Environmental effects of ozone depletion, UV radiation and interactions with climate change : UNEP Environmental Effects Assessment Panel, update 2017

Peer reviewe

Atypical teratoid rhabdoid tumors: a population-based clinical outcomes study involving 174 patients from the Surveillance, Epidemiology, and End Results database (1973–2010)

Christine SM Lau,1,2 Krishnaraj Mahendraraj,1 Ronald S Chamberlain1–31Department of Surgery, Saint Barnabas Medical Center, Livingston, NJ, USA; 2Saint George's University School of Medicine, Grenada, West Indies; 3Department of Surgery, New Jersey Medical School, Rutgers University, Newark, NJ, USA Introduction: Atypical teratoid rhabdoid tumors (ATRTs) are rare, highly malignant embryonal tumors of the central nervous system (CNS) accounting for 20% of CNS tumors in children under the age of 3. This study examines a large cohort of ATRT patients to determine demographic, clinical, and pathologic factors which impact prognosis and survival. Methods: Demographic and clinical data were abstracted on 174 ATRT patients (171 pediatric patients age <20 and 3 adult patients age ≥20) from the Surveillance, Epidemiology, and End Results database (1973–2010). Standard statistical methodology was used. Results: A total of 174 ATRT cases (mean age of 2.84 years) were identified. ATRT had a higher incidence in males (56.3%), Caucasians (59.1%), and children <3 years of age (80.5%), P<0.001. The most common primary sites were the cerebellum (17.8%), ventricles (16.1%), and frontal lobe (12.6%). Mean overall survival was 3.2±0.4 years, while overall and cancer-specific mortality were 63.2% and 56.3%, respectively, P=0.005. Most ATRT cases were treated with surgery alone (58.0%), followed by a combination of surgery and radiation (34.3%), no treatment (6.5%), and radiation alone (1.2%). The use of combination therapy has increased significantly (16.1%) since 2005 (P<0.001), while primary surgical resection and radiation therapy rates remain relatively unchanged. The longest survival was observed among ATRT patients receiving combination therapy (5.9±0.7 years), followed by radiation alone (2.8±1.2 years), and surgery alone (1.9±0.4 years), P<0.001. Multivariable analysis identified only distant metastases (OR =4.6) as independently associated with increased mortality, whereas combination therapy (OR =0.4) was associated with reduced mortality, P<0.005. Conclusion: ATRT is a rare and highly aggressive embryonal malignancy of the CNS that presents more often as locoregional tumors >4 cm in male Caucasian children of age <3 years, involving the cerebellum, ventricles, or frontal lobe. Combination therapy significantly improves survival, and its use has been increasing since 2005. Keywords: childhood brain cancer, pediatric cancer, central nervous system, rare tumors, SEER databas

Trends in incidence, survival, and management of uveal melanoma: a population-based study of 7,516 patients from the Surveillance, Epidemiology, and End Results database (1973–2012)

Krishnaraj Mahendraraj,1 Christine SM Lau,1,2 Injoon Lee,2 Ronald S Chamberlain1–3 1Department of Surgery, Saint Barnabas Medical Center, Livingston, NJ, USA; 2St George’s University School of Medicine, Grenada, West Indies; 3Department of Surgery, New Jersey Medical School, Rutgers University, Newark, NJ, USA Introduction: Uveal melanoma (UM) is the most common primary intraocular malignancy, despite comprising <5% of all melanomas. To date, relatively few case series of UM have been published. Moreover, the factors influencing survival remain largely unknown. This study sought to analyze the impact of demographics, histology, clinical presentation, and treatments on the clinical outcomes of UM in a large modern nationwide patient cohort.Methods: Demographics and clinical data were abstracted on 277,120 histologically confirmed melanoma patients from the Surveillance, Epidemiology, and End Results database between 1973 and 2012.Results: A total of 7,516 cases of UM represented 3.2% of all recorded cases of melanoma. The mean age-adjusted incidence was 5.1 per million (95% CI 4.2–6.1) and was higher in males (5.9, CI =4.4–7.6) compared to females (4.5, CI =3.3–5.8), P<0.001. UM occurred most commonly in the sixth decade of life (61.4±15) and among Caucasians (94.7%). A total of 52.3% of cases were reported in the Western US (35.7% in California). The initial diagnoses in 65.2% of cases were by histopathology, followed by clinical diagnosis (18.8%) and radiographic imaging (16.0%). The percentage of UM cases managed by surgery alone decreased by 69.4% between the 1973–1977 and 2006–2012 time periods, concomitant with a 62% increase in primary radiotherapy, P<0.001. The UM mean overall and cancer-specific 5-year relative survival rates were 79.8%±5.8% and 76%±5.3%, respectively. The mean 5-year cancer-specific survival rate (76%) remained stable during the study period between 1973 and 2012. The mean survival for patients treated with primary radiotherapy was significantly improved compared to those treated with surgery alone (15.4±0.4 vs 13.6±0.3, P<0.001). Multivariate analysis identified male sex (odds ratio [OR] 1.1, CI =1.0–1.3), age >50 years (OR 4.0, CI =3.4–4.6), distant metastases (OR 8.6, CI =4.7–15), and primary surgical treatment (OR 2.6, CI =2.0–3.3) as independently associated with increased mortality, P<0.005. Conversely, patients identified as Hispanic (OR 0.6, CI =0.5–0.8) and patients receiving radiation treatment (OR 0.5, CI =0.4–0.7) were independently associated with reduced mortality, P<0.005.Conclusion: UM remains a rare form of melanoma that occurs primarily in Caucasian patients older than 50 years. More than two-thirds of UM patients are curatively treated with primary radiotherapy as opposed to surgery, which has resulted in a significant improvement in both overall survival and cancer-specific survival. Despite this shift in management strategy, the mean 5-year cancer-specific survival rate remained relatively unchanged during the study period. Male sex, older age, distant disease, and primary surgical therapy rather than radiotherapy are associated with an increased risk of mortality. Keywords: uveal melanoma, ocular melanoma, SEER&nbsp

Ocular melanoma-when you have seen one, you have not seen them all: a clinical outcome study from the Surveillance, Epidemiology and End Results (SEER) database (1973–2012)

Krishnaraj Mahendraraj,1 Sneha Shrestha,1 Christine SM Lau,1,2 Ronald S Chamberlain1–4 1Department of Surgery, Saint Barnabas Medical Center, Livingston, NJ, USA; 2Saint George’s University School of Medicine, Grenada, West Indies; 3Department of Surgery, Banner MD Anderson Cancer Center, Gilbert, AZ, USA; 4Department of Surgery, Rutgers University, New Jersey Medical School, Newark, NJ, USA Background: Ocular melanoma (OM) comprises <5% of all melanomas. Uveal melanoma (UM) is the most common subtype of OM, while conjunctival melanoma (CM) is rare and differs significantly from UM. The purpose of this study is to evaluate a large cohort of OM patients to differentiate demographic, pathologic, and clinical factors between these two neoplasms, which may affect treatment and outcomes. Methods: The Surveillance, Epidemiology, and End Results database (1973–2012) was used to extract demographic and clinical data on 8,165 OM patients (92.1% UM and 7.9% CM). Results: Both CM and UM were most prevalent among Caucasian males in the seventh decade of life. UM patients presented more often with localized disease (90.9% vs 81.2, P<0.01). Surgery (42.8%), radiation (43.0%), or combined surgery and radiation (7.0%) were used in the treatment of UM, while CM was treated almost exclusively with surgery (88.7%). Mean overall survival was longer (15.4 vs 14.6 years; P<0.01) and mortality rates were lower in patients (38.8% vs 46.1%; P<0.01) with CM. Conclusion: Despite presenting with more advanced disease than UM, CM is associated with an increased overall survival. Surgery is the primary therapy for CM, whereas radiotherapy is the primary therapy for UM and is associated with prolonged survival. Keywords: ocular melanoma, uveal melanoma, conjunctival melanoma, SEE

Determining 30-day readmission risk for heart failure patients: the Readmission After Heart Failure scale

Ronald S Chamberlain,1–5 Jaswinder Sond,1 Krishnaraj Mahendraraj,1 Christine SM Lau,1,3 Brianna L Siracuse1 1Department of Surgery, Saint Barnabas Medical Center, Livingston, 2Department of Surgery, Rutgers New Jersey Medical School, Rutgers University, Newark, NJ, USA; 3St. George’s University School of Medicine, Grenada, West Indies; 4Department of Surgery, Banner MD Anderson Cancer Center, Gilbert, AZ, USA; 5Department of Surgery, Valley Cancer Surgical Specialists, Phoenix, AZ, USA Background: Chronic heart failure (CHF), which affects >5 million Americans, accounts for >1 million hospitalizations annually. As a part of the Hospital Readmission Reduction Program, the Affordable Care Act requires that the Centers for Medicare and Medicaid Services reduce payments to hospitals with excess readmissions. This study sought to develop a scale that reliably predicts readmission rates among patients with CHF. Methods: The State Inpatient Database (2006–2011) was utilized, and discharge data including demographic and clinical characteristics on 642,448 patients with CHF from California and New York (derivation cohort) and 365,359 patients with CHF from Florida and Washington (validation cohort) were extracted. The Readmission After Heart Failure (RAHF) scale was developed to predict readmission risk.Results: The 30-day readmission rates were 9.42 and 9.17% (derivation and validation cohorts, respectively). Age <65 years, male gender, first income quartile, African American race, race other than African American or Caucasian, Medicare, Medicaid, self-pay/no insurance, drug abuse, renal failure, chronic pulmonary disorder, diabetes, depression, and fluid and electrolyte disorder were associated with higher readmission risk after hospitalization for CHF. The RAHF scale was created and explained the 95% of readmission variability within the validation cohort. The RAHF scale was then used to define the following three levels of risk for readmission: low (RAHF score <12; 7.58% readmission rate), moderate (RAHF score 12–15; 9.78% readmission rate), and high (RAHF score >15; 12.04% readmission rate). The relative risk of readmission was 1.67 for the high-risk group compared with the low-risk group. Conclusion: The RAHF scale reliably predicts a patient’s 30-day CHF readmission risk based on demographic and clinical factors present upon initial admission. By risk-stratifying patients, using models such as the RAHF scale, strategies tailored to each patient can be implemented to improve patient outcomes and reduce health care costs. Keywords: heart failure, readmission, risk factors, risk assessment, RAHF scale, hospital readmission reduction program, HRRP, SID databas

Protocol for a multicenter, randomised controlled trial of surgeon-directed home therapy vs. outpatient rehabilitation by physical therapists for reverse total shoulder arthroplasty: the SHORT trial

Abstract Background Reverse total shoulder arthroplasty (RTSA) has emerged as a successful surgery with expanding indications. Outcomes may be influenced by post-operative rehabilitation; however, there is a dearth of research regarding optimal rehabilitation strategy following RTSA. The primary purpose of this study is to compare patient reported and clinical outcomes after RTSA in two groups: in one group rehabilitation is directed by formal, outpatient clinic-based physical therapists (PT group) as compared to a home therapy group, in which patients are instructed in their rehabilitative exercises by surgeons at post-operative appointments (HT group). Secondary aims include comparisons of complications, cost of care and quality of life between the two groups. Methods This randomised controlled trial has commenced at seven sites across the United States. Data is being collected on 200 subjects by clinical research assistants pre-operatively and post-operatively at 2, 6, and 12 weeks, 6 months, 1 and 2 year visits. The following variables are being assessed: American Shoulder and Elbow Surgeons (ASES), pain level using the numeric pain scale, the Single Assessment Numeric Evaluation (SANE) score, and shoulder active and passive range of motion for analysis of the primary aim. Chi square and t-tests will be used to measure differences in baseline characteristics of both groups. Repeated measures linear mixed effects modeling for measurement of differences will be used for outcomes associated with ASES and SANE and scores, and range of motion measures. Secondary aims will be analyzed for comparison of complications, cost, and quality of life assessment scores using data obtained from the PROMIS 29 v. 2, questionnaires administered at standard of care post-operative visits, and the electronic health record. Subjects will be allowed to crossover between the PT and HT groups, and analysis will include both intention-to-treat including patients who crossed over, and a second with cross-over patients removed, truncated to the time they crossed over. Discussion RTSA is being performed with increasing frequency, and the optimal rehabilitation strategy is unclear. This study will help clarify the role of formal physical therapy with particular consideration to outcomes, cost, and complications. In addition, this study will evaluate a proposed rehabilitation strategy. Trial registration This study is registered as NCT03719859 at ClincialTrials.gov