An analysis of the resource use and costs of febrile neutropenia events in pediatric cancer patients in Australia.

BACKGROUND: Febrile neutropenia (FN) in children with cancer generally requires in-hospital care, but low-risk patients may be successfully managed in an outpatient setting, potentially reducing the overall healthcare costs. Updated data on the costs of FN care are lacking. METHODS: A bottom-up microcosting analysis was conducted from the healthcare system perspective using data collected alongside the Australian PICNICC (Predicting Infectious Complications of Neutropenic sepsis In Children with Cancer) study. Inpatient costs were accessed from hospital administrative records and outpatient costs from Medicare data. Costs were stratified by risk status (low/high risk) according to the PICNICC criteria. Estimated mean costs were obtained through bootstrapping and using a linear model to account for multiple events across individuals and other clinical factors that may impact costs. RESULTS: The total costs of FN care were significantly higher for FN events classified as high-risk ($17,827, 95% confidence interval [CI]: $17,193-$18,461) compared to low-risk ($10,574, 95% CI: $9818-$11,330). In-hospital costs were significantly higher for high-risk compared to low-risk events, despite no differences in the cost structure, mean cost per day, and pattern of resource use. Hospital length of stay (LOS) was the only modifiable factor significantly associated with total costs of care. Excluding antineoplastics, antimicrobials are the most commonly used medications in the inpatient and outpatient setting for the overall period of analysis. CONCLUSION: The FN costs are driven by in-hospital admission and LOS. This suggests that the outpatient management of low-risk patients is likely to reduce the in-hospital cost of treating an FN event. Further research will determine if shifting the cost to the outpatient setting remains cost-effective overall.

Clinical practice guideline for the prevention of oral and oropharyngeal mucositis in pediatric cancer and hematopoietic stem cell transplant patients: 2021 update.

PURPOSE: To update the 2015 clinical practice guideline for the prevention of oral mucositis in pediatric cancer or hematopoietic stem cell transplant (HSCT) patients. METHODS: We performed seven systematic reviews of mucositis prevention. Three reviews included randomized controlled trials (RCTs) conducted in pediatric and adult patients evaluating cryotherapy, keratinocyte growth factor (KGF) or photobiomodulation therapy with a focus on efficacy. Three reviews included studies of any design conducted in pediatric patients evaluating these same interventions with a focus on adverse events and feasibility. One review included all RCTs of any intervention for mucositis prevention in pediatric patients. Primary outcome was severe oral mucositis. RESULTS: We included 107 unique studies of cryotherapy (22 RCTs and 4 pediatric studies); KGF (15 RCTs and 12 pediatric studies); photobiomodulation therapy (29 RCTs and 8 pediatric studies) and any intervention (31 pediatric RCTs). Effects on severe mucositis reduction from RCTs were cryotherapy risk ratio (RR) 0.49 and 95% confidence interval (CI) 0.31-0.76; palifermin RR 0.81 and 95% CI 0.69-0.95 and photobiomodulation therapy RR 0.40 and 95% CI 0.27-0.60. Cryotherapy was not feasible in young children while photobiomodulation therapy was feasible across age groups. Palifermin was associated with adverse effects. CONCLUSIONS: Cryotherapy should be used for older cooperative pediatric patients who will receive short infusions of melphalan or 5-fluorouracil. Intraoral photobiomodulation therapy (620-750 nm spectrum) should be used in pediatric patients undergoing autologous or allogeneic HSCT and for pediatric head and neck carcinoma patients undergoing radiotherapy. Palifermin should not be used routinely in pediatric cancer or HSCT patients.

Uniting Public Health and Primary Care for Healthy Communities in the COVID-19 Era and Beyond.

The Coronavirus disease 2019 (COVID-19) pandemic has laid bare the dis-integrated health care system in the United States. Decades of inattention and dwindling support for public health, coupled with declining access to primary care medical services have left many vulnerable communities without adequate COVID-19 response and recovery capacity. "Health is a Community Affair" is a 1966 effort to build and deploy local communities of solution that align public health, primary care, and community organizations to identify health care problem sheds, and activate local asset sheds. After decades of independent effort, the COVID-19 pandemic offers an opportunity to reunite and align the shared goals of public health and primary care. Imagine how different things might look if we had widely implemented the recommendations from the 1966 report? The ideas and concepts laid out in "Health is a Community Affair" still offer a COVID-19 response and recovery approach. By bringing public health and primary care together in community now, a future that includes a shared vision and combined effort may emerge.

Research priorities for young people with cancer: a UK priority setting partnership with the James Lind Alliance.

OBJECTIVES: To conduct a UK-wide survey of young people who have experienced cancer, carers and professionals, to identify and prioritise research questions to inform decisions of research funders and support the case for research with this unique cancer population. DESIGN: James Lind Alliance Priority Setting Partnership. SETTING: UK health service and community. METHODS: A steering group oversaw the initiative and partner organisations were recruited. Unanswered questions were collected in an online survey. Evidence searching verified uncertainties. An interim survey was used to rank questions prior to a final prioritisation workshop. PARTICIPANTS: Young people aged 13-24 years with a current or previous cancer diagnosis, their families, friends, partners and professionals who work with this population. RESULTS: Two hundred and ninety-two respondents submitted 855 potential questions. Following a refining process and removal of 'out of scope' questions, 208 unique questions remained. Systematic evidence checking identified seven answered questions and 16 were the subject of ongoing studies. The interim survey was completed by 174 participants. The top 30 questions were prioritised at a workshop attended by 25 young people, parents and multidisciplinary professionals. The top three priorities are: (1) What psychological support package improves psychological well-being, social functioning and mental health during and after treatment? (2) What interventions, including self-care, can reduce or reverse adverse short-term and long-term effects of cancer treatment? (3) What are the best strategies to improve access to clinical trials? The remaining questions reflect the complete cancer pathway: new therapies, life after cancer, support, education/employment, relapse and end-of-life care. CONCLUSIONS: We have identified shared research priorities for young people with cancer using a rigorous, person-centred approach involving stakeholders typically not involved in setting the research agenda. The breadth of priorities suggest future research should focus on holistic and psychosocial care delivery as well as traditional drug/biology research.

Residency Program Characteristics and Individual Physician Practice Characteristics Associated With Family Physician Scope of Practice.

PURPOSE: A family physician's ability to provide continuous, comprehensive care begins in residency. Previous studies show that patterns developed during residency may be imprinted upon physicians, guiding future practice. The objective was to determine family medicine residency characteristics associated with graduates' scope of practice (SCoP). METHOD: The authors used (1) residency program data from the 2012 Accreditation Council for Graduate Medicine Education Accreditation Data System and (2) self-reported data supplied by family physicians when they registered for the first recertification examination with the American Board of Family Medicine (2013-2016)-7 to 10 years after completing residency. The authors used linear regression analyses to examine the relationship between individual physician SCoP (measured by the SCoP for primary care [SP4PC] score [scale of 0-30; low = small scope]) and individual, practice, and residency program characteristics. RESULTS: The authors sampled 8,261 physicians from 423 residencies. The average SP4PC score was 15.4 (standard deviation, 3.2). Models showed that SCoP broadened with increasing rurality. Physicians from unopposed (single) programs had higher SCoP (0.26 increase in SP4PC); those from major teaching hospitals had lower SCoP (0.18 decrease in SP4PC). CONCLUSIONS: Residency program characteristics may influence family physicians' SCoP, although less than individual characteristics do. Broad SCoP may imply more comprehensive care, which is the foundation of a strong primary care system to increase quality, decrease cost, and reduce physician burnout. Some residency program characteristics can be altered so that programs graduate physicians with broader SCoP, thereby meeting patient needs and improving the health system.

Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR study.

The DiscovEHR collaboration between the Regeneron Genetics Center and Geisinger Health System couples high-throughput sequencing to an integrated health care system using longitudinal electronic health records (EHRs). We sequenced the exomes of 50,726 adult participants in the DiscovEHR study to identify ~4.2 million rare single-nucleotide variants and insertion/deletion events, of which ~176,000 are predicted to result in a loss of gene function. Linking these data to EHR-derived clinical phenotypes, we find clinical associations supporting therapeutic targets, including genes encoding drug targets for lipid lowering, and identify previously unidentified rare alleles associated with lipid levels and other blood level traits. About 3.5% of individuals harbor deleterious variants in 76 clinically actionable genes. The DiscovEHR data set provides a blueprint for large-scale precision medicine initiatives and genomics-guided therapeutic discovery.

Development of a Drinkable, Peanut-Based Dietary Supplement and Comparison of Its Nutritional and Microbiological Qualities with Commercial Products.

This study was undertaken to formulate, using peanuts as a major ingredient, a beverage which will benefit older adults who are at a high risk of protein-energy malnutrition and other health complications, and to compare its nutritional and microbiological qualities to commercial products. Peanuts, rice flour, and flaxseed meal in a ratio of 48.0:49.8:2.2 were mixed with water (20% solids) and cooked into gruel which was sequentially treated with BAN(®) , (480 KNU-B/g, 75 °C 1 h), Alcalase(®) (2.4 AU-A/g, 60 °C 1 h), and Flavourzyme(®) (1000 LAPU/g, 55 °C 1 h) to predigest starch and protein, respectively. The degree of hydrolysis and product viscosity during hydrolysis was measured. The nutritional and microbiological qualities of the product were compared to 10 commercial products. Results indicate that 60% of starch was hydrolyzed while a total of 1.62% protein hydrolysis was observed. Product viscosity reduced from 228.55 to 3.60 cP at the end of hydrolysis. The formulation had no cholesterol and low sodium which was a functional property that was absent in the commercial products. Results of this study suggest that the formulation can be further optimized into a unique product that could cater for the protein needs and other nutritional requirements of older adults.

Nutritional support in children and young people with cancer undergoing chemotherapy.

BACKGROUND: It is well documented that malnutrition is a common complication of paediatric malignancy and its treatment. Malnutrition can often be a consequence of cancer itself or a result of chemotherapy. Nutritional support aims to reverse malnutrition seen at diagnosis, prevent malnutrition associated with treatment and promote weight gain and growth. The most effective and safe forms of nutritional support in children and young people with cancer are not known. OBJECTIVES: To determine the effects of any form of parenteral (PN) or enteral (EN) nutritional support, excluding vitamin supplementation and micronutrient supplementation, in children and young people with cancer undergoing chemotherapy and to determine the effect of the nutritional content of PN and EN. This is an update of a previous Cochrane review. SEARCH METHODS: We searched the following databases for the initial review: CENTRAL (The Cochrane Library, Issue 2, 2009), MEDLINE (1950 to 2006), EMBASE (1974 to 2006), CINAHL (1982 to 2006), the National Research Register (2007) and Dissertations & Theses (2007). Experts in the field were also contacted for information on relevant trials. For this update, we searched the same electronic databases from 2006 to September 2013. We also scrutinised the reference lists of included articles to identify additional trials. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing any form of nutritional support with another, or control, in children or young people with cancer undergoing chemotherapy. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials. At least two authors independently assessed quality and extracted data. We contacted trialists for missing information. MAIN RESULTS: The current review included the eight trials from the initial review and six new trials which randomised 595 participants (< 21 years of age) with leukaemias or solid tumours undergoing chemotherapy. The trials were all of low quality with the exception of two of the trials looking at glutamine supplementation. One small trial found that compared to EN, PN significantly increased weight (mean difference (MD) 4.12, 95% CI 1.91 to 6.33), serum albumin levels (MD 0.70, 95% CI 0.14 to 1.26), calorie intake (MD 22.00, 95% CI 5.12 to 38.88) and protein intake (MD 0.80, 95% CI 0.45 to 1.15). One trial comparing peripheral PN and EN with central PN found that mean daily weight gain (MD -27.00, 95% CI -43.32 to -10.68) and energy intake (MD -15.00, 95% CI -26.81 to -3.19) were significantly less for the peripheral PN and EN group, whereas mean change in serum albumin was significantly greater for that group (MD 0.47, 95% CI 0.13 to 0.81, P = 0.008). Another trial with few participants found an increase in mean energy intake (% recommended daily amount) in children fed an energy dense feed compared to a standard calorie feed (MD +28%, 95% CI 17% to 39%). Three studies looked at glutamine supplementation. The evidence suggesting that glutamine reduces severity of mucositis was not statistically significant in two studies (RR 0.64, 95% CI 0.19 to 2.2 and RR 0.85, 95% CI 0.66 to 1.1) and differences in reduction of infection rates were also not significant in two studies (RR 1.0, 95% CI 0.72 to 1.4 and RR 0.98, 95% CI 0.63 to 1.51). Only one study compared olive oil based PN to standard lipid containing PN. Despite similar calorie contents in both feeds, the standard lipid formula lead to greater weight gain (MD -0.34 z-scores, 95% CI -0.68 to 0.00). A single study compared standard EN with fructooligosaccharide containing EN. There was no difference in weight gain between groups (mean difference -0.12, 95% CI -0.57 to 0.33), with adverse effects (nausea) occurring equally between the groups (RR 0.92, 95% CI 0.48 to 1.74). AUTHORS' CONCLUSIONS: There is limited evidence from individual trials to suggest that PN is more effective than EN in well-nourished children and young people with cancer undergoing chemotherapy. The evidence for other methods of nutritional support remains unclear. Limited evidence suggests an energy dense feed increases mean daily energy intake and has a positive effect on weight gain. Evidence suggesting glutamine supplementation reduces incidence and severity of mucositis, infection rates and length of hospital stay is not statistically significant. Further research, incorporating larger sample sizes and rigorous methodology utilising valid and reliable outcome measures, is essential.

The use of nutrient-optimizing/cost-minimizing software to develop ready-to-use therapeutic foods for malnourished pregnant women in Mali.

Malnutrition affects people of all ages in many countries in the developing world. One treatment for malnutrition is the intervention involving ready-to-use therapeutic foods (RUTFs). This study developed RUTFs for pregnant women in Mali using formulation computer software and largely local, plant-based ingredients. Mali has the world's second highest birth rate and infant mortality rate. Nutrient profiles of possible ingredients and their prices from 2004 to 2009 were entered into the software. Computer-selected ingredients included peanuts, cowpeas, and millet as well as rice or barley koji (sources of α-amylase and ingredients). Components of the six selected formulations were milled, hydrolyzed with koji α-amylase, and heated at 121°C for 15 min. The contents of protein, fat, ash, fiber, carbohydrates, amino acid, and energy of dehydrated products were determined and compared with software-predicted values. Actual and predicted values were comparable: the protein content was 1.45-2.04% higher, and ash content was 0.60-0.89% higher than the predicted values, while the fat content was 0.18-0.88% lower, the lysine content was 0.17-0.25% lower, and fiber content was 0.16% lower to 2.06% higher than the predicted values. The difference in actual and predicted energy levels were 14.8-22.2%. The amount of RUTF needed to meet the requirement of most limiting nutrients, lysine and energy, ranged from 2620 to 3002 g. The costs for producing the RUTFs were substantially lower than importing commercial RUTFs even with increased ingredient prices in Mali from 2004 to 2009.

Current and Future Treatment of Hypertension in the SPRINT Era.

Based on the SPRINT trial, it is highly likely that new SPRINT-era guidelines will establish a blood pressure (BP) goal of < 130/80 mm Hg for those aged 50 or older who are at high risk for a cardiovascular event. In this group, SPRINT demonstrated that assignment to an intensive-treatment systolic BP (SBP) goal of < 120 mm Hg significantly reduced cardiovascular events and mortality compared to those assigned to a standard-treatment SPB goal of < 140 mm Hg. This review critically assesses current hypertension guidelines and presents predictions for SPRINT-era guidelines in the elderly, African Americans, and patients with uncomplicated essential hypertension, diabetes, chronic kidney disease, cardiovascular disease, and coronary artery disease. Specific attention is paid to BP goals and preferred pharmacological antihypertensive therapy in these populations, and an algorithm that incorporates the SPRINT trial results is presented. Inhibitors of the renin-angiotensin-aldosterone system as well as calcium channel blockers are universally accepted as first-line therapy in uncomplicated hypertension, but controversy exists over the role of thiazide diuretics and beta blockers. This review also discusses a physiologically and outcomes-based approach to combination therapy for treatment of hypertension.

Proximity of providers: Colocating behavioral health and primary care and the prospects for an integrated workforce.

Integrated behavioral health and primary care is emerging as a superior means by which to address the needs of the whole person, but we know neither the extent nor the distribution of integration. Using the Centers for Medicare and Medicaid Services' National Plan and Provider Enumeration System (NPPES) Downloadable File, this study reports where colocation exists for (a) primary care providers and any behavioral health provider and (b) primary care providers and psychologists specifically. The NPPES database offers new insights into where opportunities are limited for integration due to workforce shortages or nonproximity of providers and where possibilities exist for colocation, a prerequisite for integration.

Most family physicians work routinely with nurse practitioners, physician assistants, or certified nurse midwives.

The U.S. physician workforce is struggling to keep pace with the demand for health care services, a situation that may worsen without efforts to enhance team-based care. More than half of family physicians work with nurse practitioners, physician assistants, or certified nurse midwives, and doing so helps ensure access to health care services, particularly in rural areas.

The primary care extension program: a catalyst for change.

The Affordable Care Act authorized, but did not fund, the Primary Care Extension Program (PCEP). Much like the Cooperative Extension Program of the US Department of Agriculture sped the modernization of farming a century ago, the PCEP could speed the transformation of primary care. It could also help achieve other goals such as integrating primary care with public health and translating research into practice. The urgency of these goals and their importance to achieving the Triple Aim for health care should increase interest in rapidly building the PCEP, much as the need to feed the country did a century ago.

Integrating community health centers into organized delivery systems can improve access to subspecialty care.

The Affordable Care Act is funding the expansion of community health centers to increase access to primary care, but this approach will not ensure effective access to subspecialty services. To address this issue, we interviewed directors of twenty community health centers. Our analysis of their responses led us to identify six unique models of how community health centers access subspecialty care, which we called Tin Cup, Hospital Partnership, Buy Your Own Subspecialists, Telehealth, Teaching Community, and Integrated System. We determined that the Integrated System model appears to provide the most comprehensive and cohesive access to subspecialty care. Because Medicaid accountable care organizations encourage integrated delivery of care, they offer a promising policy solution to improve the integration of community health centers into "medical neighborhoods."

Antibacterial activities of blueberry and muscadine phenolic extracts.

Phenolics are one category of phyto-antimicrobials that refer to the antimicrobial substances extracted from plant sources. This study was undertaken to determine the influence of blueberry and muscadine phenolic extracts on the growths of 2 important foodborne bacterial pathogens, Salmonella Enteritidis and Listeria monocytogenes. Cells of S. Enteritidis (n = 4) or L. monocytogenes (n = 4) strains were inoculated (3 log CFU/mL) into tryptic soy broth (TSB) supplemented with 46.25 ppm of muscadine phenolics and 24 ppm of blueberry phenolics, respectively. The inoculated and un-inoculated broth with or without the supplemented phenolics were incubated at 37 °C for 24 h. Samples were drawn periodically, and cell populations of Salmonella and Listeria were determined on tryptic soy agar (TSA). It was observed that Salmonella was relatively more susceptible than Listeria to the phenolic extracts used in the study. The growth of Salmonella was significantly inhibited in all samples at all sampling points except for the sample that was supplemented with muscadine water extract and drawn at the 24-h sampling point. Blueberry phenolics were relatively more effective than muscadine phenolic extracts in inhibiting the growth of Salmonella. One tested strain of Listeria was more susceptible to ethanol than water phenolic extracts. The study revealed the potentials and limitations of using blueberry and muscadine phenolics to control the growths of selected Salmonella and Listeria strains.

The gastrointestinal tract "tastes" nutrients: evidence from the intestinal taste aversion paradigm.

To develop and use a behavioral paradigm for assessments of what nutrient properties are detected by intestinal chemoreceptors, we combined features of the "electronic esophagus" preparation (Elizalde G and Sclafani A. Physiol Behav 47: 63-77, 1990) and the conditioned taste aversion protocol (Garcia J and Koelling RA. Psychon Sci 4: 123-124, 1966). In four experiments, separate groups of food-deprived rats with gastric (experiments 1-4) or duodenal (experiment 4) catheters were infused with either carbohydrates (maltodextrin) or fats (corn oil) into their stomachs or small intestines, either while they consumed nonnutritive flavored solutions (experiments 1 and 2) or in the absence of any intake (experiments 3 and 4). For some animals, one of the macronutrient infusions was paired with lithium chloride injections shown to support conventional conditioned aversions. After training, in various oral preference test trials, animals were given opportunities to taste and consume the nonnutritive solutions that had served as oropharyngeal conditioned stimuli as well as the nutrients that had been infused intragastrically, with or without poisoning, but never sampled by mouth. As previously established, preferences for the nonnutritive flavors were enhanced by association with intragastric infusions of macronutrients, with carbohydrates producing the greater preference. On first exposure to the two macronutrients for oral consumption, animals reduced their intake of the nutrient that had been previously poisoned when it was infused into the gastrointestinal tract. These results, along with additional controls, suggest that nutrient tastes detected in the intestines can be recognized centrally based on oropharyngeal gustatory stimulation.