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BackgroundHeart failure decompensation is a major driver of hospitalizations and represents a significant burden to the health care system. Identifying those at greatest risk of admission can allow for targeted interventions to reduce this risk. ObjectiveThis paper aims to compare the predictive value of objective and subjective heart failure respiratory symptoms on imminent heart failure decompensation and subsequent hospitalization within a 30-day period. MethodsA prospective observational pilot study was conducted. People living at home with heart failure were recruited from a single-center heart failure outpatient clinic. Objective (blood pressure, heart rate, weight, B-type natriuretic peptide) and subjective (4 heart failure respiratory symptoms scored for severity on a 5-point Likert scale) data were collected twice weekly for a 30-day period. ResultsA total of 29 participants (median age 79 years; 18/29, 62% men) completed the study. During the study period, 10 of the 29 participants (34%) were hospitalized as a result of heart failure. For objective data, only heart rate exhibited a between-group difference. However, it was nonsignificant for variability (P=.71). Subjective symptom scores provided better prediction. Specifically, the highest precision of heart failure hospitalization was observed when patients with heart failure experienced severe dyspnea, orthopnea, and bendopnea on any given day (area under the curve of 0.77; sensitivity of 83%; specificity of 73%). ConclusionsThe use of subjective respiratory symptom reporting on a 5-point Likert scale may facilitate a simple and low-cost method of predicting heart failure decompensation and imminent hospitalization. Serial collection of symptom data could be augmented using ecological momentary assessment of self-reported symptoms within a mobile health monitoring strategy for patients at high risk for heart failure decompensation.

Objective: The purpose of this study was to assess the rate of spontaneous resolution of grade 1 cervical intraepithelial neoplasia in a private practice patient population.Study Design: One hundred consecutive women with biopsy-proven grade 1 cervical intraepithelial neoplasia were offered expectant management in the form of repeat Papanicolaou smears every 3 months up to 1 year or treatment. Women with inadequate colposcopic examination, positive endocervical sampling, or discordant Papanicolaou smears were excluded.Results: Eighty-nine (89%) women agreed to undergo expectant management. Of these, 67 (75.3%) experienced spontaneous resolution of lesions on the basis of 2 subsequent and consecutive normal smears corroborated by colposcopy. The median time to resolution was 9 months (n = 38). Seventeen (19.9%) women were treated at 1 year for persistent atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions by loop electrosurgical conization. Of these, 1 (1.1%) had a more advanced lesion (grade 2 cervical intraepithelial neoplasia). Four (4.5%) had progression before 1 year and were treated. Only 1 (1.1%) patient was lost to follow-up.Conclusion: Expectant management of grade 1 cervical intraepithelial neoplasia is safe and cost-effective in a reliable patient population. [ABSTRACT FROM AUTHOR]

Introduction: There is growing evidence to support the use of co-design in developing interventions across many disciplines. This scoping review aims to examine how co-design methodology has been used in the development of cardiovascular disease (CVD) secondary prevention interventions within health and community settings., Methods: We searched four academic databases for studies that used the co-design approach to develop their intervention. Studies were included if consumers (adults with CVD) and key stakeholders (e.g. clinicians, service providers) were involved in the co-design process. The review focused on methodology rather than traditional study outcomes; therefore, co-design processes and activities were extracted and evaluated against a selected co-design framework., Results: Twenty-two studies were included in this review. Studies were implemented across various settings with consumers and stakeholder groups most frequently consisting of patients and healthcare professionals, respectively. Most studies specifically stated that they used a 'co-design' approach (n = 10); others used terms such as participatory action research (n = 3), user-centred design (n = 3) and community-based participatory research (n = 2). Although there was variability in terminology, co-design processes, and participants, all studies adhered to the key principles of consumer engagement. Predominant co-design activities included semistructured interviews, focus groups, co-design/development workshops and advisory group meetings. Intervention effectiveness was assessed in eight studies showing mixed results., Conclusions: This review provides an overview of how the co-design approach has previously been used in the development of CVD secondary prevention interventions. These findings provide methodological considerations that can guide researchers and healthcare services when implementing co-design to develop feasible and acceptable interventions that can improve outcomes for CVD populations., Patient or Public Contribution: No patients, service users, caregivers, people with lived experience or members of the public were involved in this scoping review. This review article was written by academics who have undertaken a significant amount of co-design work with consumers and stakeholders., (© 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Aims: Health services worldwide face the challenge of providing care for increasingly culturally and linguistically diverse (CALD) populations. The aims of this study were to determine whether CALD patients hospitalized with acute heart failure (HF) are at increased risk of rehospitalization and emergency department (ED) visitation after discharge, compared to non-CALD patients, and within CALD patients to ascertain the impact of limited English proficiency (LEP) on outcomes., Methods and Results: A cohort of 1613 patients discharged from hospital following an episode of acute HF was derived from hospital administrative datasets. CALD status was based on both country of birth and primary spoken language. Comorbidities, HF subtype, age, sex and socioeconomic status, and hospital readmission and ED visitation incidences, were compared between groups. A Cox proportional hazard model was employed to adjust for potential confounders. The majority of patients were classified as CALD [1030 (64%)]. Of these, 488 (30%) were designated as English proficient (CALD-EP) and 542 (34%) were designated CALD-LEP. Compared to non-CALD, CALD-LEP patients exhibited a greater cumulative incidence of HF-related readmission and ED visitation, as expressed by an adjusted hazard ratio (HR) [1.27 (1.02-1.57) and 1.40 (1.18-1.67), respectively]; this difference was not significant for all-cause readmission [adjusted HR 1.03 (0.88-1.20)]. CALD-EP showed a non-significant trend towards increased rehospitalization and ED visitation., Conclusion: This study suggests that CALD patients with HF, in particular those designated as CALD-LEP, have an increased risk of HF rehospitalization and ED visitation. Further research to elucidate the underlying reasons for this disparity are warranted., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

A 'cardio-geriatric' heart failure model of care was implemented to address the high rates of readmission in elderly acute decompensated heart failure patients. Despite demonstrably intensified management in both the cardiology and geriatric domains, this study did not demonstrate a positive effect on the primary outcome of all cause readmissions at 30 days., (© 2020 Royal Australasian College of Physicians.)

Background: Acute heart failure (AHF) is a frequent reason for hospitalization worldwide and effective treatment options are limited. It is known that AHF is a condition characterized by impaired vasorelaxation, together with reduced nitric oxide (NO) bioavailability, an endogenous vasodilatory compound. Supplementation of inorganic sodium nitrate (NaNO 3 ) is an indirect dietary source of NO, through bioconversion. It is proposed that oral sodium nitrate will favorably affect levels of circulating NO precursors (nitrate and nitrite) in AHF patients, resulting in reduced systemic vascular resistance, without significant hypotension., Methods and Outcomes: We propose a single center, randomized, double-blind, placebo-controlled pilot trial, evaluating the feasibility of sodium nitrate as a treatment for AHF. The primary hypothesis that sodium nitrate treatment will result in increased systemic levels of nitric oxide pre-cursors (nitrate and nitrite) in plasma, in parallel with improved vasorelaxation, as assessed by non-invasively derived systemic vascular resistance index. Additional surrogate measures relevant to the known pathophysiology of AHF will be obtained in order to assess clinical effect on dyspnea and renal function., Discussion: The results of this study will provide evidence of the feasibility of this novel approach and will be of interest to the heart failure community. This trial may inform a larger study.

Background: The interim (12-month) results of two similarly designed, ongoing studies (the Zometa-Femara Adjuvant Synergy Trials [Z-FAST and ZO-FAST]) suggest that zoledronic acid (4 mg intravenously every 6 months) when initiated with adjuvant letrozole increases bone mineral density (BMD) of the lumbar spine (LS) in postmenopausal women with early-stage breast cancer compared with patients who receive zoledronic acid only when bone loss became clinically significant or a fragility fracture occurred., Methods: An integrated analysis was performed to maximize the value of the large pool of data from the two studies in answering clinically relevant questions. The primary objective was to compare the change in LS BMD at month 12. Secondary objectives included comparing (a) the change in total hip (TH) BMD, (b) changes in bone turnover marker concentrations, (c) time to disease recurrence, and (d) safety at month 12., Findings: The integrated analysis included 1,667 patients. At month 12, LS BMD was 5.2% higher in the upfront group than in the delayed group; TH BMD was 3.5% higher. N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 21.3% and 12.8% in the upfront group and increased by 21.7% and 24.9% in the delayed group, respectively (p < .0001 for intergroup comparisons). Fewer patients receiving upfront zoledronic acid experienced disease recurrence than patients in the delayed group-seven patients (0.84%) versus 17 patients (1.9%) (p = .0401). Fracture rates were similar. No confirmed osteonecrosis of the jaw was reported., Conclusions: The results of this analysis strengthen the statistical validity of the preliminary results of the Z-FAST and ZO-FAST studies, showing that upfront zoledronic acid prevents aromatase inhibitor-associated bone loss more effectively than delayed-start zoledronic acid in postmenopausal women with early-stage breast cancer receiving letrozole. Additionally, disease recurrence appears to be lower with upfront zoledronic acid, but further follow-up is needed to confirm these interim results.

Background: The optimal trastuzumab-based chemotherapy regimen for HER2-overexpressing, metastatic breast cancer is not known. The trastuzumab and vinorelbine or taxane (TRAVIOTA) study was a prospective, multicenter, randomized trial that was designed to compare these regimens., Methods: Eligible patients had HER2-overexpressing, metastatic breast cancer and had received no prior chemotherapy for advanced disease. Patients were randomized 1:1 to receive either trastuzumab with weekly vinorelbine therapy or weekly taxane therapy (paclitaxel or docetaxel at the investigator's choice). Originally planned for 250 patients, the study was closed because of poor accrual with 81 evaluable patients, including 41 patients who received vinorelbine and 40 patients who received taxane., Results: Response rates were 51% and 40% for the vinorelbine/trastuzumab arm and the taxane/trastuzumab arm, respectively (Fisher exact test; P = .37). The median time to disease progression was 8.5 months and 6.0 months for the vinorelbine- and taxane-based arms, respectively (log-rank test; P = .09). Treatment with either regimen generally was well tolerated, yielding comparable rates of neurologic and gastrointestinal toxicity. Vinorelbine-based treatment was associated with more anemia and neutropenia and with 2 episodes of cardiotoxicity. Taxane-based therapy was associated with more dermatologic toxicity, myalgias, and fluid retention., Conclusions: Both vinorelbine/trastuzumab and taxane/trastuzumab treatments were active as first-line therapy for HER2-positive, metastatic breast cancer and had comparable rates of efficacy and tolerability. The toxicities observed were the result of recognized side effects associated with each of the chemotherapy agents and schedules. These data can inform treatment decision making in this clinical setting.

Purpose: In order to evaluate the feasibility of dose-dense docetaxel followed by dose-dense AC (doxorubicin/cyclophosphamide) as adjuvant chemotherapy for operable breast cancer, we conducted a phase II study., Patients and Methods: In cohort 1, 28 patients received docetaxel 100 mg/m2 followed by doxorubicin 60 mg/m2 with cyclophosphamide 600 mg/m2, each every 2 weeks for 4 weeks (total of 8 cycles). Enrollment was discontinued because of stopping criteria based on significant toxicity (grade 4 hematologic toxicity or grade >or= 3 nonhematologic toxicity). In cohort 2, the docetaxel dose was reduced to 75 mg/m2; enrollment was discontinued after 18 patients., Results: Significant toxicity occurred in 79% and 72% of patients in cohorts 1 and 2, respectively, resulting in treatment delays in 50% and 17% of patients, respectively. The most common grade 4 hematologic toxicity was neutropenia, which occurred in 7% and 42% of cohort 1 patients during docetaxel and AC, respectively, and in none and 19% of cohort 2 patients, respectively. The most common grade >or= 3 nonhematologic toxicity was palmar-plantar erythrodysesthesia, which occurred in 25% and none of cohort 1 patients during docetaxel and AC, respectively. With docetaxel 75 mg/m2 and patient education encouraging routine use of topical strategies, grade 3 palmar-plantar erythrodysesthesia occurred in only 11% of cohort 2 patients. Grade 2 nail changes were also debilitating and occurred in 33% of cohort 1 patients during AC., Conclusion: These phase II findings suggest that dose-dense docetaxel 100 mg/m2 followed by AC is not feasible and, until more studies are conducted, should be restricted to clinical studies.

Purpose: Trastuzumab-based therapy improves survival for women with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. We conducted a multicenter phase II study to evaluate the efficacy and safety of trastuzumab combined with vinorelbine, and to assess cardiac surveillance algorithms and tumor markers as prognostic tools., Patients and Methods: Patients with HER2-positive (immunohistochemistry [IHC] 3+-positive or fluorescence in situ hybridization [FISH]-positive) metastatic breast cancer received first-line chemotherapy with trastuzumab and vinorelbine to determine response rate. Eligibility criteria were measurable disease and baseline ejection fraction >or= 50%. Serial testing for HER2 extracellular domain (ECD) was performed., Results: Fifty-four women from 17 participating centers were entered onto the study. The overall response rate was 68% (95% confidence interval, 54% to 80%). Response rates were not affected by method of HER2 status determination (FISH v IHC) or by prior adjuvant chemotherapy. Median time to treatment failure was 5.6 months; 38% of patients were progression free after 1 year. Concurrent therapy was quite feasible with maintained dose-intensity. Patients received both chemotherapy and trastuzumab on 90% of scheduled treatment dates. Two patients experienced cardiotoxicity in excess of grade 1; one patient experienced symptomatic heart failure. A surveillance algorithm of screening left ventricular ejection fraction (LVEF) at 16 weeks successfully identified women at risk for experiencing cardiotoxicity. Other acute and chronic side effects were tolerable. Lack of decline in HER2 ECD during cycle 1 predicted tumor progression., Conclusion: Trastuzumab and vinorelbine constitute effective and well-tolerated first-line treatment for HER2-positive metastatic breast cancer. Patients with normal LVEF can be observed with surveillance of LVEF at 16 weeks to identify those at risk for cardiotoxicity.

Random-source dogs (n = 100) in Virginia and North Carolina were surveyed for the microfilariae of Dirofilaria immitis. Microscopic examination of fresh thin-films and modified Knott preparations were made. Dirofilaria immitis and Dipetalonema reconditum were found in 19% and 6% of the animals, respectively. There was no animal that harbored both species. Prevalence was significantly higher in North Carolina (28.6%) than in Virginia (13.6%) (P less than 0.025). Mean PCV was significantly lower (P less than 0.005) in infected vs noninfected animals.

The subcutaneous injection of 5 to 6 mg/kg of body weight of N-nitroso-N-methylurethane (NNNMU) has been reported to cause acute alveolar injury in animals. To determine the permeability characteristics of the alveolar epithelium, we employed the in vivo saline-filled dog lung model and determined the time to 50 percent equilibration in minutes of a specific tracer in the blood and the lung model and determined the time to 50 percent equilibration in minutes of a specific tracer in the blood and the lung liquid (T 1/2) for endogenous serum albumin (MW 69,000 daltons, molecular radius 35 A) and exogenously administered 500,000 MW polydispersed dextrans (molecular radius 200 A). Compared to control animals, T1/2 decreased (permeability increased) in NNNMU-injected dogs from 3,500 +/- 100 to 682 +/- 160 minutes for albumin and from 20,000 +/- 250 to 2,790 +/- 750 minutes for 500,000 MW dextran (P less than 0.001). To determine the permeability characteristics of the pulmonary microvasculature, we employed the right lymph duct cannulation dog model and measured lymph flow/30 minutes, lymph albumin and dextran concentration, and lymph/plasma albumin and dextran ratios in control and NNNMU-injected dogs. Compared to control animals, lymph flow was significantly greater in NNNMU dogs, 2.07 +/- 1.1 vs .71 +/- .50 ml/30 minutes (P less than 0.01), respectively. We conclude that NNNMU injection increases permeability in both the alveolar epithelium and the pulmonary microvasculature.

We describe a patient with biopsy-proven pulmonary talc granulomas (secondary to the long-term intravenous injection of crushed tablets of pentazocine) who had two episodes of transient pulmonary hypertension following the injection of this oral medication. We established a canine model and measured the right lymph duct flow, mean pulmonary arterial pressures, and pulmonary vascular resistance to determine the short-term effects on hemodynamics and the flow of lymph after intravenous administration of crushed pentazocine tablets (3 to 4 mg/kg of body weight) or pure talc (2.5 to 3 mg/kg). A typical response to both agents consisted of short-term elevations of mean pulmonary arterial pressure and pulmonary vascular resistance to approximately twice baseline values, with a slow decrement over 30 to 45 minutes. The average flow of lymph tripled, peaking at approximately two hours after injection. The lymph contained high levels of albumin. We concluded that the talc filler in oral tablets of pentazocine induces the pulmonary hypertension, probably by mechanical obstruction of the pulmonary vasculature. Association with this transient pulmonary hypertension is an increase in the permeability of the pulmonary microvasculature.

We studied anesthetized dogs with right lymph duct (RLD) preparations and measured lymph flow, albumin concentrations in lymph (L) and plasma (P), pulmonary artery pressure (PAP), and pulmonary capillary wedge pressure (PCWP). Intravenous (iv) injection of ethchlorvynol (15-25 mg/kg) was followed by significant (p less than 0.02) increases in right lymph duct flow from 0.9 +/- 0.3 to 5.4 +/- 1.6 ml/h with stable PAP, PCWP, and L/P albumin (0.8 +/- 0.05 and 0.9 +/- 0.1). Similar results in RLD flow were obtained in dogs given 1) diphenhydramine, 3 mg/kg iv loading dose and 1.5 mg.kg-1 .h -1 infusion; 2) indomethacin, 4 gm/kg iv loading dose and 4 mg.kg-1h-1 infusion; 3) methylprednisolone, 30 mg/kg iv; 4) cyclophosphamide (40 mg/kg iv) to induce leukopenia (900 WBC/mm3) prior to ethchlorvynol injection. Cardiac lymph flow increased also and cardiac L/P albumin remained stable. Total hemolytic complement remained normal. We conclude that lung vascular permeability is increased following ethchlorvynol injection. Ethchlorvynol may have a direct effect on lung vascular permeability since, unlike other experimental models, complement activation, leukocytes, prostaglandins, and histamine play insignificant roles. A "final common pathway" may not exist for all forms of increased permeability pulmonary edema.

Employing a modification of the in vivo model of a liquid-filled canine lung, we measured the movement of substances of specific sizes (albumin, 69,000 daltons with a molecular radius of 35 A; and dextran with a molecular weight of 150,000 to 170,000 and an approximate molecular radius of 100 A) from the pulmonary capillary blood to the liquid-filled lung. A solution with a specific pH (1.5 to 4.5) was instilled into the left lung of the animals at a dosage of 3 to 5 ml/kg of body weight. For both albumin and dextran with a molecular weight of 150,000 to 170,000, the time for 50 percent equilibration between the specific substance in the blood and the same substance in the pulmonary liquid decreased significantly with instillation of pulmonary liquid with a pH of 1.5 and 2.5 but did not with a pH of 3.5 or above (P less than 0.05). In addition, since histamine has been implicated as a possible humoral mediator leading to increased permeability of alveolar membranes, the levels of histamine were measured in pulmonary liquids and blood in all groups. Levels of histamine in the pulmonary liquid (but not blood) were significantly higher in animals with instillation of liquids with a pH of 1.5 and 2.5 compared to all other groups.

Using the in vivo, liquid-filled dog lung model, we found that aspriation of acid with a pH of 2.5 or less led to increased alveolar epithelial permeability for albumin (molecular weight, 69,000 daltons; molecular radius, 35 a) and exogenously administered, polydispersed dextrans (molecular weight, 150,000 to 170,000 daltons: approximately molecular radius, 100 a). This increased permeability occurred with a large-volume (3 to 5 ml/kg) or small-volume (1 to 1.5 ml/kg) aspirate and with acid nebulization (1 to 1.5 ml/kg). When animals were either pretreated (30 min before aspiration) or post-treated (30 min after aspiration) with 30 mg of methylprednisolone/kg of body weight, there was no improvement in the increased permeability associated with acid aspiration. We conclude that, acutely, steroids have no effect on the increased alveolar epithelial permeability associated with acid aspiration.