Per Person-year Research Articles

#2011 Reduced hospitalisation or emergency department visits with long- versus short-term SZC in patients with history of hyperkalaemia: GALVANIZE Outcomes

Abstract Background and Aims Hyperkalaemia is associated with increased healthcare resource use and often requires long-term management. The GALVANIZE Outcomes study is a comparison of hyperkalaemia-related and all-cause hospitalisations or emergency department visits between matched patients treated with long- or short-term sodium zirconium cyclosilicate (SZC), using real-world data. This analysis evaluated outcomes in patients with a history of hyperkalaemia. Method A large US insurance claims database (from HealthVerity) was used to identify adults who initiated SZC (index date) in the outpatient setting between 1 January 2019 and 30 June 2022, with a diagnosis of hyperkalaemia within 6 months prior to the index date. Exclusion criteria included patients without either 6 months of continuous insurance coverage prior to index, or 30 days of continuous insurance coverage post-index. Patients were followed to the earliest of 6 months post-index, loss of coverage, end of the study period or (re) initiation of a potassium binder. Patients with short-term SZC use (≤30 days) were exact and propensity score–matched to patients with long-term SZC use (>90 days). Hyperkalaemia-related hospitalisations and emergency department visits were identified by the International Classification of Diseases (tenth revision) diagnosis code for hyperkalaemia. Rates of the composite outcomes of the number of hyperkalaemia-related hospitalisations or emergency department visits (primary endpoint) and all-cause hospitalisations or emergency department visits (exploratory endpoint) per person-year (PPY) were compared during follow-up using generalised estimating equations. Results Among 2088 eligible matched pairs with a history of hyperkalaemia, the mean age was 63.8 years and 41.4% of the population was female. Most patients (94.9%) had a diagnosis of chronic kidney disease, which mostly included stage 3 (27.3%), stage 4 (25.4%) and stage 5/end-stage (38.7%) kidney disease, while one-third (34.4%) had a diagnosis of heart failure irrespective of ejection fraction. The median (interquartile range) duration of follow-up was 183 (183, 183) days for long-term SZC and 169 (82, 183) days for short-term SZC. During follow-up, in patients with a history of hyperkalaemia, those with long-term SZC use had a 43% lower rate of hyperkalaemia-related hospitalisations or emergency department visits than matched patients with short-term SZC use (rate [95% confidence interval] PPY: 0.89 [0.79–0.98] vs 1.56 [1.35–1.76]; P<0.001) (Fig. 1). Similarly, patients with long-term SZC use had a 35% lower rate of all-cause hospitalisations or emergency department visits than those with short-term SZC use (2.63 [2.44–2.82] vs 4.05 [3.71–4.40]; P<0.001]) (Fig. 2). Conclusion In this real-world study of patients with hyperkalaemia, individuals treated with long-term SZC experienced significantly lower rates of hyperkalaemia-related and all-cause hospitalisations or emergency department visits compared with matched patients with short-term SZC use.

Healthcare resource utilization and costs among patients with alpha-1 antitrypsin deficiency with liver and/or lung disease: a longitudinal retrospective study in the USA.

Aim: To evaluate all-cause and liver-associated healthcare resource utilization (HCRU) and costs among patients with alpha-1 antitrypsin deficiency (AATD) with liver disease (LD) and/or lung disease (LgD). Materials & methods: This was a retrospective analysis of linked administrative claims data from the IQVIA PharMetrics® Plus and the IQVIA Ambulatory Electronic Medical Records (AEMR) databases from 1July2021 to 31January 2022. Patients with AATD in the IQVIA PharMetrics Plus database were included with ≥1 inpatient or ≥2 outpatient medical claims ≥90days apart with a diagnosis of AATD, or with records indicating a protease inhibitor (Pi)*ZZ/Pi*MZ genotype in the IQVIA AEMR database with linkage to IQVIA PharMetrics Plus. For a patient's identified continuous enrollment period, patient time was assigned to health states based on the initial encounter with an LD/LgD diagnosis. A unique index date was defined for each health state, and HCRU and costs were calculated per person-year (PPY). Results: Overall, 5136 adult and pediatric patients from the IQVIA PharMetrics Plus and IQVIA AEMR databases were analyzed. All-cause and liver-associated HCRU and costs were substantially higher following onset of LD/LgD. All-cause cost PPY ranged from US $11,877 in the absence of either LD/LgD to US $74,015 in the presence of both LD and LgD. Among liver transplant recipients in the AATD with LD health state, liver-associated total costs PPY were US $87,329 1-year pre-transplantation and US $461,752 1-year post-transplantation. In the AATD with LgD and AATD with LD and LgD health states, patients who received augmentation therapy were associated with higher all-cause total costs PPY and lower liver-associated total costs PPY than their counterparts who did not receive augmentation therapy. Conclusion: Patients with AATD had increased HCRU and healthcare costs in the presence of LD and/or LgD. HCRU and healthcare costs were highest in the AATD with LD and LgD health state.

Efficacy and Safety of Lumasiran in Patients With Primary Hyperoxaluria Type 1: Results from a Phase III Clinical Trial

Patients with primary hyperoxaluria type 1 (PH1), a genetic disorder associated with hepatic oxalate overproduction, frequently experience recurrent kidney stones and worsening kidney function. Lumasiran is indicated for the treatment of PH1 to lower urinary and plasma oxalate (POx). ILLUMINATE-A (NCT03681184) is a phase III trial in patients aged≥6 years with PH1 and estimated glomerular filtration rate (eGFR)≥30 ml/min per 1.73 m2. A 6-month double-blind placebo-controlled period is followed by an extension period (≤54 months; all patients receive lumasiran). We report interim data through month36. Of 39 patients enrolled, 24 of 26 (lumasiran/lumasiran group) and 13 of 13 (placebo/lumasiran group) entered and continue in the extension period. At month 36, in the lumasiran/lumasiran group (36 months of lumasiran treatment) and placebo/lumasiran group (30 months of lumasiran treatment), mean 24-hour urinary oxalate (UOx) reductions from baseline were 63% and 58%, respectively; 76% and 92% of patients reached a 24-hour UOx excretion≤1.5× the upper limit of normal (ULN). eGFR remained stable. Kidney stone event rates decreased from 2.31 (95% confidence interval: 1.88-2.84) per person-year (PY) during the 12 months before consent to 0.60 (0.46-0.77) per PY during lumasiran treatment. Medullary nephrocalcinosis generally remained stable or improved; approximately one-third of patients (both groups) improved to complete resolution. The most common lumasiran-related adverse events (AEs) were mild, transient injection-site reactions. In patients with PH1, longer-term lumasiran treatment led to sustained reduction in UOx excretion, with an acceptable safety profile and encouraging clinical outcomes.See for Video Abstract.

Incidence and Risk Factors for Adrenal Crisis in Pediatric-onset Adrenal Insufficiency: A Prospective Study.

Adrenal crisis (AC) is a life-threatening complication that occurs during follow-up of patients with adrenal insufficiency (AI). No prospective study has thoroughly investigated AC in children with primary and secondary AI. This work aimed to determine the incidence and risk factors for AC in patients with pediatric-onset AI. This multicenter, prospective cohort study conducted in Japan enrolled patients diagnosed with AI at age ≤15 years. The incidence of AC was calculated as events per person-year (PY), and risk factors for AC were assessed using Poisson regression multivariable analysis. The study population comprised 349 patients (164 male, 185 female) with a total follow-up of 961 PY. The median age at enrollment was 14.3 years (interquartile range [IQR] 8.5-21.2 years), and the median follow-up was 2.8 years (IQR 2.2-3.3 years). Of these patients, 213 (61%) had primary AI and 136 (39%) had secondary AI. Forty-one AC events occurred in 31 patients during the study period. The calculated incidence of AC was 4.27 per 100 PY (95% CI, 3.15-5.75). Poisson regression analysis identified younger age at enrollment (relative risk [RR] 0.93; 95% CI, 0.89-0.97) and increased number of infections (RR 1.17; 95% CI, 1.07-1.27) as significant risk factors. Female sex (RR 0.99; 95% CI, 0.53-1.86), primary AI (RR 0.65; 95% CI, 0.30-1.41), or equivalent dosage of hydrocortisone per square meter of body area (RR 1.02; 95% CI, 0.96-1.08) was not a significant risk factor. A substantial proportion of patients with pediatric-onset AI experience AC. Younger age and an increased number of infections are independent risk factors for developing AC in these patients.

Abstract 18880: Ventricular Arrhythmia Prevalence and Burden in Patients With Third Generation Continuous Flow Left Ventricular Assist Devices

Background: Ventricular arrhythmias (VAs) are common in patients with left ventricular assist devices (LVADs). Little is known about the impact of third-generation LVADs (Heartmate 3, HM3) on VAs prevalence and burden. Aims : To characterize the impact of HM3 LVAD implantation on VAs prevalence and burden in patients with advanced heart failure (HF) and implantable cardioverter-defibrillators (ICDs). Methods: We included consecutive patients with advanced HF and ICDs who received HM3 devices at our center between 2016 and 2022. The study outcomes were the prevalence of sustained VAs, defined as >30s VA episode detected by the ICD monitor zone or appropriately treated (ATP or shock), sustained VA burden (total number of episodes), and VA storm (≥3 appropriate ICD interventions in 24/h period). Data was collected over the 1 year before and after HM3 implantation. Results: A total of 321 patients were included (28% female, mean age 60±12 years, mean INTERMACS score 3±0.95). At 1 year follow-up after HM3 implantation, 27 patients died. A total of 128 patients (43%) had at least one sustained VA episode in the year before the HM3 implantation compared to 51 patients (17%) in the year following the HM3 (p<0.001 for comparison). The sustained VA burden decreased from a mean of 3.8 events per person-year (PPY) to a mean of 0.8 events PPY (p=0.005). Similarly, appropriate ICD therapy occurred in 123 patients (38%) before implantation and 46 patients (14%) after implantation (p<0.001). The burden of appropriate therapy was also reduced (from a mean of 2.57 events PPY to a mean 1.32 events PPY; p=0.03). The prevalence of VA storm was reduced from 19% to 8% (p<0.001). Conclusions: In patients with advanced HF and ICDs undergoing HM3 implantation, the prevalence of sustained VAs, VAs burden, appropriate ICD interventions, and VA storm were all significantly reduced in the year following HM3 implantation.

Clinical Outcomes of Congenital Thrombotic Thrombocytopenic Purpura: A Multinational Chart Review Study

Background: Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare, life-threatening genetic disorder. Severe deficiency of the von Willebrand factor-cleaving metalloprotease ADAMTS13 results in the formation of platelet-rich microthrombi, leading to platelet consumption and thrombocytopenia. Current treatment strategies primarily focus on replenishing ADAMTS13 through plasma-derived products. Research into the natural history of cTTP, clinical outcomes, disease burden, and treatment patterns is limited. Aims: The primary objectives of this chart review were to describe the characteristics of cTTP patients, and the prevalence and incidence of clinical manifestations of cTTP and its complications. The secondary objectives were to describe the treatment patterns, treatment-related outcomes, and healthcare resource utilization in patients with cTTP. Methods: This retrospective chart review, conducted across 9 sites in France, Germany, Italy, Spain, Switzerland, the United Kingdom, and the United States, collected patient-level data from medical records between January 1, 2009 and December 31, 2020. Patients with cTTP were included if they experienced any of the following index events between January 1, 2009 and December 31, 2017: diagnosis with cTTP, receipt of prophylactic treatment for cTTP, receipt of treatment on demand for an acute cTTP episode or isolatedthrombotic thrombocytopenic purpura (TTP) manifestation; or another cTTP-related major clinical event (Table 1). The date of the first qualifying index event was defined as the study index date. Patients were followed until loss to follow-up, enrollment in a clinical trial, the end of the study period, or death. All results were summarized using descriptive statistics. Ethics approval and informed consent were obtained where applicable. Results: A total of 78 patients met the criteria for inclusion with a mean (SD) follow-up of 8.1 (3.1) years. The mean (SD) age at initial cTTP diagnosis and study index were 26.2 (17.3) years and 29.5 (15.7) years, respectively. Most patients were female (78.2%). The initial diagnosis was characterized clinically by systemic (n=44, 56.4%), neurological (n=26, 33.3%), gastrointestinal (n=23, 29.5%) and renal (n=22, 28.2%) manifestations (Table 2). A total of 92 acute cTTP episodes were reported by 55/78 (70.5%) patients during the study period, resulting in an event rate of 0.145 episodes per person-year (PPY). Most episodes (n=70/92, 76.1%) resolved without complications, 16/92 (17.4%) resolved but resulted in organ damage, and 2/92 (2.2%) resulted in death. The majority of acute cTTP episodes (n=85/92, 92.4%) required hospitalization, with 32/85 (37.6%) resulting in intensive care unit (ICU) admission. Four isolated TTP manifestations were reported at study index, all required hospitalization, with 1 patient admitted to ICU. A total of 64 isolated TTP manifestations were documented in 29 patients (37.2%) during the study period. The event rate of isolated TTP manifestations was 0.101 events PPY. Thrombocytopenia was the most commonly reported (n=49/64, 76.6%) symptom of isolated TTP manifestations recorded during the study period. Clinical resolution was achieved in most isolated TTP manifestations (n=58/64, 90.6%) and none resulted in death. Organ damage was reported in 22/78 (28.2%) patients during acute episodes during the study period or during isolated TTP manifestations at index, of which neurological (n=15), renal (n=11), and cardiac (n=8) damage were most common. Prophylaxis was initiated in 47/78 patients, with clinical symptoms (n=13/47, 27.7%) and pregnancy (n=13/47, 27.7%) as the most common reasons for initiation. Of the 65 prophylactic treatments administered, 41 (63.1%) were stopped or interrupted with the most common reasons being pregnancy (n=17; childbirth, stillbirth, prophylaxis during pregnancy), failure to achieve normalization of levels (n=6), and normalization of levels achieved (n=3). Conclusions: These findings demonstrate a substantial burden arising from disease-related manifestations in cTTP patients. Managing patients with cTTP is additionally burdensome to healthcare systems as many patients require multiple hospital and ICU stays. Novel, effective therapies with demonstrated efficacy and safety profiles may offer substantial benefits to patients and healthcare systems.

142-LB: Cost-Effectiveness of Real-Time Continuous Glucose Monitoring (rt-CGM) vs. Intermittent-Scanning Continuous Glucose Monitoring (is-CGM) in Patients with Type 2 Diabetes on Multiple Daily Injections of Insulin (T2D MDI) in Canada

Rt-CGM systems provide real-time glucose values, hypo- and hyperglycemia alerts, and predictive “urgent low soon” alerts that have been shown to improve glycemic outcomes and reduce severe hypoglycemic events (SHEs) in patients with T2D, without the need for periodic scanning. The economic value of rt-CGM vs is-CGM is unknown for patients with T2D MDI in Canada. We conducted a cost-effectiveness analysis comparing the two systems for this patient population using the INESSS Canadian payer perspective. ­ A 30-year analysis was performed using the validated ECHO-T2DM. Patient characteristics were sourced from Karter (2021). Efficacy and safety were derived from the DIAMOND T2D and REPLACE RCTs. The HbA1c difference of -0.33 (favoring rt-CGM) was derived using Bucher's adjusted indirect comparison, SHE rates were 0.014 and 0 Per Person-Year (PPY) for is-CGM and rt-CGM, respectively, and severe hyperglycemia/DKA rates were proxied by the difference in time above range (0.0313 and 0 PPY, respectively). Costs and disutility weights were sourced from published Canadian literature and discounted at 1.5% annually. A reduction in fear of hypoglycemia (FOH) utility was sourced from the ALERTT1 RCT. Sensitivity analyses were performed. Rt-CGM was associated with quality-adjusted life year gains of 0.346 and incremental costs of CAD 5,737, with an incremental cost-effectiveness ratio (ICER) of CAD 16,598. No DKA events for is-CGM and a 50% reduction in FOH utility increased the ICERs to CAD 30,987 and CAD 29,116, respectively. ICER was CAD 2,278 when both CGM costs were reduced by 50% and rt-CGM became cost-saving (dominant) at a 65% reduction. These results suggest rt-CGM is cost-effective vs is-CGM in patients with T2D MDI in Canada. These findings can inform government and commercial healthcare decision-makers when considering reimbursement of CGM systems. Disclosure H. Alshannaq: Employee; Dexcom, Inc., Other Relationship; Vertex Pharmaceuticals Incorporated. G. J. Norman: Employee; Dexcom, Inc. M. Willis: None. A. Nilsson: None. Funding Dexcom, Inc.

141-LB: Cost-Effectiveness of Real-Time Continuous Glucose Monitoring (rt-CGM) vs. Intermittent-Scanning Continuous Glucose Monitoring (is-CGM) from a U.S. Payer Perspective in Patients with Type 2 Diabetes on Multiple Daily Injections of Insulin (PwT2D on MDI)

Diabetes management for PwT2D on MDI requires access to timely glucose readings to inform treatment decisions and avoid acute events like severe hypoglycemia (SHE) and Diabetic Ketoacidosis (DKA). CGM systems have different features that can impact glycemic outcomes and disease complications and costs. There is a gap in the literature on the cost-effectiveness of rt-CGM vs is-CGM systems. We conducted lifetime projections of disease outcomes and costs from a US payer perspective using the IQVIA Core Diabetes Model v9.5+. Cohort characteristics and clinical inputs were sourced from the DIAMOND T2D and REPLACE RCTs. Applying Bucher's adjusted indirect comparison method resulted in an HbA1c effect of -0.33 favoring rt-CGM, SHE incidence rates of 0.014 and 0 Per Person-Year (PPY) for is-CGM and rt-CGM, respectively, and DKA rates were estimated using Time-Above-Range (0.0313 and 0 PPY, respectively). The cost of both CGM systems is based on Medicare pricing and 80% reimbursement (HCPCS code A4239). A utility for fear of hypoglycemia (FoH) reduction was applied from the ALERTT1 RCT. The model associates rt-CGM use with reduced eye (-5.64%), renal (-7.42%), neural (-4.08%), and cardiovascular (-2.56%) complications compared to is-CGM. It projects rt-CGM users to have higher quality-adjusted life years (QALYs) by 0.454 with cost savings of -$1,355, and an incremental cost-effectiveness ratio of -$2,983/QALY. Rt-CGM remained cost-effective under the $50,000 willingness-to-pay threshold even when its cost was increased by 70% (+$1,713). Scenario analysis with 50% lower FoH utility, SHE, and DKA rates reduced QALYs gained to 0.264. Our analysis suggests that rt-CGM is cost-saving and cost-effective vs is-CGM in PwT2D on MDI in the US and can inform US payers of the economic value of different CGM systems. Disclosure H. Alshannaq: Employee; Dexcom, Inc., Other Relationship; Vertex Pharmaceuticals Incorporated. G. J. Norman: Employee; Dexcom, Inc. P. M. Lynch: Employee; Dexcom, Inc., Stock/Shareholder; Dexcom, Inc.

Health Care Use and Spending Among Need-Based Subgroups of Medicare Beneficiaries With Full Medicaid Benefits

Beneficiaries dual eligible for Medicare and Medicaid account for a disproportionate share of expenditures due to their complex care needs. Lack of coordination between payment programs creates misaligned incentives, resulting in higher costs, fragmented care, and poor health outcomes. To inform the design of integrated programs by describing the health care use and spending for need-based subgroups in North Carolina's full benefit, dual-eligible population. This cross-sectional study using Medicare and North Carolina Medicaid 100% claims data (2014-2017) linked at the individual level included Medicare beneficiaries with full North Carolina Medicaid benefits. Data were analyzed between 2021 and 2022. Need-based subgroups: community well, home- and community-based services (HCBS) users, nursing home (NH) residents, and intensive behavioral health (BH) users. Medicare and Medicaid utilization and spending per person-year (PPY). The cohort (n = 333 240) comprised subgroups of community well (64.1%, n = 213 667), HCBS users (15.0%, n = 50 095), BH users (15.2%, n = 50 509), and NH residents (7.5%, n = 24 927). Overall, 61.1% reported female sex. The most common racial identities included Asian (1.8%), Black (36.1%), and White (58.7%). Combined spending for Medicare and Medicaid was $26 874 PPY, and the funding of care was split evenly between Medicare and Medicaid. Among need-based subgroups, combined spending was lowest among community well at $19 734 PPY with the lowest portion (38.5%) of spending contributed by Medicaid ($7605). Among NH residents, overall spending ($68 359) was highest, and the highest portion of spending contributed by Medicaid (70.1%). Key components of spending among HCBS users' combined total of $40 069 PPY were clinician services on carrier claims ($14 523) and outpatient facility services ($9012). Federal and state policy makers and administrators are developing strategies to integrate Medicare- and Medicaid-funded health care services to provide better care to the people enrolled in both programs. Substantial use of both Medicare- and Medicaid-funded services was found across all need-based subgroups, and the services contributing a high proportion of the total spending differed across subgroups. The diversity of health care use suggests a tailored approach to integration strategies with comprehensive set benefits that comprises Medicare and Medicaid services, including long-term services and supports, BH, palliative care, and social services.

Opioid prescribing patterns after arthroplasty of the knee and hip: a Dutch nationwide cohort study from 2013 to 2018.

Background and purposeNumbers on opioid prescriptions over time in arthroplasty patients are currently lacking. Therefore we determined the annual opioid prescribing rate in patients who received a hip/knee arthroplasty (HA/KA) between 2013 and 2018.Patients and methodsThe Dutch Foundation for Pharmaceutical Statistics, which provides national coverage of medication prescriptions, was linked to the Dutch Arthroplasty Register, which provides arthroplasty procedures. The opioid prescription rates were expressed as the number of defined daily dosages (DDD) and morphine milligram equivalent (MME) per person year (PY) and stratified for primary and revision arthroplasty. Amongst subgroups for age (< 75; ≥ 75 years) and sex for primary osteoarthritis arthroplasties, prescription rates stratified for opioid type (weak/strong) and prevalent preoperative opioid prescriptions (yes/no) were assessed.Results48,051 primary KAs and 53,964 HAs were included, and 3,540 revision KAs and 4,118 HAs. In 2013, after primary KA 58% were dispensed ≥ 1 opioid within the first year; this increased to 89% in 2018. For primary HA these numbers increased from 38% to 75%. In KAs the prescription rates increased from 13.1 DDD/PY to 14.4 DDD/PY, mainly due to oxycodone prescriptions (2.9 DDD/PY to 7.3 DDD/PY), while tramadol decreased (7.3 DDD/PY to 4.6 DDD/PY). The number of MME/PY also increased (888 MME/PY to 1224 MME/PY). Similar changes were observed for HA and revision arthroplasties. Irrespective of joint, prescription of opioid medication increased over time, with highest levels in groups with preoperative opioid prescriptions while weak opioid prescriptions decreased.InterpretationIn the Netherlands, between 2013 and 2018 postoperative opioid prescriptions after KA and HA increased, mainly due to increased oxycodone prescriptions with highest levels after surgeries with preoperative prescriptions.

Impact of rectal dissection technique on primary-school-age outcomes for a British and Irish cohort of children with Hirschsprung disease

BackgroundThis prospective cohort study compared primary-school-aged outcomes between children with Hirschsprung disease (HD) following Soave, Duhamel or Swenson procedures. MethodsChildren with histologically proven HD were identified in British/Irish paediatric surgical centers (01/10/2010-30/09/2012). Parent/clinician outcomes were collected when children were 5–8 years old and combined with management/early outcomes data. Propensity score/covariate adjusted multiple-event-Cox and multivariable logistic regression analyses were used. Results277 (91%) of 305 children underwent a pull-through (53% Soave, 37% Duhamel, 9% Swenson). Based upon 259 children (94%) with complete operative data, unplanned reoperation rates (95% CI) per-person year of follow-up were 0.11 (0.08–0.13), 0.34 (0.29–0.40) and 1.06 (0.86–1.31) in the Soave/Duhamel/Swenson groups respectively. Adjusted Hazard Ratios for unplanned reoperation compared with the Soave were 1.50 (95% CI 0.66-3.44, p = 0.335) and 7.57 (95% CI 3.39-16.93, p < 0.001) for the Duhamel/Swenson respectively. Of 217 post-pull-through children with 5–8 year follow-up, 62%, 55%, and 62% in Soave/Duhamel/Swenson groups reported faecal incontinence. In comparison to Soave, Duhamel was associated with lower risk of faecal incontinence (aOR 0.34,95%CI 0.13-0.89,p = 0.028). Of 191 children without a stoma, 42%, 59% and 30% in Soave/Duhamel/Swenson groups required assistance to maintain bowel movements; compared to Soave, the Duhamel group were more likely to require assistance (aOR 2.61,95% CI 1.03–6.60,p = 0.043). ConclusionsCompared with Soave, Swenson was associated with increased risk of unplanned reoperation, whilst Duhamel was associated with reduced risk of faecal incontinence, but increased risk of constipation at 5–8 years of age. The risk profiles described can be used to inform consent discussions between surgeons and parents. Level of evidenceLevel II

Health-care resource use and costs associated with diabetic and idiopathic gastroparesis: A claims analysis of the first 3years following the diagnosis of gastroparesis.

BackgroundDue to limited treatment options, many patients with diabetic gastroparesis (DG) or idiopathic gastroparesis (IG) experience inadequate symptom control resulting in increased health‐care resource utilization (HRU) and associated costs. We compared all‐cause HRU and health‐care costs over the 3 years after patients’ first gastroparesis diagnosis with that of matched controls without gastroparesis.MethodsNewly diagnosed adults with DG or IG were identified in Optum's de‐identified Clinformatics® Data Mart Database (Q1‐2007 to Q1‐2019). Patients with DG/IG were matched 1:1 to controls using a mixed approach of exact matching and propensity score matching. The index date was the first gastroparesis diagnosis for cases or randomly selected for controls. All‐cause HRU and direct health‐care costs per person‐year (PPY) were compared between DG/IG cases and controls in Years 1–3 post‐index.Key ResultsDemographics and comorbidities were balanced between patients with gastroparesis (n = 18,015 [DG]; n = 14,305 [IG]) and controls. In each of the Years 1–3 post‐index, patients with DG or IG had significantly higher annual HRU and costs versus controls (mean total cost differences PPY: DG Year 1 $34,885, Year 2 $28,071, Year 3 $25,606; IG Year 1 $23,176, Year 2 $16,627, Year 3 $14,396) (all p < 0.05). Across all 3 years, DG/IG cohorts had approximately twice the costs of controls. HRU and costs were highest in Year 1 post‐index for both DG and IG.Conclusions & InferencesThe economic burden of gastroparesis remains high several years after diagnosis, emphasizing the need for chronic treatment to effectively manage symptoms and consequently reduce the burden of this disorder.

Treatment Outcomes in Birdshot Chorioretinitis: Corticosteroid Sparing, Corticosteroid Discontinuation, Remission, and Relapse

To describe treatment-related outcomes among patients with birdshot chorioretinitis (BSCR). Retrospective cohort study. Patients diagnosed with BSCR at 2 tertiary care academic medical centers. Clinical and treatment-related data were collected for all patients with BSCR diagnosed between 2003 and 2017 at the 2 centers and for each eye at each clinical visit. Four outcomes were considered: (1) corticosteroid-sparing success, defined as inactive disease and prednisone dose of ≤7.5 mg/day; (2) corticosteroid-discontinuation success, defined as inactive disease and discontinuation of prednisone; (3) sustained drug-free remission, defined as inactive disease off all medications for ≥3 months; and (4) relapse of BSCR after remission. A total of 107 patients with BSCR were identified, of whom 94 had follow-up data. Corticosteroid-sparing success was achieved in 95.4% of the oral corticosteroid-treated patients at a rate of 0.60 successes per person-year (PY) (95% CI: 0.50/PY, 0.70/PY). The median time to corticosteroid-sparing success was 12 months. Corticosteroids were discontinued successfully in 76.5% of oral corticosteroid-treated patients (rate= 0.28/PY; 95% CI: 0.21/PY, 0.35/PY). The median time to successful corticosteroid discontinuation was 2.0 years. A sustained drug-free remission was achieved in 24 patients (rate= 0.06/PY; 95% CI: 0.04/PY, 0.09/PY), with approximately 25% of patients achieving remission by 4 years of follow-up. Relapse of inflammation in patients after achieving a sustained, drug-free remission occurred at a rate of 0.24/PY (95% CI: 0.14/PY, 0.37/PY). Successful corticosteroid sparing and discontinuation was achieved in the majority of patients with BSCR. Remission occurred less often, but data were limited by the time needed to induce a remission (4 years) and the amount of follow-up (median, 4.6 years). The relapse rate after a remission was 0.24/PY.

Benefit of Prompt versus Delayed Use of Single-Inhaler Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Following a COPD Exacerbation.

PurposeTriple therapy (TT; inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting β2-agonist) is recommended for patients with chronic obstructive pulmonary disease (COPD) at risk of exacerbation, although the optimum timing of TT initiation remains unclear. This study evaluated the impact of prompt versus delayed initiation of single-inhaler TT (fluticasone furoate, umeclidinium, and vilanterol [FF/UMEC/VI]) following a COPD exacerbation.Patients and MethodsThis retrospective cohort study used data from the IQVIA PharMetrics® Plus database. Patients initiating FF/UMEC/VI following a COPD exacerbation between September 18, 2017 and September 30, 2019 (exacerbation = index date) were categorized as prompt (within 30 days of index) or delayed (31–180 days after index) FF/UMEC/VI initiators. Patients were aged ≥40 years at index, had ≥12 months’ continuous health insurance coverage before index (baseline), and ≥6 months’ coverage after index (follow-up). Patients with a COPD exacerbation or claim for FF/UMEC/VI during baseline were excluded. Inverse probability weighting was used to adjust for differences in baseline characteristics between cohorts. Exacerbations (overall, moderate, and severe), healthcare costs, and readmissions were evaluated during follow-up.ResultsA total of 1904 patients (prompt: 529; delayed: 1375) were included. After weighting, baseline characteristics were well balanced between cohorts. Patients in the prompt cohort had significantly lower rates per person-year (PPY) of overall (0.98 vs 1.23; rate ratio [RR] [95% CI] = 0.79 [0.65–0.94], p = 0.004), moderate (0.86 vs 1.03; RR [95% CI] = 0.84 [0.69–0.99], p = 0.038), and severe (0.11 vs 0.20; RR [95% CI] = 0.57 [0.37–0.79], p = 0.002) exacerbations, compared with delayed initiators. Mean all-cause and COPD-related healthcare costs were significantly lower among prompt initiators (all-cause: $26,107 vs $32,400 PPY, p = 0.014; COPD-related: $12,694 vs $17,640 PPY, p = 0.002).ConclusionPrompt initiation of FF/UMEC/VI following a moderate or severe COPD exacerbation was associated with significant reductions in exacerbations and healthcare costs relative to delayed initiation.

Comparative All-Cause Mortality Among a Large Population of Patients with Spinal Muscular Atrophy Versus Matched Controls.

IntroductionThere is little information about survival of spinal muscular atrophy (SMA) patients into adulthood, in particular from population-based samples. We estimated and compared age-specific, all-cause mortality rates in patients with SMA and matched controls in a large, retrospective cohort study using electronic health records (EHRs) from the pre-treatment era.MethodsThe US Optum® de-identified EHR database contains EHRs for ~ 104 million persons (study period: January 1, 2007–December 22, 2016). SMA cases were identified by one or more International Classification of Diseases, Ninth/Tenth Edition codes for SMA. Controls with no SMA diagnosis code were matched 10:1 to SMA cases based on birth year, gender, and first diagnostic code date. For both groups, ≥ 1 month of observation and (if deceased) a valid date of death were required for inclusion. Age-specific mortality rates per person-year (PY) and hazard ratios were calculated.ResultsFive thousand one hundred seventy-nine SMA cases and 51,152 controls were analyzed. The overall hazard ratio comparing cases with controls was 1.76 (95% CI 1.63–1.90). In patients with SMA type III diagnostic codes only, the all-age mortality rate was 1059/100,000 PYs in cases and 603/100,000 PYs in controls. In older age groups (13–20, 21–30, 31–40, 41–50, 51–60, and > 60 years), age-specific mortality rates for cases consistently exceeded those of controls. Limitations of this study included the inability to confirm the SMA diagnosis or SMA type by genetic or clinical confirmation.ConclusionPatients with SMA of all ages, including adults and type III patients, had a higher all-cause mortality rate as compared to age-matched controls during the pre-treatment era.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-021-00307-7.

Epidemiology and Long-Term Outcomes of Estrogen/Progesterone Associated Distal Deep-Vein Thrombosis

Background: Isolated distal deep-vein thrombosis (iD-DVT), defined as infra-popliteal DVT without pulmonary embolism (PE), is the most frequent presentation of venous thromboembolism (VTE). iD-DVT generally shares the same triggering risks factors as proximal DVT. In women of childbearing age, a frequent triggering risk factor is use of estrogen/progesterone (EP) birth control pills. However, data on the epidemiology and longterm outcomes of EP-associated iD-DVT are lacking.Objectives: To assess the epidemiology and long-term outcomes of EP-associated iD-DVT.Methods: Using data from the OPTIMEV multicentre cohort study of patients with objectively confirmed VTE (all suspected DVT was assessed with standardized bilateral whole leg ultrasound), in women <50 years old and without cancer: i) the proportion of EP-related iD-DVT among women with iD-DVT and among women with EP-related VTE (iD-DVT, proximal DVT or PE); ii) clinical characteristics of EP-related iD-DVT; iii) the attributable risk of EP on the occurrence of VTE (compared with controls: i.e., OPTIMEV women <50 years old and without VTE and cancer, nested case control study); iv) the 3-year incidence of death, bleeding and VTE recurrence after stopping anticoagulants.Results: 283 women fulfilled our study criteria; of these, 56 had EP-related iD-DVT, which represented 37.8% of all iD-DVT and 51.4% of EP-related VTE. Table 1 shows that demographics and clinical characteristics did not markedly differ between EP-related iD-DVT vs. EP-related proximal DVT. The attributable risk of EP for the occurrence of iD-DVT was 21%, for proximal DVT was 17%, and for PE was 9%. Among women with EP-related iD-DVT, 97.7% were treated with therapeutic anticoagulation for a median duration of 90 days, and there were no major bleeds on treatment. At 3 years follow-up, all women were alive and only one experienced a VTE recurrence (a superficial vein thrombosis) after stopping anticoagulants (recurrence incidence = 0.8% per person-year (PY)). Similar results were found in patients with EP-related proximal DVT and EP-related PE (VTE recurrence incidence 1.5% per PY and 0% per PY, respectively; no deaths and no major bleeds in both groups).Conclusions: iD-DVT is the most frequent clinical presentation of EP-related VTE. Clinical characteristics of patients with EP-related distal DVT and EP-related proximal DVT are very similar. The prognosis of EP-related iD-DVT is good, with a very low incidence of adverse outcomes in the long-term. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Estimating malaria incidence from routine health facility-based surveillance data in Uganda

BackgroundAccurate measures of malaria incidence are essential to track progress and target high-risk populations. While health management information system (HMIS) data provide counts of malaria cases, quantifying the denominator for incidence using these data is challenging because catchment areas and care-seeking behaviours are not well defined. This study’s aim was to estimate malaria incidence using HMIS data by adjusting the population denominator accounting for travel time to the health facility.MethodsOutpatient data from two public health facilities in Uganda (Kihihi and Nagongera) over a 3-year period (2011–2014) were used to model the relationship between travel time from patient village of residence (available for each individual) to the facility and the relative probability of attendance using Poisson generalized additive models. Outputs from the model were used to generate a weighted population denominator for each health facility and estimate malaria incidence. Among children aged 6 months to 11 years, monthly HMIS-derived incidence estimates, with and without population denominators weighted by probability of attendance, were compared with gold standard measures of malaria incidence measured in prospective cohorts.ResultsA total of 48,898 outpatient visits were recorded across the two sites over the study period. HMIS incidence correlated with cohort incidence over time at both study sites (correlation in Kihihi = 0.64, p < 0.001; correlation in Nagongera = 0.34, p = 0.045). HMIS incidence measures with denominators unweighted by probability of attendance underestimated cohort incidence aggregated over the 3 years in Kihihi (0.5 cases per person-year (PPY) vs 1.7 cases PPY) and Nagongera (0.3 cases PPY vs 3.0 cases PPY). HMIS incidence measures with denominators weighted by probability of attendance were closer to cohort incidence, but remained underestimates (1.1 cases PPY in Kihihi and 1.4 cases PPY in Nagongera).ConclusionsAlthough malaria incidence measured using HMIS underestimated incidence measured in cohorts, even when adjusting for probability of attendance, HMIS surveillance data are a promising and scalable source for tracking relative changes in malaria incidence over time, particularly when the population denominator can be estimated by incorporating information on village of residence.

Geographic variations in dental sealant utilization by Medicaid enrollees.

To investigate geographical variations and their relationship to race/ethnicity in dental sealant utilization for first molars among Wisconsin Medicaid enrollees from 2010 to 2013. Wisconsin Medicaid dental claims for sealants in children aged 6-16 years were analyzed. County-level population density, urban influence code, presence of dental health professional shortage areas, and population-per-dentist ratio were considered as geographic predictors. Descriptive statistics and mixed effects Poisson regression models were used to examine the effect of county level covariates on the number of dental sealants received per person-year (PY) of eligibility adjusting for patient-level characteristics. Over-dispersion was modeled by a random residual effect, and all models adjusted for single-year age and gender interaction and race/ethnicity main effect. Medicaid claims for sealants on first permanent molars for 2010-2013 totaled 288,019 over 1,130,000 PY. The age- and gender-standardized rate of first molar sealant applications per 100 PY were 27.9, 25.7, and 16.6 for White, Hispanic, and Black children, respectively. County-specific rates ranged from a low of 8.9 per 100 PY to a high of 62.6 per 100 PY. In the multivariate analysis after adjusting for geography, compared to Whites, Hispanics had highest rates (rate ratio (RR)=1.33, 95% CI=1.30-1.37) of dental sealant utilization followed by Blacks (RR=1.25, 95% CI=1.21-1.29). Population density was the only significant geographic predictor (RR=0.56 per 10-fold increase, 95% CI=0.45-0.69). Substantial geographic variability in the utilization of sealants for first molars was identified. Lower population density was the main geographical predictor of high sealant utilization.

High Healthcare Resource Utilization and Cost for PTLD Patients Following Kidney Transplants

Background: Post-transplant lymphoproliferative disease (PTLD) is a rare and aggressive disease with high mortality rates, and may have substantial healthcare resource utilization (HRU) and cost. Objectives: To describe the HRU and Medicare paid amounts up to 3 years after kidney transplants for PTLD patients and for all kidney transplant patients. Methods: The United States Renal Data System (USRDS) is a national data system that collects, analyzes and distributes information about chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the United States. It is a claim dataset that provides Medicare paid amounts and HRU for these patients, including their kidney transplants. Patients are Medicare-eligible for 3 years after a successful kidney transplant. The Scientific Registry of Transplant Recipients (SRTR) is a national data system that reports data from transplant centers on all solid organ transplants in the US, including data on malignancies after transplants, including PTLD. The USRDS data was used to identify Medicare-covered kidney transplant recipients from 2007 until 2016. SRTR malignancy data were used to obtain patients with a PTLD diagnosis, which was linked to the USRDS. Patients had to have a USRDS claim on the date of transplantation. Only patients enrolled in Medicare Part A and Part B fee-for-service were included. Solitary kidney re-transplants were included but not multi-organ transplants, due to a potential difference in HRU and cost in the latter. Medicare Part A (inpatient, outpatient, home health, hospice, skilled nursing) and B HRU and paid amounts were tabulated for up to 3 years' post-transplant. The year post-transplant was calculated using 365.25 days per year following the kidney transplant. For example, recipients with a PTLD diagnosis any time within 365.25 days following their kidney transplant were considered a PTLD patients within 1-year post-transplant. A per person-year (PPY) was computed to standardize costs. Patients were censored at loss of Medicare eligibility or death or at the end of 3-year post-transplant. Results: A total of 83,818 Medicare-covered kidney transplants were included in this study with a mean age of 51.55 (SD: 15.11) at transplant and 60.77% male. Average paid amount from transplant to 1-year post-transplant was $83,546 PPY, with approximately two-thirds of the cost coming from inpatient hospitalization. For year 2 and 3 post-transplant, the average paid amount was $26,148 PPY and $25,326 PPY, respectively, with similar cost coming from inpatient and Part B (~39% each). Among these kidney transplant recipients, 281 transplant recipients had PTLD while Medicare-eligible with an average age of 53.98 (SD: 19.19) years at transplant and 67.97% male. Median time from transplant to PTLD diagnosis was 1.02 years (IQR: 0.60-1.93 years). For patients who were diagnosed with PTLD within the first year after transplant (n=139), average paid amount from date of the first PTLD diagnosis to 1-year post-transplant was $222,336 PPY, with approximately two-thirds of the cost from inpatient hospitalization. Of these patients who survived or were eligible in year 2 (n=94) and 3 (n=64), the average cost was $60,981 PPY and $36,118 PPY, respectively. For patients who were diagnosed with PTLD in the second year after transplant (n=81), average paid amount in year 2 post-transplant was $203,374 PPY with approximately 60% coming from inpatient hospitalization. Year 3 post-transplant cost for these PTLD patients who survived or were eligible (n=59) was $58,879 PPY. For patients who were diagnosed with PTLD in the third year after transplant (n=61), average paid amount in year 3 post-transplant was $211,941 PPY with 68% coming from inpatient hospitalization. Conclusions: PTLD is associated with substantial HRU and cost (&amp;gt;$200k PPY in the year diagnosed), regardless of the year diagnosed post-transplant, while patients without PTLD and patients who haven't developed PTLD yet had a cost of ~$83k PPY in year 1, and ~$26k PPY for year 2 and 3 post-transplant. Disclosures Ahn: Medtronic: Current equity holder in publicly-traded company; Bristol-Myers Squibb: Research Funding. Watson:Atara Biotherapeutics: Current Employment, Current equity holder in publicly-traded company. Skeans:Bristol-Myers Squibb: Research Funding; Astellas: Research Funding; Atara Biotherapeutics: Research Funding. Barlev:Atara Biotherapeutics: Current Employment, Current equity holder in publicly-traded company. Thompson:Atara Biotherapeutics: Research Funding; Bristol-Myers Squibb: Research Funding. Dharnidharka:Atara Biotherapeutics: Consultancy, Honoraria, Research Funding; CareDx: Honoraria, Research Funding, Speakers Bureau.

Postdischarge Decolonization of Patients Harboring MRSA USA300 Strains: Secondary Analysis of the CLEAR Trial

Background: The Changing Lives by Eradicating Antibiotic Resistance (CLEAR) Trial was a trial of 2,121 recently discharged methicillin-resistant Staphylococcus aureus (MRSA) carriers randomized to MRSA education plus a 5-day decolonization regimen repeated twice monthly for the 6 months following discharge versus MRSA education alone. Decolonization resulted in a 30% reduction in MRSA infection and a 17% reduction in all-cause infection (Huang SS et al, NEJM, 2019) in the year following discharge. We pursued an evaluation of USA300 carriers to determine whether the decolonization benefit differed for this strain type. Methods: A secondary analysis of the CLEAR randomized controlled trial (RCT) was performed, limiting the cohort to participants known to harbor USA300 at or within 30 days of enrollment and who attended all follow-up visits in the year following discharge. Within this subset, we conducted a time-to-event analysis using unadjusted and adjusted Cox proportional-hazard models. Variables in adjusted analyses included demographic data, insurance type, presence of coexisting conditions or medical devices at enrollment, hospitalization or residence in a nursing home in the year before enrollment, receipt of anti-MRSA antibiotics, protocol adherence, and randomization strata. Results: USA300 was identified in 420 of the 783 participants who attended all visits and had strains genetically tested. MRSA infections occurred in 27 of 207 education group participants (0.149 per person year) and in 19 of 213 decolonization group participants (0.099 per-person year). Point estimates from the unadjusted hazard ratios of infection reduction were similar (0.59; 95% CI, 0.32–1.09) to the full trial population (0.61; 95% CI, 0.44–0.85), suggesting nondifferential benefit for the USA300 strain type. Adjusted models were highly similar. Conclusions: The reduction in MRSA infection associated with postdischarge decolonization in the subgroup of participants who harbored the USA300 strain-type was consistent with overall trial findings. Although the original trial was not powered for the evaluation of a USA300 subset, this RCT provides a valuable design for assessing the magnitude of strain-specific responsiveness to decolonization during a time when national rates of MRSA invasive disease have plateaued and USA300 is responsible for an increasing proportion of infections. These data suggest that postdischarge decolonization should be similarly effective in carriers of either USA300 or healthcare-associated MRSA strains.Funding: NoneDisclosure: Gabrielle M. Gussin, Stryker (Sage Products): Conducting studies in which antiseptic product is provided to participating hospitals and nursing homes. Clorox: Conducting studies in which antiseptic product is provided to participating hospitals and nursing homes. Medline: Conducting studies in which antiseptic product is provided to participating hospitals and nursing homes. Xttrium: Conducting studies in which antiseptic product is provided to participating hospitals and nursing homes. Mohamad Sater, Salary-Day Zero Diagnostics.