Impact of social deprivation on the outcome of major head and neck cancer surgery in England: A national analysis.

BACKGROUND: Socioeconomic status plays an important role in the incidence and prognosis of many cancers. We examined the relationship between social deprivation and clinical outcomes in patients undergoing major surgery for head and neck cancer. METHODS: A retrospective population-based observational study was performed. Patients undergoing head and neck surgical procedures in England between 2002 and 2012 were identified. This totaled 5051 patients in the less socially deprived (LSD) and 7282 in the more socially deprived (MSD) group. RESULTS: MSD patients were younger (61 vs 63) and were more likely to present with hypopharyngeal-laryngeal cancers (41% vs 30%). They had higher burdens of morbidity and more frequently required emergency surgery (odds ratio [OR] 1.74 [95% CI 1.52-1.99]). Following surgery, MSD patients had higher lengths of inpatient stay (OR 1.72 [95% CI 1.57-1.88]) and higher proportions of both inpatient (OR 1.47 [95% CI 1.19-1.82]) and overall mortality (OR 1.34 [95% CI 1.24-1.45]). CONCLUSION: Increasing socioeconomic deprivation is associated with poor health outcomes in patients with head and neck cancer.

Evaluation of hospital outcomes: the relation between length-of-stay, readmission, and mortality in a large international administrative database.

BACKGROUND: Hospital mortality, readmission and length of stay (LOS) are commonly used measures for quality of care. We aimed to disentangle the correlations between these interrelated measures and propose a new way of combining them to evaluate the quality of hospital care. METHODS: We analyzed administrative data from the Global Comparators Project from 26 hospitals on patients discharged between 2007 and 2012. We correlated standardized and risk-adjusted hospital outcomes on mortality, readmission and long LOS. We constructed a composite measure with 5 levels, based on literature review and expert advice, from survival without readmission and normal LOS (best) to mortality (worst outcome). This composite measure was analyzed using ordinal regression, to obtain a standardized outcome measure to compare hospitals. RESULTS: Overall, we observed a 3.1% mortality rate, 7.8% readmission rate (in survivors) and 20.8% long LOS rate among 4,327,105 admissions. Mortality and LOS were correlated at the patient and the hospital level. A patient in the upper quartile LOS had higher odds of mortality (odds ratio = 1.45, 95% confidence interval 1.43-1.47) than those in the lowest quartile. Hospitals with a high standardized mortality had higher proportions of long LOS (r = 0.79, p < 0.01). Readmission rates did not correlate with either mortality or long LOS rates. The interquartile range of the standardized ordinal composite outcome was 74-117. The composite outcome had similar or better reliability in ranking hospitals than individual outcomes. CONCLUSIONS: Correlations between different outcome measures are complex and differ between hospital- and patient-level. The proposed composite measure combines three outcomes in an ordinal fashion for a more comprehensive and reliable view of hospital performance than its component indicators.

Nontraumatic Testicular Pain due to Sacroiliac-Joint Dysfunction: A Case Report.

OBJECTIVE: To discuss the case of a 49-year-old man who presented to the sports medicine staff with pelvic pain of 10 years' duration consistent with pudendal neuralgia. BACKGROUND: Testicular pain in men is often provoked by direct trauma or may indicate an oncologic process. DIFFERENTIAL DIAGNOSIS: Epididymitis, athletic pubalgia, testicular tumor, sacroiliac joint dysfunction, lumbar radiculopathy. TREATMENT: The patient responded positively to treatment and rehabilitation to restore normal mechanics to the lumbo-pelvic-hip complex. Several flare-ups since the initial treatment have been of short duration (<2 days) and less intense. UNIQUENESS: Pudendal neuralgia tends to affect females more than males due to changes in the alignment and stability of the pelvis from a combination of a shorter, wider pelvis and muscle imbalances associated with childbirth. Typically, males with testicular pain suffer from epididymitis or some type of testicular torsion, which was not the situation in this case. Compression is also a common cause of pudendal neuralgia, although it was not responsible for this patient's pain, making diagnosis and treatment complex. CONCLUSIONS: Many pain syndromes can be treated with removal of the original stimulus. However, recognizing the factors contributing to pelvic pain and dysfunction in males can be a challenge for the sports medicine professional. A vigilant and unassuming approach to male pelvic pain is warranted, particularly by health care providers in diverse practice settings.

Results of the Phase I Trial of RG7112, a Small-Molecule MDM2 Antagonist in Leukemia.

PURPOSE: RG7112 is a small-molecule MDM2 antagonist. MDM2 is a negative regulator of the tumor suppressor p53 and frequently overexpressed in leukemias. Thus, a phase I study of RG7112 in patients with hematologic malignancies was conducted. EXPERIMENTAL DESIGN: Primary study objectives included determination of the dose and safety profile of RG7112. Secondary objectives included evaluation of pharmacokinetics; pharmacodynamics, such as TP53-mutation status and MDM2 expression; and preliminary clinical activity. Patients were divided into two cohorts: Stratum A [relapsed/refractory acute myeloid leukemia (AML; except acute promyelocytic leukemia), acute lymphoblastic leukemia, and chronic myelogenous leukemia] and Stratum B (relapsed/refractory chronic lymphocytic leukemia/small cell lymphocytic leukemia; CLL/sCLL). Some Stratum A patients were treated at the MTD to assess clinical activity. RESULTS: RG7112 was administered to 116 patients (96 patients in Stratum A and 20 patients in Stratum B). All patients experienced at least 1 adverse event, and 3 dose-limiting toxicities were reported. Pharmacokinetic analysis indicated that twice-daily dosing enhanced daily exposure. Antileukemia activity was observed in the 30 patients with AML assessed at the MTD, including 5 patients who met International Working Group (IWG) criteria for response. Exploratory analysis revealed TP53 mutations in 14% of Stratum A patients and in 40% of Stratum B patients. Two patients with TP53 mutations exhibited clinical activity. p53 target genes were induced only in TP53 wild-type leukemic cells. Baseline expression levels of MDM2 correlated positively with clinical response. CONCLUSIONS: RG7112 demonstrated clinical activity against relapsed/refractory AML and CLL/sCLL. MDM2 inhibition resulted in p53 stabilization and transcriptional activation of p53-target genes. We provide proof-of-concept that MDM2 inhibition restores p53 function and generates clinical responses in hematologic malignancies.

An estimation of the population incidence of adult unilateral vocal fold mobility impairment in England.

We estimate the population incidence of adult unilateral vocal fold mobility impairment at 5.13 per 100,000 per year.

Management and prognosis of primary tracheal cancer: a national analysis.

OBJECTIVES/HYPOTHESIS: To perform a national review of the incidence and treatment of primary tracheal cancer and to identify gaps in service provision and factors associated with survival. STUDY DESIGN: Retrospective analysis of Hospital Episode Statistics data for England between 1996 and 2011. METHODS: Information about age, sex, morbidity, provider trust, diagnostic delay, nature of hospital admission and treatment, and palliation-free survival were recorded. The relationship between variables and survival was explored with Cox regression. RESULTS: There were 874 patients, giving an incidence of 0.9 per million. Mean age at diagnosis was 66 ± 13, and there were 456 (52%) males. Mean presentation to diagnosis latency was 2.5 ± 8 months, and 40% of patients presented as emergency admissions. There were 19 cases of oesophageal involvement and 241 cases of bronchopulmonary involvement; and 188 patients developed distant metastases. There were 60 curative resections (6.9%), which was the most significant predictor of palliation-free survival (hazard ratio: 0.23; 95% confidence interval 0.13-0.38). Other prognostic variables included age, sex, emergency admission, interventional bronchoscopy, chemotherapy, oesophageal involvement, and distant metastases. Ten-year palliation-free survival was 60.8% with curative resection and 19.5% overall. Eighty-six percent of patients were treated in units that treated fewer than one patient per year. CONCLUSION: Tracheal cancer is under-recognized and under-treated. Early diagnosis, access to interventional bronchoscopy, and surgical treatment in specialist units may improve the survival of patients with this condition.

Synthesis and evaluation of N-acyl sulfonamides as potential prodrugs of cyclin-dependent kinase inhibitor JNJ-7706621.

A novel prodrug strategy for cyclin-dependent kinase inhibitor JNJ-7706621 has been explored. Through N-acylation of a sulfonamide substituent, tails containing different solubilizing groups (amino, carboxyl, alkoxyl, and hydroxyl) were attached to JNJ-7706621. Most of the prodrugs exhibited good aqueous solubility and the N-acyl groups on the sulfonamide were metabolically cleaved to generate active drug in rat PK study.