Cape Cod Healthcare

M ore than 25% of the U.S. population aged 65 years has diabetes mellitus (hereafter referred to as diabetes), 1 and the aging of the overall population is a significant driver of the diabetes epidemic. Although the burden of diabetes is often described in terms of its impact on working-age adults, diabetes in older adults is linked to higher mortality, reduced functional status, and increased risk of institutionalization. 2 Older adults with diabetes are at substantial risk for both acute and chronic microvascular and cardiovascular complications of the disease.

Importance: Suicide is a leading cause of deaths in the United States. Although the emergency department (ED) is an opportune setting for initiating suicide prevention efforts, ED-initiated suicide prevention interventions remain underdeveloped. Objective: To determine whether an ED-initiated intervention reduces subsequent suicidal behavior. Design, Setting, and Participants: This multicenter study of 8 EDs in the United States enrolled adults with a recent suicide attempt or ideation and was composed of 3 sequential phases: (1) a treatment as usual (TAU) phase from August 2010 to December 2011, (2) a universal screening (screening) phase from September 2011 to December 2012, and (3) a universal screening plus intervention (intervention) phase from July 2012 to November 2013. Interventions: Screening consisted of universal suicide risk screening. The intervention phase consisted of universal screening plus an intervention, which included secondary suicide risk screening by the ED physician, discharge resources, and post-ED telephone calls focused on reducing suicide risk. Main Outcomes and Measures: The primary outcome was suicide attempts (nonfatal and fatal) over the 52-week follow-up period. The proportion and total number of attempts were analyzed. Results: A total of 1376 participants were recruited, including 769 females (55.9%) with a median (interquartile range) age of 37 (26-47) years. A total of 288 participants (20.9%) made at least 1 suicide attempt, and there were 548 total suicide attempts among participants. There were no significant differences in risk reduction between the TAU and screening phases (23% vs 22%, respectively). However, compared with the TAU phase, patients in the intervention phase showed a 5% absolute reduction in suicide attempt risk (23% vs 18%), with a relative risk reduction of 20%. Participants in the intervention phase had 30% fewer total suicide attempts than participants in the TAU phase. Negative binomial regression analysis indicated that the participants in the intervention phase had significantly fewer total suicide attempts than participants in the TAU phase (incidence rate ratio, 0.72; 95% CI, 0.52-1.00; P = .05) but no differences between the TAU and screening phases (incidence rate ratio, 1.00; 95% CI, 0.71-1.41; P = .99). Conclusions and Relevance: Among at-risk patients in the ED, a combination of brief interventions administered both during and after the ED visit decreased post-ED suicidal behavior.

OBJECTIVE: Binge eating disorder appears to be an important factor in obesity treatment. Researchers have proposed that specialized treatment programs be developed to address chronic binge eating behavior. This study was conducted to examine the relationships between binge eating, depression, body image, and self-efficacy. Based on related research, it was hypothesized that depression and negative body image would be greater for binge eaters whereas weight self-efficacy would be lower. RESEARCH METHODS AND PROCEDURES: Subjects were 159 clinic patients participating in a multidisciplinary weight management program. Baseline measurements of binge eating status, body image and related eating behaviors, depression, and self-efficacy were obtained, whereas follow-up measures consisted of weight loss and attendance. Exploratory factor analyses were performed to obtain factors for items contained in the Eating Habits Questionnaire. Chi-square, t-tests, and logistic regression analyses determined relationships between binge eating, body image, depression, and self-efficacy. RESULTS: Univariate comparisons indicated that increased perceptions of poor body image were significantly related to binge eating. Higher levels of depression and lower weight self-efficacy were related to binge eating, but the results were qualified after applying corrective statistics for multiple comparisons. A stepwise regression analysis indicated that body image, particularly characterized by a sense of shame and concern with public appearance, had the strongest relationship to binge eating among all the factors examined in this study. DISCUSSION: These findings extend current understanding of the relationships between binge eating, body image, depression, and self-efficacy. The significance of body image, especially in relation to negative social consciousness, was determined when comparing several psychological and behavioral factors thought to influence binge eating. Further research is needed to determine the causal relationships between binge eating and the other factors examined in this study.

PURPOSE: To provide a review of the literature regarding programs for mentoring new nurse practitioners (NPs) to accelerate their development as primary care providers. DATA SOURCES: A search was conducted in PubMed, Ovid, CINAHL, and Cochrane Database of Systematic Reviews. CONCLUSIONS: There is currently a critical shortage of primary care providers and an aging population requiring management of chronic medical conditions. Although NPs are trained in health promotion, disease prevention, and medical management and are well equipped to treat patients in primary care, the work can be overwhelming to the novice NP. A mentoring program could help the new NP further develop competencies and capabilities as a provider. However, there is a gap in the literature concerning any mentoring programs for novice NPs. Nonetheless, the literature review has provided a mentoring definition, program models, desired characteristics of nurse mentors, and barriers to mentoring programs. It has also described the benefits, goals and outcomes of a mentoring relationship. These insights from the literature provide a foundation for future mentoring program development. IMPLICATIONS FOR PRACTICE: A mentoring program for new NPs working in primary care could accelerate productivity, increase job satisfaction, and provide longevity in the primary care setting.

We examined 26 consecutive patients with subjective tinnitus. All subjects were treated with the tricyclic antidepressant trimipramine in a double-blind study, each subject acting as his own control. All subjects were evaluated with pure tone audiometry, site of lesion testing, and auditory brain stem evoked response. The tinnitus assessment consisted of frequency and intensity matching, the determination of masking levels, and a subjective evaluation of severity. Plasma levels of trimipramine were monitored at regular intervals, and the Zung and Millon inventories were administered at the beginning and end of each study period. Nineteen subjects completed the study. Within the trimipramine group, one reported complete disappearance of his tinnitus, eight reported improvement, three no change, and seven that tinnitus was worse. Within the placebo group, eight reported improvement, seven no change, and four that tinnitus was worse. The natural history of tinnitus is such that what has been observed may reflect the evolution of the disease itself, rather than the effect of treatment. We feel that while tricyclics may not have been shown to be effective, the placebo effect played a significant role in the results obtained.

BACKGROUND: Family caregivers contribute to engagement in treatment and adherence, reduced substance misuse and relapse, and increased well-being of recipients with substance use disorder. However, providing care has also been associated with negative emotional and physical health outcomes for caregivers. The purpose of this integrative review was to determine what instruments are used to measure caregiver burden in informal caregivers of individuals with substance use disorder. METHODS: An integrative review framework was applied to examine empirical and theoretical literature to answer the guiding research question, "How is caregiver burden measured in caregivers of individuals with substance use disorder?" PubMed, CINAHL, and APA PsychINFO were searched using a combination of search terms. The initial 1,198 articles were narrowed to 32 that fit the search criteria and purpose of the review. RESULTS: A variety of scales have been used to measure caregiver burden. Caregiver burden is operationalized as objective or subjective burden. Objective burden refers to changes in the home, finances, employment, social life, and leisure, whereas subjective burden refers to the emotional reaction of the caregiver in coping with providing care. Caregiver burden was most often reported as moderate to severe in populations with substance use disorder. Attributes measured included anxiety, depression, stress, worry, displeasure, care recipient behavioral problems and substance abuse, stigma, relationship strain, financial expenses, social support, family disruption, and the effect on caregiver physical and emotional health. CONCLUSIONS: Specific instruments that can accurately evaluate objective and subjective caregiver burden are needed to measure the quality of caregiver health. More research is necessary to better understand the physical and emotional health of caregivers of persons with substance use disorder and the factors that contribute to increased quality of life. Understanding the relationship between outcomes and protective factors could help nurses to develop prevention strategies and treatment interventions aimed at decreasing the psychosocial trauma and stress associated with caregiver burden.

Langerhans cell histiocytosis is most common in children and is unusual in the elderly. We describe 3 cases of langerhans cell histiocytosis limited to the skin in elderly patients. Biopsy specimens showed a dermal infiltrate abutting the epidermis composed of atypical langerhans cells with abundant eosinophilic cytoplasm and a "kidney-shaped" nucleus. Immunoperoxidase stain CD1a was positive in all 3 cases and S-100 stain was positive in 2. Electron microscopy revealed Birbeck granules in the cytoplasm of the atypical langerhans cells in 2 cases. Langerhans cell histiocytosis with skin involvement has a chronic course with an overall good prognosis. However, cutaneous manifestations may precede systemic involvement by many years.

BACKGROUND AND PURPOSE: In the coming decades, the world will face an increasing burden of neurological disorders (ND) and an urgent need to promote brain health. These challenges contrast with an insufficient neurological workforce in most countries, as well as decreasing numbers of general neurologists and neurologists attracted to work in general neurology (GN). This white paper aims to review the current situation of GN and reflect on its future. METHODS: The European Academy of Neurology (EAN) task force (TF) met nine times between November 2021 and June 2023. During the 2023 EAN annual meeting, attendees were asked to answer five questions concerning the future of GN. The document was sent for suggestions and eventually approval to the board and the presidents of the 47 national societies of the EAN. RESULTS: The TF first identified four relevant current and future challenges related to GN: (i) definition, (ii) practice, (iii) education, and (iv) research. The TF then identified seven initiatives to further develop GN at both the academic and community level. Finally, the TF formulated 16 recommendations to promote GN in the future. CONCLUSIONS: GN will remain essential in the coming decades to provide rapid, accessible, and comprehensive management of patients with ND that is affordable and cost-effective. There is also a need for research, education, and other initiatives aiming to facilitate improved working conditions, recognition, and prestige for those pursuing a career in GN.

PURPOSE Screening and prevention decisions for women at increased risk of developing breast cancer depend on genetic and clinical factors to estimate risk and select appropriate interventions. Integration of polygenic risk into clinical breast cancer risk estimators can improve discrimination. However, correlated genetic effects must be incorporated carefully to avoid overestimation of risk. MATERIALS AND METHODS A novel Fixed-Stratified method was developed that accounts for confounding when adding a new factor to an established risk model. A combined risk score (CRS) of an 86–single-nucleotide polymorphism polygenic risk score and the Tyrer-Cuzick v7.02 clinical risk estimator was generated with attenuation for confounding by family history. Calibration and discriminatory accuracy of the CRS were evaluated in two independent validation cohorts of women of European ancestry (N = 1,615 and N = 518). Discrimination for remaining lifetime risk was examined by age-adjusted logistic regression. Risk stratification with a 20% risk threshold was compared between CRS and Tyrer-Cuzick in an independent clinical cohort (N = 32,576). RESULTS Simulation studies confirmed that the Fixed-Stratified method produced accurate risk estimation across patients with different family history. In both validation studies, CRS and Tyrer-Cuzick were significantly associated with breast cancer. In an analysis with both CRS and Tyrer-Cuzick as predictors of breast cancer, CRS added significant discrimination independent of that captured by Tyrer-Cuzick ( P < 10 −11 in validation 1; P < 10 −7 in validation 2). In an independent cohort, 18% of women shifted breast cancer risk categories from their Tyrer-Cuzick–based risk compared with risk estimates by CRS. CONCLUSION Integrating clinical and polygenic factors into a risk model offers more effective risk stratification and supports a personalized genomic approach to breast cancer screening and prevention.

The professional use of social media is increasingly prevalent today, particularly in medicine and surgery. Several recent movements have highlighted the strengths of this forum for networking and mentorship for females in surgery who otherwise may lack mentors locally. We sought to describe modern uses for and strengths of social media for women in surgery globally via a systematic review of the literature. Multiple efforts and avenues have promoted gender equality in surgery, while also uniting female surgeons in a collaborative virtual network of colleagues. In particular, movements on Twitter, such as #ILookLikeASurgeon and #NYerORCoverChallenge, as well as other collaborative virtual fora have brought visibility to female surgeons, while drawing the young population of students and trainees toward surgical careers. Social media provides a unique opportunity for female trainees and established surgeons alike to network and establish mentorship relationships, which may aid in fostering interest in surgery and closing the gender gap in our field.

Background: This study investigated the sparing of the extracellular matrix (ECM) and blood vessels at the site of lung irreversible electroporation (IRE), and its impact on postablation T cell and macrophage populations. Materials and Methods: Normal swine ( n = 8) lung was treated with either IRE or microwave ablation (MWA), followed by sacrifice at 2 and 28 days (four animals/timepoint) after treatment. En bloc samples of ablated lung were stained for blood vessels (CD31), ECM proteins (Collagen, Heparan sulfate, and Decorin), T cells (CD3), and macrophages (Iba1). Stained slides were analyzed with an image processing software (ImageJ) to count the number of positive staining cells or the percentage area of tissue staining for ECM markers, and the statistical difference was evaluated with Student's t -test. Results: Approximately 50% of the blood vessels and collagen typically seen in healthy lung were evident in IRE treated samples at Day 2, with complete destruction within MWA treated lung. These levels increased threefold by Day 28, indicative of post-IRE tissue remodeling and regeneration. Decorin and Heparan sulfate levels were reduced, and it remained so through the duration of observation. Concurrently, numbers of CD3 + T cells and macrophages were not different from healthy lung at Day 2 after IRE, subsequently increasing by 2.5 and 1.5-fold by Day 28. Similar findings were restricted to the peripheral inflammatory rim of MWA samples, wherein the central necrotic regions remained acellular through Day 28. Conclusion: Acute preservation of blood vessels and major ECM components was observed in IRE treated lung at acute time points, and it was associated with the increased infiltration and presence of T cells and macrophages, features that were spatially restricted in MWA treated lung.

We report a specimen of Cardicola forsteri Cribb, Daintith, and Munday, 2000 (Digenea: Sanguinicolidae) from the lumen of the heart of a northern bluefin tuna, Thunnus thynnus (Linnaeus, 1758) (Scombridae), that was 218 cm in total length (TL) and caught in the northwest Atlantic Ocean 12 km south of Cape Lookout, North Carolina. The hearts of 12 similarly sized northern bluefin tuna (127–262 cm TL) from George's Bank, northwest Atlantic Ocean, were not infected. This is the first report of C. forsteri from a wild host and of a sanguinicolid from any scombrid in the northwest Atlantic Ocean. Bluefin tuna is cultured in sea cages because of its highly prized flesh, and the fact that a blood fluke infects this host is significant because some blood flukes have been identified as serious pathogens of cage-cultured fish.

BACKGROUND: Durotomy during endoscopic spine surgery can cause a patient's neurological or cardiovascular status to deteriorate unexpectedly intra- or postoperatively. There is currently limited literature regarding appropriate fluid management strategies, irrigation-related risk factors, and clinical consequences of incidental durotomy during spinal endoscopy, and no validated irrigation protocol exists for endoscopic spine surgery. Thus, the present article sought to (1) describe 3 cases of durotomy, (2) investigate standard epidural pressure measurements, and (3) survey endoscopic spine surgeons on the incidence of adverse effects believed to result from durotomy. MATERIALS AND METHODS: The authors first reviewed clinical outcomes and analyzed complications in 3 patients with intraoperatively recognized incidental durotomy. Second, the authors conducted a small case series with intraoperative epidural pressure measurements during gravity-assisted irrigated video endoscopy of the lumbar spine. Measurements were conducted on 12 patients with a transducer assembly that was introduced through the endoscopic working channel of the RIWOSpine Panoview Plus and Vertebris endoscope to the decompression site in the spine. Third, the authors conducted a retrospective, multiple-choice survey of endoscopic spine surgeons to better understand the frequency and seriousness of problems they attributed to irrigation fluid escaping from the surgical decompression site into the spinal canal and neural axis. Descriptive and correlative statistical analyses were performed on the surgeons' responses. RESULTS: In the first part of this study, durotomy-related complications during irrigated spinal endoscopy were observed in 3 patients. Postoperative head computed tomographic (CT) images revealed massive blood in the intracranial subarachnoid space, the basal cisterns, the III and IV ventricle, and the lateral ventricles characteristic of an arterial fisher grade IV subarachnoid hemorrhage, and hydrocephalus without evidence of aneurysms or angiomas. Two additional patients developed intraoperative seizures, cardiac arrhythmia, and hypotension. The head CT image in 1 of these 2 patients had intracranial air entrapment.In the second part, epidural pressure measurements in 12 patients who underwent uneventful routine lumbar interlaminar decompression for L4-L5 and L5-S1 disc herniation showed an average epidural pressure of 24.5 mm Hg.In the third part, the online survey was accessed by 766 spine surgeons worldwide and had a response rate of 43.6%. Irrigation-related problems were reported by 38% of responding surgeons. Only 11.8% used irrigation pumps, with 90% running the pump above 40 mm Hg. Headaches (4.5%) and neck pain (4.9%) were observed by nearly a 10th (9.4%) of surgeons. Seizures in combination with headaches, neck and abdominal pain, soft tissue edema, and nerve root injury were reported by another 5 surgeons. One surgeon reported a delirious patient. Another 14 surgeons thought that they had patients with neurological deficits ranging from nerve root injury to cauda equina syndrome related to irrigation fluid. Autonomic dysreflexia associated with hypertension was attributed by 19 of the 244 responding surgeons to the noxious stimulus of escaped irrigation fluid that migrated from the decompression site in the spinal canal. Two of these 19 surgeons reported 1 case associated with a recognized incidental durotomy and another with postoperative paralysis. CONCLUSIONS: Patients should be educated preoperatively about the risk of irrigated spinal endoscopy. Although rare, intracranial blood, hydrocephalus, headaches, neck pain, seizures, and more severe complications, including life-threatening autonomic dysreflexia with hypertension, may arise if irrigation fluid enters the spinal canal or the dural sac and migrates from the endoscopic site along the neural axis rostrally. Experienced endoscopic spine surgeons suspect a correlation between durotomy and irrigation-related extra- and intradural pressure equalization that could be problematic if associated with high volumes of irrigation fluid LEVEL OF EVIDENCE: 3.

Verbal and spatial tests of learning were administered in five repeated sessions to nine subjects who were in post-traumatic amnesia (PTA) following extremely severe closed head injuries. PTA was operationally defined as having a score of 75 or less on the Galveston Orientation and Amnesia Test. Subjects showed no ability to learn verbal information (free recall and recognition of a word list) but showed some savings of spatial location information over the first three sessions. Results were interpreted as suggestive of a primarily passive mode of learning during PTA, regardless of the nature of the material to be learned.

A retrospective descriptive study (n = 44) was conducted on the response styles of post-acute traumatic brain-injured patients on the MMPI. The sample profiles were examined on indices of consistency, random responding, and bias to look good or bad. The results showed that about 20% of the profiles were markedly inconsistent, including two profiles which met the criteria for random responding. Depending on the cut-off score used, between 0 and 9% were identified as biased to look bad, while between 18 and 30% were identified as biased to look good. A mean profile on the primary clinical and research scales was developed and a frequency count of the high two-point codes was conducted. This profile approached clinically significant levels on the Psychopathic deviant, Schizophrenia, Depression, and Mania scales, respectively. The three most frequently occurring two-point codes (2-4, 4-8, and 4-9) have been classified as characterological in nature. The primary implication of these results for clinicians was the need for careful scrutiny of indices of consistency, random responding and bias to look good when interpreting self-report measures such as the MMPI with the TBI population.

BACKGROUND: The prevalence of chronic disease and do-not-intubate status increases with age. Thus, we aimed to determine characteristics and outcomes associated with noninvasive ventilation (NIV) use for acute respiratory failure (ARF) in different age groups. METHODS: A database comprising prospective data collected on site on all adult patients with ARF requiring ventilatory support from 8 acute care hospitals in Massachusetts was used. RESULTS: From a total of 1,225 ventilator starts, overall NIV utilization, success, and in-hospital mortality rates were 22, 54, and 18% in younger (18-44 y); 34, 65, and 13% in middle-aged (45-64 y); 49, 68, and 17% in elderly (65-79 y); and 47, 76, and 24% in aged (≥ 80 y) groups, respectively (P < .001, P = .08, and P = .11, respectively). NIV use for cardiogenic pulmonary edema and subjects with a do-not-intubate order increased significantly with advancing age (25, 57, 57, and 74% and 7, 12, 18, and 31%, respectively, in the 4 age groups [P < .001 and P = .046, respectively]). For subjects receiving NIV with a do-not-intubate order, success and in-hospital mortality rates were similar in different age groups (P = .27 and P = .98, respectively). CONCLUSIONS: NIV use and a do-not-intubate status are more frequent in subjects with ARF ≥ 65 y than in those <65 y, especially for subjects with cardiogenic pulmonary edema. However, NIV success and mortality rates were similar between age groups. (ClinicalTrials.gov registration NCT00458926.).

Abstract Background: Multiple myeloma (MM) is primarily a disease of older adults with a median age at diagnosis of 66 years. Despite significant improvements in patient outcomes, there is a lag in survival in older transplant-ineligible patients compared to their younger counterparts. Traditionally, melphalan and prednisone-based regimens were the most widely accepted treatment options in this older, transplant-ineligible population. More recently, the FIRST trial has explored the use of lenalidomide and dexamethasone in these patients. Here, we sought to incorporate optimal novel agent-containing regimens in transplant-ineligible, older patients that balance efficacy with toxicity. Building on our prior experience with RVD in predominantly younger patients, our study evaluated a 3-drug regimen of modified RVD in the transplant-ineligible population. Methods: Modified RVD (“RVD-lite”) was administered over a 35-day cycle. Lenalidomide was given as a single daily oral dose of 15 mg days 1-21; bortezomib 1.3 mg/m2 once weekly subcutaneously on days 1, 8, 15, and 22; and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22 and 23 for patients ≤75 yrs and days 1, 8, 15, 22 for patients older than 75 yrs. Intravenous bortezomib was used only in cycle 1 for the first 10 patients for pharmacokinetic analysis. Eligibility requirements included ECOG performance status ≤ 2 and acceptable hepatic, renal and hematologic function. The primary objective was to evaluate the objective response rate (ORR) of modified RVD in transplant-ineligible patients. Secondary objectives included evaluation of the safety profile of modified RVD, progression free survival, overall survival, time to response, response duration, the response rate with respect to cytogenetics, and the pharmacokinetic profile of intravenous and subcutaneous bortezomib. Exploratory analysis will determine minimal residual disease (MRD) status by genotyping and correlate with outcomes in patients who achieve a VGPR or better. Results: Forty-one eligible patients have enrolled between 4/17/13 and 7/18/14, and of those 38 received at least one dose of therapy. Median age at study entry was 73 years (range 65-91) with 22 women and 16 men. ECOG performance status of patients enrolled was 0 in 19 (46.3%), 1 in 15 (36.6%), and 2 in 6 (14.6%) patients. The ISS stage was I in 15 (36.6%), II in 9 (22.0%), and III in 10 (24.4%) patients. Treatment-related toxicities were reported for 34 subjects. Fatigue was the most commonly reported toxicity occurring in 17/34 (50.0%), and of those 16/17 were grade 1 or 2 and manageable. Peripheral neuropathy of any grade was reported in 14/34 (41.2%) of patients including Grade 1 -7 (20.6%), 2 – 6 (17.6%), and 3 – 1 (2.9%). 12/34 (35.3%) reported edema of which 11/12 (91.7%) were grade 1. Grade 3 or greater toxicities included hypophosphatemia - 11 (32.3%), Rash - 4 (11.8%), and mood changes - 2 (5.9%). Pharmacokinetic data comparing intravenous and subcutaneous dosing of bortezomib has been completed and analysis is in process. At a planned interim analysis after 4 cycles that included 33 patients, the investigator-reported ORR of PR or better was 81.8% (CR -5, VGPR – 11, PR - 11, SD 3). Three patients withdrew from the study after less than 1 cycle. Of those, one withdrew for worsening adrenal insufficiency, one for rash attributed to lenalidomide, and one for an unrelated toxicity prompting withdrawal at the Investigator’s discretion. Five additional patients have enrolled but have not completed 4 cycles. Of those, responses thus far include 1 CR, 2 PRs, 1 SD, and 1 patient who has not completed one cycle at the time of this analysis. Exploratory data on bone marrow samples on patients achieving VGPR or better have been collected and analysis for MRD is in process. Conclusions: ModifiedRVD appears to be a well-tolerated and highly effective regimen in the transplant-ineligible population. The ORR rate after up to 4 cycles suggests that this combination at the modified doses and on a weekly schedule is very active. The side effect profile proved manageable and well-tolerated in an older population despite the variance of performance statuses at study entrance. Interim analysis of 38 patients suggests that alternative dosing and schedule of RVD may both improve tolerability and enhance clinical benefit in newly diagnosed, transplant-ineligible MM patients. Disclosures Laubach: Onyx, Novartis, Millenium, Celgene: Research Funding. Huff:Celgene, Millenium: Consultancy. Basile:Celgene: Speakers Bureau. Ghobrial:Millennium/Takeda: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Schlossman:Millennium: Consultancy. Munshi:Celgene, Onyx, Janssen, Sanofi-Aventi, Oncopep: Consultancy; Oncopep: Equity Ownership; Oncopep: Oncopep Patents &amp; Royalties. Richardson:Celgene, Millenium, Johnson&amp;Johnson: Membership on an entity's Board of Directors or advisory committees. Raje:Amgen, Novartis, Onyx, Celgene, Millenium: Consultancy; Eli Lilly, Acetylon: Research Funding.

Currently, hyperhomocysteinemia is a well-known risk factor for variety of vascular diseases. Prevalence of hyperhomocysteinemia increases with age. Hence, the present study was aimed to investigate the prevalence of hyperhomocysteinemia in healthy upper socio-economic class population in India. Total homocysteine (tHcy) concentration was determined in 1243 (906 men & 337 women) healthy Indian doctors with different age group. Using Third National Health and Nutrition Examination Survey (NHANES III) study criteria, the prevalence of hyperhomocysteinemia was 92.85% among men (>11.4 µmol/L) and 81.60% among women (>10.4 µmol/L). The prevalence of hyperhomocysteinemia was higher among men with mean tHcy concentration (21.96 ± 0.38 µmol/L) significantly higher (P<0.0001) than women (15.90 ± 0.39 µmol/L) (95% CI, 4.733- 7.376). Our study showed very high prevalence of hyperhomocysteinemia which may point to the future risk for various pathologies in the present subset of population. Further studies to look at the plasma levels of homocysteine lowering vitamins are warranted to prevent the future risk of vascular diseases.

Allergic rhinosinusitis has three forms of therapy: pharmacotherapy, immunotherapy, and surgical therapy. Pharmacotherapeutically, there are six classes of drugs that give symptomatic relief: mucolytics, decongestants, anti-cholinergic agents, antihistamines, mast cell stabilizers, and corticosteroids. All six classes are discussed individually and in detail. For immunotherapeutic therapy of allergic rhinosinusitis, there are four types of skin testing in current use: scratch testing, prick testing, single intradermal testing, and skin end point titration testing. Only the latter is able to quantitate the antigenicity of each antigen, and thus the treatment vial made from only this type of skin testing can adequately treat all antigens to which the patient is sensitive. These differences in testing and vial mixing are explained. The last form of therapy is surgical therapy, which corrects the obstructive phenomenon caused by allergic rhinosinusitis. The procedures described are reduction inferior turbinectomies and endoscopic sinus surgery. It is felt by the authors that the specialist who is uniquely positioned to offer a patient suffering from allergic rhinosinusitis all three forms of therapy is the rhinologist.

Abstract Background: Multiple myeloma (MM) is primarily a disease of older adults with median age at diagnosis of 66 years. Although melphalan and prednisone-based regimens were traditionally the most accepted treatment options, recent use of lenalidomide and dexamethasone in this older, transplant-ineligible population as presented in the FIRST trial is the new standard of care in these patients (pts) (NEJM 2014). Here, we sought a regimen that incorporates optimal novel agents in transplant-ineligible, older pts that balances efficacy with toxicity. Building on our promising prior experience with RVD in predominantly younger pts (Blood 2010), our study evaluated a 3-drug regimen of modified RVD in the transplant-ineligible population. Methods: Modified RVD ("RVD-lite") was administered over a 35-day cycle. Lenalidomide 15 mg was given on days 1-21; bortezomib 1.3 mg/m2 once weekly subcutaneously (SC) on days 1, 8, 15, and 22; and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22 and 23 for pts ≤75 yrs and days 1, 8, 15, 22 for pts older than 75 yrs. Intravenous (IV) bortezomib was used in cycle 1 for the first 10 pts for pharmacokinetic (PK) analysis. Eligibility requirements included ECOG performance status ≤ 2 and acceptable hepatic, renal and hematologic function. The primary objective was to evaluate the objective response rate (ORR) of modified RVD in transplant-ineligible pts. Secondary objectives included evaluation of the safety profile, progression free survival (PFS), overall survival, response rate with respect to cytogenetics, and the PK profile of IV and SC bortezomib. Exploratory analysis will determine minimal residual disease (MRD) status by deep sequencing and correlate with outcomes in patients who achieve a VGPR or better. Results: Fifty-three eligible pts have enrolled between 4/17/13 and 7/25/15, and of those, 50 received at least one dose of therapy. Median age at study entry was 72 years (range 65-91) with 29 women and 24 men. ECOG performance status of pts enrolled was 0 in 25 (47%), 1 in 20 (38%), and 2 in 8 (15 %) pts. The ISS stage was I in 21 (40%), II in 16 (30%), and III in 16 (30%) pts. Treatment-related toxicities were reported for 49 pts. Fatigue was the most commonly reported toxicity occurring in 31/49 (63%), and was mostly grade 1 or 2 and manageable (25/31). Peripheral neuropathy of any grade was reported in 21/49 (43%) pts including grade 1 (11, 22%), 2 (9, 18%), and 3 (1, 2%). Grade 3 or greater toxicities included hypophosphatemia in 15 (31%) and rash in 5 (10%) pts. PK data comparing IV and SC dosing showed no significant differences in plasma concentrations of bortezomib at 5 hours. In the SC route, high body mass index (BMI) patients tended to have low concentration at both the 5 and 30 minute measures but not at 5 hours. There was no correlation with BMI using the IV route. At the planned analysis after 4 cycles that now includes 40 pts, the investigator-reported ORR of PR or better was 90% (CR - 10, VGPR - 14, PR - 12, SD - 4). Five pts withdrew from the study after less than 4 cycles. Of those, one withdrew for worsening adrenal insufficiency, one for rash attributed to lenalidomide, one at the Investigator's discretion, and two for excessive travel distance. Five additional pts have been enrolled but have not completed 4 cycles. Of 48 evaluable patients, the median survival has not been reached. Median duration of follow-up is 17.2 months and the 1-year PFS is 95% (95% CI 0.888, 1) and 2-year PFS is 68% (95% CI 0.512, 0.908). Exploratory data on bone marrow samples on pts achieving VGPR or better have been collected and analysis for MRD is in process. Gene expression profiling was performed using MMprofiler (SkylineDx). High-risk signature will be correlated with pt outcomes. Conclusions: ModifiedRVD is a well-tolerated and highly effective regimen in the transplant-ineligible population. The ORR rate after 4 cycles suggests that this combination at modified doses and on a weekly schedule is very active. The side effect profile proved manageable and was well tolerated in an older population despite the variance of performance status at study entry. There were no significant differences in plasma concentrations of bortezomib observed between IV and SC dosing. The study is fully accrued and this analysis suggests that alternative dosing and schedule of RVD may both improve tolerability and enhance clinical benefit in newly diagnosed, transplant-ineligible MM pts. Disclosures O'Donnell: Millennium: Consultancy. Laubach:Novartis: Research Funding; Onyx: Research Funding; Celgene: Research Funding; Millennium: Research Funding. Schlossman:Millennium: Consultancy. Anderson:Millennium: Consultancy; BMS: Consultancy; Gilead: Consultancy; Oncopep: Equity Ownership; Acetylon: Equity Ownership; Celgene: Consultancy. Richardson:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Raje:AstraZeneca: Research Funding; Onyx: Consultancy; Millenium: Consultancy; Acetylon: Research Funding; Eli Lilly: Research Funding; Novartis: Consultancy; Celgene Corporation: Consultancy; Takeda: Consultancy; BMS: Consultancy; Amgen: Consultancy.