Obesity and metabolic syndrome in patients with heart failure with preserved ejection fraction: a cross-sectional analysis of the Veradigm Cardiology Registry.

BACKGROUND: The proportion of heart failure patients with preserved ejection fraction has been rising over the past decades and has coincided with increases in the prevalence of obesity and metabolic syndrome. The relationship between these interconnected comorbidities and heart failure with preserved ejection fraction (HFpEF) is still poorly understood. This study characterized obesity and metabolic syndrome among real-world patients with HFpEF. METHODS: We identified adults with heart failure in the Veradigm Cardiology Registry, previously the PINNACLE Registry, with a left ventricular ejection fraction measurement ≥ 50% between 01/01/2016 and 12/31/2019. Patients were stratified by obesity diagnosis and presence of metabolic syndrome (≥ 3 of the following: diabetes, hypertension, hyperlipidemia, and obesity). We captured baseline demographic and clinical characteristics and used multivariable logistic regression to examine the odds of having cardiac (atrial fibrillation, coronary artery disease, coronary artery bypass surgery, myocardial infarction, and stroke/transient ischemic attack) and non-cardiac (chronic kidney disease, chronic liver disease, and peripheral artery disease) comorbidities of interest. The models adjusted for age and sex, and the main covariates of interest were obesity and metabolic burden score (0-3 based on the presence of diabetes, hypertension, and hyperlipidemia). The models were run with and without an obesity*metabolic burden score interaction term. RESULTS: This study included 264,571 patients with HFpEF, of whom 55.7% had obesity, 52.5% had metabolic syndrome, 42.5% had both, and 34.3% had neither. After adjusting for age, sex, and burden of other metabolic syndrome-associated diagnoses, patients with HFpEF with obesity had lower odds of a diagnosis of other evaluated comorbidities relative to patients without obesity. The presence of metabolic syndrome in HFpEF appears to increase comorbidity burden as each additional metabolic syndrome-associated diagnosis was associated with higher odds of assessed comorbidities except atrial fibrillation. CONCLUSION: Obesity was common among patients with HFpEF and not always co-occurring with metabolic syndrome. Multivariable analysis suggested that patients with obesity may develop HFpEF in the absence of other driving factors such as cardiovascular disease or metabolic syndrome.

Body Weight as a Preferred Method for Normalizing the Computed Tomography-Derived Liver Volume in Dogs without Hepatic Disease.

The assessment of liver size is usually performed using radiography in dogs. However, due to wide variations in patients' sizes and body conformations, accurate diagnosis of hepatomegaly or microhepatia is difficult. Computed tomographic (CT) volumetry can quantitatively and accurately measure liver volume. However, a reliable method for the standardization or normalization of volume in dogs without hepatic disease using CT has not yet been established. The purpose of this study was to assess seven different anatomic measures for normalizing liver volume in dogs and determine the tentative range of liver volume in dogs without hepatic disease. We retrospectively searched medical records from 1 January 2017 through to 1 June 2020 and included dogs with abdominal computed tomography without hepatic disease. The liver volume, lengths of four vertebrae (T11, T12, L2, L3), diameter of the abdominal aorta, body weight, and body condition scores (BCSs) of the dogs were recorded. Forty-one client-owned dogs without evidence of hepatic disease were included. The CT-derived liver volume was 813.8 ± 326.5 cm3 (mean ± SD). Body weight was determined to be the most reliable single-variable method for normalizing liver volume, with a raw CT-derived liver-volume-to-body-weight ratio of 22.1 cm3/kg (95% CI: 12.9-31.3 cm3/kg) and regression prediction model of volume = 19 × BWkg + 97. However, a better normalizing factor would likely be provided by the fat-free mass if it can be accurately measured.

Ultrasonographic Renal Subcapsular Thickening in Cats with Primary and Metastatic Carcinoma.

Ultrasonographic subcapsular thickening caused by renal neoplasia other than lymphoma has been previously reported in cats; however, detailed information is lacking. This study aims to describe ultrasonographic findings in renal subcapsular thickening and renal parenchyma in cats diagnosed or presumed with primary and metastatic carcinoma in the kidney. Ultrasound reports were retrospectively searched from 3 veterinary hospitals and 6 cats with 9 affected kidneys were included. Renal lesions were confirmed either cytologically or histopathologically as primary renal carcinoma with metastasis in the contralateral kidney (in 1 case), or metastatic pulmonary carcinoma (in 3 cases). Two patients were cytologically diagnosed with pulmonary carcinoma with concurrent renal subcapsular thickening. Eight kidneys affected by metastatic carcinomas showed relatively thin, focal, and homogeneously hypoechoic subcapsular thickening while a single kidney affected by primary renal carcinoma showed markedly thick, circumferential, and heterogeneously mixed iso- to hypoechoic lesion. The renal parenchyma, especially when just beneath the subcapsular lesion, exhibited at least one abnormality in all affected kidneys, most characterized by hyperechoic renal cortex with concurrent hypoechoic striations. This is the first report describing metastatic carcinoma causing renal ultrasonographic subcapsular thickening in cats. Our results suggest that renal carcinoma should be included in differential diagnoses when ultrasonographic subcapsular thickening is present in cats.

Cystoscopic-guided laser ablation of intramural ectopic ureters in a female cat.

Case summary: An 8-month-old female spayed domestic shorthair cat was presented for chronic urinary incontinence (UI). Since being adopted 6 months earlier, the cat had a history of urine leakage during both activity and rest. Baseline blood work and urine culture showed no significant abnormalities and no evidence of a urinary tract infection. An abdominal CT with excretory urography followed by a focal urinary tract ultrasound revealed a suspected right intramural ectopic ureter (EU) and potential left EU. Cystoscopy confirmed bilateral intramural EUs. Cystoscopic-guided laser ablation (CLA) of both EUs was performed. The cat developed temporary urinary obstruction (UO) 36 h after the procedure, which was medically managed with prazosin and buprenorphine. Ultimately, the cat's urinary signs completely resolved with no UI recognized after the procedure and the cat has remained continent during 18 months of follow-up. Relevance and novel information: CLA of intramural EUs is routinely performed in dogs, but this technique has not been previously reported in cats with this condition. Although post-procedural urinary tract signs were initially present, the cat ultimately had an excellent outcome with resolution of UI after this procedure.

Improved detection of air-filled lesions using computed tomography in dogs with recurrent spontaneous pneumothorax through reduction of pulmonary atelectasis via positive pressure ventilation.

Introduction: Spontaneous pneumothorax in dogs is predominantly caused by the rupture of air-filled lesions, such as bullae or blebs. The efficacy of Computed Tomography (CT) in detecting these lesions has been deemed limited due to its reportedly low sensitivity. This retrospective, cross-sectional study investigates the utility of CT in eight dogs diagnosed with recurrent pneumothorax, all of which had surgical confirmation of the cause of the pneumothorax. Materials and methods: Thoracic radiographs were obtained before and the day following the CT studies. Initially, a CT study was conducted without positive pressure ventilation (pre-PPV CT). Subsequent CT studies were performed post-evacuation of pneumothorax and with positive pressure ventilation of 15 cmH2O until lung atelectasis was resolved (post-PPV CT). The pre-PPV CT and post-PPV CT images were anonymized and reviewed by two board-certified radiologists. The presence and morphology of air-filled lesions were evaluated on all images. Surgical findings were recorded and compared to the CT findings. Results: Air-filled lesions were detected in 5 out of 8 dogs in the pre-PPV CT studies and in all 8 dogs in the post-PPV CT studies. The CT findings of air-filled lesions were consistent with surgical findings. None of the dogs showed increased severity of pneumothorax in radiographs taken the day following the CT studies. Discussions: The study concludes that the resolution of lung atelectasis by evacuation of pneumothorax and positive pressure ventilation during CT studies is feasible and enhances the detection of air-filled lesions in dogs with recurrent spontaneous pneumothorax. This could potentially aid in improving surgical planning.

Drug development for major chronic health conditions-aligning with growing public health needs: Proceedings from a multistakeholder think tank.

The global pharmaceutical industry portfolio is skewed towards cancer and rare diseases due to more predictable development pathways and financial incentives. In contrast, drug development for major chronic health conditions that are responsible for a large part of mortality and disability worldwide is stalled. To examine the processes of novel drug development for common chronic health conditions, a multistakeholder Think Tank meeting, including thought leaders from academia, clinical practice, non-profit healthcare organizations, the pharmaceutical industry, the Food and Drug Administration (FDA), payors as well as investors, was convened in July 2022. Herein, we summarize the proceedings of this meeting, including an overview of the current state of drug development for chronic health conditions and key barriers that were identified. Six major action items were formulated to accelerate drug development for chronic diseases, with a focus on improving the efficiency of clinical trials and rapid implementation of evidence into clinical practice.

A case of intestinal intussusception with unique hemorrhagic polyps due to AL amyloidosis and excessive anticoagulation.

Most adult intussusceptions are secondary to various pathological conditions that serve as a lead point. Because of their serious nature, intussusceptions often require emergency surgery. We report a surgical case of amyloidosis associated with intussusception, probably due to polypoid protrusions and bleeding tendencies. An 80-year-old man with abdominal pain was suspected of having jejunal intussusception on computed tomography. He had been prescribed warfarin for atrial fibrillation, and excessive anticoagulation was observed with a prolonged prothrombin time/international normalized ratio of 5.44 at presentation. After the excessive anticoagulation was resolved, emergency surgery was performed. The intussuscepted jejunum was resected, and a 7 cm long dark-red pedunculated polyp was identified as the lead point, which was accompanied by multiple small pedunculated polyps. Histopathological examination showed that these were all hemorrhagic polyps. Amyloid depositions were observed in the muscularis mucosae, submucosa, and the walls of the blood vessels. Immunohistochemical analysis revealed immunoglobulin light chain amyloidosis. This case is informative to discuss the clinical sequelae of gastrointestinal amyloid deposition.

Marked paraneoplastic basophilia in a cat with alimentary T-cell lymphoma.

An 8-year-old, spayed female domestic shorthair cat was presented for acute weight loss, hyporexia, intermittent vomiting, and loose stools. A caudal abdominal mass and thickened intestinal loops were palpated on initial examination. An abdominal ultrasound identified a circumferential intramural jejunal mass with complete loss of wall layering, diffuse thickening of the jejunal muscularis, and jejunal and ileocecal lymphadenomegaly. Initial routine bloodwork revealed mild monocytosis and minimal lymphopenia with reactive lymphocytes. Cytologic evaluation of the jejunal mass and enlarged lymph nodes was consistent with lymphoma (intermediate cell size), and PCR for antigen receptor rearrangement revealed a clonal T-cell receptor rearrangement consistent with T-cell lymphoma. Chemotherapy (CHOP protocol) was initiated, but despite initial improvement of clinical signs, a repeat ultrasound examination 5 weeks after initiation of treatment revealed no improvement in the lymphadenomegaly or reduction in the size of the jejunal mass. At this visit, the cat also developed a marked basophilia (basophils 12.28 × 103 /µL, RI 0.00-0.10) with low numbers of circulating atypical lymphocytes; no concurrent eosinophilia was noted. Heartworm disease, ectoparasites, and allergic diseases were evaluated for and considered unlikely. The chemotherapy protocol was changed to L-asparaginase, followed by lomustine. The basophilia was significantly reduced 2 days after the initial dose of L-asparaginase and remained within the reference interval for 40 days before an eventual decline in the cat's health. To the authors' knowledge, this is the first report of paraneoplastic basophilia without concurrent eosinophilia in a cat with T-cell lymphoma.

Bidirectional Patellar Luxation in Small- or Miniature-Breed Dogs in Japan; Patient Characteristics and Radiographic Measures Compared with Medial Patellar Luxation.

Bidirectional patellar luxation (BPL) is a relatively rare form of patellar luxation, with limited information reported regarding breed predisposition and etiology. The purpose of this study was to describe the patient characteristics and radiographic measures of proximodistal patellar position associated with BPL in dogs in Japan, compared with dogs with medial patellar luxation (MPL). A retrospective medical record search of surgically corrected MPL and BPL dogs was performed, and breed, age, sex, body weight, and presence of the patella alta in the extended-stifle position were recorded. The ratio of the patellar ligament length to patella length (PLL/PL) and the ratio of the distance between the proximal pole of the patella and the femoral condyle to patella length (A/PL) were measured on stifle radiographs. A total of 35 dogs with BPL and 95 dogs with MPL were included. The BPL was most commonly present in Toy Poodles (odds ratio compared to MPL dogs: 7.05) in the present study. There were no significant differences in age, sex, or body weight between the BPL and MPL groups. Patella alta in the extended-stifle position was more common in the BPL group (23.4%) than in the MPL group (0.8%). However, there were no significant differences in PLL/PL or A/PL between the BPL and MPL groups. The study highlights BPL in different dog breeds in Japan, and suggests that the occurrence of BPL may be related to stifle extension. However, more research is needed to fully understand the etiology of BPL.

Computed tomographic measures of renomegaly vary among dogs with different types of congenital portosystemic shunts.

Renomegaly has been reported in dogs with congenital portosystemic shunts (PSS). However, no study has objectively evaluated the degree of renomegaly in dogs with different types of PSS. The purpose of this retrospective, analytical, cross-sectional study was to determine kidney size (renal length-to-L2 vertebral body ratio; RL/L2 ratio) using CT in dogs with different types of PSS and correlate with clinical information. A medical record search for dogs with a PSS diagnosed using CT between 2016 and 2020 was conducted. Breed, age, sex, body weight, and biochemistry results were recorded. Kidney and L2 vertebral body lengths were measured using multiplanar reformatted CT images, and the RL/L2 ratio was calculated. Dogs were categorized into four groups based on PSS morphology for comparisons: intrahepatic (IH; n = 19), extrahepatic portocaval (EHPC; n = 20), extrahepatic portoazygos (EHPA; n = 7), or extrahepatic portophrenic (EHPP, n = 7). The RL/L2 ratio (mean ± SD) was largest in IH (3.55 ± 0.38) and EHPC (3.55 ± 0.38), followed by EHPP (3.10 ± 0.23), and EHPA (2.78 ± 0.18). RL/L2 ratio was significantly larger in EHPC and IH (vs. EHPA and EHPP [P < .01]). Significant correlations between kidney size and creatinine, alkaline phosphatase, albumin, total protein, and ammonia were present. Renomegaly was observed in 86.8% of dogs with PSS overall, but it was uncommon in dogs with EHPA and less common in dogs with EHPP, as these two groups showed clinical signs later in life, made evident by older age at presentation. The authors suggest that the severity of hepatic dysfunction and the shunted blood volume may influence the development of renomegaly in dogs with PSS.

Caco-2 Cell Sheet Partially Laminated with HT29-MTX Cells as a Novel In Vitro Model of Gut Epithelium Drug Permeability.

The intestinal epithelial Caco-2 cell monolayer is a well-established in vitro model useful for predicting intestinal drug absorption in humans. Coculture models of Caco-2 and goblet-cell-like HT29-MTX cells have been developed to overcome the lack of a mucus layer; however, those models are much leakier compared to the intestinal epithelium. Here, we developed a partially laminated culture model where HT29-MTX cells were superimposed onto a Caco-2 monolayer to overcome this issue. A morphological study showed that the piled HT29-MTX cells were voluntarily incorporated into the Caco-2 monolayer, and mucus production was confirmed via periodic acid-Schiff and mucin protein 2 staining. Permeability was evaluated in terms of transepithelial electrical resistance (TEER) and the apparent permeability of paracellular markers with different molecular sizes. The partially laminated model maintained the high barrier function of the Caco-2 monolayer, whose permeability appeared adjustable according to the HT29-MTX/Caco-2 cell ratio. In contrast, the coculture models showed abnormally high permeability of those markers, correlated with low TEER. Thus, the partially laminated model enabled in vitro recapitulation of effective mucosal barrier function. Consequently, this novel model may be useful as an in vitro high-throughput evaluation system for enteral mucosal permeability and mucus-penetrating efficiency of drugs and nanocarriers.

Photocatalytic 1,2-Phosphorus-Migrative [3 + 2] Cycloaddition of Tri(t-butyl)phosphine with Terminal Alkynes.

Tri(t-butyl)phosphine and terminal alkynes undergo 1,2-phosphorus-migrative [3 + 2] cycloaddition in the presence of a proton source under photocatalytic conditions. The reaction exhibits broad functional group tolerance and affords substituted cyclic phosphonium salts, which are amenable to further derivatization by Wittig olefination. Theoretical studies suggest that the phosphorus 1,2-migration of a ß-phosphonioalkyl radical proceeds through a phosphine radical cation-alkene complex as a pseudointermediate, and the two fragments in the intermediate are bound to each other through multiple noncovalent interactions.

"Click and mortar" opportunities for digitization and consumerism in trials.

BACKGROUND: Digitization (using novel digital tools and strategies) and consumerism (taking a consumer-oriented approach) are increasingly commonplace in clinical trials, but the implications of these changes are not well described. METHODS: We assembled a group of trial experts from academia, industry, non-profit, and government to discuss implications of this changing trial landscape and provide guidance. RESULTS: Digitization and consumerism can increase the volume and diversity of trial participants and expedite recruitment. However, downstream bottlenecks, challenges with retention, and serious issues with equity, ethics, and security can result. A "click and mortar" approach, combining approaches from novel and traditional trials with the thoughtful use of technology, may optimally balance opportunities and challenges facing many trials. CONCLUSION: We offer expert guidance and three "click and mortar" approaches to digital, consumer-oriented trials. More guidance and research are needed to navigate the associated opportunities and challenges.

Ultrasonographic features of gallbladder wall thickening in dogs with hypoalbuminemia.

Hypoalbuminemia has been considered as a cause of gallbladder wall thickening in humans and dogs. Recent study revealed that gallbladder wall thickening in dogs with hypoalbuminemia may not be associated with serum albumin/plasma levels within 48 h of ultrasound study. However, gallbladder wall edema may change within 48 h, and the ultrasonographic features of gallbladder wall thickening in dogs with hypoalbuminemia have not been reported. The purpose of this study is to describe the relationship between serum albumin levels within 24 h of ultrasound and gallbladder wall thickening, and to describe the ultrasonographic features of thickened gallbladder walls in dogs with hypoalbuminemia. 37 hypoalbuminemic dogs with gallbladder ultrasound images were retrospectively included. Ultrasound studies were reviewed, and gallbladder wall thickness, layering appearance, echogenicity, echotexture, distribution, evidence of gallbladder mucocele, and presence of peritoneal effusion were recorded. Additionally, serum albumin levels within 24 h of ultrasound study and the administerd sedation were recorded. The prevalence of gallbladder wall thickening in dogs with hypoalbuminemia was 13.5%. The 3-layer appearance of the gallbladder wall was observed in 4 dogs, and a single-layer gallbladder wall thickening in one dog. Diffuse thickening was observed in all 5 dogs. The serum albumin level of dogs with gallbladder wall thickening was not different (p = 0.14) from dogs without thickening. Gallbladder wall thickening was not common, occurring only with mild hypoalbuminemia, and was commonly associated with a 3-layer appearance and considered as gallbladder wall subserosal edema. Causes other than hypoalbuminemia may be responsible for thickening of the gallbladder wall in dogs with hypoalbuminemia.

Ligand-Controlled Regiodivergence in Nickel-Catalyzed Vinylcyclopropane Rearrangement.

A ligand-controlled regiodivergence in Ni-catalyzed rearrangement of vinylcyclopropanes to 1,4- or 1,5-disubstituted cyclopentenes is reported. The 1,4- or 1,5-disubstituted cyclopentene is selectively obtained depending on the choice of ligands. Detailed kinetic studies and density functional theory calculations on the catalytic cycle revealed that the product selectivity is determined at the reductive elimination step from the six-membered η1 -allyl intermediate.

Computed tomographic and magnetic resonance imaging anatomy of the coelomic cavity in market-age commercial Pekin Ducks (Anas platyrhynchos domesticus).

Approximately 27 million ducks are raised commercially in the US each year and Pekin ducks (Anas platyrhynchos domesticus) are the most commonly raised breed. Additionally, an increasing number of Americans are raising small flocks of poultry, which often include ducks, in their own backyards. This creates a need to better understand the imaging anatomy of ducks. However, in avian species, superimposition of organs limits evaluation of the coelomic cavity using the most common imaging modality, radiography. The use of cross-sectional imaging including computed tomography (CT) and magnetic resonance imaging (MRI) has increased in veterinary medicine research and clinical use. An anatomic atlas is essential for guiding research and diagnostic imaging. To date, no CT or MRI atlas exists for Pekin ducks. The purpose of the study is to generate a CT atlas of market-age Pekin ducks as well as CT attenuation values and measurements of coelomic organs with corresponding gross and MRI images. A total of 20 market-age, commercial Pekin ducks were imaged. Five male and five female ducks were imaged with CT; four of these ten ducks, two male and two female, were frozen and sliced in approximately 5 mm transverse sections for gross anatomic reference images. Six additional ducks, three male and three female ducks, were dissected to measure major organs. Four additional ducks were imaged using CT and MRI and necropsied for gross anatomical comparisons and landmarks. The atlas contained here may be used for future research projects and clinically to aid in diagnosis of disease in ducks.

Harmless and ecologically acceptable fabrication of long-acting injectable microspheres.

The use of harmful solvents during the preparation of pharmaceutical formulations is restricted to preserve environment and ensure safety of industrial operations. However, harmful solvents must be used to produce certain formulations. For instance, methylene chloride has been used in the fabrication of polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) microspheres. This review highlights the latest advances in the strategy of PLA or PLGA microsphere production from non-halogenated solvents and describes advantages and limitations of these methods. The study also discusses the development of dry fabrication techniques for microsphere fabrication and the positioning of conventional and dry fabrication in the containment concept for workers' safety.

[A Case of Rectal Neuroendocrine Carcinoma with Iris Metastasis].

A 62-year-old man with anal pain was diagnosed with rectal neuroendocrine carcinoma. There were multiple metastases in the liver, lung, paraaortic lymph node, and bone of the patient. After performing a diverting colostomy, irinotecan and cisplatin were administered. Partial response was obtained after 2 courses, and anal pain improved. However, after 8 courses, multiple skin metastases were found on his back. At the same time, the patient also complained of redness, pain, and impaired vision in the right eye. Iris metastasis was diagnosed clinically by ophthalmologic examination and with contrast- enhanced MRI. Iris metastasis was treated with 5 doses of 4 Gy irradiation, ameliorating the eye symptoms. The patient died of the original disease 13 months after the initial diagnosis; however, multidisciplinary treatment appeared effective for palliating cancer symptoms.

Pilot Study: The Effects of Slice Parameters and the Interobserver Measurement Variability in Computed Tomographic Hepatic Volumetry in Dogs without Hepatic Disease.

Manual computed tomographic (CT) hepatic volumetry is a non-invasive method for assessing liver volume. However, it is time-consuming with large numbers of slices. Reducing the slice number would expedite the process, but the effect of fewer slices on the accuracy of volumetric measurements in dogs has not been investigated. The objectives of this study were to evaluate the relationship between slice interval and the number of slices on hepatic volume in dogs using CT hepatic volumetry and the interobserver variability of CT volumetric measurements. We retrospectively reviewed medical records for dogs without evidence of hepatobiliary disease with abdominal CT from 2019 to 2020. Hepatic volumes were calculated by using all slices, and interobserver variability was calculated using the same dataset in 16 dogs by three observers. Interobserver variability was low, with a mean (±SD) percent difference in the hepatic volume of 3.3 (±2.5)% among all observers. The greatest percent differences in hepatic volume were decreased when using larger numbers of slices; the percent differences were <5% when using ≥20 slices for hepatic volumetry. Manual CT hepatic volumetry can be used in dogs to non-invasively assess liver volume with low interobserver variability, and a relatively reliable result can be acquired using ≥20 slices in dogs.

Patient-reported outcome measures and patient engagement in heart failure clinical trials: multi-stakeholder perspectives.

There are many consequences of heart failure (HF), including symptoms, impaired health-related quality of life (HRQoL), and physical and social limitations (functional status). These have a substantial impact on patients' lives, yet are not routinely captured in clinical trials. Patient-reported outcomes (PROs) can quantify patients' experiences of their disease and its treatment. Steps can be taken to improve the use of PROs in HF trials, in regulatory and payer decisions, and in patient care. Importantly, PRO measures (PROMs) must be developed with involvement of patients, family members, and caregivers from diverse demographic groups and communities. PRO data collection should become more routine not only in clinical trials but also in clinical practice. This may be facilitated by the use of digital tools and interdisciplinary patient advocacy efforts. There is a need for standardization, not only of the PROM instruments, but also in procedures for analysis, interpretation and reporting PRO data. More work needs to be done to determine the degree of change that is important to patients and that is associated with increased risks of clinical events. This 'minimal clinically important difference' requires further research to determine thresholds for different PROMs, to assess consistency across trial populations, and to define standards for improvement that warrant regulatory and reimbursement approvals. PROs are a vital part of patient care and drug development, and more work should be done to ensure that these measures are both reflective of the patient experience and that they are more widely employed.