Outpatient Study Research Articles

Medication Adherence and Belief about Medication among Vietnamese Patients with Chronic Cardiovascular Diseases within the Context of Implementing Measures to Prevent COVID-19.

Background: Long-term adherence is crucial for optimal treatment outcomes in chronic cardiovascular diseases (CVDs), especially throughout the COVID-19 wide-spreading periods, making patients with chronic CVDs vulnerable subjects. Aim: To investigate the relationship between the characteristics, beliefs about prescribed medication, COVID-19 prevention measures, and medication adherence among patients with chronic CVDs. Methods: This is a cross-sectional study of outpatients with chronic CVDs in Southern Vietnam. The specific parts regarding the Beliefs about Medicines Questionnaires (BMQ—Specific) and the General Medication Adherence Scale (GMAS) were applied to assess the beliefs about and adherence to medication. The implementation measures to prevent COVID-19 in patients were evaluated according to the 5K message (facemask, disinfection, distance, no gathering, and health declaration) of the Vietnam Ministry of Health. A multivariable logistic regression with the Backward elimination (Wald) method was used to identify the associated factors of medication adherence. Results: A slightly higher score in BMQ-Necessity compared to BMQ-Concerns was observed. A total of 40.7% of patients were recorded as having not adhered to their medications. Patients’ behavior was most frequently self-reported by explaining their non-adherence (34.7%). Statistical associations were found between rural living place, unemployment status, no or only one measure(s) of COVID-19 prevention application, and medication adherence. Conclusion: During the COVID-19 spreading stage, patients generally showed a positive belief about medication when they rated the importance of taking it higher than its side effects. The data analysis suggested that rather than patients’ beliefs, the clinicians should consider the patient factors, including living place, employment, and the number of epidemic preventive measures applied for guiding the target patients for improving medication adherence.

Obesity and Frailty Syndrome in the Elderly: Prospective Study in Primary Care.

Background: Obesity is a chronic pathology that affects people of all ages, from infants to the elderly, residing in both developed and developing countries. Objective: Our aim is to study the link between obesity and frailty in the elderly. Method: A prospective study was carried out in 12 General Medicine practices in Champagne-Ardenne, in the Departments of Marne and the Ardennes, France, for a period of 12 months (from 2 May 2019 through 30 April 2020). All patients included were aged 65 or older, in consultation with a general practitioner, and had an ADL (Activity of Daily Living) greater than or equal to 4. Frailty was measured using the Fried scale and the simplified ZULFIQAR frailty scale. Results: 268 patients aged 65 and over were included, with an average age of 77.5 years. A total of 100 were obese according to BMI. The mean Fried (/5) in the series was 1.57, and the mean sZFS (/5) was 0.91. Our study shows that obesity is not significantly correlated with frailty according to the FRIED sarcopenic scale, but is significantly correlated with frailty according to the sZFS scale. Conclusions: The link between obesity and frailty remains much debated, with the underlying emergence of sarcopenic obesity equally prevalent among the elderly. This is a preliminary study that should be followed by large-scale outpatient studies to better clarify the links between sarcopenia and obesity.

Impact of COVID-19 pandemic on epilepsy care in Japan: A national-level multicenter retrospective cohort study.

ObjectiveThe impact of the coronavirus disease 2019 (COVID‐19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study.MethodsThis study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy center‐specific monthly data divided by the 12‐month average in 2019 for each facility. We determined whether the COVID‐19 pandemic‐related factors (such as year [2019 or 2020], COVID‐19 cases in each prefecture in the previous month, and a state of emergency) were independently associated with these outcomes.ResultsIn 2020, the frequency of outpatient EEG studies (−10.7%, P < .001) and cases with telemedicine (+2608%, P = .031) were affected. The number of COVID‐19 cases was an independent associated factor for epilepsy admission (−3.75 × 10−3% per case, P < .001) and EEG monitoring (−3.81 × 10−3% per case, P = .004). Furthermore, a state of emergency was an independent factor associated with outpatient with epilepsy (−11.9%, P < .001), outpatient EEG (−32.3%, P < .001), telemedicine for epilepsy (+12,915%, P < .001), epilepsy admissions (−35.3%; P < .001), EEG monitoring (−24.7%: P < .001), and epilepsy surgery (−50.3%, P < .001).SignificanceWe demonstrated the significant impact that the COVID‐19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic‐related factor on epilepsy care.

Effectiveness of vortioxetine in real-world clinical practice: Italian cohort results from the global RELIEVE study

IntroductionMajor depressive disorder (MDD) is a debilitating disease in Italy affects 5.4% of people over 15 and 11.6% for the elderly. Efficacy of vortioxetine in adult patients with MDD was demonstrated in randomised controlled trials, there is a need for data on treatment in daily practice in Italy.ObjectivesTo present the effectiveness and safety data of vortioxetine in real-world setting from patients enrolled from Italy in the RELIEVE study.MethodsRELIEVE was a prospective, multi-national, observational study of outpatients initiating vortioxetine treatment for MDD at physician’s discretion. Data and outcomes of treatment of patients were collected at routine clinical visits. The primary outcome was functioning measured by SDS. Secondary outcomes included depressive symptoms measured by PHQ-9, cognitive funcion measured by PDQ-5, quality of life measured by EQ-5D-5L. Changes from baseline to month 6 were estimated with a linear mixed model of repeated measures approach.ResultsA total of 231 patients (mean age, 55.5 years, 27.3% over 65 years, 62% female) were enrolled from Italy and included in the analysis. Mean(SD) SDS total score, PHQ-9, PDQ-5 scores at baseline were 17.8(7.58), 15.7(5.97) and 9.8(4.99), the scores(SE) decreased by 6.6(0.64), 5.9(0.47) and 3.6(0.36) from baseline to last visit. Mean(SE) EQ-5D-5L utility index increased by 0.13(0.01). Safety and tolerability profile of vortioxetine was in line with the established profile.ConclusionsImprovements in overall functioning, depressive symptoms, cognitive function and quality of life were observed in patients treated with vortioxetine, including a wide proportion of elderly patients in a real-world setting.DisclosureA. Pugliese is an employee of Lundbeck Italy. K. Simonsen and H. Ren are employees of H. Lundbeck A/S.

Study design of VGOAL-J: an observational, prospective cohort study to assess effectiveness of vortioxetine on goal achievement and work productivity in patients with MDD in Japan

IntroductionGoal attainment scaling (GAS) is a method to assess the patient experience of whether a treatment is successful and capture outcomes across a diverse range of goal areas. However, this approach has not yet been used in assessing the treatment of Major Depressive Disorder (MDD) in Japan. GAS was first developed by Kiresuk and Sherman in the 1968, it is increasingly recognised as a sensitive method for recording patient-centred outcomes throughout the course of treatment.ObjectivesTo demonstrate the effectiveness of vortioxetine on patient’s goal achievement and depressive symptoms, emotional, cognitive, overall function and quality of life.MethodsVGOAL-J is a prospective, multi-center, observational cohort study of outpatients initiating vortioxetine treatment for MDD in Japan. Patients with a diagnosis of MDD according to DSM-5 who are 18 to 65 years will be enrolled from 20 sites in Japan and followed for 24 weeks. A total number of 120 patients is planned for enrolment. Primary outcome measures are GAS-D, WPAI, secondary outcome measures include Montgomery – Åsberg Depression Rating Scale (MADRS), Sheehan Disability Scale (SDS), Perceived Deficits Questionnaire-Depression 5-item (PDQ-D-5), Oxford Depression Questionnaire (ODQ), EuroQol-5 Dimension (EQ-5D). Safety will be also assessed with Adverse Events collected during the study.ResultsThe results will be disseminated in late 2022 and provide new insights on GAS-D as an effective strategy to assess MDD treatment in Japan.ConclusionsWe expect to observe patients treated with vortioxetine achieving their treatment goals as assessed by GAS-D and improvements on patient- and clinician-reported measures in real-world settings.DisclosureProf. K. Watanabe reports consultancies undertaken for Eli Lilly, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, and Takeda Pharmaceutical, honoraria received from Daiichi Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, J

Effectiveness of vortioxetine in real-world clinical practice: French cohort results from the global RELIEVE study

IntroductionMajor depressive disorder (MDD) affects around 10% of the French population annually and significantly impacts patient functioning. Efficacy of vortioxetine was demonstrated in randomised controlled trials, data on its real-world performance is needed.ObjectivesTo describe the effectiveness and safety of vortioxetine in real-world setting from patients enrolled from France in the global RELIEVE study.MethodsRELIEVE was a prospective, multi-national, observational study of outpatients initiating vortioxetine treatment for MDD at physician’s discretion. Data were collected at routine clinical visits. Here we present the outcomes of treatment of patients in France. The primary outcome was functioning measured by SDS. Secondary outcomes included depressive symptoms measured by PHQ-9, cognitive symptoms measured by PDQ-5 and DSST. Changes from baseline to month 6 were estimated with a linear mixed model of repeated measures approach.ResultsA total of 184 patients (mean age, 50.2 years, 65% female, 67.9% of patients had at least one comorbidity) were enrolled from France and included in the analysis. Mean(SD) SDS total score, PHQ-9, PDQ-5 scores at baseline were 21.1(5.4), 17.5(4.7) and 11.7(4.4), the scores(SE) decreased by 10.9(0.59), 9.3(0.48) and 6.1(0.37) from baseline to month 6. Mean(SD) DSST improved from 41.6(15.2) at baseline to 49.1(19.0) at month 6. Safety and tolerability profile of vortioxetine was in line with previous studies.ConclusionsSustained improvements in overall functioning, depressive symptoms, cognitive function were observed in patients treated with vortioxetine in a real-world setting, which provided further evidence of effectiveness and safety of vortioxetine in a broad MDD population in France.DisclosureM. Rabbani is an employee of Lundbeck France. K. Simonsen and H. Ren are employees of H. Lundbeck A/S.

257-OR: Pen-Administered Low-Dose Dasiglucagon vs. Usual Care for Prevention and Treatment of Nonsevere Hypoglycemia in People with Type 1 Diabetes during Free-Living Conditions: A Phase 2, Randomized, Two-Period, Crossover Outpatient Study

Objective: To evaluate the efficacy, safety and feasibility of pen-administered low-dose dasiglucagon for prevention and treatment of non-severe hypoglycemia in people with type 1 diabetes during free-living conditions. Methods: Twenty-four adults with insulin pump-treated type 1 diabetes completed a phase 2, randomized, open-label, 2-period cross-over study with 2-week periods. During the usual care (UC) and dasiglucagon (DASI) period, participants managed impending and manifest episodes of hypoglycemia with regular carbohydrate consumption or pen-administered low-dose (80 µg) s.c. dasiglucagon, respectively. Glycemic control was evaluated using continuous glucose monitoring (Dexcom G6) and event-registration of prevention and treatment episodes. Patient-reported outcomes (PRO) were collected following study completion. Results: Participants administered dasiglucagon (IQR: 7-15) times during the 2-week period. Compared with UC, the mean difference (±SEM) in time in range (70-180 mg/dL) was 2.4%-point (±1.5%) (UC: 61.5%, DASI: 63.9%, p=0.129) , difference in time below range (&amp;lt;70 mg/dL) was 0.5%-point (±0.4%) (UC: 3.1%, DASI: 2.6%, p=0.170) , while total daily carbohydrate intake was significantly reduced (UC: 192 g, DASI: 172 g, p=0.007) . Dasiglucagon use was safe and well tolerated with nausea being the most frequent adverse effect (no. of participants: UC: 4, DASI: 8, p=0.206) . PRO demonstrated that 96% (p&amp;lt;0.001) of participants were likely to include dasiglucagon as part of their future routine management of hypoglycemia. Conclusion: Utilization of pen-administered, low-dose dasiglucagon for prevention and treatment of non-severe hypoglycemia during free-living conditions was safe and efficacious while significantly reducing the total daily carbohydrate intake and yielding high treatment satisfaction. Disclosure C.Laugesen: None. A.G.Ranjan: None. S.Schmidt: None. K.Nørgaard: Advisory Panel; Medtronic, Novo Nordisk A/S, Consultant; Novo Nordisk A/S, Research Support; Dexcom, Inc., Medtronic, Novo Nordisk A/S, Zealand Pharma A/S, Speaker's Bureau; Medtronic, Stock/Shareholder; Novo Nordisk A/S. Funding SteDiabetes Center Copenhagen is the sponsor of this investigator-initiated trial. Zealand Pharma provided financial support to the conduct of the study and supplied the study medication.

0382 Optimizing Obstructive Sleep Apnea Screening and Education in Underserved Community

Abstract Introduction Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. There are many conditions associated with OSA, including obesity hypoventilation syndrome, congestive heart failure, atrial fibrillation, pulmonary hypertension and pulmonary diseases. Majority of patients endorse daytime sleepiness, but family often report snoring and apneas. There are multiple screening tools, including the STOP-BANG. Scores 5 or above are high risk for OSA. Untreated OSA worsens comorbidities and increases risk of myocardial infarction and stroke. We provided physicians with this screening tool to help risk stratify, thus providing better patient education and treatment. Methods Physicians educated on OSA, STOP-BANG and documentation in didactic sessions. Patients ages 18 and older provided with questionnaire. Physicians measured neck circumference and BMI. Questionnaire reviewed with patient and education given. If high risk, sleep medicine referral recommended. Physicians documented in charts about discussion, risk category and referral status. Results Total of 407 patients completed the questionnaire, but 67 patients were excluded for no neck circumference. Remaining 340 patients stratified by STOP-BANG scores: 128 Low, 142 Intermediate, 70 High Risk. From High Risk category, 20 patients referred to Sleep Medicine. Only 18 charts from the 50 not referred explained why, which included patient declining, already on CPAP, referral already in, and because outpatient sleep study was ordered instead. Data stratified for age, gender, BMI and neck circumference. Age range from the 340 total was 19-87-years-old. From High Risk, 39 were male and 31 female. BMI range for total was 17-61, while High Risk was 22-61. Neck circumference range for total was 12-21 inches, while High Risk was 12.5-17.5 inches. Conclusion The goal was not only to provide a validated screening tool, but also provide better OSA education for physicians and patients. Results indicate many patients were intermediate or high risk. Majority of patients had multiple comorbidities, including obesity, hypertension and diabetes. This study highlights the prevalence of OSA in an inner-city primary care clinic and challenges involved in screening all at risk patients. Further investigations could include the effect of more education, continued screening and effect of lifestyle changes in this vulnerable population. Support (If Any)

A real-world, non-interventional, prospective study of the effectiveness and safety of apremilast in bio-naïve adults with moderate plaque psoriasis treated in the routine care in Greece - the 'APRAISAL' study.

Real-world data in patients with moderate psoriasis treated with apremilast is limited. To evaluate the effectiveness and safety of apremilast in bio-naïve patients with moderate psoriasis in real-world clinical settings. This was a 52-week multicenter, observational, prospective study of adult outpatients with moderate psoriasis {[10% < body surface area < 20% or 10 < psoriasis area severity index (PASI) < 20] and 10 < dermatology quality of life index (DLQI) < 20} initiated on apremilast ≤7 days before enrollment. Missing data were imputed using the last observation carried forward method. A total of 287 eligible patients (median age: 54.2 years; median psoriasis duration: 9.8 years) were consecutively enrolled. At baseline, the median DLQI and PASI scores were 12.0 and 11.8, respectively. The 52-week DLQI ≤ 5 and PASI75 response rates were 68.3% and 61.0%. At 52 weeks, 70.8% and 72.7% of the patients shifted from moderate/severe/very severe to clear/minimal scalp and palmoplantar psoriasis involvement, respectively; the pruritus severity state improved in 67.2%. The 52-week Kaplan-Meier estimated drug continuation rate was 85.3%. The adverse drug reaction rate was 19.9%. Apremilast is a safe and effective treatment for bio-naïve patients with moderate psoriasis and specific psoriasis manifestations.

18F-FDG Brain PET Findings in Narcolepsy Type 2.

A 16-year-old adolescent boy with extensive travel throughout West Africa presented with a 6-year history of social withdrawal, anhedonia, and daytime sleepiness. The patient's electroencephalography was normal. Initial MRI revealed small pituitary gland and left temporal developmental venous anomaly. Subsequently obtained 18F-FDG brain PET was notable for markedly severe hypometabolism in the brainstem. Further workup revealed a normal orexin, autoimmune encephalitis panel, and negative titers for Trypanosoma brucei and cruzi in the CSF. Outpatient sleep study showed mild obstructive sleep apnea, and multiple sleep latency test revealed reduced mean sleep latency at 7 minutes with sleep-onset REM in 3/5 naps, findings consistent with narcolepsy type 2.

A Heavy Burden: Preexisting Physical and Psychiatric Comorbidities and Differential Increases Among Male and Female Participants After Initiating Antiretroviral Therapy in the HIV Outpatient Study, 2008-2018.

Attention to non-AIDS comorbidities is increasingly important in the HIV care and management in the United States. We sought to assess comorbidities before and after antiretroviral therapy (ART) initiation among persons with HIV (PWH). Using the 2008-2018 HIV Outpatient Study (HOPS) data, we assessed changes in prevalence of physical and psychiatric comorbidities, by sex, among participants initiating ART. Cox proportional hazards models were fit to investigate factors associated with the first documented occurrence of key comorbidities, adjusting for demographics and other covariates, including insurance type, CD4+ cell count, ART regimen, and smoking status. Among 1,236 participants who initiated ART (median age 36 years, CD4 cell count 375 cells/mm3), 79% were male, 66% non-white, 44% publicly insured, 53% ever smoked, 33% had substance use history, and 22% had body mass index ≥30 kg/m2. Among females, the percentages with at least one condition were: at ART start, 72% had a physical and 42% a psychiatric comorbidity, and after a median of 6.1 years of follow-up, these were 87% and 63%, respectively. Among males, the percentages with at least one condition were: at ART start, 61% had a physical and 32% a psychiatric comorbidity, and after a median of 4.6 years of follow-up, these were 82% and 53%, respectively. In multivariable Cox proportional hazards analyses, increasing age and higher viral loads (VL) were associated with most physical comorbidities, and being a current/former smoker and higher VL were associated with all psychiatric comorbidities analyzed. HOPS participants already had a substantial burden of physical and psychiatric comorbidities at the time of ART initiation. With advancing age, PWH who initiate ART experience a clinically significant increase in the burden of chronic non-HIV comorbidities that warrants continued surveillance, prevention, and treatment.

Essentials in saline pharmacology for nasal or respiratory hygiene in times of COVID-19

Purpose: Nasal irrigation or nebulizing aerosol of isotonic or hypertonic saline is a traditional method for respiratory or nasal care. A recent small study in outpatients with COVID-19 without acute respiratory distress syndrome suggests substantial symptom resolution. We therefore analyzed pharmacological/pharmacodynamic effects of isotonic or hypertonic saline, relevant to SARS- CoV-2 infection and respiratory care. Methods: Mixed search method. Results: Due to its wetting properties, saline achieves an improved spreading of alveolar lining fluid and has been shown to reduce bio-aerosols and viral load. Saline provides moisture to respiratory epithelia and gels mucus, promotes ciliary beating, and improves mucociliary clearance. Coronaviruses and SARS-CoV-2 damage ciliated epithelium in the nose and airways. Saline inhibits SARS- CoV-2 replication in Vero cells; possible interactions involve the viral ACE2-entry mechanism (chloride-dependent ACE2 configuration), furin and 3CLpro (inhibition by NaCl), and the sodium channel ENaC. Saline shifts myeloperoxidase activity in epithelial or phagocytic cells to produce hypochlorous acid. Clinically, nasal or respiratory airway care with saline reduces symptoms of seasonal coronaviruses and other common cold viruses. Its use as aerosol reduces hospitalization rates for bronchiolitis in children. Preliminary data suggest symptom reduction in symptomatic COVID-19 patients if saline is initiated within 48 h of symptom onset. Conclusions: Saline interacts at various levels relevant to nasal or respiratory hygiene (nasal irrigation, gargling or aerosol). If used from the onset of common cold symptoms, it may represent a useful add-on to first-line interventions for COVID-19. Formal evaluation in mild COVID-19 is desirable as to establish efficacy and optimal treatment regimens.

Circulating levels and prognostic cut-offs of sST2, hs-cTnT, and NT-proBNP in women vs. men with chronic heart failure.

AimsTo define plasma concentrations, determinants, and optimal prognostic cut‐offs of soluble suppression of tumorigenesis‐2 (sST2), high‐sensitivity cardiac troponin T (hs‐cTnT), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in women and men with chronic heart failure (HF).Methods and resultsIndividual data of patients from the Biomarkers In Heart Failure Outpatient Study (BIOS) Consortium with sST2, hs‐cTnT, and NT‐proBNP measured were analysed. The primary endpoint was a composite of 1 year cardiovascular death and HF hospitalization. The secondary endpoints were 5 year cardiovascular and all‐cause death. The cohort included 4540 patients (age 67 ± 12 years, left ventricular ejection fraction 33 ± 13%, 1111 women, 25%). Women showed lower sST2 (24 vs. 27 ng/mL, P < 0.001) and hs‐cTnT level (15 vs. 20 ng/L, P < 0.001), and similar concentrations of NT‐proBNP (1540 vs. 1505 ng/L, P = 0.408). Although the three biomarkers were confirmed as independent predictors of outcome in both sexes, the optimal prognostic cut‐off was lower in women for sST2 (28 vs. 31 ng/mL) and hs‐cTnT (22 vs. 25 ng/L), while NT‐proBNP cut‐off was higher in women (2339 ng/L vs. 2145 ng/L). The use of sex‐specific cut‐offs improved risk prediction compared with the use of previously standardized prognostic cut‐offs and allowed to reclassify the risk of many patients, to a greater extent in women than men, and for hs‐cTnT than sST2 or NT‐proBNP. Specifically, up to 18% men and up to 57% women were reclassified, by using the sex‐specific cut‐off of hs‐cTnT for the endpoint of 5 year cardiovascular death.ConclusionsIn patients with chronic HF, concentrations of sST2 and hs‐cTnT, but not of NT‐proBNP, are lower in women. Lower sST2 and hs‐cTnT and higher NT‐proBNP cut‐offs for risk stratification could be used in women.

COVID-19 patients with documented alcohol use disorder or alcohol-related complications are more likely to be hospitalized and have higher all-cause mortality.

BackgroundCoronavirus Disease 2019 (COVID‐19) has affected every country globally, with hundreds of millions of people infected with the SARS‐CoV‐2 virus and over 6 million deaths to date. It is unknown how alcohol use disorder (AUD) affects the severity and mortality of COVID‐19. AUD is known to increase the severity and mortality of bacterial pneumonia and the risk of developing acute respiratory distress syndrome. Our objective is to determine whether individuals with AUD have increased severity and mortality from COVID‐19.MethodsWe utilized a retrospective cohort study of inpatients and outpatients from 44 centers participating in the National COVID Cohort Collaborative. All were adult COVID‐19 patients with and without documented AUDs.ResultsWe identified 25,583 COVID‐19 patients with an AUD and 1,309,445 without. In unadjusted comparisons, those with AUD had higher odds of hospitalization (odds ratio [OR] 2.00, 95% confidence interval [CI] 1.94 to 2.06, p < 0.001). After adjustment for age, sex, race/ethnicity, smoking, body mass index, and comorbidities, individuals with an AUD still had higher odds of requiring hospitalization (adjusted OR [aOR] 1.51, CI 1.46 to 1.56, p < 0.001). In unadjusted comparisons, individuals with AUD had higher odds of all‐cause mortality (OR 2.18, CI 2.05 to 2.31, p < 0.001). After adjustment as above, individuals with an AUD still had higher odds of all‐cause mortality (aOR 1.55, CI 1.46 to 1.65, p < 0.001).ConclusionThis work suggests that AUD can increase the severity and mortality of COVID‐19 infection. This reinforces the need for clinicians to obtain an accurate alcohol history from patients hospitalized with COVID‐19. For this study, our results are limited by an inability to quantify the daily drinking habits of the participants. Studies are needed to determine the mechanisms by which AUD increases the severity and mortality of COVID‐19.

Feasibility of Closed-Loop Insulin Delivery with a Pregnancy-Specific Zone Model Predictive Control Algorithm.

Objective: Evaluating the feasibility of closed-loop insulin delivery with a zone model predictive control (zone-MPC) algorithm designed for pregnancy complicated by type 1 diabetes (T1D). Research Design and Methods: Pregnant women with T1D from 14 to 32 weeks gestation already using continuous glucose monitor (CGM) augmented pump therapy were enrolled in a 2-day multicenter supervised outpatient study evaluating pregnancy-specific zone-MPC based closed-loop control (CLC) with the interoperable artificial pancreas system (iAPS) running on an unlocked smartphone. Meals and activities were unrestricted. The primary outcome was the CGM percentage of time between 63 and 140 mg/dL compared with participants' 1-week run-in period. Early (2-h) postprandial glucose control was also evaluated. Results: Eleven participants completed the study (age: 30.6 ± 4.1 years; gestational age: 20.7 ± 3.5 weeks; weight: 76.5 ± 15.3 kg; hemoglobin A1c: 5.6% ± 0.5% at enrollment). No serious adverse events occurred. Compared with the 1-week run-in, there was an increased percentage of time in 63-140 mg/dL during supervised CLC (CLC: 81.5%, run-in: 64%, P = 0.007) with less time >140 mg/dL (CLC: 16.5%, run-in: 30.8%, P = 0.029) and time <63 mg/dL (CLC: 2.0%, run-in:5.2%, P = 0.039). There was also less time <54 mg/dL (CLC: 0.7%, run-in:1.6%, P = 0.030) and >180 mg/dL (CLC: 4.9%, run-in: 13.1%, P = 0.032). Overnight glucose control was comparable, except for less time >250 mg/dL (CLC: 0%, run-in:3.9%, P = 0.030) and lower glucose standard deviation (CLC: 23.8 mg/dL, run-in:42.8 mg/dL, P = 0.007) during CLC. Conclusion: In this pilot study, use of the pregnancy-specific zone-MPC was feasible in pregnant women with T1D. Although the duration of our study was short and the number of participants was small, our findings add to the limited data available on the use of CLC systems during pregnancy (NCT04492566).

COVID-19 Outcomes: Does the Use of Psychotropic Drugs Make a Difference? Accumulating Evidence of a Beneficial Effect of Antidepressants-A Scoping Review.

Purpose/BackgroundStudies for repurposed drugs in severe acute respiratory syndrome coronavirus type 2–infected and coronavirus disease 2019 (COVID-19) patients are ongoing. According to preclinical research, antidepressants (ADs) might be useful in the treatment of COVID-19.Methods/ProceduresWe conducted a scoping review including clinical studies on AD effects on SARS-CoV-2 infection and COVID-19.Finding/ResultsAs of January 2, 2022, we found 14 clinical studies, which could be included into this review. Among them, there were 2 randomized, placebo-controlled studies and 2 prospective parallel-group studies about the efficacy/effectiveness and tolerability of fluvoxamine. The remaining studies were mainly retrospective studies considering COVID-19 hospital populations predominantly exposed to fluoxetine (N = 3), other selective serotonin reuptake inhibitors (SSRI), selective norepinephrine reuptake inhibitors (SNRI), and trazodone. The vast majority were hospital studies and assessed COVID-19 severity (morbidity) and mortality as primary endpoints. The only outpatient study (fluvoxamine) investigated the COVID-19–related hospitalization rate, and 1 psychiatric hospital study (SSRI, SNRI, trazodone) focused on the SARS-CoV-2 infection rate.Implications/ConclusionsAt present, the best evidence of an “anti–COVID-19” potential of ADs exists for fluvoxamine and, to a lesser extent, for fluoxetine. Preliminary evidence had found that patients exposed to SSRI or SNRI substance classes might have a reduced mortality risk and that trazodone might reduce SARS-CoV-2 infection rates. Three studies found no relevant influence of ADs on COVID-19 morbidity and mortality, and 1 study described increased mortality. The latter study, however, did not differentiate between psychotropic medication and ADs. Tricyclics and monoamine oxidase inhibitors are still absolute “dark zones” in COVID-19 research. Further controlled studies testing the effectiveness/efficacy and tolerability/safety (as well as the treatment timing and duration) of different AD substance classes in COVID-19 and post/long-COVID patients of various populations are warranted.

Association of Subcutaneous or Intravenous Administration of Casirivimab and Imdevimab Monoclonal Antibodies With Clinical Outcomes in Adults With COVID-19

Monoclonal antibody (mAb) treatment decreases hospitalization and death in high-risk outpatients with mild to moderate COVID-19; however, only intravenous administration has been evaluated in randomized clinical trials of treatment. Subcutaneous administration may expand outpatient treatment capacity and qualified staff available to administer treatment, but the association with patient outcomes is understudied. To evaluate whether subcutaneous casirivimab and imdevimab treatment is associated with reduced 28-day hospitalization and death compared with nontreatment among mAb-eligible patients and whether subcutaneous casirivimab and imdevimab treatment is clinically and statistically similar to intravenous casirivimab and imdevimab treatment. This prospective cohort study evaluated high-risk outpatients in a learning health system in the US with mild to moderate COVID-19 symptoms from July 14 to October 26, 2021, who were eligible for mAb treatment under emergency use authorization. A nontreated control group of eligible patients was also studied. Subcutaneous injection or intravenous administration of the combined single dose of 600 mg of casirivimab and 600 mg of imdevimab. The primary outcome was the 28-day adjusted risk ratio or adjusted risk difference for hospitalization or death. Secondary outcomes included 28-day adjusted risk ratios and differences in hospitalization, death, a composite end point of emergency department admission and hospitalization, and rates of adverse events. Among 1959 matched adults with mild to moderate COVID-19, 969 patients (mean [SD] age, 53.8 [16.7] years; 547 women [56.4%]) who received casirivimab and imdevimab subcutaneously had a 28-day rate of hospitalization or death of 3.4% (22 of 653 patients) compared with 7.0% (92 of 1306 patients) in nontreated controls (risk ratio, 0.48; 95% CI, 0.30-0.80; P = .002). Among 2185 patients treated with subcutaneous (n = 969) or intravenous (n = 1216; mean [SD] age, 54.3 [16.6] years; 672 women [54.4%]) casirivimab and imdevimab, the 28-day rate of hospitalization or death was 2.8% vs 1.7%, which resulted in an adjusted risk difference of 1.5% (95% CI, -0.6% to 3.5%; P = .16). Among all infusion patients, there was no difference in intensive care unit admission (adjusted risk difference, 0.7%; 95% CI, -3.5% to 5.0%) or need for mechanical ventilation (adjusted risk difference, 0.2%; 95% CI, -5.8% to 5.5%). In this cohort study of high-risk outpatients with mild to moderate COVID-19 symptoms, subcutaneously administered casirivimab and imdevimab was associated with reduced hospitalization and death when compared with no treatment. These results provide preliminary evidence of potential expanded use of subcutaneous mAb treatment, particularly in areas that are facing treatment capacity and/or staffing shortages.

Trial of Early Antiviral Therapies during Non-hospitalized Outpatient Window (TREAT NOW) for COVID-19: a summary of the protocol and analysis plan for a decentralized randomized controlled trial

BackgroundCoronavirus disease 2019 (COVID-19) has a heterogeneous outcome in individuals from remaining asymptomatic to death. In a majority of cases, mild symptoms are present that do not require hospitalization and can be successfully treated in the outpatient setting, though symptoms may persist for a long duration. We hypothesize that drugs suitable for decentralized study in outpatients will have efficacy among infected outpatientsMethodsThe TREAT NOW platform is designed to accommodate testing multiple agents with the ability to incorporate new agents in the future. TREAT NOW is an adaptive, blinded, multi-center, placebo-controlled superiority randomized clinical trial which started with two active therapies (hydroxychloroquine and lopinavir/ritonavir) and placebo, with the hydroxychloroquine arm dropped shortly after enrollment began due to external evidence. Each arm has a target enrollment of 300 participants who will be randomly assigned in an equal allocation to receive either an active therapy or placebo twice daily for 14 days with daily electronic surveys collected over days 1 through 16 and on day 29 to evaluate symptoms and a modified COVID-19 ordinal outcome scale. Participants are enrolled remotely by telephone and consented with a digital interface, study drug is overnight mailed to study participants, and data collection occurs electronically without in-person interactions.DiscussionIf effective treatments for COVID-19 can be identified for individuals in the outpatient setting before they advance to severe disease, it will prevent progression to more severe disease, reduce the need for hospitalization, and shorten the duration of symptoms. The novel decentralized, “no touch” approach used by the TREAT NOW platform has distinction advantages over traditional in-person trials to reach broader populations and perform study procedures in a pragmatic yet rigorous manner.Trial registrationClinicalTrials.gov NCT04372628. Registered on April 30, 2020. First posted on May 4, 2020.

Longitudinal Changes in, and Factors Associated with, the Frequency of Condomless Sex Among People in Care for HIV Infection, HIV Outpatient Study USA, 2007-2019.

During 2007-2019, the percentage of HIV Outpatient Study participants reporting anal or vaginal condomless sex in the past 6months ranged from a low of 17% among heterosexual males to 59% for men who have sex with men (MSM). MSM reported having had condomless sex more frequently than heterosexual males and females and were the only group in which an increase in condomless sex was observed during the study period (from 39 to 59%). Although persons with undetectable HIV viral load have effectively no risk of transmitting HIV sexually (U = U), there is still the potential risk of transmission or acquisition of other sexually transmitted infections (STIs) when engaging in condomless sex. Continuing education about risks of HIV and STI transmission as well as ongoing screening for and treatment of STIs, retention in HIV treatment, and support for sexual health are critical components of care for people living with HIV.

Intermittent WPW Pattern in a Heart Transplant Recipient with Normal Donor Electrocardiogram

<h3>Introduction</h3> The use of a heart from donors with symptomatic Wolff-Parkinson-White (WPW) syndrome has been previously described in few case reports. However, intermittent pre-excitation (IPX) is a rare variant of WPW that can make the diagnosis and treatment challenging. <h3>Case Report</h3> A 53-year-old male with chronic non-ischemic cardiomyopathy and ventricular tachycardia, experienced an out-of-hospital (OOH) cardiac arrest secondary to ventricular fibrillation (VF) and a second VF arrest while hospitalized necessitating temporary mechanical circulatory support. He was stabilized and subsequently listed for a heart transplant (HT). A donor became available whose cause of death was an OOH cardiac arrest presumably due to drug overdose. Immediately post HT, the recipient was noted to have a classic WPW pattern on his electrocardiogram (EKG) with short PR interval and a delta wave axis compatible with a right anterior accessory pathway (AP). The only available donor EKG was normal. Two days later the recipient EKG normalized. Post-operative changes or ionic disturbances were postulated to have caused this IPX and an outpatient electrophysiology study (EPS) was recommended. Two weeks later, while still hospitalized, the WPW pattern reappeared and remained persistent without tachyarrhythmias (Figure). An inpatient EPS indicated that this was a high-risk pathway and successful radiofrequency ablation was performed. <h3>Summary</h3> Few reported cases of donor hearts with pre-existing AP amenable to ablation suggest that this is an acceptable approach to expanding the donor pool. However, IPX with normal donor EKG is less well described. IPX conveys the same risk of life-threatening arrhythmias as persistent pre-excitation. Cardiac denervation in HT recipients can make the approach to IPX challenging in the early post-operative period. Our case highlights the importance of early risk stratification of IPX pathways in HT recipients with otherwise limited historical information about arrhythmias in the donor.