2 vs. 0.8, P &lt; 0.01). Complication rates were similar. Older patients did not require more postoperative dilatations (22 patients vs. 10 patients; P = 0.7) or revisional surgery for recurrent or persistent symptoms (3 vs. 1 patients; P = 0.6). Satisfaction scores did not differ, and more than 90% of patients in both groups said in retrospect they would have undergone the procedure if they had known beforehand how it would turn out. This retrospective review with long follow-up supports laparoscopic esophagomyotomy as first-line therapy in older patients with achalasia. They appeared to benefit even more than younger patients

Analytic validity of DecisionDx-Melanoma, a gene expression profile test for determining metastatic risk in melanoma patients

Abstract Background The DecisionDx-Melanoma test provides prognostic information for patients with cutaneous melanoma (CM). Using formalin-fixed paraffin-embedded primary tumor tissue, the RT-PCR-based test classifies patients into a low- (Class 1) or high-risk (Class 2) category for recurrence based on expression of 31 genes. The current study was designed to assess the analytical validity of this test. Methods Inter-assay, inter-instrument, and inter-operator studies were performed to evaluate reliability of the 31-gene expression test results, sample stability and reagent stability. From March 2013 through June 2016, the gene expression test was performed on 8244 CM tumors. De-identified data from Pathology Reports were used to assess technical success. Results Robust sample and reagent stability was observed. Inter-assay concordance on 168 specimens run on 2 consecutive days was 99% and matched probability scores were significantly correlated (R2 = 0.96). Inter-instrument concordance was 95%, and probability scores had a correlation R2 of 0.99 (p < 0.001). From 8244 CM specimens submitted since 2013, 85% (7023) fulfilled pre-specified tumor content parameters. In these samples with sufficient tumor requirements, the technical success of the test was 98%. Conclusion DecisionDx-Melanoma is a robust gene expression profile test that demonstrates strong reproducibility between experiments and has high technical reliability on clinical samples

Gene expression profiling in uveal melanoma: technical reliability and correlation of molecular class with pathologic characteristics

Abstract Background A 15-gene expression profile test has been clinically validated and is widely utilized in newly diagnosed uveal melanoma (UM) patients to assess metastatic potential of the tumor. As most patients are treated with eye-sparing radiotherapy, there is limited tumor tissue available for testing, and technical reliability and success of prognostic testing are critical. This study assessed the analytical performance of the 15-gene expression test for UM and the correlation of molecular class with pathologic characteristics. Methods Inter-assay, intra-assay, inter-instrument/operator, and inter-site experiments were conducted, and concordance of the 15-gene expression profile test results and associated discriminant scores for matched tumor samples were evaluated. Technical success was determined from de-identified clinical reports from January 2010 - May 2016. Pathologic characteristics of enucleated tumors were correlated with molecular class results. Results Inter-assay concordance on 16 samples run on 3 consecutive days was 100%, and matched discriminant scores were strongly correlated (R2 = 0.9944). Inter-assay concordance of 46 samples assayed within a one year period was 100%, with an R2 value of 0.9747 for the discriminant scores. Intra-assay concordance of 12 samples run concurrently in duplicates was 100%; discriminant score correlation yielded an R2 of 0.9934. Concordance between two sites assessing the same tumors was 100% with an R2 of 0.9818 between discriminant scores. Inter-operator/instrument concordance was 96% for Class 1/2 calls and 90% for Class 1A/1B calls, and the discriminant scores had a correlation R2 of 0.9636. Technical success was 96.3% on 5516 samples tested since 2010. Increased largest basal diameter and thickness were significantly associated with Class 1B and Class 2 vs. Class 1A signatures. Conclusions These results show that the 15-gene expression profile test for UM has robust, reproducible performance characteristics. The technical success rate during clinical testing remains as high as first reported during validation. As molecular testing becomes more prevalent for supporting precision medicine efforts, high technical success and reliability are key characteristics when testing such limited and precious samples. The performance of the 15-gene expression profile test in this study should provide confidence to physicians who use the test’s molecular classification to inform patient management decisions