Depletion of a putatively druggable class of phosphatidylinositol kinases inhibits growth of p53-null tumors.

Here, we show that a subset of breast cancers express high levels of the type 2 phosphatidylinositol-5-phosphate 4-kinases α and/or ß (PI5P4Kα and ß) and provide evidence that these kinases are essential for growth in the absence of p53. Knocking down PI5P4Kα and ß in a breast cancer cell line bearing an amplification of the gene encoding PI5P4K ß and deficient for p53 impaired growth on plastic and in xenografts. This growth phenotype was accompanied by enhanced levels of reactive oxygen species (ROS) leading to senescence. Mice with homozygous deletion of both TP53 and PIP4K2B were not viable, indicating a synthetic lethality for loss of these two genes. Importantly however, PIP4K2A(-/-), PIP4K2B(+/-), and TP53(-/-) mice were viable and had a dramatic reduction in tumor formation compared to TP53(-/-) littermates. These results indicate that inhibitors of PI5P4Ks could be effective in preventing or treating cancers with mutations in TP53.

Urologic Chronic Pelvic Pain Syndrome Flares: A Comprehensive, Systematic Review and Meta-Analysis of the Peer-Reviewed Flare Literature.

PURPOSE: We sought to systematically review and summarize the peer-reviewed literature on urologic chronic pelvic pain syndrome flares, including their terminology, manifestation, perceived triggers, management and prevention strategies, impact on quality of life, and insights into pathophysiologic mechanisms, as a foundation for future empirical research. MATERIALS AND METHODS: We searched 6 medical databases for articles related to any aspect of symptom exacerbations for interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. A total of 1486 abstracts and 398 full-text articles were reviewed, and data were extracted by at least 2 individuals. RESULTS: Overall, we identified 59 articles, including 36 qualitative, cross-sectional, or case-control; 15 cohort-based; and 8 experimental articles. The majority of studies described North American patients with confirmed diagnoses. "Flare" was a commonly used term, but additional terminology (eg, exacerbation) was also used. Most flares involved significant increases in pain intensity, but less data were available on flare frequency and duration. Painful, frequent, long-lasting, and unpredictable flares were highly impactful, even over and above participants' nonflare symptoms. A large number of perceived triggers (eg, diet, stress) and management/prevention strategies (eg, analgesics, thermal therapy, rest) were proposed by participants, but few had empirical support. In addition, few studies explored underlying biologic mechanisms. CONCLUSIONS: Overall, we found that flares are painful and impactful, but otherwise poorly understood in terms of manifestation (frequency and duration), triggers, treatment, prevention, and pathophysiology. These summary findings provide a foundation for future flare-related research and highlight gaps that warrant additional empirical studies.

Believing women: a qualitative exploration of provider disbelief and pain dismissal among women with interstitial cystitis/bladder pain syndrome from the MAPP research network.

INTRODUCTION AND HYPOTHESIS: Although allusions to the importance of a good physician-patient relationship are present throughout the interstitial cystitis/bladder pain syndrome (IC/BPS) literature, qualitative analysis of patients' perspectives on the clinical encounter is lacking, particularly among women who are most commonly affected by IC/BPS. Therefore, we adopted a patient-centered experiential approach to understanding female patients' perception of clinical encounters. METHODS: We re-analyzed previously collected data from a qualitative study on patient flare experiences including eight focus groups of female IC/BPS patients (n = 57, mean = 7/group). Qualitative analysis applied grounded theory to index all physician-patient interactions, then thematically coded these interactions to elucidate common experiences of clinical encounters. RESULTS: Women with IC/BPS shared common experiences of provider disbelief and pain dismissal. Discussions with participants demonstrated the extent to which these negative encounters shape patients' health care-seeking behavior, outlook, and psychosocial well-being. Appearing in more than one guise, provider disbelief and dismissal occurred as tacit insinuations, explicit statements, silence, oversimplification, and an unwillingness to listen and discuss alternative treatment. As a result, women adopted several strategies including: rotating specialists; "testing" physicians; self-advocacy; self-management; avoiding the stigma of chronic pain; crying; and opting for alternative medicine over biomedicine. CONCLUSIONS: The prevalence of provider disbelief and pain dismissal among women with IC/BPS indicates a need to improve physician-patient communication, informed by the struggles, anxieties, and gendered inequities that female patients with chronic pain experience in their diagnostic journey. Results suggest that further investigation into the power dynamics of clinical encounters might be required.

Developing an integrated nurse and physiotherapist-led bladder, bowel and pelvic health team.

A service redesign in 2019 led to the formation of an integrated team of nurses and physiotherapists working together to form a bladder, bowel and pelvic health team across two hospitals and the community in Lewisham and Greenwich NHS Trust. The last few years have had their challenges, but the team is now very successful and has won awards for the integration and achievements, particularly in the redesign of the containment product service. Integrating two professional groups has led to excellent team-work and smoother patient journeys.

Evaluation of a menu box delivery service for Australian long-day care services to improve food provision and child intake: a cluster randomised controlled trial.

OBJECTIVE: To evaluate the impact of a menu box delivery service tailored to the long-day care (LDC) setting on improving menu compliance with recommendations, children's diet quality and dietary intake while in care. DESIGN: A cluster randomised controlled trial in LDC centres randomly assigned to an intervention (menu box delivery) or comparison (menu planning training) group. The primary outcome was child food provision and dietary intake. Secondary outcomes include menu compliance and process evaluation, including acceptability, fidelity and menu cost (per child, per day). SETTING: South Australian LDC centres. PARTICIPANTS: Eight LDC centres (n 224 children) provided data. RESULTS: No differences were observed in serves/d between intervention and comparison centres, for provision (intervention, 0·9 inter-quartile range (IQR) 0·7-1·2; comparison, 0·8 IQR 0·5-1·3) or consumption (intervention, 0·5 IQR 0·2-0·8; comparison, 0·5 IQR 0·3-0·9) of vegetables. Child food provision and dietary intake were similar across both groups for all food groups (P < 0·05). At follow-up, all intervention centres met menu planning guidelines for vegetables, whereas only one comparison centre met guidelines. Intervention centre directors found the menu box delivery more acceptable than cooks. Cost of the intervention was AUD$2·34 greater than comparison centres (intervention, AUD$4·62 (95 % CI ($4·58, $4·67)); comparison, AUD$2·28 (95 % CI ($2·27, $2·30)) per child, per day). CONCLUSIONS: Menu compliance can be improved via a menu delivery service, delivering equivalent impacts on child food provision and dietary intake compared with an online training programme. Further exploration of cooks acceptability and cost is essential before scaling up to implementation.

Understanding weight status and dietary intakes among Australian school children by remoteness: a cross-sectional study.

OBJECTIVE: To determine whether primary school children's weight status and dietary behaviours vary by remoteness as defined by the Australian Modified Monash Model (MMM). DESIGN: A cross-sectional study design was used to conduct secondary analysis of baseline data from primary school students participating in a community-based childhood obesity trial. Logistic mixed models estimated associations between remoteness, measured weight status and self-reported dietary intake. SETTING: Twelve regional and rural Local Government Areas in North-East Victoria, Australia. PARTICIPANTS: Data were collected from 2456 grade 4 (approximately 9-10 years) and grade 6 (approximately 11-12 years) students. RESULTS: The final sample included students living in regional centres (17·4 %), large rural towns (25·6 %), medium rural towns (15·1 %) and small rural towns (41·9 %). Weight status did not vary by remoteness. Compared to children in regional centres, those in small rural towns were more likely to meet fruit consumption guidelines (OR: 1·75, 95 % CI (1·24, 2·47)) and had higher odds of consuming fewer takeaway meals (OR: 1·37, 95 % CI (1·08, 1·74)) and unhealthy snacks (OR = 1·58, 95 % CI (1·15, 2·16)). CONCLUSIONS: Living further from regional centres was associated with some healthier self-reported dietary behaviours. This study improves understanding of how dietary behaviours may differ across remoteness levels and highlights that public health initiatives may need to take into account heterogeneity across communities.

Effect of resistance exercise dose components for tendinopathy management: a systematic review with meta-analysis.

OBJECTIVE: To investigate potential moderating effects of resistance exercise dose components including intensity, volume and frequency, for the management of common tendinopathies. DESIGN: Systematic review with meta-analysis and meta-regressions. DATA SOURCES: Including but not limited to: MEDLINE, CINAHL, SPORTDiscus, ClinicalTrials.gov and ISRCTN Registry. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised and non-randomised controlled trials investigating resistance exercise as the dominant treatment class, reporting sufficient information regarding ≥2 components of exercise dose. RESULTS: A total of 110 studies were included in meta-analyses (148 treatment arms (TAs), 3953 participants), reporting on five tendinopathy locations (rotator cuff: 48 TAs; Achilles: 43 TAs; lateral elbow: 29 TAs; patellar: 24 TAs; gluteal: 4 TAs). Meta-regressions provided consistent evidence of greater pooled mean effect sizes for higher intensity therapies comprising additional external resistance compared with body mass only (large effect size domains: ß BodyMass: External = 0.50 (95% credible interval (CrI): 0.15 to 0.84; p=0.998); small effect size domains (ß BodyMass: External = 0.04 (95% CrI: -0.21 to 0.31; p=0.619)) when combined across tendinopathy locations or analysed separately. Greater pooled mean effect sizes were also identified for the lowest frequency (less than daily) compared with mid (daily) and high frequencies (more than once per day) for both effect size domains when combined or analysed separately (p≥0.976). Evidence for associations between training volume and pooled mean effect sizes was minimal and inconsistent. SUMMARY/CONCLUSION: Resistance exercise dose is poorly reported within tendinopathy management literature. However, this large meta-analysis identified some consistent patterns indicating greater efficacy on average with therapies prescribing higher intensities (through inclusion of additional loads) and lower frequencies, potentially creating stronger stimuli and facilitating adequate recovery.

Home versus outpatient hospital intravenous immunoglobulin infusion and health care resource utilization.

BACKGROUND: Home health care delivery is projected to increase. Intravenous immunoglobulin (IVIG) therapy has high potential to move from the outpatient hospital (OPH) setting to home delivery. OBJECTIVE: This study examined the relationship between home and OPH IVIG infusions and health care utilization. METHODS: We used a retrospective cohort study design and the Humana Research Database to identify patients with 1 or more medical or pharmacy claims for an IVIG infusion agent from January 1, 2017, to December 31, 2018. Eligible patients were enrolled in a Medicare Advantage Prescription Drug (MAPD) or commercial health plan, with at least 12 months of continuous enrollment before and after their first infusion (i.e., index date) received in the home or OPH setting. We measured the odds of experiencing an inpatient (IP) stay or emergency department (ED) visit, adjusted for baseline differences in age, sex, race, region, population density, low-income, and dual eligibility status, MAPD or commercial health plan, plan type, treatment-naïve status, home health use, RxRisk-V comorbidity burden score, and indications for IVIG use. RESULTS: A total of 208 and 1079 patients received IVIG infusions in the home and OPH setting, respectively. The odds for an IP stay (odds ratio [OR] 0.56 [95% CI 0.38-0.82]) and ED visit (OR 0.62 [95% CI 0.41-0.93]) were significantly lower in patients who received IVIG infusion in the home than patients receiving infusion in the OPH setting. CONCLUSIONS: Our findings suggest there may be value to increasing referrals for IVIG home infusion. Decreased health care utilization provides value to the system in cost savings and to patients and families owing to less disruption and improved clinical outcomes. Further study can help inform health policy designed to maximize the benefits of IVIG home infusion while minimizing potential risks.

A Systematic Review of Clinical Trials on Lumateperone and Its Effects on Body Weight.

BACKGROUND: Antipsychotic-induced weight gain (AIWG) is a clinically relevant and concerning adverse effect of contemporary antipsychotic medications. Lumateperone is a novel antipsychotic, which became commercially available in 2020 and received Food and Drug Administration approval for schizophrenia and bipolar disorder in 2019 and 2021, respectively. To date, no comprehensive review exists on its AIWG profile. This systematic review aims to assess the association between lumateperone and AIWG. METHODS: Data Sources: A comprehensive search of published studies on "lumateperone" OR "ITI-007" OR "Caplyta" was conducted on PubMed, CINAHL Complete, APA PsychInfo, Cochrane Library, and Embase databases until January 2022.Study Selection: A total of 149 articles in English were collected. After removing duplicates, all human trials on lumateperone were screened for the inclusion criteria.Data Extraction: Two reviewers conducted an independent screening followed by full-text analysis of extracted studies adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Third reviewer resolved the conflicts as tiebreaker. RESULTS: Primary search generated 77 articles, excluding 72 duplicates, of which 51 were deemed appropriate for exclusion. Full-text analysis of the remaining 26 articles concluded with 5 studies for finalized review per inclusion criteria. Excluded studies were manually reviewed for relevant citation of studies per inclusion criteria. Three randomized, double-blinded, placebo-controlled clinical trials and 2 open-label trials were derived from this systematic review. Lumateperone showed a favorable weight profile compared with placebo and alternate antipsychotics. CONCLUSIONS: Lumateperone displays minimal to no weight gain among participants in the studies reviewed.

Chelating the Alpha Therapy Radionuclides 225Ac3+ and 213Bi3+ with 18-Membered Macrocyclic Ligands Macrodipa and Py-Macrodipa.

The radionuclides 225Ac3+ and 213Bi3+ possess favorable physical properties for targeted alpha therapy (TAT), a therapeutic approach that leverages α radiation to treat cancers. A chelator that effectively binds and retains these radionuclides is required for this application. The development of ligands for this purpose, however, is challenging because the large ionic radii and charge-diffuse nature of these metal ions give rise to weaker metal-ligand interactions. In this study, we evaluated two 18-membered macrocyclic chelators, macrodipa and py-macrodipa, for their ability to complex 225Ac3+ and 213Bi3+. Their coordination chemistry with Ac3+ was probed computationally and with Bi3+ experimentally via NMR spectroscopy and X-ray crystallography. Furthermore, radiolabeling studies were conducted, revealing the efficient incorporation of both 225Ac3+ and 213Bi3+ by py-macrodipa that matches or surpasses the well-known chelators macropa and DOTA. Incubation in human serum at 37 °C showed that ∼90% of the 225Ac3+-py-macrodipa complex dissociates after 1 d. The Bi3+-py-macrodipa complex possesses remarkable kinetic inertness reflected by an EDTA transchelation challenge study, surpassing that of Bi3+-macropa. This work establishes py-macrodipa as a valuable candidate for 213Bi3+ TAT, providing further motivation for its implementation within new radiopharmaceutical agents.

Py-Macrodipa: A Janus Chelator Capable of Binding Medicinally Relevant Rare-Earth Radiometals of Disparate Sizes.

Nuclear medicine leverages different types of radiometals for disease diagnosis and treatment, but these applications usually require them to be stably chelated. Given the often-disparate chemical properties of these radionuclides, it is challenging to find a single chelator that binds all of them effectively. Toward addressing this problem, we recently reported a macrocyclic chelator macrodipa with an unprecedented "dual-size-selectivity" pattern for lanthanide (Ln3+) ions, characterized by its high affinity for both the large and the small Ln3+ ( J. Am. Chem. Soc, 2020, 142, 13500). Here, we describe a second-generation "macrodipa-type" ligand, py-macrodipa. Its coordination chemistry with Ln3+ was thoroughly investigated experimentally and computationally. These studies reveal that the Ln3+-py-macrodipa complexes exhibit enhanced thermodynamic and kinetic stabilities compared to Ln3+-macrodipa, while retaining the unusual dual-size selectivity. Nuclear medicine applications of py-macrodipa for chelating radiometals with disparate chemical properties were assessed using the therapeutic 135La3+ and diagnostic 44Sc3+ radiometals representing the two size extremes within the rare-earth series. Radiolabeling and stability studies demonstrate that the rapidly formed complexes of these radionuclides with py-macrodipa are highly stable in human serum. Thus, in contrast to gold standard chelators like DOTA and macropa, py-macrodipa can be harnessed for the simultaneous, efficient binding of radiometals with disparate ionic radii like La3+ and Sc3+, signifying a substantial achievement in nuclear medicine. This concept could enable the facile incorporation of a breadth of medicinally relevant radiometals into chemically identical radiopharmaceutical agents. The fundamental coordination chemistry learned from py-macrodipa provides valuable insight for future chelator development.

Addressing the variation in adjuvant chemotherapy treatment for colorectal cancer: Can a regional intervention promote national change?

Analysis of routine population-based data has previously shown that patterns of surgical treatment for colorectal cancer can vary widely, but there is limited evidence available to determine if such variation is also seen in the use of chemotherapy. This study quantified variation in adjuvant chemotherapy across both England using cancer registry data and in more detail across the representative Yorkshire and Humber regions. Individuals with Stages II and III colorectal cancer who underwent major resection from 2014 to 2015 were identified. Rates of chemotherapy were calculated from the Systemic Anticancer Treatment database using multilevel logistic regression. Additionally, questionnaires addressing different clinical scenarios were sent to regional oncologists to investigate the treatment preferences of clinicians. The national adjusted chemotherapy treatment rate ranged from 2% to 46% (Stage II cancers), 19% to 81% (Stage III cancers), 24% to 75% (patients aged <70 years) and 5% to 46% (patients aged ≥70 years). Regionally, the rates of treatment and the proportions of treated patients receiving combination chemotherapy varied by stage (Stage II 4%-26% and 0%-55%, Stage III 48%-71% and 40%-84%) and by age (<70 years 35%-68% and 49%-91%; ≥70 years 15%-39% and 6%-75%). Questionnaire responses showed significant variations in opinions for high-risk Stage II patients with both deficient and proficient mismatch repair tumours and Stage IIIB patients aged ≥70 years. Following a review of the evidence, open discussion in our region has enabled a consensus agreement on an algorithm for colorectal cancer that is intended to reduce variation in practice.

Real-World Incidence and Management of Immune-Related Adverse Events from Immune Checkpoint Inhibitors: Retrospective Claims-Based Analysis.

PURPOSE: We assessed real-world spectrum and patterns of irAEs for patients treated with anti-PD(L)1 ICIs. METHODS: irAEs were defined using medical and pharmacy claims for patients enrolled in a Medicare Advantage Prescription Drug plan who initiated treatment with anti-PD(L)-1 and received ≥ 1 dose of therapy between 1 September 2014 and 28 February 2018. RESULTS: Treatment was discontinued for 46.6% of patients, and withheld and subsequently restarted for 10.3%. While toxicity profiles did not differ by age, RiskRx-V co-morbidity index was higher in patients with irAEs. CONCLUSION: These data underscore the needs for tailored irAE diagnostic and management pathways.

Tuning the Kinetic Inertness of Bi3+ Complexes: The Impact of Donor Atoms on Diaza-18-Crown-6 Ligands as Chelators for 213Bi Targeted Alpha Therapy.

The radionuclide 213Bi can be applied for targeted α therapy (TAT): a type of nuclear medicine that harnesses α particles to eradicate cancer cells. To use this radionuclide for this application, a bifunctional chelator (BFC) is needed to attach it to a biological targeting vector that can deliver it selectively to cancer cells. Here, we investigated six macrocyclic ligands as potential BFCs, fully characterizing the Bi3+ complexes by NMR spectroscopy, mass spectrometry, and elemental analysis. Solid-state structures of three complexes revealed distorted coordination geometries about the Bi3+ center arising from the stereochemically active 6s2 lone pair. The kinetic properties of the Bi3+ complexes were assessed by challenging them with a 1000-fold excess of the chelating agent diethylenetriaminepentaacetic acid (DTPA). The most kinetically inert complexes contained the most basic pendent donors. Density functional theory (DFT) and quantum theory of atoms in molecules (QTAIM) calculations were employed to investigate this trend, suggesting that the kinetic inertness is not correlated with the extent of the 6s2 lone pair stereochemical activity, but with the extent of covalency between pendent donors. Lastly, radiolabeling studies of 213Bi (30-210 kBq) with three of the most promising ligands showed rapid formation of the radiolabeled complexes at room temperature within 8 min for ligand concentrations as low as 10-7 M, corresponding to radiochemical yields of >80%, thereby demonstrating the promise of this ligand class for use in 213Bi TAT.

Trends in the delivery of care to oncology patients in the United States: Emphasis on the role pharmacists on the healthcare team.

OBJECTIVE: The purpose of this study was to identify trends in oncology care that allow one to forecast workforce supply and demand, the training and skills needed by the oncology pharmacist for the likely future of oncology care. METHODS: Interviews were conducted with experienced oncology pharmacists in leadership roles at 20 organizations balanced by geographic region and type of practice site (academic or community/ambulatory). Results were analyzed using descriptive statistics and theme identification. RESULTS: Practice sites differed widely in numbers of patient visits, practitioner/patient ratios, residency program presence, and other structural features. Despite this, the majority reported an expectation of growth in cancer patients, oncology physicians, oncology pharmacists, pharmacy technicians, oncology nurses, and advanced practice practitioners in the next two to five years. Fifty percent of sites currently support Post Graduate Year 2 (PGY2) oncology residencies. At least 50% reported routine pharmacist involvement in 12 clinical functions. More future involvement was predicted for immunotherapy (80%) and oral oncolytic therapy (90%). Interprofessional involvement was reported for a broad variety of practice-related committees and patient education teams. Limited pharmacist involvement in credentialing, quality measurement, and value-based reimbursement systems was found. CONCLUSION: Anticipated increases in demand for oncology pharmacists strongly suggest the need for more PGY2 oncology residency programs and on-the-job oncology training programs. Oncology pharmacists are currently involved in many clinical and administrative functions including multidisciplinary management. While a core set of clinical functions has been identified, oncology pharmacists must prepare for the increased use of oral oncology agents and immunotherapy. Pharmacist involvement in value-based reimbursement and other data-based quality outcome measurements should be increased to optimize involvement in team-based patient care.

Comfort measures for peripheral I.V. catheter placement in children.

ABSTRACT: I.V. catheter placement is one of the most common causes of procedural pain in children. Interventions to address this pain are readily available but inconsistently used in practice. The focus of this article is to identify and encourage best practice for pain mitigation in peripheral I.V. catheter placement in children.

Evaluation of the head and neck cancer patient population and the incidence of hospitalization at an academic medical center.

PURPOSE: Patients with head and neck cancer are at risk for disease- and treatment-related toxicities that may be severe enough to require hospitalization. The risk factors associated with hospitalization in these patients are not well defined. METHODS: We conducted a single-center, retrospective observational study of patients with head and neck cancer receiving chemotherapy at an academic medical center infusion clinic in a one-year period. The primary objective was to characterize the head and neck cancer population at an academic medical center. Secondary objectives included describing the clinical and social factors associated with hospitalization. RESULTS: There were 109 patients with head and neck cancer included in the analysis. Of these patients, 38 (35%) were hospitalized. The factors that were significantly associated with hospitalization on univariable logistic regression were former alcohol abuse, being on a nonstandard of care chemotherapy regimen, and having a chemotherapy agent discontinued. On multivariable logistic regression, the factor that was significantly associated with hospitalization was having a chemotherapy agent discontinued. The most common reasons for hospitalization included shortness of breath/respiratory failure, fever/neutropenic fever, and infection. The most common new supportive care medications prescribed at discharge were stool softeners or laxatives and opioids. CONCLUSION: This study identified several factors which may be useful to identify patients as high risk for hospitalization and the next steps will be to determine and study the role of the pharmacist in preventing hospitalization of these patients. Further studies are needed to assess the impact of adding a pharmacist to the head and neck cancer multidisciplinary team.

Patterns and costs of health-care utilisation in Australian children: The first 5 years.

AIM: To describe patterns of health-care utilisation and costs of a cohort of Australian children in the first 5 years of life and to investigate demographic factors associated with high health-care utilisation. METHODS: This was a secondary data analysis of prospectively linked health-care utilisation data, including primary and secondary health-care consults, hospitalisations and emergency. The subjects were 350 children from a disadvantaged area of Sydney. Outcomes were the frequency and cost of all health-care consults from birth to 5 years of age. Multivariable logistic regression examined the odds of being a high health-care user in relation to child and family characteristics. RESULTS: Children had more health-care consults and higher annual health-care costs in the first 2 years of life (mean 12 health-care visits per year, mean cost Australian dollars (AUD) 1400 per child) than in the next 3 years (8 visits per year, AUD 900 per child). Primary care consults formed 86% of all health-care encounters but only contributed to 30% of the total costs. Factors positively associated with frequent use of health care in the first 2 years of life included being male, mother not married/de facto and annual household income of less than AUD 40000. Frequent users mostly accessed primary care services. There was no association between demographic factors and frequent use of health care in years 3-5 of life. CONCLUSIONS: Children from low-income or single-parent families may require additional support services during the first 2 years of life. Maintaining or increasing access to free or very low-cost primary health-care services for disadvantaged families will promote equity in health.

Talking Together, Thinking Alone: Relations among Co-Rumination, Peer Relationships, and Rumination.

Girls are more likely to engage in rumination, associated with the development of mental health problems, as well as report higher levels of friendship quality, hypothesized to protect against these disorders. The current study examined whether co-rumination may drive simultaneous increases in rumination and changes in friendship quality among adolescents. The project included 360 participants (43% boys), ages 9.8 to 15.8 years, and analyses revealed that co-rumination mediated the link between female sex and both rumination and negative friendship quality. There was also a bidirectional relation between co-rumination and positive friendship quality. These findings highlight several pathways by which co-rumination mediates the relation between sex and both maladaptive (i.e. rumination, negative friendship quality) and adaptive (i.e. positive friendship quality) outcomes.

Is there an association between early weight status and utility-based health-related quality of life in young children?

PURPOSE: Few studies focus on the health-related quality of life (HRQoL) of preschool children with overweight or obesity. This is relevant for evaluation of obesity prevention trials using a quality-adjusted life year (QALY) framework. This study examined the association between weight status in the preschool years and HRQoL at age 5 years, using a preference-based instrument. METHODS: HRQoL [based on parent proxy version of the Health Utilities Index Mark 3 (HUI3)] and weight status were measured in children born in Australia between 2007 and 2009. Children's health status was scored across eight attributes of the HUI3-vision, hearing, speech, ambulation, dexterity, emotion, cognition and pain, and these were used to calculate a multi-attribute utility score. Ordinary least squares (OLS), Tobit and two-part regressions were used to model the association between weight status and multi-attribute utility. RESULTS: Of the 368 children for whom weight status and HUI3 data were available, around 40% had overweight/obesity. After adjusting for child's sex, maternal education, marital status and household income, no significant association between weight status in the preschool years and multi-attribute utility scores at 5 years was found. CONCLUSIONS: Alternative approaches for capturing the effects of weight status in the preschool years on preference-based HRQoL outcomes should be tested. The application of the QALY framework to economic evaluations of obesity-related interventions in young children should also consider longitudinal effects over the life-course. Clinical Trial Registration The Healthy Beginnings Trial was registered with the Australian Clinical Trial Registry (ACTRNO12607000168459).