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To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.

RATIONALE: People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, there is scant evidence to support a standard treatment duration. OBJECTIVES: To test differing durations of intravenous antimicrobials for CF exacerbations. METHODS: STOP2 (Standardized Treatment of Pulmonary Exacerbations 2) was a multicenter, randomized, controlled clinical trial in exacerbations among adults with CF. After 7–10 days of treatment, participants exhibiting predefined lung function and symptom improvements were randomized to 10 or 14 days’ total antimicrobial duration; all others were randomized to 14 or 21 days’ duration. MEASUREMENTS AND MAIN RESULTS: The primary outcome was percent predicted FEV(1) (ppFEV(1)) change from treatment initiation to 2 weeks after cessation. Among early responders, noninferiority of 10 days to 14 days was tested; superiority of 21 days compared with 14 days was compared for the others. Symptoms, weight, and adverse events were secondary. Among 982 randomized people, 277 met improvement criteria and were randomized to 10 or 14 days of treatment; the remaining 705 received 21 or 14 days of treatment. Mean ppFEV(1) change was 12.8 and 13.4 for 10 and 14 days, respectively, a ‒0.65 difference (95% CI [‒3.3 to 2.0]), excluding the predefined noninferiority margin. The 21- and 14-day arms experienced 3.3 and 3.4 mean ppFEV(1) changes, a difference of ‒0.10 (‒1.3 to 1.1). Secondary endpoints and sensitivity analyses were supportive. CONCLUSIONS: Among adults with CF with early treatment improvement during exacerbation, ppFEV(1) after 10 days of intravenous antimicrobials is not inferior to 14 days. For those with less improvement after one week, 21 days is not superior to 14 days. Clinical trial registered with www.clinicaltrials.gov (NCT02781610).

Cleaning chemistries are detergent-based formulations that are used during the processing of reusable medical devices. Manufacturers are responsible for demonstrating the safety of cleaning formulations when they are used during a device processing cycle, including the risk of device-associated cytotoxicity over the concentration ranges for recommended use and rinsing during cleaning. However, no regulation currently exists requiring manufacturers to demonstrate such safety. Although manufacturers' safety data sheets (SDSs) provide information on the safe use of chemicals for users, this information may not provide sufficient detail to determine the risks of residual chemicals on device surfaces. SDSs are not required to contain a comprehensive list of chemicals used, only those of risk to the user. They should be supplemented with information on the correct concentrations that should be used for cleaning, as well as instructions on the rinsing required to reduce the levels of chemicals to safe (nontoxic) levels prior to further processing. Supporting data, such as toxicity profiles or cytotoxicity data that support the instructions for use, would provide medical device manufacturers and healthcare personnel with the necessary information to make informed decisions about selection and correct use of detergents. In the current work, cytotoxicity profiles for eight commonly used cleaning formulations available internationally were studied. Although all of these products are indicated for use in the cleaning of reusable medical devices, results vary across the serial dilution curves and are not consistent among detergent types. The information presented here can be leveraged by both medical device manufacturers and processing department personnel to properly assess residual detergent risks during processing. This work also serves as a call to cleaning formulation manufacturers to provide this information for all chemistries.

Background: Salmonella enteric serovars Typhi and Paratyphi are known to cause enteric fever. Multidrug resistance in S. Typhi and S.Paratyphi has emerged as a cause of concern. Aims: To evaluate antimicrobial susceptibility patterns of Salmonella enteric serovar Typhi (S. Typhi) and S.Paratyphi obtained from blood culture. Materials and Methods: All S. enteric isolates obtained from blood cultures of clinically suspected cases of enteric fever coming to microbiology laboratory, Nirmal hospital, from January 2015 to September 2017 were included in the study. Antimicrobial susceptibility patterns were determined using commercial antimicrobial disks chloramphenicol (30 g), nalidixic acid (30 g), ampicillin (10 g), azithromycin (15 g), cotrimoxazole (1.25/23.75 g), ciprofloxacin (5 g), and ceftriaxone (30 g). Antimicrobial susceptibility testing was performed in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines of respective year by KirbyBauer disc diffusion method. Result: Total 330 isolates of salmonella are there out of that 298 is Salmonella typhi. 32 are Salmonella para A, while 1 is of Salmonella para B. Enteric fever cases pick month are April, May, June and July. Sensitivity to first line drugs are > 80%, Nalidixic acid resistant Salmonella (NARS) are 79%, while Multi drug resistant (resistant to ampicillin, chloramphenicol and co-trimoxazole all three)Salmonella are 3%. Conclusion: Periodic evaluation of antibiotic susceptibility pattern is necessary to see changing pattern of antibiotics. Evaluation of Nalidixic acid resistant Salmonella and periodic evaluation of multi drug resistant Salmonella is also important as emergence of MDR strain is observed in our study. Keywords: Multi drug resistant, Nalidixic acid resistance, Salmonella typhi, Typhoid

Papillary thyroid cancer (PTC) is the most prevalent form of thyroid cancer with a reported incidence of 4.7-5.3 per 100,000 people over the past 10 years. PTC is more commonly seen in females during the fourth and fifth decades of life. Radiation exposure during childhood and family history are known risk factors for thyroid cancer. Thyroid cancer typically presents as a thyroid nodule detected on physical exam or incidental finding on imaging. Patients may feel swollen glands or a lump in the neck that can cause dysphagia. It is uncommon for PTC to present as hyperthyroidism. However, patients with Graves’ disease have an increased risk of thyroid cancer. We share a rare case of PTC detected following newly diagnosed Grave's disease presenting as thyroid storm. A 27-year-old male with history of polysubstance abuse and bipolar disorder presented to the hospital for altered mentation. He appeared anxious, tremulous, and was persistently tachycardic and febrile. There was an initial concern for drug intoxication or overdose. However, the patient's mother stated that he had not used drugs for the past six months and that his prescription bottles were appropriately filled. Blood alcohol level was elevated however urine toxicology screen was unrevealing. Due to worsening mentation and inability to protect his airway, the patient was intubated and transferred to the ICU. Thyroid levels were checked and TSH was less than 0. 01 with free T4 of 3.6 and free T3 of 13.80. The patient's Burch-Warsofsky score was 40. With endocrinology input, the patient was started on thyroid storm protocol with propylthiouracil, iodine solution, hydrocortisone, and beta blocker. He had significant improvement and was able to be extubated. Propylthiouracil was transitioned to methimazole. Thyroid stimulatingimmunoglobulin was found to be elevated, consistent with Grave's disease. Patient did have a known enlarged thyroid with heterogeneity from a recent ultrasound that had not yet been investigated. A CT scan of the neck was ordered, and this showed cervical lymphadenopathy, diffuse thyroid enlargement without nodule, and anterior mediastinum density. An ultrasound guided cervical lymph node biopsy was consistent with metastatic papillary thyroid cancer. A PET CT showed metastatic adenopathy in the upper neck and chest. Patient is planned to undergo thyroidectomy with lymphadenectomy. He is being followed by oncology and endocrinology for further management outpatient. Concurrent hyperthyroidism from Grave's disease with thyroid cancer is rare, though with increasing reports, particularly with PTC. Thyroid stimulatingimmunoglobulins are thought to accelerate thyroid cancer cell turnover and promote angiogenesis through up-regulation of vascular endothelial growth factors, facilitating invasive and metastatic potential. Thyroid cancer with coexisting hyperthyroidism has a poorer prognosis. Having a high clinical suspicion of thyroid cancer in patients with hyperthyroidism can result in prompter diagnosis and treatment which is imperative. Presentation: No date and time listed

Introduction Adherence to lifestyle modifications can prevent diabetes; however, this poses a challenge for most individuals. CGM is an effective tool for glycemic control and lifestyle modifications in patients with diabetes on insulin therapy. We explored the impact of CGM use in individuals with prediabetes. Hypothesis Individuals using CGM in addition to diabetes education will show improved adherence to lifestyle modifications and greater reduction of HbA1c as compared to those receiving diabetes education alone.Design57 individuals with prediabetes were randomized to use CGM for 3 months along with diabetes education (CGM group) or receive diabetes education alone (EDU group). Food frequency (UKDDQ) and physical activity (IPAQ) questionnaires were completed by participants at the beginning and at the end of the study (6 months). Primary outcomes were lifestyle modifications and changes in HbA1c. Secondary outcomes were changes in weight and blood pressure. Results Both groups reported an increase in healthy food choices; however, EDU group performed better (EDU: 12.4 vs 9.2, p Conclusions CGM use in addition to diabetes education resulted in improvement in physical activity, food choices, HbA1c, weight, and BP in individuals with prediabetes. The significance of diabetes education was noted by greater improvement in food choices in EDU group. CGM can be an effective tool for diabetes prevention with lifestyle modifications in prediabetes. The long-term impact of CGM use and cost-benefit analysis in high-risk patients needs to be explored further. Presentation: Saturday, June 11, 2022 12:00 p.m. - 12:15 p.m.

Non-functioning pituitary macroadenomas (NFPAs) account for 14-54% of all pituitary adenomas. NFPAs are benign, but mass effects may lead to significant symptoms, including visual impairment and pituitary insufficiency, of which secondary hypogonadism is present in 75% of reported cases. Patients with hypogonadism may experience decreased bone density, libido, muscle mass/strength, and fatigue. We describe a patient who presented with osteopenia, in addition to atypical symptoms of secondary hypogonadism, associated with low testosterone levels. Further workup disclosed a large pituitary macroadenoma. A 56-year-old male presented to the clinic for a two-year history of diffuse joint pain. X-rays were significant for bone loss. This led to a bone density scan that showed osteopenia with a T score of -2.3 in the lumbar spine and left femoral neck. He had no prior history of fractures or loss in height. Risk factors for bone disease were only pertinent for history of osteoporosis in his mother. He was referred to endocrinology for further evaluation. Work up included normal vitamin D levels, 24-hour urine calcium excretion, morning cortisol, and TSH. Given the patient's osteopenia and additional complaints of decreased appetite, weight loss, fatigue, and muscle weakness, testosterone levels were checked and found to be low. Free testosterone level was 14.3 pg/ml with inappropriately low FSH and LH. Prolactin was normal at 12.5 ng/ml. He subsequently had an MRI brain which revealed a pituitary macroadenoma measuring 2. 0×2.4×2.4 cm with mass effect on the optic chiasm. However, the patient did not complain of headaches or visual disturbances and visual field testing was normal. He underwent transsphenoidal resection of the pituitary tumor which led to normalization of testosterone levels and resolution of all his symptoms. This case exemplifies how non-specific symptoms of hypogonadism and absence of mass effect symptoms can lead to a delay in diagnosis of NFPA. Typically, NFPAs are detected when they are large enough to cause symptoms of mass effect which, interestingly, were absent in this patient despite compression of the optic chiasm. Male hypogonadism increases the risk for bone disease. Thus, it is important to pursue work up for secondary hypogonadism in males presenting with osteopenia/osteoporosis despite lack of overt symptoms. A thorough history and workup are essential in diagnosing NFPA. Prompt detection of NFPA can facilitate timely management leading to clinical improvement. The first line of treatment for NFPAs causing neurological symptoms is transsphenoidal surgical resection. Surgery is also recommended for NFPAs that are at high risk for causing visual deficits due to involvement of optic chiasm, as was seen in this patient. Post-surgical follow up includes long-term routine monitoring of hormone levels and neuroimaging. Presentation: No date and time listed

In 2015, the Food and Drug Administration (FDA) updated its guidance on test methods for cleaning validations for reusable medical devices. The changes include the condition and contamination of devices, test samples and controls, cleaning process performed during validation, extraction methods, and endpoints. This article reviews the FDA's changes to cleaning validations. Examples are presented using flexible endoscopes in order to provide a practical guide to performing cleaning validations.

Introduction: Continuous femoral analgesia provides extended pain relief for surgeries over thigh. Successful continuous peripheral nerve analgesia depends on catheter proximity to the target nerve and stimulating catheters may allow more accurate placement of catheters. Hence we conducted a study to compare the efficacy of stimulating nerve catheter and non stimulating nerve catheter in femoral 3-in-1 nerve block for postoperative analgesia. Materials and Methods: 60 ASA grade I & II patients of either sex between 18 to 65 years of age posted for total knee replacement surgery were randomly allocated into two groups: Group SC (stimulating catheter) and Group NSC(non stimulating catheter). All patients received subarachnoid block and after completion of surgery femoral catheter (stimulating/non stimulating depending on the group) was placed using peripheral nerve stimulator for postoperative analgesia. When spinal level regressed to T12 dermatomal level, Inj.Bupivacaine (0.25%) 20ml with Inj.Lignocaine (1%) 10ml was given. The patients were followed for next 24 hours from the time of first bolus. After the 1st bolus when the VRS score was ?3, intermittent boluses of Inj.Bupivacaine (0.25%) 15 ml with Inj.Fentanyl 0.5µg/kg were given. All patients received Inj. Paracetamol 20 mg/kg IV 6 hourly. In case patient still had VRS score ?3 then rescue analgesia in the form of Inj.Diclofenac sodium 1 mg/kg IV was given. Two groups were observed for total duration of sensory block (time from 1st bolus dose till the time VAS score was ?3); requirement of analgesic solution; requirement of rescue analgesia; and any complication or side effects. Results: Total duration of sensory block in group SC was 9.40±0.21 hours compared to 7.10±0.23 hours in group NSC (p=0.0001). Total requirement of analgesic solution was less in SC group in comparison to NSC group. No significant complication observed in either group. Conclusion: Stimulating nerve catheter provides lon

Coronavirus disease (COVID-19) has emerged as one of the largest pandemics ever experienced globally and has already affected 216 countries (WHO, 2020). Severe acute respiratory syndrome coronaviru...

Background MAT9001 is an omega‐3 free fatty acid (FFA) formulation containing mainly eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA). Compared with icosapent ethyl (EPA‐ethyl esters [EE]), EPA+DPA‐FFA previously showed enhanced triglyceride lowering and higher plasma EPA when both were administered once daily with a very–low fat diet. This trial compared pharmacodynamic responses and plasma omega‐3 levels following twice daily dosing, with meals, of EPA+DPA‐FFA and EPA‐EE in hypertriglyceridemic subjects consuming a Therapeutic Lifestyle Changes diet. Methods and Results This open‐label, randomized, 2‐way crossover trial, with 28‐day treatment periods separated by ≥28‐day washout, was conducted at 8 US centers and included 100 subjects with fasting triglycerides 1.70 to 5.64 mmol/L (150–499 mg/dL) (median 2.31 mmol/L [204 mg/dL]; 57% women, average age 60.3 years). The primary end point was least squares geometric mean percent change from baseline plasma triglycerides. In the 94 subjects with analyzable data for both treatment periods, EPA+DPA‐FFA and EPA‐EE reduced least squares geometric mean triglycerides from baseline: 20.9% and 18.3%, respectively ( P =not significant). EPA+DPA‐FFA reduced least squares geometric mean high‐sensitivity C‐reactive protein by 5.8%; EPA‐EE increased high‐sensitivity C‐reactive protein by 8.5% ( P =0.034). EPA+DPA‐FFA increased least squares geometric mean plasma EPA, DPA, and total omega‐3 (EPA+docosahexaenoic acid+DPA) concentrations by 848%, 177%, and 205%, respectively, compared with corresponding changes with EPA‐EE of 692%, 140%, and 165% (all P P =0.011). Lipoprotein cholesterol and apolipoprotein responses did not differ between treatments. Conclusions EPA+DPA‐FFA raised plasma EPA, DPA, and total omega‐3 significantly more than did EPA‐EE. EPA+DPA‐FFA also reduced triglycerides and high‐sensitivity C‐reactive protein without increasing low‐density lipoprotein cholesterol. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04177680.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in subjects with cystic fibrosis (CF); however, the effects on pancreatic manifestations are not well characterized. We hypothesized that CFTR modulators would improve measures of exocrine pancreatic function and outcomes.We performed a systematic search to identify studies reporting measures of the exocrine pancreas in humans treated with CFTR modulators. Only studies reporting baseline and on-treatment assessments were included.Of 630 identified studies, 41 met inclusion criteria. CFTR modulators reduced acute pancreatitis events by 85% overall (rate ratio 0.15, 95% confidence interval (CI) 0.04, 0.52), with a greater effect seen in the subgroup with pancreas sufficient CF (PS-CF) (rate ratio 0.13 (95% CI 0.03, 0.53). Among 293 subjects with baseline and on-treatment evaluation of pancreas sufficiency, 253 were pancreas insufficient at baseline and 54 (21.3%) converted to pancreas sufficiency. Of 32 subjects with baseline FE-1 values200 mcg/g, 16 (50%) increased to ≥200 mcg/g. Serum trypsin decreased by a mean of 565.9 ng/mL (standard deviation (SD) 311.8), amylase decreased by 38.2 U/L (SD 57.6), and lipase decreased by 232.3 U/L (SD 247.7).CFTR modulator use reduces acute pancreatitis frequency and improves indirect measures of exocrine pancreas function. Future interventional studies that evaluate the mechanism and impact of CFTR modulators on acute pancreatitis and pancreas sufficiency in patients with CFTR dysfunction are warranted.

Flexible endoscopes are implicated in deaths from healthcare-associated infections (HAIs), in particular antibiotic-resistant infections. This article analyzes whether terminal sterilization should be required as part of endoscope reprocessing to reduce or eliminate HAIs and thus improve patient safety. Reusable flexible endoscopes are processed to make them ready for clinical use by the processing department of the healthcare facility. Unlike most critical and semicritical medical devices, the final step of processing an endoscope is high-level disinfection and not terminal sterilization. This is because most flexible endoscopes come in contact with mucosal membranes (versus contact with direct blood stream) and cannot withstand sterilization. However, sterilization currently is performed by a small number of U.S. healthcare facilities on reusable flexible endoscopes with the belief that they are safer for use compared to flexible endoscopes that are high-level disinfected. Based on the analysis in this article, terminal sterilization is not a required or necessary step to eliminate HAIs.

Parathyroid crisis is a rare and life-threatening manifestation of hyperparathyroidism. Patients present with severe hypercalcemia and associated symptoms of bone disease, nephrolithiasis, abdominal pain, and fatigue. Multi-organ dysfunction in the form of encephalopathy, cardiac dysrhythmias, and renal failure is often present. There have also been reports of bleeding duodenal ulcers secondary to marked elevated parathyroid hormone. The most common etiology is a single parathyroid adenoma (85%) followed by hyperplasia (10%), double adenomas (4%), and carcinoma (1%). Parathyroid crisis requires immediate medical management of hypercalcemia and in recalcitrant cases, urgent parathyroidectomy. A 67-year-old female presented to the hospital with weakness and intermittent hematochezia. She was found to have acute renal failure, new onset anemia, and profound hypercalcemia of 17.1 mg/dl. On exam, she was slow to respond and exhibited diffuse muscle weakness. EKG showed sinus tachycardia, a right bundle branch block, and normal QTc. She received aggressive intravenous fluids and calcitonin. Bisphosphonate was not given due to renal failure. Due to refractory hypercalcemia, she was initiated on cinacalcet. She ultimately required hemodialysis due to failure of medical therapy. Further work-up showed a PTH of 2627 pg/ml. Vitamin D levels, TSH, and serum and urine protein electrophoresis were unremarkable. Renal ultrasound did not show nephrolithiasis. Given hematochezia and anemia in the setting of parathyroid crisis, endoscopy was done and was unrevealing of ulcers. A parathyroid ultrasound and nuclear medicine CT scan showed bilateral parathyroid adenomas. She underwent left superior and right inferior parathyroidectomy with biopsies revealing hypercellular parathyroid tissue with no features of malignancy. Following surgery, calcium levels gradually normalized. However, she remained dialysis dependent. This case exhibits a rare presentation of parathyroid crisis from double adenomas, requiring urgent double parathyroidectomy due to refractory hypercalcemia. This patient had an astoundingly elevated PTH level of 2627 pg/dl, one of the highest values documented in literature, which may attribute to the recalcitrant nature of hypercalcemia. Prompt diagnosis and treatment of parathyroid crisis is critical in preventing life-threatening complications. Presentation: No date and time listed

BACKGROUND: Pheochromocytoma is a rare catecholamine producing tumor of the adrenal gland. The anaesthetic management of the tumor can be challenging because of hemodynamic uctuations encountered preoperatively, during induction of anaesthesia, manipulation of tumor & after the excision. OBJECTIVE: To report perioperative anaesthetic management of a 63-year old female with pheochromocytoma for surgical excision, the major challenges were uncontrolled hypertension, diabetes with history of ischaemic heart disease. METHOD: Combined general and epidural anaesthesia was used in this patient. Preoperatively, the patient presented with high blood pressure which was adequately controlled with alpha and beta blockers. Intra- operatively she developed severe hypertension during manipulation of the tumor which was managed pharmacologically with nitroglycerin, esmolol, magnesium sulphate & epidural anaesthesia while hypotension that developed after the excision of the tumor was managed with intravenous uid, packed cell volume and noradrenaline. Post operatively she was transferred to intensive care unit for monitoring and pain management and she made an uncomplicated recovery. CONCLUSION: Pheochromocytoma is a rare tumor with its management being challenging and patient is at signicant risk for major adverse cardiac as well as neurological complications. Successful management requires careful preoperative optimization, intra operative planning, post operative close supervision and hemodynamic management with thorough knowledge of the physiology & pharmacology of drugs will lead to good outcome.

Extensive atherosclerotic plaque burden in the lower extremities often leads to symptomatic peripheral artery disease (PAD) including impaired walking performance and claudication. Interleukin-1β (IL-1β) may play an important pro-inflammatory role in the pathogenesis of this disease. Interruption of IL-1β signaling was hypothesized to decrease plaque progression in the leg macrovasculature and improve the mobility of patients with PAD with intermittent claudication. Thirty-eight patients (mean age 65 years; 71% male) with symptomatic PAD (confirmed by ankle–brachial index) were randomized 1:1 to receive canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. The mean vessel wall area (by 3.0 T black-blood magnetic resonance imaging (MRI)) of the superficial femoral artery (SFA) was used to measure plaque volume. Mobility was assessed using the 6-minute walk test. Canakinumab was safe and well tolerated. Markers of systemic inflammation (interleukin-6 and high-sensitivity C-reactive protein) fell as early as 1 month after treatment. MRI (32 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA in either placebo-treated or canakinumab-treated patients. Although an exploratory endpoint, placebo-adjusted maximum and pain-free walking distance (58 m) improved as early as 3 months after treatment with canakinumab when compared with placebo. Although canakinumab did not alter plaque progression in the SFA, there is an early signal that it may improve maximum and pain-free walking distance in patients with symptomatic PAD. Larger studies aimed at this endpoint will be required to definitively demonstrate this. ClinicalTrials.gov Identifier: NCT01731990

Aim: To determine factors responsible for loss of follow up and thereby to improve compliance and adherence to treatment in a palliative care unit. Methods: Among the data of patients maintained in our department, we found 81 patients out of 1200 OPD visits who didn't turn up for follow up after the rst outpatient department (O.P.D) visit in the study period [July 2017-June 2018] . After taking the institutional ethical committee approval we did telephonic interview of those patients and/or their relatives, took their consent to participate after explaining the study in brief. We noted the reason of not coming for follow up in our questionnaire. Out of 81, 61 patients could be contacted on phone. Results: Major reason for loss of follow up was death after the rst visit (n=31). 7 patients had started alternate medicine. Factors like exhaustion due to prolong treatment and difculty in bringing patients were noted in 3 patients and 1 patient respectively. Other factors like lack of palliative care awareness, nancial incapability, or no benet from treatment were not found in any of the patient. Conclusion: Death after the rst visit was leading cause for loss of follow up. Majority of the deaths were within one month of the visit. Early referral and early palliative care interventions of those could have helped us to serve those patients better.

A better understanding of SARS-CoV-2 transmission from children and adolescents is crucial for informing public health mitigation strategies. We conducted a retrospective cohort study among household contacts of primary cases defined as children and adolescents aged 7⍰19 years with laboratory evidence of SARS-CoV-2 infection acquired during an overnight camp outbreak. Among household contacts, we defined secondary cases using the Council of State and Territorial Epidemiologists definition. Among 526 household contacts of 224 primary cases, 48 secondary cases were identified, corresponding to a secondary attack rate of 9% (95% confidence interval [CI], 7%–12%). Our findings show that children and adolescents can transmit SARS-CoV-2 to adult contacts and other children in a household setting.

Introduction There are limited studies evaluating the role of pulmonary rehabilitation (PR) in pediatric asthma. Methods A retrospective chart review was performed of all pediatric patients with a diagnosis of asthma enrolled in PR. Demographics, medications, and clinical records were reviewed. In addition, PFTs, 6-min walk test (6MWT), and patient/parent symptom and quality of life surveys before and after PR were evaluated. Results A total of 38 patients were enrolled in PR; 18 (47%) female and 20 (53%) male. Mean participant age was 11.33 ± 3.37 (range 4-19) years. Twenty-two (58%) were Caucasian and nine (24%) African American. Chart review was limited by incomplete data sets for many participants. Following PR, significant improvement was noted in mean 6MWT distance (1541 vs 1616 feet, P = 0.05) and FEV1 (89.9% of predicted versus 96.4%, P = 0.04). Survey instruments demonstrated improvement in several clinical factors, however, there was no significant change in weight following PR despite scheduled cardiovascular exercise and dietary counseling. Conclusions Structured PR for pediatric patients with asthma can improve 6MWT distance and FEV1 as well as subjective measures of SOB and QOL, suggesting a role for PR in the chronic management of pediatric asthma. Further prospective investigation is needed to determine if PR has positive effects on other clinical parameters of asthma control and its overall impact on childhood obesity.

Supplemental material, 10.1177_1358863X19859072_supplementary_material for A randomized, placebo-controlled trial of canakinumab in patients with peripheral artery disease by Kerry S Russell, Denise P Yates, Christopher M Kramer, Andrea Feller, Ping Mahling, Laurence Colin, Timothy Clough, Tianke Wang, Lucy LaPerna, Alpa Patel, Holger Lawall, Mustafa M Shennak, James Fulmer, Sigrid Nikol, William B Smith, Oliver J Müller, Elizabeth V Ratchford and Craig T Basson in Vascular Medicine

OBJECTIVES: To improve the mental health (MH) referral process for children referred from primary care to community mental health clinics (CMHCs) by using a community-partnered approach. METHODS: Our partners were a multisite federally qualified health center and 2 CMHCs in Los Angeles County. We randomly assigned 6 federally qualified health center clinics to the intervention or as a control and implemented a newly developed telehealth-enhanced referral process (video orientation to the CMHC and a live videoconference CMHC screening visit) for all MH referrals from the intervention clinics. Our primary outcome was CMHC access defined by completion of the initial access point for referral (CMHC screening visit). We used multivariate logistic and linear regression to examine intervention impact on our primary outcome. To accommodate the cluster design, we used mixed-effect regression models. RESULTS: A total of 342 children ages 5 to 12 were enrolled; 86.5% were Latino, 61.7% were boys, and the mean age at enrollment was 8.6 years. Children using the telehealth-enabled referral process had 3 times the odds of completing the initial CMHC screening visit compared with children who were referred by using usual care procedures (80.49% vs 64.04%; adjusted odds ratio 3.02 [95% confidence interval 1.47 to 6.22]). Among children who completed the CMHC screening visit, intervention participants took 6.6 days longer to achieve it but also reported greater satisfaction with the referral system compared with controls. Once this initial access point in referral was completed, >80% of eligible intervention and control participants (174 of 213) went on to an MH visit. CONCLUSIONS: A novel telehealth-enhanced referral process developed by using a community-partnered approach improved initial access to CMHCs for children referred from primary care.

Objective: To develop an intervention to improve the mental health referral and care process for children referred by primary care providers (PCPs) to community mental health clinics (MHCs) using a community partnered approach. Design: A Project Working Group (PWG) with representatives from each partner orga­nization met monthly for 6 months. Setting: Multi-site federally qualified health center (FQHC) and two community MHCs in Los Angeles county. Participants: 26 stakeholders (14 FQHC clinic providers/staff, 8 MHC providers/staff, 4 parents) comprised the PWG. Data Sources: Qualitative interviews, PWG meeting notes, intervention processes and workflow reports. Intervention: The PWG reviewed qualita­tive data from stakeholders (interviews of 7 parents and 13 providers/staff). The PWG met monthly to identify key transition points where access to and coordination of care were likely compromised and to develop solutions. Results: Three critical transition points and system solutions were identified: 1) Parents refuse initial referral to the MHC due to stigma regarding mental health services. Solution: During initial referral, parents watch a video introducing them to the MHC. 2) Parents don’t complete the MHC’s screening after referral. Solution: A live videoconference session connecting parents at the FQHC with MHC staff ensures completion of the screening and eligibility process. 3) PCPs reject transfer of patients back to primary care for ongoing psycho­tropic medication management. Solution: Regularly scheduled live videoconferences connect PCPs and MHC providers. Conclusions: A community partnered ap­proach to care design utilizing telehealth for care coordination between clinics can potentially be used to address key chal­lenges in MHC access for children. Ethn Dis. 2018;28(Suppl 2):457-466; doi:10.18865/ed.28.S2.457.

The synthesis of a number of 6-arylisocytosines, including linked bis-isocytosines, from the reaction of guanidine with β-ketoesters is described. The compounds were investigated for their ability to form hydrogen-bonded structural networks, and for their potential interactions with the telomeric quadruplex forming sequence AGGG(TTAGGG)3.

Context: Osteopathic manipulative treatment (OMT) has been studied in patients with various respiratory diseases. However, to the authors' knowledge, no studies have assessed the efficacy of OMT in patients with cystic fibrosis (CF). Objective: To evaluate pulmonary function and perceptions of breathing, anxiety, and pain of CF patients who receive OMT in addition to standard inpatient management of pulmonary exacerbation. Methods: In a single-blind randomized controlled trial, we assessed adult patients with a history of CF who were admitted to the hospital because of pulmonary exacerbation. Participants were randomly assigned to receive a daily standardized protocol of OMT or sham therapy. Both groups also received standard treatment for CF. Spirometry and questionnaire data (self-assessment of breathing, pain, and anxiety level) were collected before the first OMT or sham therapy session and after the final session. Results: A total of 33 patients were included in the study: 16 in the OMT group and 17 in the sham therapy group. Improvements in spirometric parameters were observed in both the OMT and the sham therapy groups, with no statistically significant differences found between the groups. More patients in the OMT group than in the sham therapy group had questionnaire response patterns that indicated their breathing had improved during the study period (15 of 16 vs 8 of 16, respectively). No differences were found between groups for perceived improvement of pain and anxiety. Conclusion: In the current study, CF patients who received OMT did not demonstrate statistically significant differences in pre- and posttreatment spirometry findings compared with CF patients who received sham therapy. Questionnaire findings suggest that OMT may affect CF patients' perception of overall quality of breathing. Additional studies are needed to assess the clinical use of OMT in patients with CF.

Summary Background Although pulmonary arterial hypertension (PAH) is a potential co-morbidity in cystic fibrosis (CF), right heart catheterization (RHC) is not commonly performed in this patient population until referral for lung transplantation. Material and methods An non-randomized observational pilot study was performed after an exercise protocol with an upright stationary bicycle was added to RHC performed in patients with CF undergoing evaluation for lung transplantation (LT). Results Twelve consecutive patients with advanced lung disease due to CF referred for LT completed RHC with exercise protocol. Transthoracic echocardiography (TTE) prior to the RHC did not identify evidence of PAH or significant structural abnormalities; right and left ventricular systolic function were normal. non-randomized RHC in this same cohort found 75% (9/12) had PAH with an elevation of the mean pulmonary artery pressure (PAP) at rest with a mean (±SD) of 27.8 ± 4.9 mmHg that significantly increased during exercise to 47.2 ± 5.4 mmHg, p = 0.0025. For the last 6 patients, pulmonary vascular resistance was calculated during exercise, with a significant increase from 3.15 ± 0.3 to 12.8 ± 0.6 Wood Units (p = 0.0313) comparing measurements at rest to exercise. Conclusion RHC at rest and during exercise was safely and effectively performed in patients with CF referred for LT. Furthermore, central hemodynamic measurements found significant worsening of PAH during exercise in a small cohort of CF patients with advanced lung disease.

1. Alpa Patel Shah, DO* 2. Mary Lu Angelilli, MD* 1. *Children’s Hospital of Michigan, Detroit, MI. A 4-month-old twin infant boy presents to the emergency department (ED) with a 10-hour history of increased work of breathing, poor feeding, and decreased activity. Prior to arrival, the patient’s mother administered 2 albuterol treatments via nebulizer, which helped transiently. Then she took the child to his pediatrician’s office, where he was given an additional albuterol treatment and subsequently referred to the ED for persistent respiratory distress. The infant has had 2 hospital admissions for bronchiolitis. His parents deny any history of fever, cough, wheezing, runny nose, or vomiting. His twin brother remains asymptomatic. In the ED, the child is alert but tachypneic, with intercostal and subcostal retractions and nasal flaring. His initial vital signs include a temperature of 37.8°C (100°F), heart rate of 174 beats per minute, respiratory rate of 34 breaths per minute, blood pressure of 111/53 mm Hg, and pulse oximetry of 80% in room air. He weighs 4.8 kg (less than the third percentile). Findings on physical examination include a reddish discoloration on both sides of the neck and petechiae on the right cheek. A subconjunctival hemorrhage is also noted in the right eye. His lungs are clear to auscultation bilaterally, without wheezing, stridor, rales, or crackles, despite persistent and …

The imidazole ring is widespread in biologically active compounds, and hence imidazole-containing scaffolds are useful starting points for drug discovery programmes. We report the synthesis of a series of novel imidazole-containing compounds fused with either phenanthrene or phenanthroline, which show enhanced growth inhibitory potency against human colon, breast and melanoma cancer cell lines, as well as evidence of inhibition of the molecular chaperone heat shock protein 70 (Hsp70) pathway in cells, as shown by depletion of downstream oncogenic client proteins of the Hsp90 chaperone pathway, and induction of apoptosis.

The synthesis of a number of 6-arylisocytosines, including linked bis-isocytosines, from the reaction of guanidine with β-ketoesters is described. The compounds were investigated for their ability to form hydrogen-bonded structural networks, and for their potential interactions with the telomeric quadruplex forming sequence AGGG(TTAGGG)3.

The Centers for Disease Control and Prevention (CDC), Division of HIV/AIDS Prevention (DHAP) conducted outcome monitoring studies on evidence-based interventions (EBIs) provided by CDC-funded community-based organizations (CBOs). Critical to the success of outcome monitoring was the ability of CBOs to recruit and retain clients in evaluation studies. Two EBIs, Video Opportunities for Innovative Condom Education and Safer Sex (VOICES/VOCES) and Healthy Relationships, were evaluated using repeated measure studies, which require robust follow-up retention rates to increase the validity and usefulness of the findings. The retention rates were high for both VOICES/VOCES CBOs (95.8% at 30 days and 91.1% at 120 days), and Healthy Relationships CBOs (89.5% at 90 days and 83.5% at 180 days). This paper presents an overview of the retention of clients, challenges to follow-up, and strategies developed by CBOs to achieve high retention rates. These strategies and rates are discussed within the context of the CBOs’ target populations and communities.

The objective of this study was to identify factors related to failure to receive recommended interventions for the prevention of mother-to-child HIV transmission among HIV-infected pregnant women in the United States. Using Enhanced Perinatal Surveillance data from 2005 through 2008, we identified characteristics of HIV-infected women (n = 5,391) that increased their odds of missing an opportunity to prevent perinatal HIV transmission. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were calculated by using backward step-wise logistic regression analyses to determine the relationship between demographic variables and missed opportunities. Of 4,220 HIV-infected pregnant women with complete data, 2,545 (60%) did not receive all of the recommended interventions. Missed opportunities for prevention occurred more often among HIV-infected women aged 25-34 years (aOR = 1.9, 95% CI = 1.4-2.5), and greater than 34 years (aOR = 2.0, 95% CI = 1.5-2.7) compared to those 13-19 years and among injection drug users (aOR = 1.3, CI = 1.0-1.5) compared to women infected with HIV through heterosexual contact. Clinicians can decrease missed opportunities by routinely providing recommended interventions, especially among HIV-infected women who are injection drug users or aged 25 years or older.

PurposeThe purpose of this paper is to explain the results of a June 18, 2009 Joint US Department of Labor‐Securities and Exchange Commission hearing regarding Target Funds as investment options for individual and company‐sponsored retirement plans.Design/methodology/approachThe paper explains the background of Target Funds, the meaning of “target” dates and “glide paths,” the popularity of Target Funds with investors, recent losses suffered by Target Funds, areas of confusion among investors and plan sponsors such as fund naming conventions and differing target date strategies, asset allocation strategies, and glide paths; improvements in disclosure that are needed; possible problems with proprietary funds; and the prospects for new SEC and DOL regulations.FindingsGiven the extensive use of Target Funds as an investment option in retirement plans, particularly as a safe harbor “default” option, the SEC and DOL are expected to promulgate regulations governing some aspects of Target Funds, in order to protect investors by providing greater disclosure, especially regarding the glide path.Originality/valueThe paper provides practical guidance by experienced employee benefits, executive compensation, financial services and private funds lawyers.

Objectives Mesoporous fillers have been investigated for use in dental composites because of their potential for creating micromechanical filler/resin matrix interphase bonding. Such a micromechanical bonding could eliminate the need for the silane treatment of fillers for interfacial chemical bonding that is prone to hydrolysis in the oral environment. In the case of micromechanical bonding, dental polymer chains are threaded mechanically (like a “necklace”) through nanosized channels in the fillers. Methods A combination of mesoporous silica, which was synthesized using the non-surfactant templating method, and nonporous spherical silica (500 nm) was used to prepare experimental dental composites. The porous silica used in this study contained interconnected pores and channels as opposed to porous fillers containing surface pores. The compressive strength, compressive modulus, flexural modulus, and flexural strength of these composites were evaluated. Results The results showed that composites containing a combination of mesoporous and nonporous fillers have better mechanical properties than the composites having either of these fillers alone. Significance The results showed that a combination of mesoporous and nonporous materials can be used to prepare stronger dental materials that may resist hydrolysis and wear.

BACKGROUND: Nitroxide adducts 1,1-ditertbutyl-1-(1-methyl-1-cyanoethoxy)-amine (AIBN/DBN), 1,1-ditertbutyl-1-(benzoylperoxy)-amine (BPO/DBN) and 2,2,6,6,-tetramethyl-4-oxo-1-(1-methyl-1-cyanoethoxy)-piperidine (AIBN/4-OXO-TEMPO) were prepared and evaluated as stabilized unimolecular initiators for controlled radical polymerization of methacrylate monomers using sulfuric acid as an accelerating additive. Their effectiveness was evaluated from polymerization rates, molecular weight control and dispersity (D) of the polymers. Thermal stabilities of the polymers were also examined. The monomers used were methyl methacrylate, triethylene glycol dimethacrylate (TEGDMA) and ethoxylated bisphenol A dimethacrylate (EBPADMA). RESULTS: Polymerization was accomplished at 70 and 130 °C in 5 min to 144 h. The value of D of poly(methyl methacrylate) (PMMA) was 1.05–1.22. The glass transition temperature (Tg) for PMMA was 122–127 °C. The activity of the chain ends was established by chain extension and controlled polymerization was established by plotting Mnversus monomer conversion. First-order kinetics in monomer consumption was established and an electron paramagnetic resonance study was conducted. Decomposition temperature (Td) for PMMA was 360–380 °C, for poly(TEGDMA) was 300–380 °C and for poly(EBPADMA) was 360–440 °C. Photoinitiation without additive yielded no polymer. Thermal initiation by AIBN/4-OXO-TEMPO was the fastest. CONCLUSIONS: The initiators are applicable in low-temperature additive-enhanced controlled polymerization of methacylates and dimethacrylates, producing polymers with excellent attributes and a low value of D. Copyright © 2008 Society of Chemical Industry

BACKGROUND: This investigation evaluates the effectiveness of initiator adducts for living and controlled polymerization of methacrylates, crosslinking of dimethacrylates and thermal stabilities of the resulting polymers. Adducts of 2,2,6,6-tetramethyl-1-piperidinyloxy with benzoyl peroxide and with azobisisobutyronitrile were prepared and evaluated as stabilized unimolecular initiators for the free radical polymerization of methacrylate monomers using sulfuric acid as catalyst. The monomers used were methyl methacrylate, triethylene glycol dimethacrylate (TEGDMA) and ethoxylated bisphenol A dimethacrylate (EBPADMA). RESULTS: Successful polymerization was achieved at 70 and 130 °C with reaction times ranging from 45 min to 120 h. The dispersity (D) of poly(methyl methacrylate) (PMMA) was 1.09–1.28. The livingness and extent of control over polymerization were confirmed with plots of Mn evolution as a function of monomer conversion and of the first-order kinetics. The glass transition temperature (Tg) for PMMA was 123–128 °C. The degradation temperature (Td) for PMMA was 350–410 °C. Td for poly(TEGMA) was 250–310 °C and for poly(EBPADMA) was 320–390 °C. CONCLUSION: The initiators are suitable for free radical living and controlled polymerization of methacrylates and dimethacrylates under mild thermal and acid-catalyzed conditions, yielding medium to high molecular weight polymers with low dispersity, high crosslinking and good thermal stability. Copyright © 2008 Society of Chemical Industry

The presence of low-molecular-weight by-products is a major problem in poly[2-hydroxethyl methacrylate (HEMA)-silica] hybrids prepared using sol-gel synthesis. Low-molecular-weight by-products have a detrimental effect on the optical transparency, and mechanical and storage properties of poly(HEMA-silica) hybrids. To solve this problem, a new sol-gel synthesis procedure was developed to prepare organic–inorganic hybrids. Glycidyl methacrylate (GMA) was used as a comonomer to form poly(HEMA-GMA-silica) (PHGS) hybrids. In addition to forming a copolymer, GMA has two more functions. It facilitates the removal of almost all of the low-molecular-weight by-product molecules formed during sol-gel synthesis and also prevents further condensation of free silanol groups during the polymerization, storage, and use. The mechanical properties of PHGS hybrids were evaluated by using compression testing. The mechanical properties of PHGS hybrids were higher compared to Plexiglas G poly(methyl methacrylate), and the hybrids can be synthesized with reproducible mechanical properties.

Arhinia is defined as the congenital absence of the nose. It is an extremely rare condition, which is usually associated with other craniofacial abnormalities. An extensive literature search revealed that the prenatal diagnosis of this anomaly has only been reported on 1 previous occasion at 29 weeks' gestation, and the diagnosis at birth has been reported only 29 times in the pediatric literature. 1-29 To our knowledge, there has not been a previously reported case of congenital arhinia diagnosed during the second trimester. This report describes the 2- and 3-dimensional sonographic appearance of arhinia shown during second-trimester genetic sonography and reviews this exceedingly rare craniofacial defect. Early diagnosis of this defect allows the patient to consider all her options regarding pregnancy management. The detection of arhinia in the second trimester provides evidence that this rare disorder can be diagnosed through appropriate evaluation of craniofacial anatomy on a comprehensive second-trimester sonographic examination.