Prognostic Value of Fibroblast Growth Factor Receptor Genetic Alterations in Metastatic Urothelial Carcinoma.

INTRODUCTION: Evidence is limited on whether fibroblast growth factor receptor gene alterations (FGFRalt) impact clinical outcomes in patients with locally advanced or metastatic urothelial cancer (mUC). This study evaluated progression-free survival (PFS) in patients with mUC based on FGFRalt status in the first-line setting (1L). PATIENTS AND METHODS: Data on mUC patients were retrieved via convenience sampling of oncologists/urologists surveyed between August and September 2020 who treated at least 1 FGFRalt patient between July 2017 and June 2019. The questionnaire included information on patient demographics, FGFR status, treatment, and clinical and radiographic measures of progression. Primary endpoint was time from metastatic diagnosis to disease progression from initial treatment for FGFRalt and FGFRwt (wild-type) mUC. Cox proportional hazards models quantified adjusted risk of FGFR status relating to PFS. RESULTS: A total of 414 patients were analyzed. Mean age was 64.5 years, 73.9% were male, and 52.7% had an FGFRalt. Among FGFRalt, 47.2% received chemotherapy, 27.5% immune checkpoint inhibition (ICI), 11.5% chemotherapy+ICI, and 13.8% other treatments in 1L. FGFR status did not influence PFS from time of mUC diagnosis or among 224 stratified patients receiving either chemotherapy or chemotherapy+ICI. However, among 97 patients with an FGFRalt receiving 1L ICI therapy only, adjusted risk of progression was twice that of FGFRwt (HR: 2.12; 95% CI: 1.13-4.00). CONCLUSION: Although FGFRalt did not predict outcomes in the overall cohort, for patients treated with 1L ICI, FGFRalt had significantly higher rates of progression than FGFRwt patients. Further validation is needed to determine whether FGFRalt has a decreased benefit from ICI therapy.

2023 ISTH update of the 2022 ISTH guidelines for antithrombotic treatment in COVID-19.

Based on emerging evidence from the COVID-19 pandemic, the International Society on Thrombosis and Haemostasis (ISTH) guidelines for antithrombotic treatment in COVID-19 were published in 2022. Since then, at least 16 new randomized controlled trials have contributed additional evidence, which necessitated a modification of most of the previous recommendations. We used again the American College of Cardiology Foundation/American Heart Association methodology for assessment of level of evidence (LOE) and class of recommendation (COR). Five recommendations had the LOE upgraded to A and 2 new recommendations on antithrombotic treatment for patients with COVID-19 were added. Furthermore, a section was added to answer questions about COVID-19 vaccination and vaccine-induced immune thrombotic thrombocytopenia (VITT), for which studies have provided some evidence. We only included recommendations with LOE A or B. Panelists agreed on 19 recommendations, 4 for nonhospitalized, 5 for noncritically ill hospitalized, 3 for critically ill hospitalized, and 2 for postdischarge patients, as well as 5 for vaccination and VITT. A strong recommendation (COR 1) was given for (a) use of prophylactic dose of low-molecular-weight heparin or unfractionated heparin in noncritically ill patients hospitalized for COVID-19, (b) for select patients in this group, use of therapeutic-dose low-molecular-weight heparin/unfractionated heparin in preference to prophylactic dose, and (c) for use of antiplatelet factor 4 enzyme immunoassays for diagnosing VITT. A strong recommendation was given against (COR 3) the addition of an antiplatelet agent in hospitalized, noncritically ill patients. These international guidelines provide recommendations for countries with diverse healthcare resources and COVID-19 vaccine availability.

ISTH guidelines for antithrombotic treatment in COVID-19.

Antithrombotic agents reduce risk of thromboembolism in severely ill patients. Patients with coronavirus disease 2019 (COVID-19) may realize additional benefits from heparins. Optimal dosing and timing of these treatments and benefits of other antithrombotic agents remain unclear. In October 2021, ISTH assembled an international panel of content experts, patient representatives, and a methodologist to develop recommendations on anticoagulants and antiplatelet agents for patients with COVID-19 in different clinical settings. We used the American College of Cardiology Foundation/American Heart Association methodology to assess level of evidence (LOE) and class of recommendation (COR). Only recommendations with LOE A or B were included. Panelists agreed on 12 recommendations: three for non-hospitalized, five for non-critically ill hospitalized, three for critically ill hospitalized, and one for post-discharge patients. Two recommendations were based on high-quality evidence, the remainder on moderate-quality evidence. Among non-critically ill patients hospitalized for COVID-19, the panel gave a strong recommendation (a) for use of prophylactic dose of low molecular weight heparin or unfractionated heparin (LMWH/UFH) (COR 1); (b) for select patients in this group, use of therapeutic dose LMWH/UFH in preference to prophylactic dose (COR 1); but (c) against the addition of an antiplatelet agent (COR 3). Weak recommendations favored (a) sulodexide in non-hospitalized patients, (b) adding an antiplatelet agent to prophylactic LMWH/UFH in select critically ill, and (c) prophylactic rivaroxaban for select patients after discharge (all COR 2b). Recommendations in this guideline are based on high-/moderate-quality evidence available through March 2022. Focused updates will incorporate future evidence supporting changes to these recommendations.

Update on use of enteral and parenteral nutrition in hospitalized patients with a diagnosis of malnutrition in the United States.

BACKGROUND: Malnutrition continues to be associated with outcomes in hospitalized patients. METHODS: An updated review of national data in patients with a coded diagnosis of malnutrition (CDM) and the use of nutrition support (enteral nutrition [EN] and parenteral nutrition [PN]) was conducted using the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project and Medicare Claims data. RESULTS: Results demonstrated a growing trend in CDM accompanied by continued low utilization of PN and EN. CONCLUSION: Underutilization of nutrition support may be due to product shortages, reluctance of clinicians to use these therapies, undercoding of nutrition support, strict adherence to published guidelines, and other factors.

Cystic Fibrosis Foundation otolaryngology care multidisciplinary consensus recommendations.

BACKGROUND: Cystic fibrosis (CF) is a multisystem disease that often requires otolaryngology care. Individuals with CF commonly have chronic rhinosinusitis but also present with hearing loss and dysphonia. Given these manifestations of CF, otolaryngologists are frequently involved in the care of patients with CF; however, there is limited consensus on optimal management of sinonasal, otologic, and laryngologic symptoms. METHODS: The Cystic Fibrosis Foundation convened a multidisciplinary team of otolaryngologists, pulmonologists, audiologists, pharmacists, a social worker, a nurse coordinator, a respiratory therapist, two adults with CF, and a caregiver of a child with CF to develop consensus recommendations. Workgroups developed draft recommendation statements based on a systematic literature review, and a ≥80% consensus was required for acceptance of each recommendation statement. RESULTS: The committee voted on 25 statements. Eleven statements were adopted recommending a treatment or intervention, while five statements were formulated recommending against a specific treatment or intervention. The committee recommended eight statements as an option for select patients in certain circumstances, and one statement did not reach consensus. CONCLUSION: These multidisciplinary consensus recommendations will help providers navigate decisions related to otolaryngology consultation, medical and surgical management of CF-CRS, hearing, and voice in individuals with CF. A collaborative and multidisciplinary approach is advocated to best care for our patients with CF. Future clinical research is needed utilizing standardized, validated outcomes with comprehensive reporting of patient outcome, effects of modulator therapies, and genetic characteristics to help continue to advance care, decrease morbidity, and improve the quality of life for individuals with CF.

Malnutrition diagnoses and associated outcomes in hospitalized patients: United States, 2018.

In the US, malnutrition is prevalent among hospitalized patients and is associated with higher morbidity, mortality, and healthcare costs when compared with those without malnutrition. Over time, national data have indicated the rate of coded malnutrition diagnoses among hospital discharges rising over time, and more current data on demographic and clinical characteristics of these patients are needed. Data on malnutrition discharges from the 2018 Healthcare Cost and Utilization Project (HCUP)-the most recent nationally representative data-were examined and compared with earlier HCUP findings. Based on International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, 8.9% of all US non-maternal, non-neonatal hospital discharges in 2018 had a coded diagnosis of malnutrition (CDM). From this 2018 data, those with a CDM were older, had longer lengths of stay, and incurred higher costs, as compared with those without a CDM. Higher readmission rates and higher inpatient mortality were also observed in this group. These findings provide more recent demographic and clinical evidence for standardized malnutrition diagnostic and interventional programs to treat and/or prevent this condition.

Microscopic Hematuria as a Screening Tool for Urologic Malignancies in Women.

INTRODUCTION: Most causes of microscopic hematuria (MH) are benign but may indicate an underlying malignancy. Current MH evaluation guidelines are reflective of male urologic malignancy risks. The objective of this systematic review was to evaluate whether the finding of MH predicts subsequent urologic malignancy in women. METHODS: MEDLINE was searched between January 1990 and June 8, 2018. The positive predictive value (PPV) of MH as a screening tool for urologic malignancy was calculated for each study individually and collectively. The pooled relative risk of urologic malignancy associated with MH was calculated. RESULTS: Seventeen studies were included. Eight studies included only women. In total, 300 urinary tract cancers were identified in 110,179 women with MH. The PPV of MH as a screening tool for cancer ranged from approximately 0.6% to 2.8%; confidence intervals (CIs) suggested this is a relatively unstable performance indicator because of small sample sizes. Average PPV across all studies was 2.13%, but the weighted average PPV was 0.24%. The risk of urologic malignancies among women with relative those without MH was 2.01 (95% CI, 1.61-2.51). Based on these limited data, we estimate that 859 (95% CI, 654-1250) women with MH would require complete evaluation to identify 1 urinary tract malignancy. CONCLUSIONS: A very small proportion of women with MH are likely to have a urologic malignancy. Approximately 859 women require full screening to identify 1 malignancy. Current evidence is limited, and further studies, specifically in women, are needed.

Cystic Fibrosis Foundation Pulmonary Guidelines. Use of Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy in Patients with Cystic Fibrosis.

RATIONALE: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators are a new class of medications targeting the underlying defect in CF. Ivacaftor (IVA) and IVA combined with lumacaftor (LUM; IVA/LUM) have been approved by the U.S. Food and Drug Administration (FDA) for use in patients with CF. However, the FDA label for these medications encompasses patient groups that were not studied as part of the drug approval process. CF clinicians, patients, and their families have recognized a need for recommendations to guide the use of these medications. OBJECTIVE: Develop evidence-based guidelines for CFTR modulator therapy in patients with CF. METHODS: A multidisciplinary committee of CF caregivers and patient representatives was assembled. A methodologist, an epidemiologist, a medical librarian, and a biostatistician were recruited to assist with the literature search, evidence grading, and generation of recommendations. The committee developed clinical questions using the Patient-Intervention-Comparison-Outcome format. A systematic review was conducted to find relevant publications. The evidence was then evaluated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach, and recommendations were made based on this analysis. RESULTS: For adults and children aged 6 years and older with CF due to gating mutations other than G551D or R117H, the guideline panel made a conditional recommendation for treatment with IVA. For those with the R117H mutation, the guideline panel made a conditional recommendation for treatment with IVA for 1) adults aged 18 years or older, and 2) children aged 6-17 years with a forced expiratory volume in 1 second (FEV1) less than 90% predicted. For those with the R117H mutation, the guideline panel made a conditional recommendation against treatment with IVA for 1) children aged 12-17 years with an FEV1 greater than 90% predicted, and 2) children less than 6 years of age. Among those with two copies of F508del, the guideline panel made a strong recommendation for treatment with IVA/LUM for adults and children aged 12 years and older with an FEV1 less than 90% predicted; and made a conditional recommendation for treatment with IVA/LUM for 1) adults and children aged 12 years or older with an FEV1 greater than 90% predicted, and 2) children aged 6-11 years. CONCLUSIONS: Using the GRADE approach, we have made recommendations for the use of CFTR modulators in patients with CF. These recommendations will be of help to CF clinicians, patients, and their families in guiding decisions regarding use of these medications.

Computerized cognitive testing norms in active-duty military personnel: Potential for contamination by psychologically unhealthy individuals.

Normative reference data used for clinical interpretation of neuropsychological testing results are only valid to the extent that the sample they are based on is composed of "normal" individuals. Accordingly, efforts are made to exclude individuals with histories and/or diagnoses that might bias test performance. In this report, we focus on these features in active-duty military personnel because published data on computerized neurocognitive testing norms for this population have not explicitly considered the consequences of neurobehavioral disorders (e.g., PTSD, depression), which are prevalent in this population and known to affect performance on some cognitive assessments. We administered DANA, a mobile, neurocognitive assessment tool, to a large sample of active-duty military personnel and found that scores on self-administered psychological assessments negatively impacted a number of neurocognitive tests. These results suggest that neurobehavioral disorders that are relatively common in this population should be controlled for when establishing normative datasets for neurocognitive outcomes.

Behavioral health characteristics of a technology-enabled sample of Alzheimer's caregivers with high caregiver burden.

BACKGROUND: Caregivers of persons with dementia/Alzheimer's disease (AD) experience considerable physical and psychological burdens associated with their caregiving role. Although mobile technologies have the potential to deliver caregiver supports, it is necessary to demonstrate that caregivers in need of these supports are technology-enabled, that they can be identified and accessed, and that they experience the same unfavorable mental health outcomes characteristic of the broader caregiving population. Our objective was to enroll a cohort of technology-enabled caregivers to determine basic demographic characteristics and assess level of caregiver burden, depression, anxiety, and sleep disturbance as part of a larger project to deliver caregiver support. METHODS: Web-based enrollment and data collection measuring caregiver burden with the Zarit Burden Interview (ZBI), anxiety and depression with the M-3, and sleep disturbance with the PROMIS Sleep Disturbance form. RESULTS: A total of 165 caregivers enrolled via an online portal, all of whom provided care for someone with AD and owned a smart phone. Mean age of this group with 57.9 years, 90.3% was female, 88.5% was White, 51.5% reported providing care for a parent, 9.3% reported providing care for more than 10 years, and 24.8% reported providing more than 100 hours of care each week. Sixty-four percent of caregivers screened positive for both anxiety and depression, and nearly 62% of the sample had moderate or severe caregiver burden. Scores on depression, anxiety, and sleep quality assessments correlated moderately or strongly with caregiver burden. CONCLUSIONS: Dementia caregivers with Internet and smartphone access demonstrate high levels of caregiver burden, depression, and anxiety, and are well-suited to receive caregiver support services delivered via mobile devices that target these issues.

Central venous catheter infections in home parenteral nutrition patients: Outcomes from Sustain: American Society for Parenteral and Enteral Nutrition's National Patient Registry for Nutrition Care.

BACKGROUND: Home parenteral nutrition (HPN) is a high-cost, complex nutrition support therapy that requires the use of central venous catheters. Central line-associated bloodstream infections (CLABSIs) are among the most serious risks of this therapy. Sustain: American Society for Parenteral and Enteral Nutrition's National Patient Registry for Nutrition Care (Sustain registry) provides the most current and comprehensive data for studying CLABSI among a national cohort of HPN patients in the United States. This is the first Sustain registry report detailing longitudinal data on CLABSI among HPN patients. OBJECTIVE: To describe CLABSI rates for HPN patients followed in the Sustain registry from 2011-2014. METHODS: Descriptive, χ2, and t tests were used to analyze data from the Sustain registry. RESULTS: Of the 1,046 HPN patients from 29 sites across the United States, 112 (10.7%) experienced 194 CLABSI events during 223,493 days of HPN exposure, for an overall CLABSI rate of 0.87 episodes/1,000 parenteral nutrition-days. Although the majority of patients were female (59%), adult (87%), white (75%), and with private insurance or Medicare (69%), CLABSI episodes per 1,000 parenteral nutrition-days were higher for men (0.69 vs 0.38), children (1.17 vs 0.35), blacks (0.91 vs 0.41), and Medicaid recipients (1.0 vs 0.38 or 0.39). Patients with implanted ports or double-lumen catheters also had more CLABSIs than those with peripherally inserted or central catheters or single-lumen catheters. Staphylococci were the most commonly reported pathogens. These data support findings of smaller studies about CLABSI risk for children and by catheter type and identify new potential risk factors, including gender, race, and insurance type. CONCLUSIONS: Additional studies are needed to determine effective interventions that will reduce HPN-associated CLABSI.

Cognitive Health Assessment and Establishment of a Virtual Cohort of Dementia Caregivers.

BACKGROUND: Many factors impact caregivers' cognitive health and, by extension, their ability to provide care. This study examined the relationship between psychosocial factors and cognitive performance among dementia caregivers and established a virtual cohort of caregivers for future research. METHODS: Data on 527 caregivers were collected via a Web-based survey that assessed cognitive performance. Caregiver data were compared to corresponding data from 527 age-, race-, gender-, and education-matched controls from a normative database. Caregiver self-reported sleep, stress, health, and social support were also assessed. RESULTS: Caregivers performed significantly worse than controls on 3 of 5 cognitive subtests. Stress, sleep, perceived support, self-rated health, years of caregiving, race, and gender were significant predictors of cognitive performance. CONCLUSION: In this sample of dementia caregivers, psychosocial factors interacted in complex ways to impact cognitive performance. Further investigation is needed to better understand how these factors affect cognitive performance among caregivers. This could be accomplished by the establishment of a virtual cohort that facilitates the development of digital tools to support the evaluation and management of caregiver needs in a manner that helps them remain effective in their caregiving roles.

From battlefield to home: a mobile platform for assessing brain health.

Cognitive testing batteries have been used for decades to diagnose deficits associated with conditions such as head injury, age-related cognitive decline, and stroke, and they have also been used extensively for educational evaluation and planning. Cognitive testing is generally office-based, administered by professionals, uses paper and pencil testing modalities, reports results as summary scores, and is a "one shot deal" whose primary objective is to identify the presence and severity of cognitive deficit. This paper explores innovative departures from historical cognitive testing strategies and paradigms. The report explores (I) a shift from disease diagnosis in the office setting to mobile tracking of cognitive health and wellness in any setting; (II) the strength of computer-based cognitive measures and their role in facilitating development of new computational methods; and (III) using cognitive testing to inform on individual-level outcomes over time rather than dichotomous metrics at a single point in time.

Characteristics of a Cohort of Home Parenteral Nutrition Patients at the Time of Enrollment in the Sustain Registry.

BACKGROUND: Home parenteral nutrition (HPN) is a vital lifesaving therapy for patients who are unable to maintain weight, fluid balance, nutrition, and functional status via oral or enteral nutrition alone. There are few current data sources describing HPN prevalence, patient demographics, or long-term outcomes in the United States. OBJECTIVE: To describe demographics and baseline characteristics of patients receiving HPN therapy. METHODS: This is a descriptive analysis of data from the first cohort of HPN patients at time of enrollment in the SustainTM Registry between August 2011 and February 2014. RESULTS: There were 1251 patients enrolled from 29 sites. Eighty-five percent of patients were adults, with a mean age of 51.3 ± 15.3 years. Fifteen percent were pediatric, with a mean age of 4.9 ± 4.9 years. For both age groups, short-bowel syndrome was the most frequently reported HPN indication (24%). Adults most commonly had a peripherally inserted central catheter (47%) or a tunneled catheter (43%) for HPN administration. In contrast, most pediatric patients (72%) had a tunneled catheter. Most patients received parenteral nutrition daily and consumed some oral nutrition. Twenty-eight percent of all patients were expected to require HPN indefinitely. CONCLUSIONS: This is the first report of descriptive data from the Sustain Registry. The data reveal important characteristics of patients receiving HPN in 29 U.S. sites.

Provider behavior and treatment intensification in diabetes care.

OBJECTIVES: To review the literature relating to treatment intensification in diabetes care and provider traits. STUDY DESIGN: Literature review and synthesis. METHODS: A literature search was conducted using PubMed and Google Scholar for papers published in or after 2000 that examined treatment intensification in diabetes care. Results from the searches were combined with a conventional Google search and a supplemental review of papers that were identified from reference lists of identified studies. RESULTS: The majority of papers that were identified used administrative data to assess treatment intensification, and these showed that individuals with diabetes and elevated glucose frequently do not receive timely changes in therapy in response to hyperglycemia. Relatively few reports address provider and practice characteristics associated with these treatment decisions. Many of the studies focusing on the relationship between provider traits and treatment intensification are based on small studies in a limited number of practices. Factors such as practice size, location, or experience in treating patients with diabetes were often not addressed in the literature despite their potentially far-reaching impact on treatment. CONCLUSIONS: Our literature search on treatment intensification in diabetes care shows that the majority of papers using administrative data to assess treatment intensification suggest that care is often discordant with recommended guidelines. However, there is a dearth of literature based on large databases examining physician and practice traits related to this discordance. Better understanding physician behavior and practice traits associated with treatment intensification may permit greater targeting of interventions aimed at improving care.

Malnutrition diagnoses in hospitalized patients: United States, 2010.

Malnutrition is common among hospitalized patients in the United States, and its coded prevalence is increasing. Malnutrition is known to be associated with increased morbidity, mortality and healthcare costs. Although national data indicate that the number of malnutrition diagnoses among hospital discharges has been steadily rising, an in-depth examination of the demographic and clinical characteristics of these patients has not been conducted. We examined data from the 2010 Healthcare Cost and Utilization Project (HCUP), the most recent nationally-representative data describing U.S. hospital discharges. Using ICD-9 codes, we constructed a composite variable indicating a diagnosis of malnutrition. Based on our definition, 3.2% of all U.S. hospital discharges in 2010 had this diagnosis. Relative to patients without a malnutrition diagnosis, those with the diagnosis were older, had longer lengths of stay and incurred higher costs. These patients were more likely to have 27 of 29 comorbidities assessed in HCUP. Finally, discharge to home care was twice as common among malnourished patients, and a discharge of death was more than 5 times as common among patients with a malnutrition diagnosis. Taken together, these nationally representative, cross-sectional data indicate that hospitalized patients discharged with a diagnosis of malnutrition are older and sicker and their inpatient care is more expensive than their counterparts without this diagnosis.

Diabetes and risk of hospitalized fall injury among older adults.

OBJECTIVE: To determine whether older adults with diabetes are at increased risk of an injurious fall requiring hospitalization. RESEARCH DESIGN AND METHODS: The longitudinal Health, Aging, and Body Composition Study included 3,075 adults aged 70-79 years at baseline. Hospitalizations that included ICD-9-Clinical Modification codes for a fall and an injury were identified. The effect of diabetes with and without insulin use on the rate of first fall-related injury hospitalization was assessed using proportional hazards models. RESULTS: At baseline, 719 participants had diabetes, and 117 of them were using insulin. Of the 293 participants who were hospitalized for a fall-related injury, 71 had diabetes, and 16 were using insulin. Diabetes was associated with a higher rate of injurious fall requiring hospitalization (hazard ratio [HR] 1.48 [95% CI 1.12-1.95]) in models adjusted for age, race, sex, BMI, and education. In those participants using insulin, compared with participants without diabetes, the HR was 3.00 (1.78-5.07). Additional adjustment for potential intermediaries, such as fainting in the past year, standing balance score, cystatin C level, and number of prescription medications, accounted for some of the increased risk associated with diabetes (1.41 [1.05-1.88]) and insulin-treated diabetes (2.24 [1.24-4.03]). Among participants with diabetes, a history of falling, poor standing balance score, and A1C level ≥8% were risk factors for an injurious fall requiring hospitalization. CONCLUSIONS: Older adults with diabetes, in particular those using insulin, are at greater risk of an injurious fall requiring hospitalization than those without diabetes. Among those with diabetes, poor glycemic control may increase the risk of an injurious fall.