Search

A longer acting, removable implant for HIV prevention has the potential to improve uptake of HIV pre-exposure prophylaxis (PrEP) by removing the need for daily adherence to an oral tablet, reducing potential side effects, and eliminating concerns about residual drug following injections. To end the HIV epidemic, we must understand the needs and preferences of groups most affected by HIV (e.g., men who have sex with men; MSM), and the physicians who prescribe PrEP to them. This article describes a discrete choice experiment to estimate the preference share for the implant within a competitive context of other PrEP products (including the oral tablet, dissolvable implant, and injection) and evaluate the impact of potential implant attributes. Physicians who had prescribed oral PrEP (n = 75) and MSM at risk for HIV (n = 175) completed a web-based survey that prompted decision-making about PrEP product preferences. The findings from both physicians and MSM demonstrated that the removable implant could capture a meaningful portion of the preference share, making it feasible to advance in the development pipeline as an important addition to the biomedical HIV prevention toolkit. Among MSM, specifically, the cost of treatment was the most important attribute impacting product preference. Our findings inform implant developers and future payers (e.g., commercial manufacturers, insurance companies) about specific device attributes that will likely affect MSM's willingness to use and physicians' willingness to prescribe this HIV prevention strategy.

BackgroundContemporary data on national trends and outcomes in cardiac resynchronization therapy with defibrillator (CRT-D) recipients following the 2012 updated guidelines has not been studied.ObjectivesThis study assessed the trends in long-term outcomes among CRT-D Medicare-aged recipients implanted in 2011-2015.MethodsPatients aged ≥65 years undergoing de novo CRT-D implantation in the National Cardiovascular Data Implantable Cardiac Defibrillator Registry from 2011-2015 with follow-up through 2017 using Medicare data were included and stratified by year of implant. Patient characteristics, in-hospital outcomes, and outcomes up to 2 years following implant were evaluated.ResultsAmong 53,174 patients (aged 75.6-6.4 years, 29.7% women) implanted with CRT-D from 2011 to 2015, there was an increase in implantations based on guideline-concordant recommendations (81.0% to 84.7%, P < .001). Compared to 2011, in-hospital procedural complications decreased in 2015 (3.9% vs 2.9%; adjusted odds ratio, 0.76, 95% confidence interval, 0.66-0.88, P< .001), driven in part by decreased lead dislodgement (1.4% vs 1.0%). After multivariable adjustment, there was a lower risk of all-cause hospitalization, cardiovascular hospitalization, and mortality at 2-year follow-up in 2015 as compared to 2011, while there were no differences in heart failure hospitalizations at follow-up.ConclusionAmong Medicare beneficiaries receiving CRT-D from 2011 to 2015, there was an increase in implantations based on guideline-concordant recommendations. Furthermore, there has been a reduction in in-hospital complications and long-term outcomes, including cardiovascular hospitalization, all-cause hospitalization, and mortality; however, there has been no difference in the risk of heart failure hospitalization after adjustment.

Neurologic complications of the human immunodeficiency virus (HIV) are common in treated individuals, and toxicity of certain antiretroviral therapies (ART) may contribute to cognitive impairment. We investigated exposures to specific ART and cognition among women living with HIV (WLWH). Virologically suppressed (viral load

Background : Venous thromboembolism (VTE) is a common complication in acute COVID-19 and those with hematologic malignancy (HM) may be at an even higher risk. We performed a retrospective analysis of patients with history of HM and acute COVID-19 to evaluate thrombotic and clinical outcomes. Methods : Patients with COVID-19 were identified by positive SARS-CoV-2 PCR test. Our primary endpoints were rate of VTE and CVA in patients with HM compared to the general population (GP). Secondary outcomes included composite thrombotic events (CVA + VTE), COVID-19 fatality, respiratory support, ICU admission rates, and length of ICU stay Results : 833 patients were evaluated, 709 in the GP cohort, 124 patients in the HM cohort. CVA was more prevalent in the HM cohort (5.4% vs. 1.6%, p = 0.011). Rates of VTE were numerically higher for the HM cohort (8.0% vs. 3.6%, p = 0.069). The composite thrombotic rate was increased in the HM cohort (13.4% vs 5.2%, p = 0.005). Patients with HM had a higher inpatient fatality rate (35.5% vs 11.3%, p < 0.001), required more respiratory support (74.6% vs 46.5%, p < 0.001) and had a higher rate of ICU admission (31.9% vs 12.1%, p = 0.001). Conclusion : Our data demonstrated an increased rate of composite thrombotic (CVA + VTE) outcomes, indicating HM patients with acute COVID-19 are at increased risk of thrombosis. Irrespective of disease status, HM patients also have significantly increased need for intensive care, respiratory support, and have higher fatality rates., MicroAbstract: Background: We performed a retrospective analysis of patients with history of HM and acute COVID-19 to evaluate thrombotic and clinical outcomes., Methods: We evaluated various clinical parameters in patients with HM (n=124) compared to the general population (GP; n=709)., Results: The composite thrombotic rate (VTE + CVA) was increased in the HM cohort (13.4% vs 5.2%, p = 0.005)., Conclusion: HM patients with acute COVID-19 are at increased risk of thrombosis and have significantly increased need for intensive care, respiratory support, and have higher fatality rates.

Introduction The high cost of viral load (VL) testing limits its use for antiretroviral treatment (ART) adherence support. A low-cost lateral flow urine tenofovir (TFV) rapid assay predicts PrEP breakthroughs but has not yet been investigated in HIV treatment. We therefore evaluated its utility in a pilot cross-sectional study of TFV-containing ART recipients at increased risk of virologic failure. Methods Participants who had a treatment interruption ≥30 days or had ≥1 episode of viremia (VL≥400 copies/mL) in the previous year were recruited from a public health setting in Cape Town, South Africa. Self-reported adherence data were collected, the urine TFV assay performed, and concurrent TFV-diphosphate (DP) analysed in dried blood spots. VL testing was done concurrently and, if viremic, genotypic HIV drug resistance testing performed. Results Of 48 participants, 18 (37.5%) had virologic failure (VL>400 copies/mL) at the time of the study including 16 of 39 receiving efavirenz (EFV), 2 of 6 receiving protease inhibitors (PI) and 0 of 3 receiving dolutegravir (DTG). Resistance testing succeeded in 17/18, of which 14 had significant mutations compromising ≥2 agents of the current EFV-based regimen. Of these 14, all had detected urine TFV. Urine TFV was undetectable in 2 out of 3 without regimen-relevant resistance; p=0.02. Conclusion In participants on EFV-based regimens returning to care, virologic failure was largely due to viral resistance, where detectable urine TFV had 100% sensitivity (14/14 participants) in predicting resistance. Conversely, when undetectable, the urine-based assay could be used to preclude participants with poor adherence from undergoing costly HIV drug resistance testing.

It is unknown whether antiretroviral (ARV) drugs in women living with HIV (WLHIV) are associated with mitochondrial toxicity and altered fat oxidation and branched-chain amino acid metabolism in the placenta and fetus. Immediately after delivery, we froze placental biopsies from 20 WLHIV and 20 matched uninfected women. We analyzed global biochemical profiles using high-performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We used t-tests, principle component analysis, hierarchical clustering, and random forest analysis (RFA) in our analysis. Twelve WLHIV were on protease inhibitors, six on non-nucleoside reverse inhibitors, and two on integrase strand inhibitors with optimized backbone. Mean birth weight of HIV-exposed neonates was significantly lower than unexposed neonates (3,075 g vs. 3,498 g, p = .01) at similar gestational age. RFA identified 30 of 702 analytes that differentiated the placental profiles of WLHIV from uninfected women with 72.5% predictive accuracy. Placental profiles of non-nucleoside reverse transcriptase inhibitor (NNRTI)-treated WLHIV exhibited lower levels of amino acids, including essential and branched-chain amino acids, and some medium-chain acylcarnitines. Placental metabolism may be altered in WLHIV, possibly associated with ARV exposure. The lower birth weight among neonates of WLHIV suggests the need for further studies considering potential deleterious effects of altered placenta metabolism on fetal growth and development.

This exploratory study sought to characterize the anal microbiome and explore associations among the anal microbiome, risk factors for anal cancer, and clinical factors. A pilot sample of 50 HIV infected and high-risk HIV negative women were recruited from the former Women's Interagency HIV Study. Microbiome characterization by 16S rRNA gene sequencing and datasets were analyzed using QIIME 2™. Composition of the anal microbiome and its associations with anal cancer risk factors and clinical factors were analyzed using linear decomposition model and permutational multivariate analysis of variance. Composition of the anal microbiome among HIV positive and high-risk negative women was dominated by Bacteroides, Prevotella, and Campylobacter. The overall taxonomic composition and microbial diversity of the anal microbiome did not significantly differ by HIV status. However, the abundance of Ruminococcus 1 belonging to the Rumincoccaceae family was associated with HIV status (q = .05). No anal cancer risk factors were associated with the anal microbiome composition. Clinical factors marginally associated with the anal microbiome composition included body mass index (BMI; p = .05) and hepatitis C virus (HCV; p = .05). Although HIV and risk factors for anal cancer were not associated with the composition of the anal microbiome in this pilot sample, other clinical factors such as BMI and HCV, may be worth further investigation in a larger study. Future research can build on these findings to explore the role of the microbiome and HIV comorbidities in women.

Most patients with COVID-19 are asked to self-isolate and monitor their symptoms at home. However, their conditions may decline rapidly and unpredictably. The authors studied the use of a remote patient monitoring service via text messaging with clinical support to facilitate emergency department and hospital care for patients who require it., Visual Abstract. Outcomes of Automated Home Monitoring for COVID-19. Most patients with COVID-19 are asked to self-isolate and monitor their symptoms at home. However, their conditions may decline rapidly and unpredictably. The authors studied the use of a remote patient monitoring service via text messaging with clinical support to facilitate emergency department and hospital care for patients who require it., Background: Although most patients with SARS-CoV-2 infection can be safely managed at home, the need for hospitalization can arise suddenly. Objective: To determine whether enrollment in an automated remote monitoring service for community-dwelling adults with COVID-19 at home (“COVID Watch”) was associated with improved mortality. Design: Retrospective cohort analysis. Setting: Mid-Atlantic academic health system in the United States. Participants: Outpatients who tested positive for SARS-CoV-2 between 23 March and 30 November 2020. Intervention: The COVID Watch service consists of twice-daily, automated text message check-ins with an option to report worsening symptoms at any time. All escalations were managed 24 hours a day, 7 days a week by dedicated telemedicine clinicians. Measurements: Thirty- and 60-day outcomes of patients enrolled in COVID Watch were compared with those of patients who were eligible to enroll but received usual care. The primary outcome was death at 30 days. Secondary outcomes included emergency department (ED) visits and hospitalizations. Treatment effects were estimated with propensity score–weighted risk adjustment models. Results: A total of 3488 patients enrolled in COVID Watch and 4377 usual care control participants were compared with propensity score weighted models. At 30 days, COVID Watch patients had an odds ratio for death of 0.32 (95% CI, 0.12 to 0.72), with 1.8 fewer deaths per 1000 patients (CI, 0.5 to 3.1) (P = 0.005); at 60 days, the difference was 2.5 fewer deaths per 1000 patients (CI, 0.9 to 4.0) (P = 0.002). Patients in COVID Watch had more telemedicine encounters, ED visits, and hospitalizations and presented to the ED sooner (mean, 1.9 days sooner [CI, 0.9 to 2.9 days]; all P < 0.001). Limitation: Observational study with the potential for unobserved confounding. Conclusion: Enrollment of outpatients with COVID-19 in an automated remote monitoring service was associated with reduced mortality, potentially explained by more frequent telemedicine encounters and more frequent and earlier presentation to the ED. Primary Funding Source: Patient-Centered Outcomes Research Institute.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with substantial clinical burden as individuals transition to adulthood, including higher rates of comorbidities, mortality, incarceration, and psychiatric hospitalizations than in individuals without ADHD. These higher rates likely contribute to substantial economic burden as well. OBJECTIVE: To provide a comprehensive evaluation of the economic burden associated with ADHD in the US adult population. METHODS: Direct health care costs were obtained by using claims data from the IBM MarketScan Research Databases (January 1, 2017, through December 31, 2018). Direct non-health care costs and indirect costs were estimated on the basis of the literature and government publications. Excess costs incurred by adults with ADHD during 2018 were evaluated from a societal perspective; per-patient costs were extrapolated to the national level. RESULTS: An estimated 8.7 million adults live with ADHD in the United States, resulting in a total societal excess cost attributable to ADHD of $122.8 billion ($14,092 per adult). Excess costs of unemployment ($66.8 billion; 54.4%) comprised the largest proportion of the total, followed by productivity loss ($28.8 billion; 23.4%) and health care services ($14.3 billion; 11.6%). CONCLUSIONS: ADHD in adults is associated with substantial economic burden. DISCLOSURES: This study was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. (Otsuka). The study sponsor contributed to and approved the study design, participated in the interpretation of data, and reviewed and approved the manuscript. Schein is an employee of Otsuka. Gagnon-Sanschagrin, Davidson, Kinkead, Cloutier, Guerin, and Lefebvre are employees of Analysis Group, Inc., a consulting company that provided paid consulting services to Otsuka to develop and conduct this study and write the manuscript. Adler has received research support from Shire/Takeda, Sunovion, and Otsuka; consulting fees from Bracket, Shire/Takeda, Sunovion, Otsuka, the State University of New York (SUNY), the National Football League (NFL), and Major League Baseball (MLB); and royalty payments (as inventor) from New York University (NYU) for license of adult ADHD scales and training materials. Childress has received research support from Allergan, Takeda/Shire, Emalex, Akili, Ironshore, Arbor, Aevi Genomic Medicine, Neos Therapeutics, Otsuka, Pfizer, Purdue, Rhodes, Sunovion, Tris, KemPharm, Supernus, and the US Food and Drug Administration; was on the advisory board of Takeda/Shire, Akili, Arbor, Cingulate, Ironshore, Neos Therapeutics, Otsuka, Pfizer, Purdue, Adlon, Rhodes, Sunovion, Tris, Supernus, and Corium; received consulting fees from Arbor, Ironshore, Neos Therapeutics, Purdue, Rhodes, Sunovion, Tris, KemPharm, Supernus, Corium, Jazz, and Tulex Pharma; received speaker fees from Takeda/Shire, Arbor, Ironshore, Neos Therapeutics, Pfizer, Tris, and Supernus; and received writing support from Takeda/Shire, Arbor, Ironshore, Neos Therapeutics, Pfizer, Purdue, Rhodes, Sunovion, and Tris. Part of the material in this study was presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2021 Virtual Meeting; May 17-20, 2021.

Biliary strictures affect 4%−12% of pediatric liver transplantations. Biliary strictures can contribute to graft loss if left untreated; however, there remains no consensus on the best course of treatment. Study objectives included analyses of outcomes associated with biliary stricture management strategies via percutaneous transhepatic cholangiography (PTC), endoscopic retrograde cholangiopancreatography (ERCP), or surgery. We identified pediatric liver transplantation recipients (2011–2016) with biliary strictures from the Society of Pediatric Liver Transplantation (SPLIT) registry and retrieved imaging, procedural, and operative reports from individual centers. Subanalyses were performed to specifically evaluate PTC and ERCP for “optimal biliary outcome” (OBO), defined as graft survival with stricture resolution and without recurrence or surgery. A total of 113 children with a median follow-up of 3.9 years had strictures diagnosed 100 days (interquartile range, 30–290) after liver transplantation; 81% were isolated anastomotic strictures. Stricture resolution was achieved in 92% within 101 days, more frequently with isolated anastomotic strictures (96%). 20% of strictures recurred, more commonly in association with hepatic artery thrombosis (32%). Patient and graft survival at 1 and 3 years were 99% and 98% and 94% and 92%, respectively. In a subgroup analysis of 79 patients with extrahepatic strictures managed by PTC/ERCP, 59% achieved OBO following a median of 4 PTC, and 75% following a median of 3 ERCP (P < 0.001). Among patients with OBO, those with ERCP had longer time intervals between successive procedures (41, 47, 54, 62, 71 days) than for PTC (27, 31, 36, 41, 48 days; P < 0.001). Allograft salvage was successful across all interventions. Stricture resolution was achieved in 92%, with 20% risk of recurrence. Resolution without recurrence was highest in patients with isolated anastomotic strictures and without hepatic artery thrombosis.

We review evidence regarding the use of 0.9% benzyl alcohol in 0.9% sodium chloride solution for periocular injections ('preserved saline') including botulinum toxin A injections and local anaesthesia. A literature search was undertaken using search terms 'bacteriostatic saline', 'benzyl-alcohol saline', 'benzyl alcohol sodium chloride' and 'preserved saline'. Bibliographies identified further sources. There have been 62 studies published on the subject of preserved-saline since 1928. Significantly lower injection-associated pain levels for periocular/facial botulinum toxin injections reconstituted with preserved-saline rather than preservative-free saline are reported by 5 studies. Significantly lower injection-associated pain with preserved-saline diluted lidocaine and epinephrine solution for eyelid anaesthesia compared with unmodified or buffered lidocaine with epinephrine, and adequate anaesthesia, was reported by one study. Thirty-one studies have explored preserved-saline for anaesthetic and seven for bacteriostatic properties, with very low infection rates after periocular botulinum toxin injections, and reduced rates of infection in indwelling catheters when preserved saline is used to flush. A meta-analysis concluded that lidocaine-containing solutions are more effective at reducing pain from insertion of intravenous catheters. Patient-perceived pain related to periorbital injections of local anaesthesia is reduced when the anaesthetic is diluted with benzyl alcohol-preserved saline compared with other dilution or buffering options. Pain is similarly reduced for periocular botulinum toxin injections reconstituted with preserved saline compared with unpreserved saline. Benzyl-alcohol preserved-saline is inexpensive but costlier than unpreserved-saline, with minimal reported complications, particularly with periocular administration, and offers the opportunity to improve the patient experience.摘要: 我们回顾了眼周注射使用0.9%氯化钠溶液含0.9%苯甲醇(“防腐生理盐水”)的研究证据, 包括A型肉毒杆菌注射和局部麻醉。使用“抑菌生理盐水”、“苯乙醇生理盐水”、“苯甲醇氯化钠”和“防腐生理盐水”等关键词进行文献检索。参考目录进一步确定来源。自1928年以来, 已有62项关于防腐生理盐水的研究发表。有5项研究报道称, 眼周/面部肉毒杆菌毒素注射用的防腐生理盐水与不防腐的生理盐水相比, 前者能显著降低注射相关的疼痛水平。一项研究报告称, 在眼睑麻醉中使用盐水稀释后的利多卡因和肾上腺素, 与未稀释的该溶液相比, 注射相关的疼痛水平明显降低, 且麻醉充分。31项研究探索了防腐生理盐水用于麻醉的特点, 7项研究探索了其抑菌特性, 并发现使用该生理盐水后, 眼周注射肉毒杆菌毒素的感染率非常低, 使用该盐水冲洗留置导管的感染率也降低。一项荟萃分析得出结论, 含利多卡因的溶液在减少静脉导管插入时的疼痛方面更有效。与其他稀释或缓冲溶液的方法相比, 用含苯甲醇防腐的生理盐水稀释麻醉剂时, 可降低眶周局部麻醉相关的疼痛水平。与无防腐的生理盐水相比, 眼周注射肉毒杆菌毒素的疼痛也同样减轻。含苯甲醇防腐的生理盐水价格低廉, 但仍比无防腐的生理盐水价格高, 前者并发症报道最少, 尤其是在眼周给药中, 这为改善患者体验提供了机会。.

Breast reconstruction is an important component of comprehensive breast cancer care. Although reconstructive plans require multidisciplinary clinical-decision making, research in cross-discipline collaborations is often limited. This study aims to evaluate multidisciplinary involvement in breast reconstruction outcomes research.A systematic review of breast reconstruction literature published from 2000 to 2019 using Ovid MEDLINE, Ovid EMBASE, and PubMed databases was conducted. English language articles published in North America or Europe with n ≥ 12 nonpediatric patients were included. Articles concerning procedures not performed in the context of breast cancer care or articles that did not evaluate at least one outcome, diagnostic test, or risk factor were excluded. Authors' affiliations were used to define multidisciplinary involvement. Quality of research was evaluated using the level of evidence, journal impact factor (IF), and altmetrics.Of the 1679 articles screened, 784 met the stated eligibility criteria. Only half (50.6%) of these articles involved an author outside the discipline of plastic surgery. Compared to nonmultidisciplinary studies, multidisciplinary studies were more likely to be designated with a higher level of evidence (I or II) (p0.001), published in journals with higher IF (p0.05), have higher usage (p = 0.03), and mentions (p = 0.02). There was no difference in citations, captures, and social media posts (p0.05).Breast reconstruction outcomes research often fails to offer author collaborations from nonplastic surgery disciplines. Multidisciplinary involvement in breast cancer care research is strongly recommended to improve the quality and impact of clinical studies in breast reconstruction.

Women who experience HIV seroconversion during pregnancy are missed during early routine pregnancy HIV screening and are at high risk of perinatal HIV transmission. Male partner HIV testing during routine prenatal care may be an effective primary prevention strategy by identifying women at risk of seroconversion and mitigating their risk. Our objective was to assess interest in and uptake of male partner HIV testing services offered during prenatal care. This demonstration project included all pregnant, English-speaking, HIV-negative women receiving publicly funded prenatal care in an urban hospital-based practice located in a high HIV prevalence area. Women were offered free HIV screening for their male sexual partners. From April 2017 to June 2018, enrolled women completed surveys on social demographics, medical access characteristics, and HIV testing history. Women were invited to bring their partners to a prenatal visit where HIV testing was offered to their male partners. Factors associated with women's interest in testing and completion of partner testing were assessed using bivariable and multivariable analyses. Of 392 women approached, 70% (N = 274) completed study surveys. Although the majority (76%, N = 200 of 264 respondents) of women desired their partner undergo HIV testing, testing was underutilized as only 18 (7%) male partners completed testing. While neither maternal characteristics nor male social or attitudinal factors were associated with interest in or completion of partner HIV testing, sensitivity analyses, performed with multiple imputation, demonstrated some association between interest and completion of partner testing and partner medical care access and utilization. In conclusion, although the majority of low-income women in an urban prenatal clinic expressed interest in having their partners undergo HIV testing, uptake of free partner HIV testing services was uncommon. A focused assessment of implementation and uptake barriers is needed to optimize partner testing and eliminate HIV transmission to mothers and their babies.

Approximately 6% of deceased kidney donors (DKDs) are diabetic; their kidneys may be associated with worse allograft survival, but published studies suggest that recipient diabetes status has a greater impact on mortality and survival. Since biopsy findings are the most common reason for organ discard, we sought to understand histologic and clinical factors that influence graft survival in patients who receive a kidney from a diabetic DKD. We retrospectively reviewed our institutional experience from 2005 to 2019, and re-evaluated pre-implantation and earliest post-transplant biopsies. Histologic findings were compared against a control cohort of non-diabetic DKD. Of 829 adult DKD transplants, 37 (4.5%) came from diabetic donors. There was no significant difference in diabetic vs. non-diabetic DKD graft survival for all-comers; however, when stratified by duration of donor diabetes, donor diabetes ≥6 years was associated with graft failure. In 25 patients with post-transplant biopsies available, diabetic DKD allografts had significantly greater non-glomerular chronic injury than non-diabetic DKD allografts. Moderate arteriolar hyalinosis (in 24%), moderate tubular atrophy and interstitial fibrosis (IFTA, in 36%), and diabetic glomerulopathy (in 24%) on early post-transplant biopsy were associated with allograft failure. Pre-implantation frozen section discrepancies were more common in long-standing donor diabetes, and arteriolar hyalinosis and IFTA scores on frozen accurately prognosticated graft loss. There was no morphologic improvement in lesions of diabetic nephropathy on short-term follow-up. In conclusion, donor diabetes ≥6 years, and histologic findings on frozen section and early post-transplant biopsy are associated with diabetic DKD allograft loss.

HIV is an independent risk factor for lung disease, including chronic obstructive pulmonary disease (COPD) and emphysema. Angiotensin receptor blockers may be beneficial in COPD and emphysema through pathways that have been implicated in HIV-related lung disease. We performed a randomized comparison of the effects of losartan versus placebo on the plasma concentrations of the pneumoproteins, surfactant protein D (SPD) and club cell secretory protein (CCSP), in people living with HIV (PLWH). A total of 108 PLWH were included (52 assigned to losartan and 56 assigned to placebo). We found no difference in the change from baseline in log(2) concentrations of CCSP or SPD over 1 year of follow-up. For SPD, we found a strong interaction by CD4+ counts, where those with CD4+ counts >350 cells/mm(3) treated with losartan had more reduction (improvement) in SPD concentration than those treated with placebo (p value for interaction

As the classification of mental disorders advances towards a disease model as promoted by the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC), there is hope that a more thorough neurobiological understanding of mental illness may allow clinicians and researchers to determine treatment efficacy with less diagnostic variability. This paradigm shift has presented a variety of ethical issues to be considered in the development of psychiatric drugs. These challenges are not limited to informed consent practices, industry funding, and placebo use. The consideration for alternative research models and quality of research design also present ethical challenges in the development of psychiatric drugs. The imperatives to create valid and sound research that justify the human time, cost, risk and use of limited resources must also be considered. Clinical innovation, and consideration for special populations are also important aspects to take into account. Based on the breadth of these ethical concerns, it is particularly important that scientific questions regarding the development of psychiatric drugs be answered collaboratively by a variety of stakeholders. As the field expands, new ethical considerations will be raised with increased focus on genetic markers, personalized medicine, patient-centered outcomes research, and tension over funding. We suggest that innovation in trial design is necessary to better reflect practices in clinical settings and that there must be an emphasized focus on expanding the transparency of consent processes, regard for suicidality, and care in working with special populations to support the goal of developing sound psychiatric drug therapies.

Background Communication interventions for childhood vaccination are promising strategies to address vaccine hesitancy, but current research is limited by the outcomes measured. Most studies measure only vaccination-related outcomes, with minimal consideration of vaccine hesitancy-relevant intermediate outcomes. This impedes understanding of which interventions or elements are effective. It is also unknown which outcomes are important to the range of stakeholders affected by vaccine hesitancy. Outcome selection shapes the evidence base, informing future interventions and trials, and should reflect stakeholder priorities. Therefore, our aim was to identify which outcome domains (i.e. broad outcome categories) are most important to different stakeholders, identifying preliminary core outcome domains to inform evaluation of three common vaccination communication types: (i) communication to inform or educate, (ii) remind or recall, and (iii) enhance community ownership. Methods We conducted a two-stage online Delphi survey, involving four stakeholder groups: parents or community members, healthcare providers, researchers, and government or non-governmental organisation representatives. Participants rated the importance of eight outcome domains for each of the three communication types. They also rated specific outcomes within one domain (“attitudes or beliefs”) and provided feedback about the survey. Results Collectively, stakeholder groups prioritised outcome domains differently when considering the effects of different communication types. For communication that aims to (i) inform or educate, the most important outcome domain is “knowledge or understanding”; for (ii) reminder communication, “vaccination status and behaviours”; and for (iii) community engagement communication, “community participation”. All stakeholder groups rated most outcome domains as very important or critical. The highest rated specific outcome within the “attitudes or beliefs” domain was “trust”. Conclusion This Delphi survey expands the field of core outcomes research and identifies preliminary core outcome domains for measuring the effects of communication about childhood vaccination. The findings support the argument that vaccination communication is not a single homogenous intervention – it has a range of purposes, and vaccination communication evaluators should select outcomes accordingly.

Question: Is additional Saturday physiotherapy intervention beneficial for inpatients undergoing rehabilitation? Design: Randomised controlled trial with concealed allocation, assessor blinding, and intention-to-treat analysis. Participants: Two hundred and sixty-two inpatients undergoing rehabilitation in an Australian metropolitan hospital. Intervention: The experimental group received physiotherapy intervention from Monday to Saturday and the control group from Monday to Friday. Outcome measures: Primary outcomes were hospital and physiotherapy length of stay. Secondary measures were collected to reflect patient outcomes (health state, independence, activity, flexibility and strength) and burden of care (discharge destination, adverse events, and follow-up physiotherapy intervention). Results: There was a 3.2 day reduction for the experimental group (95% CI –0.5 to 6.9) in hospital length of stay and a 2.5 day reduction (95% CI –0.9 to 5.9) in physiotherapy length of stay. There was no significant between-group difference in change from admission to discharge for most of the secondary patient outcomes (health state, independence, activity, flexibility). The risk of the experimental group being categorised as strong relative to the control group was 1.2 (95% CI 0.99 to 1.50). The risk of not being discharged home, of having an adverse event, or requiring follow-up physiotherapy intervention was no greater for the experimental group than the control group. Conclusion: The provision of additional Saturday physiotherapy intervention resulted in a trend to shorter hospital and physiotherapy length of stay without affecting patient outcome unfavourably or increasing burden of care, suggesting that a larger multicentre trial is warranted. [Brusco NK, Shields N, Taylor NF, Paratz J (2007) A Saturday physiotherapy service may decrease length of stay in patients undergoing rehabilitation in hospital: a randomised controlled trial. Australian Journal of Physiotherapy 53: 75–81]

Introduction: Several clinical studies have demonstrated the safety, feasibility, and efficacy of machine perfusion in liver transplantation, although its economic outcomes are still underexplored. This review aimed to examine the costs related to machine perfusion and its associated outcomes. Methods: Expert opinion of several groups representing different machine perfusion modalities. Critical analysis of the published literature reporting the economic outcomes of the most used techniques of machine perfusion in liver transplantation (normothermic and hypothermic ex situ machine perfusion and in situ normothermic regional perfusion). Results: Machine perfusion costs include disposable components of the perfusion device, perfusate components, personnel and facility fees, and depreciation of the perfusion device or device lease fee. The limited current literature suggests that although this upfront cost varies between perfusion modalities, its use is highly likely to be cost-effective. Optimization of the donor liver utilization rate, local conditions of transplant programs (long waiting list times and higher MELD scores), a decreased rate of complications, changes in logistics, and length of hospital stay are potential cost savings points that must highlight the expected benefits of this intervention. An additional unaccounted factor is that machine perfusion optimizing donor organ utilization allows patients to be transplanted earlier, avoiding clinical deterioration while on the waiting list and the costs associated with hospital admissions and other required procedures. Conclusion: So far, the clinical benefits have guided machine perfusion implementation in liver transplantation. Albeit there is data suggesting the economic benefit of the technique, further investigation of its costs to healthcare systems and society and associated outcomes is needed.

Background Burn injury can dramatically deteriorate health-related quality of life. Effective burn care may minimize the impact of the burn injury and ensure optimal functional outcome. This requires continuous improvement in burn care and assessment of treatment results. The aim of this study was to translate, culturally adapt and linguistically validate the CARe Burn Scale—Adult Form, a burn-specific patient-reported outcome measure, into Finnish. Methods The translation process followed the International Society for Pharmacoeconomics and Outcomes Research guidelines consisting of forward and backward translations, pilot-testing and cognitive debriefing interviews of five burn patients, and proofreading before finalizing. The process involved expert panel meetings and continuous discussion between the developers of the Scale and the research group. Results In the forward translation 10 amendments were required. After the backward translation, 12 items were reworded. Cognitive debriefing interviews led to three alterations enhancing the comprehensiveness and accuracy of the translation. The translation was reviewed by burn occupational therapists for practicality, resulting in 12 modifications. Minor grammatical changes were made after proofreading. Conclusion The Finnish version is the first foreign translation of the CARe Burn Scale. It is equivalent to the original Scale and ready for psychometric validation with burn patients in Finland.

Background Chronic Kidney Disease (CKD) and end-stage renal disease (ESRD) are associated with poor outcomes in patients with cardiovascular disease. There is a paucity of contemporary data on in-hospital outcomes and care patterns of atrial fibrillation (AF) associated hospitalizations CKD and ESRD. Methods Outcomes and care patterns were evaluated in GWTG-AFIB database (Jan 2013-Dec 2018), including in-hospital mortality, use of a rhythm control strategy, and oral anticoagulation (OAC) prescription at discharge among eligible patients. Generalized logistic regression models with generalized estimating equations were used to ascertain differences in outcomes. Hospital-level variation in OAC prescription and rhythm control was also evaluated. Results Among 50,154 patients from 105 hospitals the median age was 70 years (interquartile range 61-79) and 47.3% were women. The prevalence of CKD was 36.0% while that of ESRD was 1.6%. Among eligible patients, discharge OAC prescription rates were 93.6% for CKD and 89.1% for ESRD. After adjustment, CKD and ESRD were associated with higher in-hospital mortality (odds ratio [OR] 3.08, 95% confidence interval [CI] 1.57-6.03 for ESRD and OR 2.02, 95% CI 1.52-2.67 for CKD), lower odds of OAC prescription at discharge (OR 0.59, 95% CI 0.44-0.79 for ESRD and OR 0.84, 95% CI 0.75-0.94 for CKD) compared with normal renal function. CKD was associated with lower utilization of rhythm control strategy (OR 0.92, 95% CI 0.87-0.98) with no significant difference between ESRD and normal renal function (OR 1.32, 95% CI 0.79-1.11). There was large hospital-level variation in OAC prescription at discharge (MOR 2.34, 95% CI 2.05-2.76) and utilization of a rhythm control strategy (MOR 2.69, 95% CI 2.34-3.21). Conclusions CKD/ESRD is associated with higher in-hospital mortality, less frequent rhythm control, and less OAC prescription among patients hospitalized for AF. There is wide hospital-level variation in utilization of a rhythm control strategy and OAC prescription at discharge highlighting potential opportunities to improve care and outcomes for these patients, and better define standards of care in this patient population

Background Social deprivation negatively affects a myriad of physical and behavioral health outcomes. Several measures of social deprivation exist, but it is unclear which measure is best suited to describe patients with orthopaedic conditions. Questions/purposes (1) Which measure of social deprivation, defined as "limited access to society's resources due to poverty, discrimination, or other disadvantage," is most strongly and consistently correlated with patient-reported physical and behavioral health in patients with orthopaedic conditions? (2) Compared with the use of a single measure alone, how much more variability in patient-reported health does the simultaneous use of multiple social deprivation measures capture? Methods Between 2015 and 2017, a total of 79,818 new patient evaluations occurred within the orthopaedic department of a single, large, urban, tertiary-care academic center. Over that period, standardized collection of patient-reported health measures (as described by the Patient-reported Outcomes Measurement Information System [PROMIS]) was implemented in a staged fashion throughout the department. We excluded the 25% (19,926) of patient encounters that did not have associated PROMIS measures reported, which left 75% (59,892) of patient encounters available for analysis in this cross-sectional study of existing medical records. Five markers of social deprivation were collected for each patient: national and state Area Deprivation Index, Medically Underserved Area Status, Rural-Urban Commuting Area code, and insurance classification (private, Medicare, Medicaid, or other). Patient-reported physical and behavioral health was measured via PROMIS computer adaptive test domains, which patients completed as part of standard care before being evaluated by a provider. Adults completed the PROMIS Physical Function version 1.2 or version 2.0, Pain Interference version 1.1, Anxiety version 1.0, and Depression version 1.0. Children ages 5 to 17 years completed the PROMIS Pediatric Mobility version 1.0 or version 2.0, Pain Interference version 1.0 or version 2.0, Upper Extremity version 1.0, and Peer Relationships version 1.0. Age-adjusted partial Pearson correlation coefficients were determined for each social deprivation measure and PROMIS domain. Coefficients of at least 0.1 were considered clinically meaningful for this purpose. Additionally, to determine the percentage of PROMIS score variability that could be attributed to each social deprivation measure, an age-adjusted hierarchical regression analysis was performed for each PROMIS domain, in which social deprivation measures were sequentially added as independent variables. The model coefficients of determination (r2) were compared as social deprivation measures were incrementally added. Improvement of the r2 by at least 10% was considered clinically meaningful. Results Insurance classification was the social deprivation measure with the largest (absolute value) age-adjusted correlation coefficient for all adult and pediatric PROMIS physical and behavioral health domains (adults: correlation coefficient 0.40 to 0.43 [95% CI 0.39 to 0.44]; pediatrics: correlation coefficient 0.10 to 0.19 [95% CI 0.08 to 0.21]), followed by national Area Deprivation Index (adults: correlation coefficient 0.18 to 0.22 [95% CI 0.17 to 0.23]; pediatrics: correlation coefficient 0.08 to 0.15 [95% CI 0.06 to 0.17]), followed closely by state Area Deprivation Index. The Medically Underserved Area Status and Rural-Urban Commuting Area code each had correlation coefficients of 0.1 or larger for some PROMIS domains but neither had consistently stronger correlation coefficients than the other. Except for the PROMIS Pediatric Upper Extremity domain, consideration of insurance classification and the national Area Deprivation Index together explained more of the variation in age-adjusted PROMIS scores than the use of insurance classification alone (adults: r2 improvement 32% to 189% [95% CI 0.02 to 0.04]; pediatrics: r2 improvement 56% to 110% [95% CI 0.01 to 0.02]). The addition of the Medically Underserved Area Status, Rural-Urban Commuting Area code, and/or state Area Deprivation Index did not further improve the r2 for any of the PROMIS domains. Conclusion To capture the most variability due to social deprivation in orthopaedic patients' self-reported physical and behavioral health, insurance classification (categorized as private, Medicare, Medicaid, or other) and national Area Deprivation Index should be included in statistical analyses. If only one measure of social deprivation is preferred, insurance classification or national Area Deprivation Index are reasonable options. Insurance classification may be more readily available, but the national Area Deprivation Index stratifies patients across a wider distribution of values. When conducting clinical outcomes research with social deprivation as a relevant covariate, we encourage researchers to consider accounting for insurance classification and/or national Area Deprivation Index, both of which are freely available and can be obtained from data that are typically collected during routine clinical care. Level of evidence Level III, therapeutic study.

Language status can be conceptualized as an equity-relevant variable, particularly for non-English-speaking populations. Deaf and hard-of-hearing (DHH) individuals who use American Sign Language (ASL) to communicate comprise one such group and are understudied in health services research. DHH individuals are at high-risk of receiving lower-quality care due to ineffective patient–provider communication. This perspective outlines barriers to health equity research serving DHH ASL-users due to systems developed by large-scale informatics networks (eg, the Patient-Centered Clinical Outcomes Research Network), and institutional policies on self-serve cohort discovery tools. We list potential to help adequate capture of language status of DHH ASL-users to promote health equity for this population.

Objective To characterize the safety of sildenafil in premature infants. Study design A phase I, open-label trial of sildenafil in premature infants receiving sildenafil per usual clinical care (cohort 1) or receiving a single IV dose of sildenafil (cohort 2). Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring. Results Twenty-four infants in cohort 1 (n = 25) received enteral sildenafil. In cohort 2, infants received a single IV sildenafil dose of 0.25 mg/kg (n = 7) or 0.125 mg/kg (n = 2). In cohort 2, there was one serious AE related to study drug involving hypotension associated with a faster infusion rate than specified by the protocol. There were no AEs related to elevated transaminases. Conclusion Sildenafil was well tolerated by the study population. Drug administration times and flush rates require careful attention to prevent infusion-related hypotension associated with faster infusions of IV sildenafil in premature infants. Clinical trial ClinicalTrials.gov Identifier: NCT01670136.

Objective To investigate racial disparities in 30-day postoperative outcomes of craniotomy for glioma resection. Methods 2006–2019 American College of Surgeons' National Surgical Quality Improvement Program files were queried for all patients who underwent a craniotomy for a supratentorial glioma resection. Racial disparities in preoperative variables were studied between the demographic cohorts of Asian, African Americans, Hispanics, and Caucasian. Fisher exact tests were used to examine association of preoperative variables with race. Multivariable logistic regression models, adjusted for all preoperative variables associated with race, were used to determine the odds ratios of postoperative outcomes for each demographic cohort in comparison with Caucasian patients. Results A total of 12,544 patients were identified: 4% Asian, 5% African American, 7% Hispanic, and 85% Caucasian. African American patients had significantly higher adjusted odds than Caucasian patients of major adverse cardiovascular events (adjusted odds ratio [aOR]: 1.827, 95% confidence interval [CI]: 1.155–2.891, P = 0.01), pulmonary events (aOR: 1.683, 95% CI: 1.145–2.473, P = 0.008), and urinary tract infection (aOR: 2.016, 95% CI: 1.221–3.327, P = 0.006). Asian patients had significantly higher odds than Caucasian patients of requiring a transfusion (aOR: 2.094, 95% CI: 1.343–3.266, P = 0.001). All demographic cohorts had higher odds of having an extended length of stay than Caucasian patients. Conclusions African American patients who undergo a craniotomy for glioma resection have almost twice the odds of Caucasian patients of having a postoperative major cardiovascular complication, pulmonary complication, or urinary tract infection. All minority groups have higher odds of an extended length of stay as compared with Caucasian patients.

Purpose Cancer survivorship starts at diagnosis. Transition readiness is an important indicator for pediatric cancer survivors to move from pediatric to adult medical care. Appropriate measurement of transition readiness can facilitate better cancer survivorship. This study aimed to translate and validate of the English version of the TRANSITION-Q into Chinese. Design and methods The translation followed the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) best-practice guidelines for the translation and cultural adaptation of patient-reported outcome measures (PROM). A cross- psychometric testing on reliability and validity were conducted from a convenient sample of Chinese adolescent cancer survivors aged 10–19 years. Results Two hundred seventy-one pediatric cancer patients were recruited for the psychometric validation. The 14-item Chinese TRANSITION-Q demonstrated adequate reliability. In exploratory factorial analyses and confirmatory factor analysis, a two-factor structure emerged with a variance of 54.78%, demonstrating construct validity. Convergent validity test showed TRANSITION-Q score was significantly positively correlated with self-efficacy (r = −0.84, p = 0.002). The known-group validity demonstrated the older group (age ≥14 years) had a significantly higher mean TRANSITION-Q score than the younger group (age Conclusion The Chinese version of the TRANSITION-Q is reliable and valid and can be used in Chinese research and clinical settings. Implications for practice This scale can be used in Chinese clinical and research settings to investigate understanding of transition readiness in Chinese pediatric cancer survivors.

Background Body mass index (BMI) does not reliably predict Surgical site infections (SSI). We hypothesize that abdominal wall thickness (AWT) would serve as a better predictor of SSI for patients undergoing emergency colon operations. Methods We retrospectively evaluated our Emergency Surgery Database (2007-2018). Emergency colon operations for any indication were included. AWT was measured by pre-operative CT scans at 5 locations. Only superficial and deep SSIs were considered as SSI in the analysis. Univariate then multivariable analyses were used to determine predictors of SSI. Results 236 patients met inclusion criteria. The incidence of post-operative SSI was 25.8% and the median BMI was 25.8kg/m2 [22.5-30.1]. The median AWT between patients with and without SSI was significantly different (2.1cm [1.4, 2.8] and 1.8cm [1.2, 2.5], respectively). A higher BMI trended toward increased rates of SSI, but this was not statistically significant. In overweight (BMI 25-29.9kg/m2) and obese (BMI ≥30kg/m2) patients, SSI versus no SSI rates were (50.0% versus 41.9% and 47.4% versus 36.4%, P = 0.365 and 0.230) respectively. The incidence of SSI in patients with an average AWT Conclusions AWT is a better predictor of SSI than BMI. Preoperative imaging of AWT may direct intraoperative decisions regarding wound management. Future clinical outcomes research in emergency surgery should include abdominal wall thickness as an important patient variable.

Attachment-based family therapy (ABFT; Diamond G.S. et al., 2014 ) is an empirically supported treatment designed to capitalize on the innate, biologically based, caregiving instinct and adolescent need for attachment security. This therapy is grounded in attachment and emotional processing theory and provides an interpersonal, process-oriented, trauma-informed approach to treating adolescents struggling with suicide and associated problems such as depression and trauma. ABFT offers a clear structure and road map to help therapists quickly address the attachment ruptures that lie at the core of family conflict, which can fuel adolescent distress. Several clinical trials and process studies have demonstrated empirical support for the model and its proposed mechanisms of change. In this paper, we provide an overview of the theories underlying the model, the clinical strategies that guide the treatment, the outcome research that demonstrates efficacy, and the process research that explores the proposed mechanisms of change.

Objectives This study set out to examine outcomes from pediatric supraventricular tachycardia ablations over a 20-year period. This study sought to examine success rates and repeat ablations over time and to evaluate whether modalities such as 3-dimensional (3D) mapping, contact force, and cryotherapy have improved outcomes. Background Ablation of supraventricular tachycardia in pediatric patients is commonly performed in most congenital heart centers with excellent long-term results. Methods Data were retrieved from the NICOR (National Institute of Clinical Outcomes Research) database in the United Kingdom. Outcomes over time were evaluated, and procedure-related details were compared. Results There were 7,069 ablations performed from January 1, 1999, to December 31, 2018, at 10 centers. Overall, ablation success rates were 92% for accessory pathways, 97% for atrioventricular node re-entry tachycardia, and 89% for atrial tachycardia. There was an improvement in procedural success rates over time (p Conclusions Overall success rates from pediatric ablations are excellent and compare favorably to other registries. Introduction of newer technologies have likely made procedures safer and reduced radiation exposure, but they have not changed success rates or the need for a repeat procedure.

BACKGROUND AND OBJECTIVE: Understanding the preferred choice of healthcare service attributes for women is important, particularly in sub-Saharan Africa where resources are constrained and improving reproductive and maternal healthcare services is of high importance. The aim of this systematic review was to identify attributes of reproductive and maternal healthcare services in sub-Saharan Africa, and summarise the factors shaping women's preference to access these services. METHODS: PubMed/MEDLINE, EMBASE, PsycINFO and CINAHL were searched from the inception of each database until March 2021 for published studies reporting stated preferences for maternal and reproductive healthcare services in sub-Saharan Africa. Data were extracted using a predefined extraction sheet, and the quality of reporting of included studies was assessed using PREFS and ISPOR (International Society for Pharmacoeconomics and Outcomes Research) checklists. The Donabedian's model for quality of healthcare was used to categorise attributes into "structure", "process" and "outcome". RESULTS: A total of 13 studies (12 discrete choice experiments and one best-worst scaling study) were included. Attributes related to the structure of healthcare services (e.g. availability of technical equipment, medications or diagnostic facilities, having good system conditions) are often included within the studies, and are considered the most important by women. Of the three dimensions of quality of healthcare, the outcome dimension was the least frequently studied across studies. All except one study explored women's preferences and the participants were pregnant women, women aged 18-49 years who had recently given birth and women living with human immunodeficiency virus. The included studies came from five sub-Saharan Africa countries of which Ethiopia and South Africa each contributed three studies. All of the included studies reported on the purpose, findings and significance of the study. However, none of the studies reported on the differences between responders vs non-responders. Nine of the 13 studies employed the ISPOR checklist and reported each item including the research question and the methods for identifying and selecting attributes, and provided the findings in sufficient detail and clarity. CONCLUSIONS: Aligning maternal healthcare service provision with women's preferences may foster client-oriented services and thereby improve service uptake and better patient outcomes.

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3–9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0–9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7–10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6–34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1–7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05–2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01–1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF., In a multicenter, randomized trial, the SGLT2 inhibitor dapagliflozin improved the health status and exercise function of patients with heart failure with preserved ejection fraction (HFpEF), a condition for which effective treatments are lacking.

Deciding on approving and granting market access to new medical technologies such as pharmaceutical products, vaccines, or medical devices is a multifactorial research problem. Balancing out clinical performance, epidemiological implications, burden of disease, economic value, and patient preferences, among other factors, is in itself a challenging endeavor. However, this should be a mandatory requirement when making approval and market access decisions that might affect millions of people in a specific country setting. The aim of this reflection research article is twofold; first, it provides context on the important role that health economics and outcomes research (HEOR) plays in informing decision making for market access and reimbursement of new medical technologies. Second, it outlines the power of HEOR studies in guiding discussions when assessing the value of new medical technologies. Overall, this article aims at highlighting key HEOR considerations for healthcare professionals, students, and institutions interested in building analytical capabilities around this exciting and uninterruptedly growing field of knowledge.

Evidence from discrete choice experiments can be used to enrich understanding of preferences, inform the (re)design of screening programmes and/or improve communication within public campaigns about the benefits and harms of screening. However, reviews of screening discrete choice experiments highlight significant discrepancies between stated choices and real choices, particularly regarding willingness to undergo cancer screening. The identification and selection of attributes and associated levels is a fundamental component of designing a discrete choice experiment. Misspecification or misinterpretation of attributes may lead to non-compensatory behaviours, attribute non-attendance and responses that lack external validity. We aimed to synthesise evidence on attribute development, alongside an in-depth review of included attributes and methodological challenges, to provide a resource for researchers undertaking future studies in cancer screening. A systematic review was conducted to identify discrete choice experiments estimating preferences towards cancer screening, dated between 1990 and December 2020. Data were synthesised narratively. In-depth analysis of attributes led to classification into four categories: test specific, service delivery, outcomes and monetary. Attribute significance and relative importance were also analysed. The International Society for Pharmacoeconomics and Outcomes Research conjoint analysis checklist was used to assess the quality of reporting. Forty-nine studies were included at full text. They covered a range of cancer sites: over half (26/49) examined colorectal screening. Most studies elicited general public preferences (34/49). In total, 280 attributes were included, 90% (252/280) of which were significant. Overall, test sensitivity and mortality reduction were most frequently found to be the most important to respondents. Improvements in reporting the identification, selection and construction of attributes used within cancer screening discrete choice experiments are needed. This review also highlights the importance of considering the complexity of choice tasks when considering risk information or compound attributes. Patient and public involvement and stakeholder engagement are recommended to optimise understanding of unavoidably complex choice tasks throughout the design process. To ensure quality and maximise comparability across studies, further research is needed to develop a risk-of-bias measure for discrete choice experiments.

Objective To evaluate vitamin D status in very low birth weight (VLBW) infants and response to vitamin D intake. Study design In this prospective cohort study of VLBW infants, 25-hydroxyvitamin D [25(OH)D] was measured regularly starting at birth. Daily vitamin D intake was estimated from parenteral and enteral sources. Results Of the included 83 infants born between November 2016 and March 2018, 44 (53%) had 25(OH)D < 30 ng/mL at birth but achieved vitamin D sufficiency (VDS) by 3 weeks while receiving 120–400 IU/day. Twenty-three (27.7%) infants had at least one 25(OH)D level >100 ng/mL during the study period. Infants whose intake was > 600 IU/day had higher prevalence of vitamin D excess (VDE). Conclusion In our study, low 25(OH)D was common in VLBW infants at birth. Vitamin D intake of 120–260 IU/day from parenteral and 200–400 IU/day from enteral route was appropriate for VLBW infants to achieve VDS. Doses > 600 IU/day increased risk of VDE.

Objectives Examine: (1) Prevalence of diagnosed venous thromboembolism (VTE) in infants

Background To better quantify the impact that breast cancer-related arm lymphedema (BCRL) has on health-related quality of life (HR-QOL), a disease-specific patient-reported outcome measure (PROM) is needed. The LYMPH-Q Upper Extremity Module was recently developed for patients with BCRL. The aim of this study was to perform an advanced translation and culturally adapt the LYMPH-Q Upper Extremity Module for use in Denmark. Methods The LYMPH-Q Upper Extremity Module was translated into Danish according to the guidelines of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the World Health Organization (WHO). The process included two forward and one back translation, an expert panel meeting, and cognitive debriefing interviews with patients. The focus of the translation was to develop a Danish version that used appropriate patient-friendly language while maintaining the meaning of the items, instructions and response options. Results The two forward translations resulted in minor differences in terminology. These discrepancies were discussed among the translators and a harmonized Danish version 1 was achieved. Comparison of the back translation to the original English version identified 14 items/instructions/response options that required re-translation. Subsequently, experts helped to identify and resolve the language for 10 items/instructions/response options that did not maintain the same meaning as the English version. Participants in the cognitive debriefing interviews did not report any difficulties with understanding the items/instructions/response options. Conclusions The translation and cultural adaption process led to the development of a conceptually equivalent Danish version of the LYMPH-Q Upper Extremity Module. Level of Evidence: Not gradable

Survivors of acute respiratory distress syndrome (ARDS) experience challenges that persist well beyond the time of hospital discharge. Impairment in physical function, cognitive function, and mental health are common and may last for years. The current coronavirus disease 2019 pandemic is drastically increasing the incidence of ARDS worldwide, and long-term impairments will remain lasting effects of the pandemic. Evaluation of the ARDS survivor should be comprehensive, and common domains of impairment that have emerged from long-term outcomes research over the past 2 decades should be systematically evaluated.

Prospective validation study. To validate and evaluate the measurement properties of the German Qualiveen short-form (SF) questionnaire in individuals with chronic neurogenic lower urinary tract dysfunction (NLUTD) resulting from spinal cord injury (SCI). Tertiary neuro-urologic referral center in Switzerland. Fifty individuals with chronic (>12 months) NLUTD resulting from SCI presenting for a urodynamic follow-up examination were enrolled to complete both the full version Qualiveen and the SF-Qualiveen questionnaires twice within three weeks. The criterion validity and test-retest reliability were evaluated by calculating the interclass correlation coefficients. Internal consistency was evaluated by calculating Cronbach’s alpha. Finally, the cross-sectional construct validity was evaluated using Spearman’s rank correlations between the scores of the two questionnaires for bladder evacuation, urinary continence, and urinary tract infection sub-groups. The mean age of the evaluated individuals was 53 years. The median duration of NLUTD was 14.9 years. The SF-Qualiveen showed good to excellent criterion validity with correlation coefficients greater than 0.8. Internal consistency was good overall and in the domains “bother with limitations” as well as “feelings” (>0.75). However, internal consistency in the domains “frequency of limitations” and “fears” was moderate-poor (0.68–0.37). The test-retest reliability was excellent with correlation coefficients greater than 0.9. Finally, the cross-sectional construct validity ranged from moderate to excellent (0.60–0.97). The German SF-Qualiveen has shown excellent reliability and validity and variable internal consistency. Its brevity will increase compliance, and we therefore recommend to include the SF-Qualiveen in urologic assessments.

Objectives To describe a surgical technique and early post-operative outcomes for a novel glaucoma drainage device—the PAUL® glaucoma implant (PGI). Methods A consecutive cohort study of subjects who had PGI surgery between February 2019 and May 2020 with a minimum of 6-month follow-up. Primary outcome measures included failure (intraocular pressure (IOP) > 21 mmHg or a 21 mmHg). Thirty-eight (38.4%) of eyes had complete success and achieved an unmedicated IOP

To demonstrate that days are important in extreme prematurity when creating survival prediction models based on gestation. Prospectively collected data were analysed for all admitted infants born 23 + 0 to 27 + 6 weeks gestation in the Australian and New Zealand Neonatal Network from 2009 to 2016. The effect of days on observed survival rates was assessed using a non-parametric test for trend. Prediction models created based on gestational age in completed weeks only or weeks plus days were compared. Seven thousand eight hundred and thirty-six extreme preterm infants were studied. Observed survival increased with days for 23, 24, 25, and 27 weeks gestational age (P = 0.01; P

Background: Patient-centered outcomes research seeks to answer patient-centered questions. The process includes varied locations and individuals throughout the care continuum to address individual differences and constraints in implementation and dissemination. Problem: This paper intends to answer this question: do academic nurses practice what they preach by assisting patient-centered outcomes research and researchers through their engagement with patients, caregivers, and other community stakeholder partners in nursing research? Approach: This paper provides an overview of how academic nurses in a single institution (the University of Texas Medical Branch at Galveston School of Nursing) began to embrace patient-centered outcomes research. Conclusion: Whether academic nurses are practicing what they preach in terms of patient-centered outcomes research remains uncertain. More examples from academia are required to make that determination. Academic nurses worldwide have embarked on a steep learning curve to embrace patient-centered outcomes research. This journey will require patience and a systematic strategy.

No studies have determined if there is a threshold whereby use of mother’s own milk (MOM) during hospitalization predicts exclusive MOM feeding at discharge. Among 113 very low birthweight neonates, the ratio of MOM to enteral feeds was measured in the first 14 days, 28 days, and overall hospital stay. The primary outcome was exclusive MOM feeding at discharge. For every 1% increase in MOM consumption in the first 14 and 28 days, the odds of being discharge home on an exclusive MOM diet increased nearly 7-fold (OR 7.01, 95% CI: 2.09–23.50) and 17-fold (OR 17.46, 95% CI 4.67–63.31), respectively. A threshold of >50%, >83%, and >85% MOM consumption compared to overall enteral feeds in the first 14 days, 28 days, and throughout hospitalization, respectively, is recommended. Promotion of MOM consumption in the first 2–4 weeks is of paramount importance, with negligible impact of increasing MOM consumption after 28 days.

Background Obtaining patient-reported outcomes (PROs) is becoming a standard component of patient care. For nonacademic practices, this can be challenging. From this perspective, we designed a nearly autonomous patient outcomes reporting system. We then conducted a prospective, cohort pilot study to assess the efficacy of the system. Methods We created an automated system to gather PROs. All operative patients for 4 surgeons in an upper-extremity private practice were asked to participate. These patients completed the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaires preoperatively and received follow-up e-mails requesting patients to complete additional QuickDASH questionnaires at 3, 6, and 12 weeks postoperatively and to complete a 13-week postoperative satisfaction survey. Response rates and satisfaction levels are reported with descriptive statistics. Results Sixty-two percent of participants completed the 3-week assessment, 55% completed the 6-week assessment, and 43% completed the 12-week assessment. Overall, 35% of patients completed all questionnaires, and 73% completed at least 1 postoperative assessment. The collection of follow-up questionnaires required no additional time from the clinical staff, surgeon, or a research associate. Conclusions Automated e-mail assessments can collect reliable clinical data, with minimal surgeon or staff intervention required to administer and collect data, minimizing the financial cost. For nonacademic practices, without access to additional research resources, such a system is feasible. Further improvements in communication with patients could increase response rates.

Purpose We examined the prevalence of, and factors associated with, serious opioid-related adverse drug events (ORADEs) that led to an emergency department (ED) visit or hospitalization among patients with chronic gastrointestinal (GI) symptoms and disorders dually enrolled in the Department of Veterans Affairs (VA) and Medicare Part D. Methods In this retrospective cohort study, we used linked national patient-level data (April 1, 2011, to October 31, 2014) from the VA and Centers for Medicare and Medicaid Services to identify serious ORADEs among dually enrolled veterans with a chronic GI symptom or disorder. Outcome measures included serious ORADEs, defined as an ED visit attributed to an ORADE or a hospitalization where the principal or secondary reason for admission involved an opioid. We used multiple logistic regression models to determine factors independently associated with a serious ORADE. Results We identified 3,430 veterans who had a chronic GI symptom or disorder; were dually enrolled in the VA and Medicare Part D; and had a serious ORADE that led to an ED visit, hospitalization, or both. The period prevalence of having a serious ORADE was 2.4% overall and 4.4% among veterans with chronic opioid use (≥90 consecutive days). Veterans with serious ORADEs were more likely to be less than 40 years old, male, white, and to have chronic abdominal pain, functional GI disorders, chronic pancreatitis, or Crohn’s disease. They were also more likely to have used opioids chronically and at higher daily doses. Conclusion There may be a considerable burden of serious ORADEs among patients with chronic GI symptoms and disorders. Future quality improvement efforts should target this vulnerable population.

Our objective was to assess the relationship between overall survival (OS) and distance travelled to the treating facility for patients undergoing liver resection for hepatocellular carcinoma and to determine whether this relationship was dependent upon the structural factors of the treating facility.Using National Cancer Database, we focused on extremes of travel: Local (12.5 miles to treating facility) and Travel (≥50 miles). We analyzed OS with Cox models; we estimated stratified models to assess interaction between distance and facility characteristics (volume, academic status).We included 6860 patients. After correction for confounding, distance travelled was not associated with OS (p = 0.444). However, Travel patients treated at high-volume, academic centers had worse OS compared to Local patients (HR 1.54, 95%CI 1.07-2.21); this association was not seen for patients treated at low volume, academic centers (p = 0.708) high volume non-academic centers (p = 0.174) or low volume non-academic centers (p = 515).For those patients treated at high-volume, academic centers, living far from the facility was associated with worse OS. The reasons for this association should be investigated further.

BACKGROUND: A key therapeutic goal of metastatic renal cell carcinoma (mRCC) treatment is delayed disease progression. The degree to which early therapeutic success affects downstream outcomes is not well established. OBJECTIVE: To assess the clinical and economic impact of early vs delayed disease progression in patients with mRCC treated with first-line (1L) tyrosine kinase inhibitors (TKIs) followed by second-line (2L) therapy in the US Veterans Health Administration (VHA) database. METHODS: Adult patients newly diagnosed with mRCC who were treated with a TKI as 1L therapy and who progressed to 2L therapy from October 1, 2013, through March 31, 2018, were identified from the US VHA database. Patients were stratified by median time from initiation of 1L therapy to initiation of 2L therapy into early (median time or sooner)and delayed (longer than the median) progression cohorts. Clinical outcomes (time to 2L therapy discontinuation, time to third-line [3L] treatment initiation, and overall survival) were assessed descriptively, and health care resource utilization and costs were compared between patients in the early and those in the delayed progression cohorts. Survival analyses (Kaplan-Meier curves) were used to estimate descriptively the median time to discontinuation, time to next line of treatment, and time to death for each cohort. Multivariate analysis was performed to adjust for the influence of differences in cohort characteristics, and Cox proportional hazards models were used to descriptively assess the impact of predictive factors on clinical outcomes. RESULTS: 289 patients were included in the analysis: 145 in the early progression cohort and 144 in the delayed progression cohort. Baseline characteristics were similar between the early and delayed progression cohorts. Median time from 1L therapy initiation to 2L therapy discontinuation was 7.9 months in the early progression cohort and 18.0 months in the delayed progression cohort, whereas time from 1L therapy initiation to 3L therapy initiation was 9.4 and 21.8 months, respectively; overall survival was 19.7 and 36.4 months, respectively. Descriptive analysis revealed generally lower risks for 2L therapy discontinuation (HR = 0.40, 95% CI = 0.31-0.52), 3L therapy initiation (HR = 0.42, 95% CI = 0.32-0.55), and death (HR = 0.46, 95% CI = 0.33-0.64) for those with delayed progression. After adjustment for possible confounding factors, comparative analysis during the follow-up period showed that delayed progression was associated with a shorter median all-cause hospital length of stay (0.4 days vs 0.8 days for early progression; P = 0.0004), fewer pharmacy visits (3.57 vs 4.08 visits; P = 0.0266), and lower total health care costs ($10,342 vs $13,388; P = 0.0347) per patient per month. CONCLUSIONS: In patients with mRCC, early progression after 1L therapy initiation is associated with generally worse clinical outcomes and statistically significantly greater health care resource utilization and costs than delayed progression. This finding highlights the importance of initiating therapy with an optimal 1L treatment regimen that has been proven to delay disease progression. DISCLOSURES This study was sponsored by EMD Serono Inc., an affiliate of Merck KGaA, and Pfizer Inc. EMD Serono Inc. and Pfizer Inc. were involved in the study design; the collection, analysis, and interpretation of the data; the writing of the report; and the decision to submit the report for publication. Liu and Bhanegaonkar are employed by EMD Serono Inc., an affiliate of Merck KGaA. Kasturi was employed by EMD Serono Inc., an affiliate of Merck KGaA, at the time of this study. Kim and Krulewicz are employed by Pfizer Inc. Dieyi is an employee of STATinMED Research, which received consulting fees from EMD Serono Inc. and Pfizer Inc. Hutson has received grants from Pfizer Inc., Astellas Pharma Inc., Janssen Pharmaceuticals, Exelixis, Inc., and Eisai Co., Ltd., outside of this work. Data from this analysis were presented at the Virtual International Society for Pharmacoeconomics and Outcomes Research 2020 conference, May 18-20, 2020; the virtual American Society of Clinical Oncology Annual Meeting, May 29-31, 2020; and AMCP Nexus 2020 Virtual, October 20-23, 2020.

Objective To evaluate the prevalence and impact of respiratory infections in cardiogenic shock complicating acute myocardial infarction (AMI-CS). Methods Using the National Inpatient Sample (2000–2017), this study identified adult (≥18 years) admitted with AMI-CS complicated by respiratory infections. Outcomes of interest included in-hospital mortality of AMI-CS admissions with and without respiratory infections, hospitalization costs, hospital length of stay, and discharge disposition. Temporal trends of prevalence, in-hospital mortality and cardiac procedures were evaluated. Results Among 557,974 AMI-CS admissions, concomitant respiratory infections were identified in 84,684 (15.2%). Temporal trends revealed a relatively stable trend in prevalence of respiratory infections over the 18-year period. Admissions with respiratory infections were on average older, less likely to be female, with greater comorbidity, had significantly higher rates of NSTEMI presentation, and acute non-cardiac organ failure compared to those without respiratory infections (all p