Phase II Study of Sequential Gemcitabine Followed by Docetaxel for Recurrent Ewing Sarcoma, Osteosarcoma, or Unresectable or Locally Recurrent Chondrosarcoma: Results of Sarcoma Alliance for Research Through Collaboration Study 003

Background Gemcitabine and docetaxel have a broad spectrum of clinical activity in patients with carcinoma. The Sarcoma Alliance for Research Through Collaboration conducted a phase II trial of gemcitabine in combination with docetaxel in children and adults with recurrent Ewing sarcoma (EWS), osteosarcoma (OS), or unresectable or recurrent chondrosarcoma. The primary objective was to determine the objective response rate using Response Evaluation Criteria in Solid Tumors (RECIST). Methods Gemcitabine (675 mg/m(2) i.v. over 90 minutes on days 1 and 8) was administered in combination with docetaxel (75 mg/m(2) i.v. over 1 hour on day 8) every 21 days. All patients received filgrastim or pegfilgrastim. A Bayesian formulation was used to determine the probability of achieving the target response rate in each subtype - 0.35 for EWS and OS or 0.20 for chondrosarcoma. If the probability of achieving the target response rate was <0.05, the combination was considered inactive. Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Results Fifty-three eligible subjects were enrolled into three subtypes, OS (n=14), EWS (n=14), and chondrosarcoma (n=25). Toxicities included neutropenia, thrombocytopenia, fatigue, dyspnea, bronchospasm, edema, neuropathy, and liver function abnormalities. Dose modification for toxicity was required for eight patients during cycle 1 and 16 patients in subsequent cycles. Seven patients withdrew from therapy due to toxicity. No complete responses were observed. Partial responses included OS (n=1), EWS (n=2), and chondrosarcoma (n=2). Conclusions Gemcitabine in combination with docetaxel was associated with the probability of reaching the target 35% response rate <5% in OS and 5.6% in EWS; the probability of reaching a 20% response rate in chondrosarcoma was 14%. Discussion. The Bayesian formulation permitted estimation of the probability of achieving the target response rate for each subtype after each response evaluation. By allowing multiple looks at the data, this design stopped the trial after considering the probability of achieving the target response rate and accrual rate. Because this design did not specify a rule for declaring the treatment as "active," a direct comparison with a standard two-stage phase II design is not appropriate. The decision to close the EWS and chondrosarcoma subtype arms was based, in part, on slow accrual and was supported by the low probability of achieving the target response rate. The rate of enrollment, rather than the statistical design, had a significant effect on the trial duration.     

Proposed clinical classification for oral submucous fibrosis

Oral Submucous Fibrosis (OSMF) is a chronic, progressive, scarring disease, that predominantly affects people of South Asia and South-East Asia, where chewing of arecanut and its commercial preparation is high. Presence of fibrous bands is the main characteristic feature of OSMF. Based on clinical and/or histopathological features of OSMF, various classifications have been put forth till date. But the advantages and drawbacks of these classification supersedes each other, leading to perplexity. Our various studies and clinical experience in the field of OSMF have initiated us to propose/introduce the new clinical classification which could assist the clinician in the categorization of this potentially malignant disorder according to its biological behaviour and hence its subsequent medical and surgical management.     

Challenges and opportunities in conducting research with older adults with dementia during COVID-19 and beyond

The coronavirus disease 19 (COVID-19) pandemic has created significant and new challenges for the conduct of clinical research involving older adults with Alzheimer's disease and related dementias (ADRD). It has also stimulated positive adaptations in methods for engaging older adults with ADRD in research, particularly through the increased availability of virtual platforms. In this paper, we describe how we adapted standard in-person participant recruitment and qualitative data collection methods for virtual use in a study of decision-making experiences in older adults with ADRD. We describe key considerations for the use of technology and virtual platforms and discuss our experience with using recommended strategies to recruit a diverse sample of older adults. We highlight the need for research funding that supports the community-based organizations on which improving equity in ADRD research participation often depends.     

The Sphenopalatine Ganglion: Anatomy,Pathophysiology, and Therapeutic Targeting in Headache

The sphenopalatine ganglion (SPG) has attracted the interest of practitioners treating head and face pain for over a century because of its anatomical connections and role in the trigemino‐autonomic reflex. In this review, we discuss the anatomy of the SPG, as well as what is known about its role in the pathophysiology of headache disorders, including cluster headache and migraine. We then address various therapies that target the SPG, including intranasal medication delivery, new SPG blocking catheter devices, neurostimulation, chemical neurolysis, and ablation procedures.     

Management of gallstone pancreatitis: cholecystectomy or ERCP and endoscopic sphincterotomy

BACKGROUND: Currently, cholecystectomy is recommended for patients with gallstone-induced pancreatitis. ERCP with endoscopic sphincterotomy (ES) within 24 to 48 hours is also suggested for the treatment of acute gallstone pancreatitis. The aim of this study was to determine outcome after cholecystectomy versus ES alone in patients with gallstone pancreatitis. METHODS: One hundred seventeen patients with gallstone pancreatitis were included in this prospective observational study. Inclusion criteria were typical abdominal pain; serum amylase level 3 times or greater than normal; and gallbladder stones and a dilated bile duct, with or without stones, by US, CT, or ERCP. RESULTS: Eighty-three patients (Group A) underwent cholecystectomy after initial evaluation including ERCP in 43 (53%) and ERCP with ES in 38 (47%). The remaining 34 (Group B) underwent successful ERCP with ES alone. Mean follow-up was 33 months for Group A and 34 months for Group B. Recurrent gallstone pancreatitis was noted in 2 patients (2.4%) in Group A (bile duct stone in 2, sludge and papillary stenosis in 1), and in 1 patient (2.9%) in Group B. Ten patients in Group B had follow-up US of the gallbladder that showed disappearance of stones in 3. During follow-up, there was no significant difference in the rates of biliary complications (Group A, 3.6% vs. Group B, 11.6%; p = 0.19) or serious complications (pancreatitis, cholecystitis, cholangitis) (Group A, 3.6% vs. Group B, 5.8%). Also, there was no significant difference in procedure-related complications. CONCLUSIONS: Recurrence of pancreatitis after ERCP with ES alone for gallstone pancreatitis is rare. In patients who have undergone ES alone, cholecystectomy should be considered only if there are overt manifestations of gallbladder disease (e.g., biliary pain, cholecystitis, cystic duct obstruction) and not for prevention of recurrent gallstone pancreatitis. Because treatment by ES alone may be associated with a higher risk of biliary complications during follow-up compared with cholecystectomy, these patients may require close surveillance.     

Stakeholder Engagement in Planning the Design of a National Needs Assessment for Cardiovascular Disease Prevention and Management in Nepal

BackgroundThere is growing support for stakeholder engagement in health research, but the actual impact of such engagement has not been well established.ObjectivesThis paper describes the stakeholder engagement process and evaluation during the planning of the national needs assessment for cardiovascular disease in Nepal.MethodsWe used personal and professional networks to identify relevant stakeholders within the 7Ps framework (Patients and the Public, Providers, Purchasers, Payers, Public Policy Makers and Policy Advocates, Product Makers and the Principal Investigators) to develop a plan for assessing cardiovascular health needs in Nepal. We consulted 40 stakeholders through 2 meetings in small groups and a workshop in a large group to develop the study methods, conceptual framework, and stakeholder engagement process. We interviewed 33 stakeholders to receive feedback on the stakeholder engagement process.ResultsWe engaged 80% of the targeted stakeholders through small group discussions and a workshop. Three of 5 recommendations from the small group discussion were aimed at improving the stakeholder engagement process and 2 were aimed to improve the research methods. Eleven of 27 recommendations from the workshop aimed to improve the research methods, 4 aimed to improve stakeholder engagement, and 2 helped to expand the scope of dissemination. Ten were irrelevant or could not be incorporated due to resource limitation. Most stakeholders noted that the workshop provided an open platform for a multisectoral group to colearn from one another and share ideas. Others highlighted that the discussion generated insights to enhance research by incorporating expertise and ideas from different perspectives. The major challenges discussed were about committing the time for engagement.ConclusionsThe stakeholder engagement process positively affected the design of our research. This study provides important insights for future researchers that aim to engage stakeholders in national-level assessment programs in the health care system in the context of Nepal.     

Meat and meat-mutagen intake, doneness preference and the risk of colorectal polyps: the Tennessee Colorectal Polyp Study

Although meat intake has been fairly consistently linked to the risk of colorectal cancer, only a few studies have evaluated meat intake by doneness level and the heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) produced by high temperature cooking of meat in relation to colorectal adenomatous and hyperplastic polyps. We evaluated these associations in a large colonoscopy-based case-control study. Included in this study were participants with adenomatous polyp only (n = 573), hyperplastic polyp only (n = 256), or both adenomatous and hyperplastic polyps (n = 199), and 1,544 polyp-free controls. In addition to information related to demographic and other lifestyle factors, meat intake by cooking method and doneness preference were obtained through telephone interviews. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals for the association between exposures and colorectal polyp risks. Presence of hyperplastic polyp was found to be positively associated with high consumption of total meat (p(trend) = 0.076) or red meat (p(trend) = 0.060), with an approximate 50-60% elevated risk observed in the highest vs. the lowest intake group. High intake of 2-amino-I-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,4,8-trimethylimidazo [4,5]quinoxaline (DiMeIQx) were associated with increased risk for hyperplastic polyp (p(trend) = 0.036 and 0.038, respectively). With a possible exception of the intake of total well-done meats (p(trend) = 0.055) or well-done red meats (p(trend) = 0.074) with the risk of large adenomas, no other positive association was found specifically for the risk of adenomas with any of the exposure variables aforementioned. This study provides additional support for a positive association of high intake of red meat with colorectal adenomas, and suggests that high intake of meats and meat carcinogens may also be associated with hyperplastic polyps.     

A study on the effect of phthalate esters and their metabolites on idiopathic infertile males

Phthalate plasticisers in medical, cosmetic and consumer products might pose serious health implications in humans including infertility. We sought to investigate the correlation, if any, between the phthalates and their metabolites and sperm quality parameters, and male infertility. Phthalate esters (15) and their metabolites (5) were estimated in the blood serum and urine samples from the age-matched 152 infertile and 75 fertile males using gas chromatography (GC) and high-performance liquid chromatography (HPLC). Finally, the data were analysed to correlate phthalate exposure and semen quality parameters in the infertility group. The estimated levels of DEHP, DBP, DIBP, BEHIP, BPBG, DPP, DIOP, DIHP, DMP, DINP, BIOP, DMOP and DICHP were significantly higher in the infertile males compared to the fertile males (p < .05 or p < .01). However, these were not found to be associated with the semen quality parameters (sperm count, motility and sperm morphology). Similarly, HPLC data revealed that the associations between semen parameters (sperm count, sperm motility and sperm morphology) and phthalate metabolite (MEHP and MBP) concentrations in urine samples from the infertile males were mostly unremarkable or statistically nonsignificant. Conclusively, environmental exposure to phthalates and their impacts on male infertility were statistically insignificant in our study groups.