CTHRC1+ fibroblasts and SPP1+ macrophages synergistically contribute to pro-tumorigenic tumor microenvironment in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal cancer that accounts for over 90% of all pancreatic cancer cases. With a 5-year survival rate of only 13%, PDAC has proven to be extremely desmoplastic and immunosuppressive to most current therapies, including chemotherapy and surgical resection. In recent years, focus has shifted to understanding the tumor microenvironment (TME) around PDAC, enabling a greater understanding of biological pathways and intercellular interactions that can ultimately lead to potential for future drug targets. In this study, we leverage a combination of single-cell and spatial transcriptomics to further identify cellular populations and interactions within the highly heterogeneous TME. We demonstrate that SPP1+APOE+ tumor-associated macrophages (TAM) and CTHRC1+GREM1+ cancer-associated myofibroblasts (myCAF) not only act synergistically to promote an immune-suppressive TME through active extracellular matrix (ECM) deposition and epithelial mesenchymal transition (EMT), but are spatially colocalized and correlated, leading to worse prognosis. Our results highlight the crosstalk between stromal and myeloid cells as a significant area of study for future therapeutic targets to treat cancer.

Burkholderia thailandensis uses a type VI secretion system to lyse protrusions without triggering host cell responses.

To spread within a host, intracellular Burkholderia form actin tails to generate membrane protrusions into neighboring host cells and use type VI secretion system-5 (T6SS-5) to induce cell-cell fusions. Here, we show that B. thailandensis also uses T6SS-5 to lyse protrusions to directly spread from cell to cell. Dynamin-2 recruitment to the membrane near a bacterium was followed by a short burst of T6SS-5 activity. This resulted in the polymerization of the actin of the newly invaded host cell and disruption of the protrusion membrane. Most protrusion lysis events were dependent on dynamin activity, caused no cell-cell fusion, and failed to be recognized by galectin-3. T6SS-5 inactivation decreased protrusion lysis but increased galectin-3, LC3, and LAMP1 accumulation in host cells. Our results indicate that B. thailandensis specifically activates T6SS-5 assembly in membrane protrusions to disrupt host cell membranes and spread without alerting cellular responses, such as autophagy.

Continuity of care during severe civil unrest with a model of community-based HIV care: a retrospective cohort study from Haiti.

Background: There are limited data on the effectiveness of differentiated service delivery (DSD) for HIV care during sociopolitical turmoil. We assessed outcomes with a DSD model of care that includes patient choice between community-based antiretroviral therapy (ART) centres, home-based ART dispensing, or facility-based care at GHESKIO clinic during a period of severe civil unrest in Port-au-Prince, Haiti. Methods: This retrospective analysis included data on patients with at least one HIV visit at GHESKIO between May 1, 2019, and December 31, 2021. Multivariable logistic regression models were used to assess predictors of attending ≥1 community visit during the study period, and failure to attend timely visits. HIV-1 RNA test results were reported among patients who had been ART for ≥3 months at last visit. Findings: Of the 18,625 patients included in the analysis, 9659 (51.9%) attended at least one community visit. The proportion of community visits ranged from 0.3% (2019) to 44.1% (2021). Predictors of ≥1 community visit included male sex (aOR: 1.13; 95% CI: 1.06, 1.20), secondary education (aOR: 1.07; 95% CI: 1.01, 1.14), income > $USD 1.00/day (aOR: 1.24; 95% CI: 1.14, 1.35), longer duration on ART (aOR: 1.08 per additional year; 95% CI: 1.07, 1.09), and residence in Carrefour/Gressier (p < 0.0001 in comparisons with all other zones). Younger age and shorter time on ART were associated with late visits and loss to follow-up. Among 12,586 patients with an on-time final visit who had been on ART for ≥3 months, 11,131 (88.4%) received a viral load test and 9639 (86.6%) had HIV-1 RNA < 1000 copies/mL. Interpretation: The socio-political situation in Haiti has presented extraordinary challenges to the health care system, but retention and viral suppression rates remain high with a model of community-based HIV care. Additional interventions are needed to improve outcomes for younger patients, and those with shorter time on ART. Funding: No funding.

Artificial Intelligence Applications in Space Medicine.

INTRODUCTION:During future interplanetary space missions, a number of health conditions may arise, owing to the hostile environment of space and the myriad of stressors experienced by the crew. When managing these conditions, crews will be required to make accurate, timely clinical decisions at a high level of autonomy, as telecommunication delays and increasing distances restrict real-time support from the ground. On Earth, artificial intelligence (AI) has proven successful in healthcare, augmenting expert clinical decision-making or enhancing medical knowledge where it is lacking. Similarly, deploying AI tools in the context of a space mission could improve crew self-reliance and healthcare delivery.METHODS: We conducted a narrative review to discuss existing AI applications that could improve the prevention, recognition, evaluation, and management of the most mission-critical conditions, including psychological and mental health, acute radiation sickness, surgical emergencies, spaceflight-associated neuro-ocular syndrome, infections, and cardiovascular deconditioning.RESULTS: Some examples of the applications we identified include AI chatbots designed to prevent and mitigate psychological and mental health conditions, automated medical imaging analysis, and closed-loop systems for hemodynamic optimization. We also discuss at length gaps in current technologies, as well as the key challenges and limitations of developing and deploying AI for space medicine to inform future research and innovation. Indeed, shifts in patient cohorts, space-induced physiological changes, limited size and breadth of space biomedical datasets, and changes in disease characteristics may render the models invalid when transferred from ground settings into space.Cheung HC, De Louche C, Komorowski M. Artificial intelligence applications in space medicine. Aerosp Med Hum Perform. 2023; 94(8):610-622.

Rationalising the use of specimen pots following colorectal polypectomy: a small step towards greener endoscopy.

Aims: In this study, we aim to determine whether combining multiple small colorectal polyps within a single specimen pot can reduce carbon footprint, without an associated deleterious clinical impact. Methods: This was a retrospective observational study of colorectal polyps resected during 2019, within the Imperial College Healthcare Trust. The numbers of pots for polypectomy specimens were calculated and corresponding histology results were extracted. We modelled the potential reduction in carbon footprint if all less than 10 mm polyps were sent together and the number of advanced lesions we would not be able to locate if we adopted this strategy. Carbon footprint was estimated based on previous study using a life-cycle assessment, at 0.28 kgCO2e per pot. Results: A total of 11 781 lower gastrointestinal endoscopies were performed. There were 5125 polyps removed and 4192 pots used, equating to a carbon footprint of 1174 kgCO2e. There were 4563 (89%) polyps measuring 0-10 mm. 6 (0.1%) of these polyps were cancers, while 12 (0.2%) demonstrated high-grade dysplasia. If we combined all small polyps in a single pot, total pot usage could be reduced by one-third (n=2779). Conclusion: A change in practice by placing small polyps collectively in one pot would have resulted in reduction in carbon footprint equivalent to 396 kgCO2e (emissions from 982 miles driven by an average passenger car). The reduction in carbon footprint from judicious use of specimen pots would be amplified with a change in practice on a national level.

Disease Progression and Longitudinal Clinical Outcomes of Lewy Body Dementia in the NACC Database.

INTRODUCTION: As the identification of Lewy body dementia (LBD) is often confirmed postmortem, there is a paucity of evidence on the progression of disease antemortem. This study aimed to comprehensively assess the course of LBD over time across cognitive, functional, and neuropsychiatric outcomes using real-world data. METHODS: Adults with at least one visit to an Alzheimer's Disease Center with a diagnosis of mild cognitive impairment/dementia (index date), indication of LBD, and at least one follow-up visit were identified in the National Alzheimer's Coordinating Center database (September 2005-June 2020). Participant characteristics, medication use, comorbidities, and changes in outcomes were assessed over a 5-year follow-up period and stratified by disease severity based on the Clinical Dementia Rating (CDR®) Dementia Staging Instrument-Sum of Boxes (CDR-SB) score at index. RESULTS: A total of 2052 participants with LBD (mean age at index 73.4 years) were included (mild, 219; moderate, 988; severe, 845). Mean annualized increase over 5 years was 0.9 points for CDR-Global Score, 5.6 points for CDR-SB, 10.4 points for the Functional Activities Questionnaire, and 2.0 points for the Neuropsychiatric Inventory-Questionnaire. Disease progression was greater among participants with moderate and severe LBD at index compared with those with mild LBD. CONCLUSION: Participants with LBD experienced decline across all outcomes over time, and impairment increased with disease severity. Findings highlight the substantial clinical burden associated with LBD and the importance of earlier diagnosis and effective treatment. Further research is needed to understand the predictors of cognitive and functional decline in LBD which may help inform clinical trials.

Profiling Disease and Economic Burden in CRSwNP Using Machine Learning.

Purpose: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with high healthcare resource utilization (HRU) and economic cost; however, heterogeneity of clinical burden among patients with differing clinical characteristics has not been fully elucidated. Here, an unsupervised machine learning approach supported by clinical validation identified distinct clusters of patients with CRSwNP and compared healthcare burden. Patients and Methods: This retrospective analysis identified adult patients with ≥2 claims for CRSwNP and date of first diagnosis (index date) between January 2015 and June 2019 from a healthcare database. Patients were required to have enrollment in the database 6-months pre- and 12-months post-index. Patients were assigned to clusters using latent class analysis. All-cause and nasal polyp (NP)-related HRU and costs were compared between clusters. Results: Among 12,807 patients, 5 clusters were identified: cluster 1: no surgery/low comorbidity/low medication use (n = 4076); cluster 2: no surgery/low comorbidity/high medication use (n = 2201); cluster 3: no surgery/high comorbidity/high medication use (n = 2093); cluster 4: surgery/low comorbidity/moderate medication use (n = 3168); cluster 5: surgery/high comorbidity/high medication use (n = 1269). All-cause HRU was similar across clusters. NP-related HRU was highest in the surgical clusters (clusters 4 and 5). All-cause costs were similar in clusters 1-3 ($15,833-$17,461) and highest in clusters 4 ($31,083) and 5 ($31,103), driven by outpatient costs. Total NP-related costs were also highest for clusters 4 and 5 ($14,193 and $16,100, respectively). Conclusion: Substantial heterogeneity exists in clinical and economic burden among patients with CRSwNP. Machine learning offers a novel approach to better understand the diverse, complex burden of illness in CRSwNP.

Real-world clinical burden among patients with and without heart failure worsening after cardiac resynchronization therapy.

OBJECTIVE: Cardiac resynchronization therapy (CRT) can improve cardiac function in patients with heart failure (HF); however, in some patients, HF worsens despite CRT. This study characterized the long-term clinical burden of patients with and without HF worsening (HFW) within 6 months post CRT implantation. METHODS: A claims database (2007-2018) was used to identify two cohorts of adults: those with HFW within 180 days post-CRT and those with no HFW (NHFW). The evaluated clinical outcomes were cardiovascular events/complications, HF-related interventions, hospice enrollment, and all-cause mortality. Inverse probability of treatment weighting (IPTW) was used to adjust for confounders; adjusted comparisons were assessed using weighted Cox proportional hazard ratios (HRs). RESULTS: Among the 12,753 adults analyzed (HFW: N = 4,785; NHFW: N = 7,968), the mean age was 72 years and the mean duration of follow-up was approximately 2 years. The clinical burden was greater for HFW than for NHFW in terms of all-cause mortality (19.7% vs. 12.1%) and occurrence of atrial fibrillation (57.4% vs. 51.2%). In the IPTW-adjusted Cox proportional hazard analyses, patients with HFW had a 54% higher average hazard of experiencing all-cause mortality compared to NHFW (adjusted average HR = 1.54, 95% confidence interval [CI]: 1.41-1.70; p < .001). Of the clinical events experienced by ≥5% of patients, the greatest differences in average hazard were for HF decompensation (adjusted average HR = 1.83, 95% CI: 1.60-2.09) and HF decompensation or death (HR = 1.63, 95%CI: 1.50-1.77). CONCLUSION: Patients with early HFW post-CRT experienced a significantly higher clinical burden than those without HFW. Vigilance for signs of worsening HF in the first 6 months post-CRT is warranted.

Epidemiology and economic burden of Lewy body dementia in the United States.

OBJECTIVE: To describe the trends in epidemiology, healthcare resource use (HCRU), and costs associated with Lewy body dementia (LBD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD) in the United States. METHODS: This retrospective study used administrative claims data for Medicare fee-for-service (2010-2018) and commercially-insured beneficiaries (2010-2017). The annual prevalence and incidence were calculated among the Medicare beneficiaries by dividing the number of prevalent or incident LBD, DLB, and PDD patients by the total eligible population of that calendar year. Baseline patient characteristics, HCRU, and costs over time were described for Medicare and commercially insured patients with continuous health plan enrollment for ≥12 months before and ≥24 months after first cognitive impairment (CI) diagnosis. RESULTS: From 2010 to 2016, the incidence and prevalence rates of LBD among Medicare beneficiaries ranged from 0.21%-0.18% and 0.90%-0.83%, respectively. Of 9019 Medicare patients with LBD who met other inclusion criteria, 4796 (53.2%) had DLB and 4223 (46.8%) had PDD. The mean age was 78 years and the mean Charlson Comorbidity Index score was 1.6. On average, patients with LBD incurred $18,309 in medical costs during the 1-year pre-diagnosis and $29,174 and $22,814 at years 1 and 5 after diagnosis, respectively. The main cost drivers were inpatient and outpatient visits. Similar trends were observed for DLB and PDD as well as for commercially-insured patients. CONCLUSIONS: Our findings highlight the substantial epidemiological and economic burden across the LBD spectrum and underscore a high unmet need for effective treatments to improve patient outcomes.

Evaluation of treatment patterns, healthcare resource utilization, and costs among patients receiving treatment for cytomegalovirus following allogeneic hematopoietic cell or solid organ transplantation.

AIM: Management of cytomegalovirus (CMV) infection/disease in transplant recipients may be complicated by toxicities and resistance to conventional antivirals, adding to the overall healthcare burden. We characterized treatment patterns, healthcare resource utilization (HCRU), and costs to elucidate the healthcare burden associated with CMV therapies post-transplant. MATERIALS AND METHODS: A retrospective, longitudinal cohort study of transplant recipients using data from a US commercial insurance claims database (2013-2017) was conducted. Patients with a claim for post-transplant CMV diagnosis and anti-CMV treatment (ganciclovir, valganciclovir, foscarnet, or cidofovir) were identified (Treated CMV cohort) and compared with patients with neither a claim for CMV diagnosis nor anti-CMV treatment (No CMV cohort) for outcomes including HCRU and associated costs. Allogeneic hematopoietic cell transplantation (HCT) or solid organ transplantation (SOT) recipients were analyzed separately. Anti-CMV treatment patterns were assessed in the Treated CMV cohort. Costs were evaluated among subgroups with myelosuppression or nephrotoxicity. RESULTS: Overall, 412 allogeneic HCT and 899 SOT patients were included in the Treated CMV cohorts, of which 41.7% and 52.5%, respectively, received multiple antiviral courses. Treated CMV cohorts compared with No CMV cohorts had higher mean monthly healthcare visits per patient (allogeneic HCT: 8.83 vs 6.61, SOT: 5.61 vs 4.45) and had an incremental adjusted mean monthly cost per patient differences of $8,157 (allogeneic HCT, p < .004) and $2,182 (SOT, p < .004). Among Treated CMV cohorts, HCRU and costs increased with additional CMV antiviral treatment courses. Mean monthly costs were higher for patients with than without myelosuppression or nephrotoxicity. LIMITATIONS: Results may not be generalizable to patients covered by government insurance or outside the USA. CONCLUSIONS: CMV post-transplant managed with conventional treatment is associated with substantial HCRU and costs. The burden remains particularly high for patients requiring multiple treatment courses for post-transplant CMV or for transplant recipients who develop myelosuppression or nephrotoxicity.

Real-World Eculizumab Dosing Patterns Among Patients with Paroxysmal Nocturnal Hemoglobinuria in a US Population.

Purpose: Current pharmacologic management of paroxysmal nocturnal hemoglobinuria (PNH) consists of C5 inhibitors, eculizumab and ravulizumab; however, because patients experience incomplete symptom control, off-label doses may be utilized. We conducted a retrospective, longitudinal cohort study of provider-based claims data to assess the real-world eculizumab dosing patterns in PNH patients. Patients and Methods: Patients were ≥12 years, received ≥2 eculizumab infusions between January 1, 2015 and September 30, 2019, and had ≥3 months of continuous clinical activity prior to index. The index date was the first claim for eculizumab. Patients with ≥1 diagnosis of another indication for eculizumab were excluded. Treatment patterns including the proportion with high, label-recommended, and low dosages during induction (first 28 days) and maintenance (beginning day 29) phases were described. The proportion and time-to-first dose escalation, defined as an increase in dose or frequency of infusion, were assessed among a subset of patients (ie, escalation analysis cohort). Results: A total of 707 patients were examined. Mean (standard deviation [SD]) starting dose was 862mg (412mg) and was higher than label-recommended 600mg for 64% of the patients. Mean (SD) dose per infusion was 859mg (391mg) during the induction phase; average dose was higher than label-recommended 600mg for 68%. Mean (SD) dose per infusion during the maintenance phase was 1005mg (335mg); average dose was higher than label-recommended 900mg for 43%. Dose escalation occurred in 40/121 escalation analysis cohort patients. Median time-to-first dose escalation was ~12 months. Conclusion: Results suggest that deviations from label-recommended dosing patterns were common. Future budget impact assessments of eculizumab should account for real-world dosing patterns to comprehensively assess costs and benefits.

Outcomes and resource use of patients with large hemispheric infarction and cerebral edema: analysis of real-world data.

OBJECTIVE: Large hemispheric infarction (LHI) is associated with a high likelihood of the evolution of life-threatening edema. Few studies have assessed real-world clinical outcomes and management strategies among patients with LHI. The objective of this study was to describe the management, in-hospital outcomes, and direct healthcare resource burden of patients with LHI, as well as those of patients with subsequent cerebral edema. METHODS: This observational, retrospective cohort study analyzed de-identified data from US adult patients using the IBM MarketScan Hospital Drug Database (Q4-2015 to Q4-2017). Patients were included in the "Possible LHI" or the "Other Ischemic Strokes" cohorts using ICD-10 diagnosis codes. Patients with possible LHI were further categorized into "LHI with Edema" and "LHI without Edema" subgroups using diagnosis and procedure codes. Select clinical and economic outcomes were compared between cohorts and subgroups using multivariable regressions. RESULTS: Of 79,201 eligible encounters with ischemic strokes, 11,772 unique patients were assigned to the Possible LHI cohort while 67,429 were assigned to the Other Ischemic Strokes cohort. Among patients with possible LHI, 869 (7%) were assigned to the LHI with Edema subgroup and 10,903 (93%) were assigned to the LHI without Edema subgroup. Patients in the Possible LHI cohort had longer hospital stays (mean difference [MD] [95%CI] = 2.6 [2.4;2.8] days), higher total facility charges (MD [95%CI] = $28,656 [26,794;30,524]), and higher odds of death (odds ratio [95%CI] = 2.2 [2.0;2.4]) than the Other Ischemic Strokes cohort. Among patients with possible LHI, the incremental clinical and resource burden was further exacerbated in the subgroup of patients with edema (hospital days: MD [95%CI] = 5.0 [3.9;6.2] days; total facility charges: MD [95%CI] = $59,585 [50,816;67,583]; mortality: odds ratio [95%CI] = 10.3 [8.5;12.4]). CONCLUSIONS: Among patients with ischemic strokes, LHI was associated with increased clinical management and direct healthcare resource burden in real-world hospital settings. The burden was substantially increased among patients who developed cerebral edema.

Persistence to hypomethylating agents and clinical and economic outcomes among patients with myelodysplastic syndromes.

OBJECTIVES: To evaluate hypomethylating agent (HMA) persistence in patients with myelodysplastic syndromes (MDS), and examine its association with healthcare resource utilization (HRU) and progression to acute myeloid leukemia (AML). METHODS: A total of 2,400 adults diagnosed with MDS initiating HMAs were included from IBM MarketScan databases during 1/1/2011-3/31/2018. The index date was HMA initiation following MDS diagnosis. Patients were classified according to their persistence status by the end of a fixed 'landmark period' of 4 months post-index. RESULTS: Median persistence to HMAs was 5.6 months (95% CI: 5.2, 6.1); HMA non-persistence increased with time. Non-persistent patients had a significantly higher non-HMA-related HRU burden than persistent patients [adjusted incidence rate ratios, outpatient visits: 1.12 (95% CI: 1.10, 1.14); inpatient visits: 1.48 (95% CI: 1.30, 1.69); emergency department visits 1.30 (95% CI: 1.12, 1.50); all p-values < 0.001]. All-cause and HMA-related outpatient visits were lower among non-persistent patients, likely because of fewer HMA administration-related visits. The incidence rate of AML was numerically, although not significantly, higher in non-persistent patients, when starting follow-up at the end of the landmark period. When follow-up began at the index date, non-persistent patients had a significantly higher rate of AML [adjusted hazard ratio, 1.88 (95% CI: 1.53, 2.32); p-value < 0.001]. CONCLUSIONS: HMA non-persistence, which increased over time, was associated with significantly higher non-HMA-related HRU, and numerically higher AML progression in MDS patients initiating HMAs. Future studies should evaluate predictors of HMA non-persistence in this patient population.

Real-World Economic Burden Among Patients With And Without Heart Failure Worsening After Cardiac Resynchronization Therapy.

INTRODUCTION: Although cardiac resynchronization therapy (CRT) has the potential to improve cardiac function in patients with heart failure (HF), a considerable portion of patients do not respond to therapy. This study assessed the economic burden among patients with and without HF worsening after receiving CRT in real-world practice. METHODS: In this retrospective claims-based study using Optum's de-identified Clinformatics® Data Mart Database (January 2007-December 2018), adults who received CRT were stratified into two cohorts based on whether they showed evidence of HF worsening within 180 days post-CRT implantation. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding, accounting for demographics (e.g., age, sex), the Quan-Charlson Comorbidity Index, other clinical characteristics, healthcare resource utilization (HRU), and healthcare costs during the 180 days pre-CRT (baseline period). Annualized all-cause and congestive HF-related HRU and healthcare costs from payer and patient perspectives were assessed from day 181 post-CRT (follow-up period), and compared between cohorts using incidence rate ratios (IRRs) and cost ratios (CRs). RESULTS: This study included 12,753 patients (n = 4785 with HF worsening; n = 7968 without). Mean age was 72 years and roughly two-thirds were male. Baseline characteristics were balanced between cohorts post-IPTW. During follow-up, patients with HF worsening had significantly greater annual all-cause inpatient [adjusted IRR (95% confidence interval) = 1.55 (1.44, 1.66), p < 0.001], outpatient [adjusted IRR = 1.46 (1.32, 1.61), p < 0.001], and emergency department [adjusted IRR = 1.31 (1.22, 1.41), p < 0.001] visits. Mean annual total per patient payer-paid amounts were significantly higher for patients with HF worsening versus without HF worsening [adjusted CR = 1.68 (1.56, 1.80), p < 0.001]. Annual patient-paid medical costs were also higher for patients with HF worsening [adjusted CR = 1.31 (1.25, 1.38), p < 0.001]. Results were similar for congestive HF-related HRU and costs. CONCLUSIONS: The incremental economic burden among patients with HF worsening following CRT is substantial. Efforts aimed at CRT optimization may help reduce this burden.

Success of community approach to HPV vaccination in school-based and non-school-based settings in Haiti.

OBJECTIVES: To assess the success of a human papillomavirus (HPV) vaccination program among adolescent girls aged 9-14 years in Haiti and to understand predictors of completion of a two-dose HPV vaccination series. METHODS: Data collection was conducted during HPV vaccination campaigns in Port-au-Prince between August 2016 and April 2017. Descriptive statistics and logistic regression models were used to examine characteristics associated with vaccination series completion of school based and non-school based vaccination delivery modalities. RESULTS: Of the 2,445 adolescent girls who participated in the awareness program, 1,994 participants (1,307 in non-school program, 687 in school program) received the first dose of the vaccine; 1,199 (92%) in the non-school program and 673 (98%) in the school program also received the second dose. Menarche (OR: 1.87; 95% CI, 1.11-3.14), if the participant was a prior patient at the GHESKIO clinics (OR: 2.17; 95% CI, 1.32-3.58), and participating in the school-based program (OR: 4.17; 95% CI, 2.14-8.12) were significantly associated with vaccination completion. CONCLUSIONS: Vaccination in school- and non-school-based settings was successful, suggesting that a nationwide HPV vaccination campaign using either approach would be successful using either approach.

Decreased antibiotic exposure using a procalcitonin protocol for respiratory infections and sepsis in US community hospitals (ProCommunity).

OBJECTIVE: Antibiotic overuse leading to antimicrobial resistance is a global public health concern. Clinical trials have demonstrated that procalcitonin-based decision-making for antibiotic therapy can safely decrease inappropriate antibiotic use in patients with respiratory infections and sepsis, but real-world data are scarce. This study sought to assess the impact of a procalcitonin-based antibiotic stewardship program (protocol plus education) on antibiotic use in community hospitals. METHODS: An observational, retrospective, matched cohort study was conducted. Eligible patients treated in hospitals with a procalcitonin-based protocol plus education (Procalcitonin cohort hospitals) were matched to patients admitted to facilities without procalcitonin testing (Control cohort hospitals) using a 1:2 ratio. The Control hospitals were facilities where procalcitonin testing was not available on site. Patient matching was based on: (1) age, (2) gender, (3) admission diagnosis code using groupings of the International Classification of Diseases, 10th Revision, (4) whether patients were admitted to the intensive care unit, and (5) whether a blood culture test was performed. Procalcitonin cohort hospitals implemented a quality improvement initiative, where procalcitonin was available, used regularly, and clinicians (physicians and pharmacists) were educated on its use. RESULTS: After adjustment, patients in the Procalcitonin cohort had 1.47 fewer antibiotic days (9.1 vs. 8.5 days, 95%CI: -2.72; -0.22, p = .021). There was no difference in length of stay or adverse clinical outcomes except for increase in acute kidney injury (odds ratio = 1.26, 95%CI: 1.01; 1.58, p = .038). CONCLUSIONS: Patients with respiratory infections and sepsis in hospitals utilizing a procalcitonin-based protocol coupled with education received fewer days of antibiotic therapy.

Temporal and Geographic Variation in the Incidence of Alzheimer's Disease Diagnosis in the US between 2007 and 2014.

OBJECTIVES: Our aim was to describe the incidence of Alzheimer's disease (AD) in the United States, overall and by geographic region. DESIGN: We conducted retrospective analyses of administrative claims data for a 5% random sample of US Medicare beneficiaries aged 65 years or older. AD incidence, defined as a diagnosis for AD (International Classification of Disease, Ninth Revision, Clinical Modification code 331.0×) in a given year, with no AD diagnosis in the beneficiary's entire medical history, was estimated for each calendar year between 2007 and 2014. Beneficiaries were required to be enrolled in Medicare for the calendar year of evaluation as well as the preceding 12 months. In addition, a cross-sectional assessment of geographic variation in AD incidence was conducted for 2014. For each population area (specifically, core-based statistical area, as defined by the US Census Bureau), AD incidence was estimated overall, as well as adjusted for differences in underlying patient demographics and metrics of access to care and quality of care. Changes in AD incidence from 2007 were also estimated. SETTING: US fee-for-service Medicare. PARTICIPANTS: US Medicare beneficiaries aged 65 years or older with no history of AD. RESULTS: Overall, the diagnosed incidence of AD decreased over time, from 1.53% in 2007 to 1.09% in 2014; trends were similar for most population areas. In 2014, the rates of AD incidence ranged from 0% to more than 3% across population areas, with the highest observed incidence rates in areas of the Midwest and the South. Statistical models explain little of the geographic variation, although following adjustment, the incidence rates increased the most (in relative terms) in rural areas of western states. CONCLUSION: Our findings are consistent with previously reported estimates of incidence of AD in the United States and its recent declining trend. Additionally, the study highlights the considerable geographic variation in the incidence of AD in the United States and suggests that further research is needed to better understand the determinants of this geographic variation. J Am Geriatr Soc 68:346-353, 2020.

Direct and Indirect Costs of Infectious Conjunctivitis in a Commercially Insured Population in the United States.

PURPOSE: To assess the direct and indirect costs of infectious conjunctivitis and quantify medical costs due to conjunctivitis transmission in families. METHODS: In this retrospective claims analysis from the OptumHealth Care Solutions, Inc. database (1998-2016), beneficiaries with or without at least one diagnosis of infectious conjunctivitis were identified. Direct and indirect costs (in 2016 US$) during the 60 days post conjunctivitis diagnosis (or imputed date for controls) were compared using cost differences in linear regressions. For transmission cost analysis, the total cost of each conjunctivitis episode was the sum of the primary episode (seed patient) and the secondary episode (infected family members) costs. A generalized estimating equation model adjusted for seed patient characteristics was used to assess the impact of number and rate of transmissions on episode cost. RESULTS: Health care resource utilization and direct costs were significantly higher for patients with conjunctivitis (n=1,002,188) versus controls (n=4,877,210): 1.67 all-cause visits per person per month (PPPM) versus 0.79 visits PPPM, respectively; total mean direct cost of $396.04 PPPM versus $289.63 PPPM, respectively. The cost of medically related absenteeism was $105.42 (95% confidence interval [CI], $104.18-$106.75) higher for patients with conjunctivitis than for controls. Episode cost, without transmission due to seed patient, was $669.43 (95% CI, $654.67-$684.85); it increased with each additional infected family member and with increased infection transmission time between family members. CONCLUSION: Conjunctivitis was associated with a notable economic burden in terms of direct medical costs and medically related absenteeism. Family health care costs increased with transmission time and with each family member infected with conjunctivitis.

ProCommunity: procalcitonin use in real-world US community hospital settings.

OBJECTIVE: Procalcitonin (PCT) is a biomarker that may help providers optimize antibiotic (AB) therapy. Numerous clinical trials have demonstrated the utility of PCT-guided decision algorithms in treating lower respiratory tract infections and sepsis, but evidence from real-world studies is limited. This study sought to evaluate the effects of PCT on select clinical outcomes in community hospitals. METHODS: An observational, retrospective, case-control study was conducted. Hospitals from a large US hospital system were categorized into "treatment" and "control" hospitals. Treatment hospitals were those with in-house PCT testing, a pharmacy team tasked with PCT testing follow-up and results in the patient's electronic medical records alongside a recommendation on AB treatment. Control hospitals either did not have PCT testing available in house or sent out tests to a laboratory or neighboring facility. Patients from treatment hospitals were matched 1:1 to patients from control hospitals based on admission diagnosis code, sex, age and whether an intensive care unit admission was observed. Clinical outcomes included number of days of AB treatment, length of stay, 30 day readmissions, mortality and acute kidney injury. Comparisons were conducted using multivariable regressions accounting for clustering at the hospital level. RESULTS: Patients from treatment hospitals had significantly shorter hospital stays (-0.68 days, 95% CI: -1.26, -0.09; p = .02). A reduction in days of AB treatment (-1.50 days, 95% CI: -3.27, 0.27; p = .10) was observed, but did not reach statistical significance. CONCLUSION: These findings suggest that PCT, along with specific treatment recommendations, may lead to shortened hospital stays with no adverse outcome on patient safety.