Days Of Therapy Research Articles

Efficacy of insulin dosing algorithms for high-fat high-protein mixed meals to control postprandial glycemic excursions in people living with type 1 diabetes: A systematic review and meta-analysis.

Optimizing postprandial blood glucose (PPG) levels after mixed meals that contain high fat and protein remains a challenge in the treatment of type 1 diabetes. This study evaluated the efficacy of different algorithms used for dosing insulin based on counting units of high fat and high protein (HFHP) meals with the current conventional method of counting carbohydrates alone to control PPG excursions. The MEDLINE, EMBASE, and Cochrane electronic databases were searched, with the analysis restricted to randomized control trials (RCTs). The primary outcome was the PPG (mean and standard deviation) at 240 min. The pooled final estimate was the mean difference (MD) of the PPGs at 240 min using random effect models to account for heterogeneity. In total, 15 studies were identified and included in the systemic review, of which 12 were RCTs, and three studies were non-randomized trials. The pooled MD of the PPG at 240 min was in favor of additional insulin doses in HFHP meals compared to the carbohydrate counting alone. The statistically significant results favored the combined bolus (30:70) that split over 2h in insulin pump therapy with pooled MD of the PPG, 240 min of -24.65; 95% CI: -36.59, -8.41; and heterogeneity, 0%. Other statistically significant results favored the additional insulin added to insulin to carb ratio (ICR) of meal bolus (25-60% ICR) in multiple daily injections therapy with the pooled MD of PPG at 240 min, -21.71; 95% CI: -38.45, -4.73; and heterogeneity, 18%. Insulin treatment based on fat and protein content, in addition to carbohydrate counting, is more effective than the carbohydrate counting method alone; however, further research is warranted to determine the best equation for fat and protein counting, particularly in people with multiple daily injections.

WHO Point Prevalence Survey to Describe the Use of Antimicrobials at a Tertiary Care Center in Pakistan: A Situation Analysis for Establishing an Antimicrobial Stewardship Program.

Antimicrobial stewardship is a systematic approach for promoting and monitoring responsible antimicrobial use globally. We conducted a prospective point prevalence survey of antimicrobial utilization among hospitalized adult patients during September 2021. The survey instrument was adapted from the WHO methodology for point prevalence surveys, and it was conducted at The Indus Hospital and Health Network, Karachi. Among the 300 admitted patients, 55% were males and the mean age was 44 (±18) years. At least 67% of the patients received one antimicrobial agent and the most common indication was surgical prophylaxis (40%). The most frequently used were antibacterial agents (97%) among all antimicrobials. Amoxicillin/Clavulanic acid and Ceftriaxone were the most frequently used antibacterial agents, i.e., 14% each. At least 56% of the antibacterial agents were amenable to antimicrobial stewardship when reviewed by infectious disease (ID) experts. Reasons for stewardship were: antibacterial not indicated (n = 39, 17.0%), unjustified prolonged duration of antibacterial (n = 32, 13.9%), extended surgical prophylaxis (n = 60, 26.2%), non-compliance to surgical prophylaxis guidelines (n = 30, 13.1%), and antibacterial not needed on discharge (n = 27, 11.7%). Median days of therapy (DOT) per agent was 3 days (IQR 2-4), while median DOT per patient was 2 days (IQR 1-4). These data have described the pattern of antimicrobial utilization in our institute. We found a higher prevalence of antimicrobial use overall as compared to the global figures, but similar to other low- and middle-income countries. Two important areas identified were the use of antimicrobials on discharge and extended surgical prophylaxis. As a result of these data, our institutional guidelines were updated, and surgical teams were educated. A post-intervention survey will help us to further determine the impact. We strongly recommend PPS at all major tertiary care hospitals in Pakistan for estimating antimicrobial utilization and identifying areas for stewardship interventions.

Renal Rehabilitation—Its Theory and Clinical Application to Patients Undergoing Daily Dialysis Therapy

An aging population and the prevalence of lifestyle-related ailments have led to a worldwide increase in the rate of chronic kidney disease requiring renal replacement therapy. The mean age of people requiring dialysis has been rising, and Japanese patients are aging more rapidly than those in the United States and Europe. Compared to people with normal kidney function, those undergoing hemodialysis are at increased risk of sarcopenia or frailty and serious health problems that limit access to kidney transplantation and lead to adverse health outcomes such as functional dependence, hospitalization, and death in patients on dialysis treatment. The Japanese Society of Renal Rehabilitation, established in 2011, published a clinical practice guideline for renal rehabilitation in 2019. Although the concept has become widely known among kidney health providers in recent years, efforts have still not focused on routine clinical care for patients with chronic kidney disease. In this review, the theory and clinical application of renal rehabilitation for patients undergoing daily hemodialysis were investigated.

ODP445 If You Can't Beat Them, Join Them: A Therapeutic Strategy for Maintaining Euthyroidism in Non-Compliant Patients

Abstract Levothyroxine (LT4) has been the mainstay therapy for hypothyroidism since synthesized in 1949, and it was depicted to be a daily, usually lifelong, therapy. LT4 may have many interactions with other medications, food, and supplements, for which it should also be taken on an empty stomach, at least thirty minutes before consuming any other product, to achieve adequate absorption. These two characteristics of LT4 therapy are two of the main reasons for patient non-compliance, leading to uncontrolled hypothyroid state shown by abnormal thyroid stimulating hormone (TSH) levels, and associated symptoms. LT4 properties, such as seven-day half-life, as well as increased peripheral conversion to metabolically active T3 by local deiodinase enzyme when there are low T4 levels, provide a scenario where it can be used at longer dosing intervals than the traditional daily dosing. This is the case of a 27-year-old female with past medical history of hypothyroidism on daily replacement therapy with 50mcg of branded LT4, presenting to the endocrinologist for continuation of care. Over the course of visits, patient showed uncontrolled thyroid disease with altered levels of TSH, ranging from 5.4 uIU/mL up to 46.8 uIU/mL (N: 0.45-5. 0 uIU/mL), despite appropriate dose adjustments and frequent TSH and free T4 (FT4) monitoring. Due to persistent clinical and biochemical hypothyroidism requiring dosage increases up to 300mcg, patient was referred for a thyroxine absorption test to rule out LT4 malabsorption versus medication non-compliance. A supervised dose of 812mcg of the same branded LT4 was provided, based on body weight, and TSH, free T3, and free T4 levels were measured before administration and sequentially at 30, 45, 60, 90, 120, 240, and 360 minutes after dose, yielding TSH values ranging from 0.11 uIU/mL to 0.18 uIU/mL, consistent with adequate TSH suppression. Patient admitted to erratic medication ingestion for which a dose of 150 mcg LT4 orally daily was started. TSH levels remained above 9. 0 uIU/mL, for which a trial of complete weekly dosage was offered and accepted by patient. Two months after therapeutic adjustment, patient became both clinically and biochemically euthyroid, with TSH level of 1.35 uIU/mL without any adverse effects from excess hormone intake. Medication non-compliance is an issue every physician must battle with. This case serves as an example of the great impact of individualized modification of LT4 administration to establish a therapeutic regimen that adjusts to each patient's lifestyle while allowing them to remain clinically stable, which is a great benefit for both the patient and the clinician. Although studies already exist in proving the benefits of weekly versus daily therapy in such patients without major risks, further investigation should be conducted, as therapeutic guidelines could potentially change altogether in the future to avoid, or at least reduce, non-compliance consequences. Presentation: No date and time listed

RF26 | PMON332 Safety and Efficacy of Treatment with Lonapegsomatropin in Children with Growth Hormone Deficiency at Week 130 in the enliGHten Trial

Abstract Background Once-weekly lonapegsomatropin (TransCon hGH) is a long-acting prodrug of somatropin, recently approved for the treatment of pediatric growth hormone deficiency (GHD) by the US FDA. In the pivotal 52-week phase 3 heiGHt trial and the 26-week fliGHt trial, lonapegsomatropin demonstrated safety and efficacy in both treatment-naïve and treatment-experienced children with GHD. Methods Results are reported from Week 130 (data snapshot date: September 01, 2021) from the open-label extension trial enliGHten. Upon entry into enliGHten, all participants received lonapegsomatropin via vial/syringe, with subsequent switch to TransCon hGH Auto-Injector when available. Results A total of 298 participants (98% of parent trials) continued from the heiGHt or fliGHt trials into enliGHten. At Week 130, 36 participants had completed the trial and 248 participants remain enrolled. The height standard deviation score (SDS) mean (standard deviation [SD]) at Week 130 was -0.64 (0.85) compared with baseline value of -1.56 (0.88) at the start of enliGHten. Participants continued to approach the average parental height SDS mean (SD) of -0.39 (0.77). The annualized height velocity mean (SD) at Week 130 was 9.32 cm/year (0.45). Average IGF-1 SDS mean (SD) at Week 130 was 1.46 (1.18) compared with 0.52 (1.58) at enliGHten baseline. For the 36 participants who had completed the trial, 14 had reached bone age of >14 years (girls) or >16 years (boys), and 24 had completed the study based on investigator judgement that treatment for growth hormone deficiency was no longer necessary. The difference between mean (SD) height SDS at last visit and average parental height SDS was -0.05 (0.75) for the 36 completers, and 61.1% of these participants had met or exceeded the average parental height SDS. The mean (SD) total duration of hGH treatment for participants who completed the trial (including daily treatment and lonapegsomatropin) was 3.53 (0.88) years, and the mean (SD) duration of treatment with lonapegsomatropin was 2.20 (0.66). With continued lonapegsomatropin treatment, the AE profile remained consistent with what was observed in the parent trials, with no new safety signals. Conclusions Children and adolescents treated with lonapegsomatropin showed continued improvement of height SDS through their 3rd year of therapy. Lonapegsomatropin continued to demonstrate a safety profile comparable to that of daily somatropin therapy. Presentation: Monday, June 13, 2022 12:30 p.m. - 12:35 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

TO CHALLENGE OR AVOID? POSSIBLE ASPIRIN ALLERGY IN PATIENTS WITH CHRONIC IDIOPATHIC URTICARIA AND ANGIOEDEMA

<h3>Introduction</h3> Aspirin remains an important component of dual antiplatelet therapy following percutaneous coronary intervention (PCI). Despite studies showing safety in discontinuing aspirin post PCI through use of P2Y12 inhibitor therapy plus anticoagulation, no large, randomized trials evaluate an initial aspirin-free regimen post PCI without systemic anticoagulation. Aspirin intolerances occur in 20% of patients, with only 2% being true allergies. Most aspirin intolerances are linked to asthma, rhinitis, and chronic idiopathic urticaria (CIU). Differentiating this population is important for optimizing care. <h3>Case Description</h3> C.P. is a 54-year-old male with CIU referred for evaluation of aspirin allergy prior to coronary angiography with possible PCI. In 2001, C.P. developed right periorbital edema an hour after his third dose of daily aspirin therapy. Antihistamines reduced the swelling within hours, however due to reaction, his physician recommended discontinuing aspirin. He noted taking aspirin as a child and ibuprofen as an adult without incident. An in-clinic open oral drug challenge to aspirin was conducted. The patient was given 1/10^th of the full dose, followed by the remaining dose then monitored for 1 hour. The patient was diagnosed with NSAID exacerbated CIU and discharged with aspirin and antihistamines for control. <h3>Discussion</h3> Without clear guidelines for managing NSAID induced CIU, many physicians recommend avoidance, resulting in suboptimal care. 20-40% of CIU patients have flares triggered by NSAIDs, and many are misdiagnosed with an aspirin allergy. Our case demonstrates that through careful history and oral challenge, aspirin exacerbated CIU can be effectively managed without forgoing quality care.

ODP329 Long-term Effect of Daily Growth Hormone Replacement Therapy on Glucose Tolerance in Adult growth Hormone Deficiency

Abstract Background Growth hormone replacement therapy (GHRT) in adults with growth hormone deficiency (AGHD) has shown to improve body composition, lipid and bone metabolism, and quality of life (QOL), but its effect on glucose tolerance can be bidirectional. Objective To investigate the long-term effect of GHRT on glucose tolerance in AGHD patients. Patients and Methods We conducted a retrospective single-center study at Kobe University Hospital. One hundred twenty-five AGHD patients who had visited our department since January 2011 to September 2021 were enrolled. The exclusion criteria was as follows: Patients 1) who never received GHRT 2) whose HbA1c was 6.5% or higher, or under antidiabetic drugs before GHRT, 3) not available data on HbA1c at baseline or after GHRT 4) with functional pituitary adenomas, 5) who had initiated GHRT at childhood and had discontinued GH for less than 1year due to transition, 6) who receiving supraphysiological doses of steroid therapy, 7) GHRT interruption period for more than 1 year or its initiation from less than 2 months. Fifty-three AGHD patients eventually met the inclusion criteria. We collected data at baseline, 3, 6, 12 months after treatment, and at each patients’ last visit. The influence of GHRT on glucose metabolism and its associated factors were analyzed. All data were presented as median [interquartile range]. Results Fifty-three patients (27 female (51. 0%), 14 childhood onset (26.4%), age at GH initiation was 45 [32 - 60] years, the duration of GHRT was 4 [2 - 6] years) were analyzed. Both IGF-I levels and IGF-I SDS increased at the last visit compared to baseline: 56 [38 - 88] to 119 [84.5 - 181] ng/mL (P&amp;lt;0. 01), and -3.4 [-5.1 - -2.4] to -0.2 [-1.8 - 1.1] (P&amp;lt;0. 01), respectively. Waist circumference and BMI remained unchanged: 85 [78 - 90.5]cm to 78.5 [72.1 - 86. 0]cm (P=0.18), 23.1 [21.3 - 26.3] kg/m 2 to 22.9 [21.9 - 26.8] kg/m 2 (P=0.53), respectively. HbA1c at baseline, 3, 6, 12 months after treatment, and the last visit were unchanged: 5.7[5.4 - 5.9]%, 5.7 [5.5 - 5.9]%, 5.8 [5.5 - 6. 0]%, 5.7 [5.5 - 6. 0]%, and 5.7 [5.5 - 6. 0]% (P=0.27). Based on the amount of change in HbA1c (ΔHbA1c) between baseline and at the last visit, we divided into two groups; Elevated/ Unchanged (E/U), and Reduced (R). Interestingly, the amount of change in BMI increased in E/U group but decreased in R group (0.9[-0.1–1.8] vs. -1.2[-1.4 - -0.1], P=0. 02). Conclusions Overall, GHRT was safely used in regard with impaired glucose tolerance at least non-diabetes mellitus patients with AGHD. Among them, cases with impaired glucose tolerance during GHRT were associated with increased BMI. Presentation: No date and time listed

PSUN236 Previously Undiagnosed Hereditary Pancreatitis Presenting as New Onset Type 3c Diabetes Mellitus

Abstract Background Type 3c Diabetes Mellitus (DM3c) or Pancreatogenic Diabetes is defined as diabetes secondary to pancreatic disease. The most common cause of Type 3c Diabetes is chronic pancreatitis, accounting for 80% of cases.1 Hereditary pancreatitis, with mutations such as SPINK1, CFTR, CTRC, is an underdiagnosed cause of chronic pancreatitis leading to Type 3c Diabetes Mellitus.1 The typical disease course for hereditary pancreatitis is recurrent episodes of acute pancreatitis that leads to chronic pancreatitis.1 The average time between hereditary pancreatitis diagnosis and development of DM3c has been shown to be 80 +/- 24 months.1 We present a case of previously undiagnosed hereditary pancreatitis presenting as new onset Type 3c Diabetes Mellitus. Clinical Case A 33-year-old male presents with a two month history of diarrhea, epigastric pain, and weight loss. Vital signs on presentation were blood pressure 105/74, heart rate 59, BMI 13. Physical exam revealed a cachectic appearing male with epigastric tenderness. Lab-work showed blood glucose 819 mg/dL, SOsm 313 mOsm/kg, lipase 21 U/L, bicarbonate 33 mmol/L. A computed tomography (CT) of the abdomen revealed punctate pancreatic parenchymal calcifications, suggestive of chronic pancreatitis. He was admitted to general medicine for management of HHS, where he was treated with IV hydration and insulin therapy. Workup for new onset diabetes revealed a negative anti-GAD Ab &amp;lt;5.0 U/mL, and C peptide level 0.5 ng/mL which suggested β cell dysfunction and decreased endogenous insulin secretion. With these lab values, along with radiographic findings consistent with chronic pancreatitis, the likely driving factor for his diabetes was pancreatic disease and he was diagnosed with DM3c. Severe pancreatic disease was further shown by a reduced fecal elastase level of &amp;lt;50, suggesting exocrine pancreatic insufficiency. Investigating the etiology of his chronic pancreatitis, history revealed no prior episodes of acute pancreatitis or abdominal pain, and no family history of pancreatitis. Workup for common causes of pancreatitis, including alcohol use, hypertriglyceridemia, and gallstones was negative, and genetic workup was pursued. The patient was found to be heterozygous for a SPINK1 mutation, which is a known mutation in hereditary pancreatitis.1 Therefore, hereditary pancreatitis was determined to be the likely cause of his chronic pancreatitis which led to Type 3c Diabetes Mellitus. He was started on daily insulin therapy and pancreatic enzymes for his endocrine and exocrine pancreatic dysfunction respectively, with improvement in symptoms. Conclusion This is a unique case of hereditary pancreatitis presenting as new onset Type 3c Diabetes Mellitus with no prior episodes of acute pancreatitis or established diagnosis of chronic pancreatitis. References Ramalho, G. X., &amp; Dytz, M. G. (2020). Diabetes of the exocrine pancreas related to hereditary pancreatitis, an update. Current Diabetes Reports, 20(6). Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

AlignRT®, Catalyst™ and RPM™ in locoregional radiotherapy of breast cancer with DIBH. Is IGRT still needed?

In locoregional radiotherapy of breast cancer with deep inspiration breath hold (DIBH), setup accuracy may depend on hospital protocol. At present, comparison between different positioning devices is challenging due to differing hospital protocols. The aim of this study was to evaluate the setup accuracy obtained with surface-guided radiation therapy (SGRT; AlignRT®, Catalyst™) or with lasers and real-time position management (RPM™) in DIBH. A total of 1692 image pairs were analyzed in three groups: positioning using AlignRT® surface guidance system (Group A, n = 45), Catalyst™ (Group C, n = 50) and conventional lasers and tattoos (Group L, n = 46). We evaluated residual errors for the bony chest wall, th1 and humeral head in kV images with laser- or SGRT-based setup with and without daily image-guided radiation therapy (IGRT). Less isocenter variance was found in Group A than in Group L or C (p ≤ 0.05) and in Group C than in L (p = 0.02-0.6). With SGRT only, the smallest random rotation error was found in Group A (p = 0.01). With daily IGRT, only a small difference was found for residual errors between the groups. Setup with SGRT improves the isocenter reproducibility compared to lasers and RPM™. Only small differences were found in setup accuracy between the SGRT devices. Due to improved isocenter accuracy, daily orthogonal IGRT is suggested in all the groups.

Fourteen Days vs 28 Days of Albendazole Therapy for Neurocysticercosis in Children: An Open Label Randomized Controlled Trial

There is a paucity of literature to support 14-days albendazole therapy for neurocysticercosis (NCC). To compare the efficacy of 14-day and 28-day albendazole therapy in the management of children with newly diagnosed active NCC. Open-labelled randomized controlled trial. Children aged 1-14 years with newly diagnosed active neurocysticercosis. Albendazole (15 mg/kg/day) for either 14 days or 28 days. The primary outcome measure was proportion of children with radiological resolution of active lesion at 6-month follow up. Secondary outcome measures were proportion of children with seizure recurrence, duration to seizure recurrence and calcification on follow up imaging. 65 children with newly diagnosed NCC were rando-mized to receive albendazole therapy for 14 days (n=32) or 28 days (n=33). The proportion of children with complete resolution was comparable between the two groups [6 (18.8%) vs. 9 (27.3%); OR (95%CI):0.61 (0.19 to 1.98); P=0.56]. Similarly, proportion of children with seizure recurrence [5(15.6%) vs 2(6.1%); OR (95%CI): 2.87(0.51-16.0); P=0.26] and proportion of children with calcification on follow-up imaging [26(81.2%) vs 23(69.7%); OR (95%CI): 1.88 (0.59-5.99); P=0.39] were also comparable. There were no major side-effects noted during the study. 14-day treatment with albendazole therapy is as effective as 28-day treatment in achieving radiological resolution at six-month follow up. However, high rate of calcification in both the groups indicates need for further evaluation with an adequately powered study and longer follow up.

Financial incentives for infection prevention and antimicrobial stewardship to reduce antibiotic use: Japan's nationwide observational study

The Japanese government introduced financial incentives to reduce nationwide antibiotic use in hospital settings. This study aimed to determine whether the nationwide financial incentives for creating infection prevention and control (IPC) teams introduced in 2012 and antimicrobial stewardship (ASP) teams introduced in 2018 were associated with changes in antibiotic use and health resource utilization at a national level. We conducted time-series analyses and a difference-in-differences study consisting of 3,057,517 inpatients with infectious diseases from 472 medical facilities during fiscal years 2011-2018 using a nationally representative inpatient database in Japan. The primary outcome was the days of therapy (DOT) of antibiotic use per 100 patient-days (PDs). The secondary outcomes consisted of types of antibiotic used, health resource utilization, and mortality. A total of 5,201,304 financial incentives were observed during 2012-2018, which resulted in a total of 12.1 billion JPY (≈110 million USD). Time-series analyses found decreasing trends in total antibiotic use (79.3-72.5 DOTs/100 PDs (8.6% reduction)) and carbapenem use (9.0-7.0 DOTs/100 PDs (7.8% reduction)) from 2011 to 2018 without adversely affecting other healthcare outcomes (e.g., mortality). In the difference-in-differences analyses, we did not observe meaningful changes in total antibiotic use between the incentivized and unincentivized hospitals for ASP teams, except for the northern part of Japan. No dose-response relationships were observed between the amount of financial incentives and reductions in antibiotic use during 2011-2019. Further research and efforts are needed to accelerate antimicrobial stewardship in hospital settings in Japan.

275 “MOVING ON UP”: FEASIBILITY OF A WARD-BASED THERAPY INITIATIVE TO IMPROVE PATIENT ACTIVITY LEVELS IN NEUROLOGICAL REHABILITATION

Abstract Background Patients admitted for neurological rehabilitation are not receiving sufficient dosage of activity to facilitate optimal recovery. Previous research has reported issues with feasibility and patient adherence to intensity programs. Methods Mixed methods were employed for this feasibility study. The “Moving On Up” program encompassed “Activitea” structured practice of sit to stands prompted by mealtimes, “Step It Up” a gradual walking program using pedometers and “Weekend Workout” increasing practice of exercise programs. These activities were in addition to daily therapy sessions over a four-week intervention period. Primary feasibility outcomes investigated recruitment, retention, adherence, adverse events, facilitators, barriers and acceptability of the program and preliminarily assessed changes in activity levels using the ActivPAL accelerometer. Functional tests assessed mobility, health-related quality of life and fear of falls. Descriptive statistics were used for analysing quantitative data. Braun and Clarke’s thematic analysis was adopted when reviewing qualitative data. Results Ten participants were recruited with zero dropouts. Median age was 72 years and five had a diagnosis of brain tumour excision. Eight participants demonstrated excellent adherence with completion of daily activity logs. There was one participant non-injurious fall, no other adverse events. Clinical outcomes demonstrated improvement in median daily step count, stepping and standing time. The median daily step count for the group increased from 1,375 steps (IQR 2,867, range 82-4,248) to 1,724 steps (IQR 2,914, range 80-8,207). All functional tests improved. Seven participants and three therapists completed semi-structured interviews. Five themes emerged; motivation to move more, empowerment, barriers to increasing activity, weekends long and boring and job satisfaction. Conclusion The “Moving On Up” program was feasible to implement without additional staffing and was accepted by key stakeholders. Future research is warranted into the program's effectiveness, incorporating a larger sample and randomised pilot trial. Inclusion of a follow-up of participants after discharge would be desirable to investigate long-term effects on activity.

Safety of Electrotherapy Treatment in Patients with Knee Osteoarthritis and Cardiac Diseases.

To assess the safety of electrotherapy applied in the knee area in patients with known atrial arrhythmias or ischemic heart disease, as it is not known whether this treatment induces or aggravates arrhythmias during or immediately after therapy. The analytical and transversal study involved 46 patients with degenerative knee osteoarthritis (OA), with or without cardiac diseases, from the Clinical Rehabilitation Hospital inpatient center, Cluj-Napoca, Romania. All patients underwent a 10-day physical therapy program for knee OA (electrotherapy, massage and kinesiotherapy). Heart rate and the total number of ventricular and supraventricular extrasystoles were evaluated before and after treatment, by 24 h Holter ECG monitoring. There was no significant increase in heart rate or in the number of ventricular or supraventricular extrasystoles before or after electrotherapy treatment, regardless of the positive or negative history of arrhythmia or ischemic heart disease (all p &gt; 0.05). Mean values during day 1 were: 35.15 (95% CI [9.60-60.75]) for ventricular ones extrasystoles and 91.7 (95% CI [51.69-131.7]) for supraventricular ones, which during day 2 were 38.09 (95% CI [3.68-72.50]), 110.48 (95% CI [48.59-172.36]), respectively. One of the most important things to consider when dealing with an OA patient is that they are most likely older than 65 years, which increases the chance of having a cardiac disease. This raises the need for viable interventions regarding the management of this disease in patients that probably have multiple comorbidities, and where pharmacological and surgical management are not possible, limited or have multiple side effects. Electrotherapy used for treating knee OA did not cause a significant increase in heart rate or number of ventricular and supraventricular extrasystoles in this category of patients.

Efficacy of Control-IQ Technology in a General Endocrine Clinic

ObjectiveRecent advances in technology have allowed for the expanded use of hybrid closed-loop insulin pump therapy and automated insulin delivery systems for the management of diabetes mellitus. We assessed the outcomes of introducing Tandem t:slim X2 with the Control-IQ technology in a general endocrine clinic. MethodsData from 66 adults with type 1 (n = 61) and type 2 (n = 5) diabetes mellitus were aggregated for analysis. Patients were either transitioned from traditional insulin pump therapy or multiple daily injection therapy to Tandem t:slim X2 with the Control-IQ technology from January 2020 to June 2021. The assessed clinical end points included changes in time below range, time above range, and time in target range. Changes in hemoglobin A1C before and after Control-IQ technology implementation were noted. The primary outcome was a change in time in target range with the Control-IQ technology. ResultsThere was a significant increase in time in target range when comparing pre- and post–Control-IQ technology (49.5% vs 63.3%, P < .0003) values. There was a reduction in time above range (46.8% vs 34.9%, P < .0013), a decrease in time below range (4.0% vs 1.7%, P = .017), and a decrease in hemoglobin A1C after transitioning to the Control-IQ technology (7.7% [61 mmol/mol] vs 7.1% [54 mmol/mol], P < .017). The patient dropout rate was low (7%). ConclusionThe Control-IQ technology system was effective in reducing hyperglycemia while increasing time in target range and decreasing hypoglycemia. This technology is a useful and effective addition to the growing number of automated insulin delivery systems. The clinical outcomes mirror the results found in the key adult pivotal trials.

An Analysis of PTV Margins for Postoperative Pelvic Nodal Radiotherapy (PNRT) Using a Dose Accumulation Workflow

<h3>Purpose/Objective(s)</h3> PTV margins are created to ensure coverage of the target volume. There is no uniform consensus on the PTV margins for prostate bed radiotherapy. Our institution's PTV margins for prostate bed are 8mm everywhere but posterior - a size that leads to PTVs on the order of 2.5 times the prostate bed. We hypothesized that the current PTV margins for prostate bed is larger than necessary in the context of daily cone-beam CT (CBCT)-guided intensity-modulated arc therapy. <h3>Materials/Methods</h3> Nineteen PCa patients treated with daily CBCT-guided intensity-modulated arc therapy were studied. Patients received 68 Gy to the prostate bed (PTV68) and 52.7 Gy to the elective pelvic nodes (CTV52.7, no PTV margins), all in 34 fractions. Patients followed strict bladder and rectal preparation protocols and had daily pretreatment CBCT images. Patient data, consisting of planning CTs and 7 representative CBCTs (1/week), were anonymized. Using a dose accumulation workflow, synthetic CTs (sCT) were created from the planning CTs and the representative CBCTs. Volumes were deformed to the sCT and checked for consistency. The sCTs were sent to the planning system, and a single fraction of the treatment plan was recalculated on the sCT. These daily dose distributions were used to assess target coverages and OAR doses on a daily/weekly basis. <h3>Results</h3> One hundred and thirty-three CBCTs were assessed. In 100% of the fractions, at least 97% of the prostate bed was covered by the prescription dose. Only 2 patients had a max, mean, and median dose to the prostate bed less than planned (though the mean, max and median doses were all greater than 2Gy/fx) at approximately 1 cGy below a value planned per fraction; the remaining 17 patients were at or above the aforementioned planned doses. Though the CTV52.7 coverage dropped slightly compared to the original plan, in 100% of the fractions the CTV52.7 received a median dose equal to or higher than planned. In 74% of the fractions, at least 95% of CTV52.7 was covered by 95% of the prescription dose. In 100% of the fractions at least 90% of the CTV52.7 received 90% of the planned prescription dose. On average there was a 2% difference in the volumes of OARs at the V40, V65 and maximum dose points. <h3>Conclusion</h3> Our results suggest that, in the context of daily CBCT-guided postoperative RT with strict bladder and rectal preparation protocols, a PTV margin of 8 mm everywhere and 6 mm posteriorly is sufficient if not slightly larger than needed. Further studies on margin reduction and its clinical implications are warranted.

Daily Artificial Intelligence-Assisted Adaptive Radiotherapy on Cone-Beam CT for Cancer of the Head and Neck

<h3>Purpose/Objective(s)</h3> Adaptive radiation therapy (ART) provides a method to modify the radiation treatment plan secondary to structural and spatial changes that occur during a treatment course. Specifically, ART is relevant in head and neck cancers as many patients will experience changes of the target volumes and organs-at-risk (OARs) during treatment due to combination of treatment response, weight loss, inflammation and effects on normal tissues. Our institution recently began performing daily ART for select cases of definitive Head and Neck cancers using a commercially available, online adaptive platform with AI-assisted workflows on daily cone-beam computed tomography (CBCT). Herein we report our initial dosimetric experience using this novel technique. <h3>Materials/Methods</h3> Twelve consecutive head and neck cancer patients (nasopharynx, oropharynx, larynx) underwent CT-simulation and planned for adaptive treatments. A reference IMRT plan was created and approved using institutional dose/fractionation schema, target goals and OAR constraints. For treatment, the patient was aligned and CBCT acquired. The simulation CT scan was subsequently registered to the CBCT using deformable registration and a synthetic CT scan was generated. AI-based auto-contour and structure deformation of OARs and Targets on CBCT were reviewed and edited by the treating physician. Two plans were generated including, a CT sim-based plan with deformed structures (scheduled) and a re-optimized plan (adaptive) of which both plans evaluated and the best one approved and delivered. Statistical analyses were performed comparing adaptive versus scheduled plans using a paired student's t-test. <h3>Results</h3> 419 adaptive and scheduled radiotherapy plans were generated of which 82.2% adaptive plans were chosen with an average time per session of 19.4 minutes. Adaptive plans demonstrated superior V95 PTV70, PTV60, PTV56 mean coverage by 0.8 (95% CI 0.5%-1.1%, p < 0.001), 2.4% (95% CI 2%-3%, p < 0.001), and 5.9% (95% CI 5.4%-6.5%, p < 0.001). Compared to scheduled plans, high priority OARs demonstrated a reduction in: mean parotid gland right and left dose by 3.2 Gy (95% CI 1.9-4.4, p < 0.001) and 2.7 Gy (95% CI 1-4.4, p < 0.001), respectively and brainstem max dose was reduced by 5.2% (95% CI 3.7%-6.7%, p < 0.001). <h3>Conclusion</h3> Daily AI-assisted adaptive radiation therapy for head and neck cancer may potentially improve the therapeutic index for different tumor types by improving the target coverage and reducing OAR dose. Prospective clinical evaluation is indicated to further this novel approach.

Comparison of Acute and Chronic Toxicities with Daily vs. QOD Partial Breast Radiation Therapy

<h3>Purpose/Objective(s)</h3> Radiation therapy for breast cancer has evolved from standard fractionation over 5-6 weeks to regimens that allow for completion in 1 week or less; additionally, the target of therapy for patients following breast conserving surgery has evolved from whole breast to partial breast for appropriately selected patients. One such regimen is a 5-fraction partial breast approach; while originally given every other day, questions regarding delivery daily have emerged. We therefore aimed to characterize the acute and chronic toxicities of daily or every-other-day (QOD) 5 fraction PBI. <h3>Materials/Methods</h3> The charts of 273 patients treated from 2017-2021 were identified from an institutional registry and retrospectively reviewed to assess for acute (within 90 days of treatment) and chronic toxicities. All patients received 30 Gy in 5 fractions. Their age, BMI, comorbidities, follow up time, tumor stage, adjuvant therapies, and type of toxicity were recorded. Toxicity related to radiation treatment includes fatigue, dermatitis, desquamation, telangiectasia, lymphedema, and cosmesis. Clinical variables were summarized using descriptive statistics and compared using the Chi-square test. <h3>Results</h3> Of the 273 patients, 64 were treated daily with APBI and 209 were treated QOD. Median follow up was 0.8 years in the daily and 1.2 years in the QOD group. With respect to stage, Tis (11% daily, 19% QOD), T1 (86% daily, 76% QOD), and T2 (3% daily, 5.8% QOD) were relatively well balanced between groups. Comorbidities in both groups were comparable and included obesity (p=0.77), COPD (p=1), CAD (p=1), asthma (p=0.79), HTN (p=0.47), diabetes (p=0.49), and dyslipidemia (p=0.38). 1.6% of patients in the daily group and 1.5% patients in the QOD group received HER2 targeted therapy. 1% of patients in the QOD group and no patients in the daily group received anthracycline. 78% of patients in the daily group and 76% of patients in the QOD group were treated with endocrine therapy. Patients who received QOD therapy had higher rates of acute grade 1 dermatitis (34% QOD vs 19% daily, p = 0.02) and grade 1 fatigue (15% QOD vs 6% daily, p = 0.11). Overall, the majority of patients in both groups did not experience any acute fatigue (93.8% daily, 84% QOD). There were very few instances of chronic toxicity overall, only 1 patient (1.7%) in the daily group with chronic dermatitis vs. 7 (3.6%) in the QOD group. 12% of QOD patients experienced chronic toxicities including hyperpigmentation or fibrosis vs. 3.4% from the daily group (p = 0.051). <h3>Conclusion</h3> Overall, there are few acute and chronic toxicities related to 5 fraction APBI, with significantly less acute toxicity among the daily group. Daily APBI treatment can be considered for patients as an alternative to QOD 5 fraction PBI.

Dosimetric Impact of Simulated Daily Adaptive Radiotherapy with Significantly Reduced Setup Margins in the Definitive Treatment of Head and Neck Cancer

<h3>Purpose/Objective(s)</h3> Even when treating head and neck cancer (HNC) with daily image-guided radiation therapy, setup margins of 3-5 mm are required to ensure adequate coverage of disease due to setup error. These margins lead to additional normal tissue dose that may compromise acute and long-term quality-of-life. The use of daily adaptive radiotherapy (ART) using an online adaptive system significantly reduces the need for a PTV margin, since the targets and organs-at-risk (OAR) are recontoured each fraction. In this study, we hypothesized using daily ART (simulated) with 1 mm margins based on our involved nodal radiotherapy (INRT) paradigm would improve coverage and reduce OAR dose. <h3>Materials/Methods</h3> Ten patients with HNC treated on our institutional phase II INRT trial were selected for this study. Cone-beam CT scans were uploaded to the ETHOS emulator for daily adaptive replanning which was simulated using fractions 5, 10, 15, 20, 25, 30, and 35. Two plans were generated with a 1 mm (reduced) and a 5 mm (conventional) PTV expansion. The dose grid from the delivered, conventional margin plan was transposed onto the CBCT and adapted contours. Separately, a reduced target margin plan optimized on the online adaptive system was created. PTV coverage (70 Gy-gross/primary disease, 66.5 Gy-suspicious nodes, 63 Gy-extended volume surrounding the primary disease) and D1 were calculated for target structures along with the dose to OARs. Comparisons performed via paired two tailed t-test. <h3>Results</h3> Six patients with oropharynx cancer and four patients with larynx cancer were included. Median V100% coverage for 70 Gy (96% vs 95.6%), 66.5 Gy (98.5% vs 76.5%), and 63 Gy (98.9% vs 74.9%) were improved with the adaptive planning (all p-values<0.03). Plan homogeneity was improved in the ART plan (e.g., PTV70 median D1% 72.8 Gy vs 74.8 Gy, all p-values<0.02). The total median dose reduction was 10.8 Gy (interquartile range, IQR 8.0-12.6 Gy) for the ipsilateral submandibular gland (SMG), 12.2 Gy (IQR 7.3-23.5 Gy) for the contralateral SMG, 8.3 Gy (IQR 3.8-12.6 Gy) for the ipsilateral parotid, 8.1 Gy (IQR 4.4-11.0 Gy) for the contralateral parotid, 7.0 Gy (IQR 4.5-9.1 Gy) for larynx, 6.6 Gy (IQR 2.7-8.4 Gy) for oral cavity, and 8.6 Gy (IQR 5.9-12.1 Gy) for constrictors. <h3>Conclusion</h3> Simulated daily ART using a 1 mm PTV margin provided significant improvement over conventional PTV margins in coverage and critical OAR dosimetry. This small proof-of-concept study suggests this approach may lead to improved quality-of-life while preserving or improving tumor coverage. Further evaluation is needed to assess the resources needed to implement daily adaptations. A phase II randomized trial of daily ART is underway to determine if dosimetric improvements lead to similar gains in patient-reported outcomes.

Efficacy of a 5-day, intensive, multidisciplinary, outpatient physical and occupational therapy protocol in the treatment of functional movement disorders: A retrospective study

BackgroundThe use of rehabilitation services has been shown to be beneficial for patients with functional movement disorders (FMD). However, there is great variability in the type of rehabilitation services utilized. In the present study we aimed at determining the efficacy of an intense outpatient physical rehabilitation program as a treatment modality for patients with FMD. MethodsEighteen participants underwent treatment in a specialized outpatient rehabilitation program utilizing a multidisciplinary approach for the treatment of FMD. Participants completed a series of tests on day one and day five of the program. ResultsResults indicated statistically significant improvements in all but one motor and gait outcomes in patients with functional movement disorders treated with physical rehabilitation. Conclusion: These results provide support for the continued use of physical and occupational therapy for functional movement disorder patients. Further research is needed to fully validate these findings and there remains a need for further study into multidisciplinary approaches that may be even more efficacious.

A Neonatologist-Driven Antimicrobial Stewardship Program in a Neonatal Tertiary Care Center in Oman.

The overuse of antimicrobials in neonates is not uncommon and has resulted in a global health crisis of antibiotic resistance. This study aimed to evaluate changes associated with a neonatologist-driven antimicrobial stewardship program (ASP) in antibiotic usage. We conducted a pre-post retrospective cohort study in a tertiary care hospital in Oman. Neonates admitted in 2014 to 2015 were considered as the pre-ASP cohort. In 2016, a neonatologist-driven ASP was launched in the unit. The program included the optimization and standardization of antibiotic use for early- and late-onset sepsis using the Centers for Disease Control and Prevention's "broad principles," an advanced antimicrobial decision-support system to resolve contentious issues, and placed greater emphasis on education and behavior modification. Data from the years 2016 to 2019 were compared with previous data. The outcome of interest included days of therapy (DOT) for antimicrobials. Baseline characteristics and outcomes were compared using standard statistical measures. The study included 2,098 neonates in the pre-ASP period and 5,464 neonates in the post-ASP period. There was no difference in baseline characteristics. The antibiotic use decreased from 752 DOT per 1,000 patient-days (PD) in the pre-ASP period to 264 DOT in the post-ASP period (64.8% reduction, p < 0.001). The proportion of neonates who received any antibiotics declined by 46% (pre-ASP = 1,161/2,098, post-ASP = 1,676/5,464). The most statistically significant reduction in DOT per 1,000 PD was observed in the use of cefotaxime (82%), meropenem (74%), and piperacillin-tazobactam (74%). There was no change in mortality, culture-positive microbial profile, or multidrug-resistant organism incidence in the post-ASP period. Empowering frontline neonatologists to drive ASPs was associated with a sustained reduction in antibiotic utilization. · Overuse of antimicrobials is not uncommon in neonatal intensive care units.. · ASPs and infection control and prevention measures may help in decreasing antibiotic consumption and culture-positive sepsis.. · Empowering frontline neonatologists resulted in a sustained decrease in antimicrobial use without extra resources or financial burden..