Sentinel Lymph Node Biopsy in Elderly Patients with Intermediate Thickness Melanoma: A Masters Thesis

Background: A landmark study suggested that wide excision of intermediate-thickness melanoma with sentinel lymph node biopsy (SLNB) and subsequent completion lymph node dissection (CLND) for regional disease may improve prognostication and disease-free survival (DFS) compared with those undergoing wide excision alone. However, these benefits were relatively small and not associated with an improvement in disease-specific survival (DSS). It remains unknown if SLNB and subsequent treatments are beneficial in elderly patients who have a decreased overall (OS) due to other causes. Methods: Adults ≥ 70 years of age, who underwent surgical intervention for intermediate-thickness cutaneous melanoma from 2000-2013 were identified from a prospectively-maintained database. Clinicopathologic variables measured included age, gender, anatomic site, histologic type, tumor thickness, ulceration, receipt and result of SLNB, completion of CLND, OS, and DFS. Results: Ninety-one patients underwent excision of an intermediate-thickness melanoma. Forty-nine patients (54%) received a SLNB. Seven of these biopsies (14%) were positive, and five patients went on to receive CLND. Five-year OS was 41% in patients who did not receive SLNB and 52% in patients who did receive SLNB (p=0.11). DFS was similar between groups independent of receipt of SLNB. Conclusion: Among elderly patients with intermediate-thickness melanoma, patients who received SLNB had similar 5-year OS and DFS compared with those who did not receive SLNB. Routine SLNB for intermediate-thickness melanoma patients may not significantly change outcomes for this age group, and clinical decision-making should consider individual patient comorbidities and goals of care

Wallarm

The nature of our project is essentially an upgraded alarm clock that ensures that the user will wake up at the time set. Figure 1 displays the hardware of the project and has colored circles to indicate different components. The alarm functions by initially sounding a loud buzzer (red) at the set alarm time. If the user decides to snooze the alarm by pressing the snooze button (purple), the alarm will wait for a given amount of time before setting off the buzzer again. It will then trigger a Servo motor (pink) that will flip a traditional toggle switch to turn the light on and then return to sounding the buzzer until the user turns off the alarm by pressing the off button (orange). This off button may be used at any time throughout the alarm. The time is displayed on a liquid crystal display screen. The brightness of the screen is adjusted automatically using a photoresistor (yellow). The photoresistor allows the screen to be brighter in a well-lit area and dims the screen in darker settings in order to conserve power. The user can use the numeric keypad to manually input the time in military time. The purpose of using military time is to avoid the complexities of differentiating between AM and PM. To set the alarm time, a switch (blue) is used to change to “set alarm” mode where the user can use the same numeric pad and instruction set to set the alarm

Reproductive strategies of the insidious fish ectoparasite, Neobenedenia sp. (Capsalidae: Monogenea)

Fish monogeneans are lethal parasites in aquaculture. We provide the first experimental evidence that a notorious fish monogenean, Neobenedenia sp., can produce viable eggs in isolation for three consecutive generations. We infected individual, isolated, farmed barramundi, Lates calcarifer (Bloch) with a single oncomiracidium (larva) of the hermaphroditic monogenean Neobenedenia sp. Isolated parasites reached sexual maturity at day 10 post-hatch (24°C, 35‰) and laid ~3,300 embryonated eggs over 17 days. Egg production rapidly increased following sexually maturity on day 10 (58±15 eggs) and peaked on day 15 (496±68 eggs) before gradually decreasing. Neobenedenia sp. exhibited egg laying and egg hatching rhythms. Parasites laid eggs continuously, but egg production increased in periods of darkness (64.3%), while the majority of oncomiracidia (81%) emerged from eggs in the first three hours of light. Eggs laid by isolated 'parent' parasites hatched and individual emerging oncomiracidia were used to infect more individual, isolated fish, with three consecutive, isolated, parasite generations (F1, F2 and F3) raised in the laboratory. Infection success and egg hatching success did not differ between generations. Our data show that one parasite, in the absence of a mate, presents a severe threat to captive fish populations

Efficacy of Intraoperative Recurrent Laryngeal Nerve Monitoring: A Single-Institutions’ Experience

Objective: To evaluate the efficacy of intraoperative nerve monitoring (IONM) during thyroidectomy in preventing recurrent laryngeal nerve (RLN) injury. Design: Retrospective cohort study. Setting: Academic institution. Patients: Consecutive sample of subjects undergoing thyroidectomy by experienced endocrine surgeons between 2006 and 2008 at a single institution. Intervention: Intraoperative RLN monitoring. Main outcome measure: RLN injury. Results: Between 2006 and 2008, 296 subjects underwent thyroid lobectomy or total thyroidectomy by the authors. One patient was excluded because of preoperative documentation of RLN injury. IONM was used in 253 (88%) cases, with a total of 403 nerves at risk of injury. Loss of RLN signal following surgical dissection occurred in 13 cases, prompting a change in surgical plan in one case. Post-operative laryngoscopy was performed in eight patients with hoarseness, documenting vocal cord paralysis in one patient who had clear intraoperative anatomic evidence of RLN injury. In no case did loss of RLN signal after dissection lead to nerve injury in the absence of anatomical evidence of injury as detected by the surgeon. Conclusions: IONM added cost and resulted in surgeon angst in cases of malfunction without a clear benefit in RLN identification and protection. Anatomic identification of the RLN should remain the gold standard in preventing RLN injury during thyroidectomy

Sentinel Lymph Node Biopsy Does Not Improve Disease-Specific Survival in Elderly Patients with Intermediate Thickness Melanoma

Objective: To determine whether sentinel lymph node biopsy (SLNB) is associated with improved disease-specific survival among elderly patients with intermediate-thickness melanoma Design: Retrospective cohort study of prospectively-maintained tumor registry Setting: Single institution tertiary care center. P atients: Adults ≥ 70 years of age, who underwent surgical intervention for melanoma from 2000-2013. Main Outcome Measures: The primary outcomes were overall survival (OS) and disease-free survival (DFS). Other clinicopathologic variables measured included age, gender, anatomic site, histologic type, tumor thickness, presence of adverse features, receipt and result of SLNB, and receipt of completion lymph node dissection (CLND). Results: Ninety-one patients (mean age 80 years, 54% male) underwent wide excision of an intermediate-thickness melanoma. Forty-nine patients (54%) received a SLNB. Seven of these biopsies (14%) were positive, and five patients (71%) went on to receive CLND. Five-year OS was 41% in patients who did not receive SLNB and 52% in patients who did receive SLNB (Fig. 1A). However, 5-year DFS was 79% in patients who did not receive SLNB and 77% in patients who did receive SLNB (Fig. 1B). Conclusions: Among elderly patients with intermediate-thickness melanoma, patients who received SLNB had higher 5-year OS than those who did not receive SLNB. However, the 5-year DFS is similar between the two groups, which suggests that the OS differences are related to non-melanoma factors. Routine SLNB for intermediate-thickness melanoma patients may not significantly change the outcome for this age group, and clinical decision-making should consider individual patient comorbidities and goals of care

Contemporary Analysis of Malignancies in Women of Child-Bearing Age: An NSQIP Analysis

Background: Recent evidence suggests that cancer incidence among pregnant women is increasing. The pattern of malignancies in pregnant women and how these compare to their nonpregnant counterparts has not been explored. Here we describe the differences in the proportion of resected malignancies in this population. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify women aged 18-49 who underwent an operation for malignancy from 2007-2012. Age-adjusted distribution of specific surgical interventions for malignancy based on ICD-9 codes were compared among pregnant and non-pregnant women using logistic regression analysis. Results: 42,732 subjects with malignancies surgically treated during child-bearing age were identified. 0.33% (n=143) were pregnant. The most common tumors requiring resection were breast (51%), thyroid (17%), and colorectal (9%). The distribution for most cancers was similar between groups. The age-adjusted proportion was significantly increased in breast, major salivary gland and oropharyngeal malignancies (p\u3c0.05). The proportion of resected colorectal cancers was significantly lower in pregnant women (p\u3c0.05; Table 1). Conclusion: This study serves as the first comprehensive and contemporary overview of malignancies resected in women of childbearing age. This study demonstrates that the proportion of resections among pregnant women was significantly greater in breast, major salivary gland and oropharyngeal cancers and lower for colorectal cancers. While these data might represent true differences in cancer incidence, further work is necessary to demonstrate if these are true differences in incidence versus differences in detection and treatment of the pregnant patient

Moxonidine increases uptake of oxidised low-density lipoprotein in cultured vascular smooth muscle cells and inhibits atherosclerosis in apolipoprotein E-deficient mice

This study aimed to investigate the effect of the sympatholytic drug moxonidine on atherosclerosis. The effects of moxonidine on oxidised low-density lipoprotein (LDL) uptake, inflammatory gene expression and cellular migration were investigated in vitro in cultured vascular smooth muscle cells (VSMCs). The effect of moxonidine on atherosclerosis was measured by examining aortic arch Sudan IV staining and quantifying the intima-to-media ratio of the left common carotid artery in apolipoprotein E-deficient (Apo

Renal denervation promotes atherosclerosis in hypertensive apolipoprotein E-Deficient mice infused with angiotensin II

Objective: To determine the effect of renal denervation (RDN) on the severity of atherosclerosis and aortic aneurysm in hypertensive mice. Methods: Hypertension, atherosclerosis and aortic aneurysm were induced by subcutaneous infusion of angiotensin II (1 μg/kg/min) for 28 days in apolipoprotein E-deficient mice. RDN was conducted using combined surgical and local chemical denervation. The norepinephrine concentration in the kidney was measured by high-performance liquid chromatography. Blood pressure was measured by the tail-cuff method. Atherosclerosis was assessed by Sudan IV staining of the aortic arch. The aortic diameter was measured by the morphometric method. The mRNA expression of genes associated with atherosclerosis and aortic aneurysm were analyzed by quantitative PCR. Results: RDN decreased the median norepinephrine content in the kidney by 93.4% (n = 5-7, P = 0.003) 5 days after the procedure, indicating that the RDN procedure was successful. RDN decreased systolic blood pressure in apolipoprotein E-deficient mice. Mice that had RDN had more severe aortic arch atherosclerosis (median percentage of Sudan IV positive area: 13.2% in control mice, n = 12, and 25.4% in mice having RDN, n = 12, P = 0.028). The severity of the atherosclerosis was negatively correlated with the renal norepinephrine content (spearman r = -0.6557, P = 0.005). RDN did not affect the size of aortic aneurysms formed or the incidence of aortic rupture in mice receiving angiotensin II. RDN significantly increased the aortic mRNA expression of matrix metalloproteinase-2 (MMP-2). Conclusion: RDN promoted atherosclerosis in apolipoprotein E-deficient mice infused with angiotensin II associated with upregulation of MMP-2. The higher MMP-2 expression could be the results of the greater amount of atheroma in the RDN mice. The findings suggest further research is needed to assess potentially deleterious effects of RDN in patients. © 2017 Wang, Dinh, Nield, Krishna, Denton and Golledge

Safety, Quality, and Acceptability of Contraceptive Subdermal Implant Provision by Community Health Extension Workers Versus Nurses and Midwives in Nigeria: Protocol for a Quasi-Experimental, Noninferiority Study.

BACKGROUND: As part of its Family Planning 2020 commitment, the Nigerian government is aiming for a contraceptive prevalence rate of 36% by 2018, and in 2014, approved a policy to allow community health extension workers (CHEWs), in addition to doctors, nurses, and midwives, to provide contraceptive subdermal implants. There is a lack of rigorous evidence on the safety of long-acting reversible contraceptive provision, such as implants, among lower cadres of health providers. OBJECTIVE: This study aimed to compare implant provision by CHEWs versus nurses and midwives up to 14 days post insertion. METHODS: The quasi-experimental, noninferiority study will take place in public sector facilities in Kaduna and Ondo States. In each state, we will select 60 facilities, and from these, we will select a total of 30 nurses and midwives and 30 CHEWs to participate. Selected providers will be trained to provide implant services. Once trained, providers will recruit a minimum of 8125 women aged between 18 and 49 years who request and are eligible for an implant, following comprehensive family planning counseling. During implant insertion, providers will record data about the process and any adverse events, and 14 days post insertion, providers will ask 4410 clients about adverse events arising from the implant. Supervisors will observe 792 implant insertions to assess service provision quality and ask clients about their satisfaction with the procedure. We will conclude noninferiority if the CI for the difference in the proportion of adverse events between CHEWs and nurses and midwives on the day of insertion or 14 days post insertion lies to the right of -2%. RESULTS: In September and October 2015, we trained 60 CHEWs and a total of 60 nurses and midwives from 12 local government areas (LGAs) in Kaduna and 23 LGAs in Ondo. Recruitment took place between November 2015 and December 2016. Data analysis is being finalized, and results are expected in March 2018. CONCLUSIONS: The strength of this study is having a standard care (nurse and midwife provision) group with which CHEW provision can be compared. The intervention builds on existing training and supervision procedures, which increases the sustainability and scalability of CHEW implant provision. Important limitations include the lack of randomization due to nurses and midwives in Nigeria working in separate types of health care facilities compared with CHEWs, and that providers self-assess their own practices. It is unfeasible to observe all procedures independently, and observation may change practice. Although providers will be trained to conduct implant removals, the study time will be too short to reach the sample size required to make noninferiority comparisons for removals. TRIAL REGISTRATION: ClinicalTrials.gov NCT03088722; https://clinicaltrials.gov/ct2/show/NCT03088722 (Archived by WebCite at http://www.webcitation.org/6xIHImWvu)

Cost and cost-effectiveness analysis of mass drug administration compared to school-based targeted preventive chemotherapy for hookworm control in Dak Lak province, Vietnam

Background: School-based targeted preventive chemotherapy (PC), the main strategy for soil-transmitted helminths (STH) control, excludes other at-risk populations including adults and preschool children. Mass drug administration (MDA), covering all age groups, would bring additional health benefits but also requires greater investment. This cost survey and cost-effectiveness analysis compared MDA with school-based targeted PC for STH control in Dak Lak, Vietnam, where STH are endemic. Methods: A cost survey was conducted in 2020 to estimate the total and per person economic and financial cost of each strategy. Monte Carlo simulation accounted for uncertainty in cost estimates. The primary effectiveness measure was hookworm-related disability-adjusted life years (DALYs) averted, and secondary measures were hookworm infection-years averted and moderate-to-heavy intensity hookworm infection-years averted. A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of MDA compared to school-based targeted PC using a government payer perspective and a ten-year time horizon. One-way and probabilistic sensitivity analyses (PSA) were performed. Costs are reported in 2020 USD ($). Findings: The economic cost per person was$0.27 for MDA and $0.43 for school-based targeted PC. MDA in Dak Lak will cost$472,000 per year, while school-based targeted PC will cost $117,000. Over 10 years, MDA is estimated to avert an additional 121,465 DALYs; 4,019,262 hookworm infection-years, and 765,844 moderate-to-heavy intensity hookworm infection-years compared to school-based targeted PC. The ICER was$28.55 per DALY averted; $0.87 per hookworm infection-years averted, and$4.54 per moderate-to-heavy intensity hookworm infection-years averted. MDA was cost-effective in all PSA iterations. Interpretation: In areas where hookworm predominates and adults suffer a significant burden of infection, MDA is cost effective compared to school based targeted PC and is the best strategy to achieve global targets. \</p