Histologic findings of gastrointestinal biopsies and clinical outcome in dogs undergoing cholecystectomy for gallbladder mucoceles: 71 cases (2014-2021).

OBJECTIVES: To determine the presence and categorise the severity of enteritis in dogs with gallbladder mucoceles, and evaluate for any associations with enteritis. This study also aimed to report clinical outcome following cholecystectomy and evaluate for associations with survival. MATERIALS AND METHODS: Medical records were retrospectively reviewed (2014 to 2021) for dogs undergoing cholecystectomy and duodenal biopsy procedures for gallbladder mucocele. Signalment, bloodwork, abdominal ultrasound findings, surgical details, histology results and outcomes were reported. Surgeries were considered elective or emergent based on each dog's clinical presentation. Enteritis was categorised based on cell type and severity. Inflammation and clinical outcome were statistically evaluated. RESULTS: Seventy-one dogs met the study criteria. Enteritis was present in 85.9% (61/71) of cases with the majority being lymphoplasmacytic (53.5%). Twelve dogs (16.9%) underwent gastrointestinal biopsies from multiple sites, which revealed the same enteritis type at each location. A total of 87.3% (n = 62) dogs survived, including 90.4% elective and 86% emergent cases. No significant differences in enteritis severity or patient survival were found between elective and emergent cases. Septic peritonitis was diagnosed in two dogs (2.82%). Mortality was significantly associated with leukocytosis, with nonsurviving dogs having a mean WBC count of 27.6 G/L (95% confidence interval: 10.6 to 21.5). CLINICAL SIGNIFICANCE: Enteritis is present in a majority of dogs with gallbladder mucocele, especially mild to moderate with lymphoplasmacytic cell type. Obtaining a duodenal biopsy had minimal impact on patient outcome. Compared to previous studies, improved survival in emergent cases was noted. Further studies with long-term follow-up are needed to determine if enteropathy-related signs persist after cholecystectomy.

CAUSES OF MORBIDITY AND MORTALITY IN STELLER SEA LIONS (EUMETOPIAS JUBATUS) UNDER PROFESSIONAL CARE IN NORTH AMERICAN AQUARIUMS FROM 1979 TO 2021.

To date, published comprehensive pathology investigations documented in Steller sea lions (SSL; Eumetopias jubatus) are from free-ranging populations, whereas health data from those under professional care in aquariums are currently lacking. A retrospective review of gross and histopathologic reports of SSL under human care in North American aquariums from 1979 to 2021 (n = 20) was performed. Associations between age, sex, or birth origin (born in aquariums versus the wild) with cause of death (COD) and comorbidities were explored. Age was significantly associated with development of endocrine organ pathology (P = 0.011). A relationship between age and both cardiovascular and ocular disease was suggested by the data, but did not reach significance (P = 0.058). Ocular disease was significantly associated with being born in aquariums (P = 0.022). The most common COD was neoplasia (n = 10), which was significantly associated with aged animals (P = 0.038). Less frequent COD included sepsis (confirmed, n = 2; suspected, n = 3), cardiomyopathy (n = 1), clostridial enteritis (n = 1), Sarcocystis spp. (n = 1), complication secondary to sedation (n = 1), and unknown (n = 1). This is the first report documenting the high prevalence of neoplasia in SSL, with tumors found incidentally in three individuals, frequent metastasis (10/13, 77%), and many cases of multiple primary malignancies (6/13, 46%). These data expand upon the current understanding of disease in SSL, highlight this species' predisposition to neoplasia with increasing longevity, and underscore the need for heightened screening in aged animals, which may ultimately serve to elevate the care of SSL under professional care in aquariums.

The effect of localized disturbance on the acoustic behavior of the common tern (Sterna hirundo).

In this study, passive acoustic monitoring was used to assess the impact of investigator disturbance on the acoustic behavior of a colony of common terns. A graded antipredator response in the colony was hypothesized, which would result in an increase in acoustic energy with increased proximity to investigator disturbance. Human disturbance was found to result in a significant increase in acoustic energy within 20 meters of recorders, though not from farther distances. Our findings provide a framework for assessing the behavioral impact of disturbance on colonies and support the existence of a graded alarm call system in common terns.

High-Frame-Rate Ultrasound Velocimetry in the Healthy Femoral Bifurcation: A Comparative Study Against 4-D Flow Magnetic Resonance Imaging.

OBJECTIVE: Local flow dynamics impact atherosclerosis yet are difficult to quantify with conventional ultrasound techniques. This study investigates the performance of ultrasound vector flow imaging (US-VFI) with and without ultrasound contrast agents in the healthy femoral bifurcation. METHODS: High-frame-rate ultrasound data with incremental acoustic outputs were acquired in the femoral bifurcations of 20 healthy subjects before (50V) and after contrast injection (2V, 5V and 10V). 2-D blood-velocity profiles were obtained through native blood speckle tracking (BST) and contrast tracking (echo particle image velocimetry [echoPIV]). As a reference, 4-D flow magnetic resonance imaging (4-D flow MRI) was acquired. Contrast-to-background ratio and vector correlation were used to assess the quality of the US-VFI acquisitions. Spatiotemporal velocity profiles were extracted, from which peak velocities (PSV) were compared between the modalities. Furthermore, root-mean-square error analysis was performed. RESULTS: US-VFI was successful in 99% of the cases and optimal VFI quality was established with the 10V echoPIV and BST settings. A good correspondence between 10V echoPIV and BST was found, with a mean PSV difference of -0.5 cm/s (limits of agreement: -14.1-13.2). Both US-VFI techniques compared well with 4-D flow MRI, with a mean PSV difference of 1.4 cm/s (-18.7-21.6) between 10V echoPIV and MRI, and 0.3 cm/s (-23.8-24.4) between BST and MRI. Similar complex flow patterns among all modalities were observed. CONCLUSION: 2-D blood-flow quantification of femoral bifurcation is feasible with echoPIV and BST. Both modalities showed good agreement compared to 4-D flow MRI. For the femoral tract the administration of contrast was not needed to increase the echogenicity of the blood for optimal image quality.

Low-cost uncrewed aerial vehicles (UAVs) as a novel tool for welfare assessments on open pen commercial crocodile farms.

BACKGROUND: The welfare of crocodiles on commercial farms in southern Africa requires precise assessment, focusing on stocking densities and pen conditions. However, disputes between animal welfare groups and farm owners persist due to inadequate methodologies for quantifying these factors. OBJECTIVES: This study aimed to address these disputes and enhance crocodile welfare assessment by introducing a novel technique using a low-cost consumer uncrewed aerial vehicle (UAV) and open-source photogrammetry software. The objective was to quantify key welfare parameters accurately and efficiently. METHOD: The study involved applying the UAV-based technique to two large Nile crocodile (Crocodylus niloticus) farms in South Africa. The approach enabled the mapping and surveying of crocodile pens, facilitating the determination of stocking densities, biomass indicators, and other pen-related attributes. Comparisons were made between UAV-derived crocodile counts and farmer estimates. RESULTS: The UAV-based crocodile counts significantly differed from the estimates provided by farmers, underscoring the need for a more precise assessment method. The technique's cost-effectiveness was evident, with implementation expenses totalling less than R10 000, a fraction of the cost associated with commercial UAV surveys. CONCLUSIONS: The introduced UAV-based technique offers a valuable solution to the ongoing debates regarding crocodile welfare on commercial farms. By quantifying key parameters accurately and economically, it empowers farmers and animal welfare groups to make informed decisions. The method's ease of adoption, demonstrated through its use by some Southern African crocodile farmers, signifies its potential for widespread application, ultimately contributing to improved crocodile welfare.

CelltypeR: A flow cytometry pipeline to characterize single cells from brain organoids.

Motivated by the cellular heterogeneity in complex tissues, particularly in brain and induced pluripotent stem cell (iPSC)-derived brain models, we developed a complete workflow to reproducibly characterize cell types in complex tissues. Our approach combines a flow cytometry (FC) antibody panel with our computational pipeline CelltypeR, enabling dataset aligning, unsupervised clustering optimization, cell type annotating, and statistical comparisons. Applied to human iPSC derived midbrain organoids, it successfully identified the major brain cell types. We performed fluorescence-activated cell sorting of CelltypeR-defined astrocytes, radial glia, and neurons, exploring transcriptional states by single-cell RNA sequencing. Among the sorted neurons, we identified subgroups of dopamine neurons: one reminiscent of substantia nigra cells most vulnerable in Parkinson's disease. Finally, we used our workflow to track cell types across a time course of organoid differentiation. Overall, our adaptable analysis framework provides a generalizable method for reproducibly identifying cell types across FC datasets in complex tissues.

Death rituals and quality of life of bereaved relatives during the COVID-19 pandemic: Results of the observational CO-LIVE study.

Grief is a normal reaction after the death of a loved one. Death rituals are an integral part of the mourning processes. Not being able to carry out death rituals can affect relatives' quality of life. The aim was to evaluate death rituals during COVID-19 and their association with relatives' quality of life. In a Swedish nation-wide study relatives to persons who died during the COVID-19-pandemic received questionnaires about their quality of life and how they could perform death rituals. Association between quality of life and death rituals was analyzed with linear regression. Of the 324 relatives, a minority indicated that their loved one's funeral (17%) met their wishes. Not being able to carry out the funeral as desired was significantly associated with a lower quality of life (p = 0.006). The experiences during the pandemic revealed that it is important for people to perform death rituals according to their wishes.

"Association between caries in anterior teeth and bullying victimization in Brazilian schoolchildren aged 6 to 10 years.: a cross sectional study".

AIM: To investigate the association between presence of caries in anterior teeth and bullying victimization in schoolchildren. METHODS: A cross-sectional study was conducted in Brazil with a sample of 387 schoolchildren aged 6 to 10 years. The presence of moderate/extensive dental caries was assessed using the International System for the Evaluation and Detection of Dental Caries (ICDAS-II). The children answered the "Olweus Bullying" (QBO). Descriptive analyses were performed, and the associations between bullying victimization and independent variables collected were determined by univariate and multivariate Poisson regression. RESULTS: The prevalence of bullying victimization was 66.4%. Bullying victimization was higher among children who had moderate/extensive caries in some anterior teeth (p = 0.010). 8-year-old (p = 0.048), 9-year-old (p = 0.001), and 10-year-old (p = 0.002) children reported greater bullying victimization when compared to 6-year-olds. CONCLUSION: The presence of moderate/extensive dental caries in anterior teeth is associated with bullying victimization in schoolchildren.

A Longitudinal Treatment Effect Analysis of Antipsychotics on Behavior of Residents in Long-Term Care.

OBJECTIVE: The proportion of long-term care (LTC) residents being treated with antipsychotic medication is high, and these medications may exacerbate behavioral symptoms. We used propensity scores to investigate the effect of antipsychotic use on the worsening of behavioral symptoms among residents in LTC facilities. DESIGN: A retrospective study. SETTING AND PARTICIPANTS: Residents in LTC in 8 provinces and 1 territory in Canada, without severe aggressive behavior at baseline and reassessed at follow-up, between March 2000 and March 2022. METHODS: We used propensity score matching and weighting to balance baseline covariates and logistic regression to estimate the effect of antipsychotics on the worsening of behavioral symptoms in the original, matched, and weighted cohorts. The treatment variable was use of antipsychotic medication at baseline and the outcome was worsening of behavior at follow-up. RESULTS: A total of 494,215 participants were included (318,234 women and 175,981 men; mean age 82.8 years [SD 10.1; range 18-112]).130 558 (26.4%) used antipsychotics at baseline and 88,632 (17.9%) had worsening behavior in follow-up. In the matched cohort, there were 249,698 participants, and 124,849 were matched (1:1) in each treatment group. There was a significant association between antipsychotic use at baseline and worsening in behavior at follow-up in the adjusted regression models (OR 1.27 [95% CI 1.25-1.29], <0.0001) as well as in matched (OR 1.20 [95% CI 1.17-1.21], <0.0001) and weighted (OR 1.26 [95% CI 1.24-1.28], <0.0001) cohorts. CONCLUSIONS AND IMPLICATIONS: This study further evidence to support the cautious use of antipsychotics in LTC facilities. Future research in LTC facilities could include a more granular analyses of behavior change, including bidirectional analyses between different symptom severity classifications.

Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial.

BACKGROUND: Patients with osteoporosis demonstrate increased vascular calcification but the effect of osteoporosis treatments on vascular calcification remains unclear. The present study aimed to examine whether coronary or aortic calcification are influenced by denosumab and alendronic acid treatment. METHODS AND RESULTS: In a double-blind randomized controlled SALTIRE2 (Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis) trial, patients with aortic stenosis were randomized 2:1:2:1 to denosumab, placebo injection, alendronic acid, or placebo capsule. Participants underwent serial imaging with computed tomography and 18F-sodium fluoride positron emission tomography for the assessment of vascular calcium burden and calcification activity, respectively. We report the prespecified secondary analyses of 24-month change in coronary calcium score, and 12-month changes in thoracic aorta calcium score, coronary and aortic 18F-sodium fluoride activity. One hundred fifty patients with aortic stenosis (72±8 years; 21% female) were randomized to denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25). There were no differences in change in coronary calcium scores between placebo (16 [-64 to 148] Agatston units) and either denosumab (94 [0-212] Agatston units, P=0.24) or alendronic acid (34 [-62 to 134], P=0.99). There were no differences in change in thoracic aorta calcium scores between placebo (132 [22-512] Agatston units) and either denosumab (118 [11-340], P=0.75) or alendronic acid (116 [26-498] Agatston units, P=0.62). There were no differences in changes in coronary or aortic 18F-sodium fluoride activity between treatment groups. CONCLUSIONS: Neither alendronic acid nor denosumab are associated with changes in the activity or progression of coronary or aortic calcification. Osteoporosis treatments do not appear to have major impact on vascular calcification of atherosclerosis. REGISTRATION: https://www.clinicaltrials.gov; Unique identifier: NCT02132026.

Prodrug activation in malaria parasites mediated by an imported erythrocyte esterase, acylpeptide hydrolase (APEH).

The continued emergence of antimalarial drug resistance highlights the need to develop new antimalarial therapies. Unfortunately, new drug development is often hampered by poor drug-like properties of lead compounds. Prodrugging temporarily masks undesirable compound features, improving bioavailability and target penetration. We have found that lipophilic diester prodrugs of phosphonic acid antibiotics, such as fosmidomycin, exhibit significantly higher antimalarial potency than their parent compounds (1). However, the activating enzymes for these prodrugs were unknown. Here, we show that an erythrocyte enzyme, acylpeptide hydrolase (APEH) is the major activating enzyme of multiple lipophilic ester prodrugs. Surprisingly, this enzyme is taken up by the malaria parasite, Plasmodium falciparum, where it localizes to the parasite cytoplasm and retains enzymatic activity. Using a novel fluorogenic ester library, we characterize the structure activity relationship of APEH, and compare it to that of P. falciparum esterases. We show that parasite-internalized APEH plays an important role in the activation of substrates with branching at the alpha carbon, in keeping with its exopeptidase activity. Our findings highlight a novel mechanism for antimicrobial prodrug activation, relying on a host-derived enzyme to yield activation at a microbial target. Mutations in prodrug activating enzymes are a common mechanism for antimicrobial drug resistance (2-4). Leveraging an internalized host enzyme would circumvent this, enabling the design of prodrugs with higher barriers to drug resistance.

Physical activity at diagnosis is associated with tumor downstaging after neoadjuvant chemoradiotherapy in patients with rectal cancer.

BACKGROUND: Patients with rectal cancer are often treated with neoadjuvant chemoradiotherapy, followed by a waiting period and surgical resection. Good or complete response to neoadjuvant chemoradiotherapy might enable organ preservation, which highlights the need to increase response rates. Pre-clinical studies suggest that physical activity during neoadjuvant chemoradiotherapy may improve tumor downstaging. PURPOSE: To investigate whether physical activity and physical functioning of patients with rectal cancer at diagnosis are associated with tumor downstaging after neoadjuvant chemoradiotherapy. MATERIALS AND METHODS: Patients were included if they participated in the Dutch Prospective ColoRectal Cancer Cohort, a nationwide cohort providing an infrastructure for scientific research, and received neoadjuvant chemoradiotherapy for rectal cancer. Tumor downstaging was dichotomized into good/complete or moderate/poor downstaging. Physical activity (total physical activity, moderate-to-vigorous physical activity (MVPA), and Dutch physical activity guideline adherence) and physical functioning were assessed using questionnaires. Logistic regression analyses were performed to examine associations of physical activity and physical functioning with tumor downstaging, adjusted for relevant confounders. RESULTS: 268 patients (aged 62 ± 11 years, 33 % female) with rectal cancer were included. Patients with moderate (OR = 2.07; 95%CI = 1.07 - 4.07; p = 0.03) or high (OR = 2.05; 95%CI = 1.05 - 4.07; p = 0.04) levels of MVPA were more likely to have good/complete tumor downstaging than patients with low levels. No significant associations with tumor downstaging were found for total physical activity, Dutch physical activity guideline adherence, and physical functioning. CONCLUSIONS: We found augmented tumor downstaging in patients with rectal cancer with moderate or high levels of self-reported MVPA before the start of neoadjuvant chemoradiotherapy compared to patients with low levels.

[Palliative care in practice]. / Palliatieve zorg in de praktijk.

In palliative care patient problems often are complex and have elements that relate to more than one dimension and therefore require a multidisciplinary approach.In this article the methodical approach of "palliative reasoning" is described, which helps to analyse, treat and follow up complex patient problems in the palliative phase. Furthermore, tips, general recommendations and treatment options are described based on existing Dutch clinical practice palliative care guidelines, literature and expert opinion.

The developing pig respiratory microbiome harbors strains antagonistic to common respiratory pathogens.

In the global efforts to combat antimicrobial resistance and reduce antimicrobial use in pig production, there is a continuous search for methods to prevent and/or treat infections. Within this scope, we explored the relationship between the developing piglet nasal microbiome and (zoonotic) bacterial pathogens from birth until 10 weeks of life. The nasal microbiome of 54 pigs was longitudinally studied over 16 timepoints on 9 farms in 3 European countries (Germany, Ireland, and the Netherlands) using amplicon sequencing targeting the V3-V4 16S rRNA region as well as the tuf gene for its staphylococcal discrimination power. The piglets' age, the farm, and the litter affected the nasal microbiome, with piglets' age explaining 19% of the variation in microbial composition between samples. Stabilization of the microbiome occurred around 2 weeks post-weaning. Notably, while opportunistic pathogens were ubiquitously present, they did not cause disease. The piglet nasal microbiome often carried species associated with gut, skin, or vagina, which suggests that contact with the vaginal and fecal microbiomes shapes the piglet nasal microbiome. We identified bacterial co-abundance groups of species that were present in the nasal microbiomes in all three countries over time. Anti-correlation between these species and known bacterial pathogens identified species that might be exploited for pathogen reduction. Further experimental evidence is required to confirm these findings. Overall, this study advances our understanding of the piglet nasal microbiome, the factors influencing it, and its longitudinal development, providing insights into its role in health and disease. IMPORTANCE: Our study on the nasal microbiota development in piglets across farms in three European countries found that the microbiomes developed similarly in all locations. Additionally, we observed that the colonization of porcine pathogens was either positively or negatively associated with the presence of other bacterial species. These findings enhance our knowledge of co-colonizing species in the nasal cavity and the identified microbial interactions that can be explored for the development of interventions to control pathogens in porcine husbandry.

Evaluating the impact of extended dosing intervals on mRNA COVID-19 vaccine effectiveness in adolescents.

BACKGROUND: Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. METHODS: We quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022, based on calendar-time proportional hazards models and matching approaches. RESULTS: We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21-27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR 1.66; 95% CI 1.07, 2.59; p = 0.02) after the first dose. CONCLUSIONS: Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

Odontogenic Myxomas Harbor Recurrent Copy Number Alterations and a Distinct Methylation Signature.

Odontogenic myxoma is a rare, benign, and locally aggressive tumor that develops in the tooth-bearing areas of the jaw. The molecular mechanisms underlying odontogenic myxomas are unknown and no diagnostic markers are available to date. The aim of this study was to analyze DNA methylation and copy number variations in odontogenic myxomas to identify new molecular signatures for diagnostic decision-making. We collected a cohort of 16 odontogenic myxomas from 2006 to 2021 located in the mandible (n = 10) and maxilla (n = 6) with available formalin-fixed paraffin-embedded or fresh frozen tumor tissue from a biopsy or resection material. Genome-wide DNA methylation and copy number variation data were generated from 12 odontogenic myxomas using the Illumina Infinium Methylation EPIC array, interrogating >850,000 CpG sites. Unsupervised clustering and dimensionality reduction (Uniform Manifold Approximation and Projection) revealed that odontogenic myxomas formed a distinct DNA methylation class. Copy number profiling showed recurrent whole-chromosome gains (trisomies) of chromosomes 5, 8, and 20 in all cases, and of chromosomes 10, 12, and 17 in all except one case. In conclusion, odontogenic myxomas harbor recurrent copy number patterns and a distinct DNA methylation profile, which can be used as an additional diagnostic tool in the appropriate clinical and radiologic context. Further research is needed to explain the genetic mechanisms caused by these alterations that drive these locally aggressive neoplasms.

Decoding drivers of carbon flux attenuation in the oceanic biological pump.

The biological pump supplies carbon to the oceans' interior, driving long-term carbon sequestration and providing energy for deep-sea ecosystems1,2. Its efficiency is set by transformations of newly formed particles in the euphotic zone, followed by vertical flux attenuation via mesopelagic processes3. Depth attenuation of the particulate organic carbon (POC) flux is modulated by multiple processes involving zooplankton and/or microbes4,5. Nevertheless, it continues to be mainly parameterized using an empirically derived relationship, the 'Martin curve'6. The derived power-law exponent is the standard metric used to compare flux attenuation patterns across oceanic provinces7,8. Here we present in situ experimental findings from C-RESPIRE9, a dual particle interceptor and incubator deployed at multiple mesopelagic depths, measuring microbially mediated POC flux attenuation. We find that across six contrasting oceanic regimes, representing a 30-fold range in POC flux, degradation by particle-attached microbes comprised 7-29 per cent of flux attenuation, implying a more influential role for zooplankton in flux attenuation. Microbial remineralization, normalized to POC flux, ranged by 20-fold across sites and depths, with the lowest rates at high POC fluxes. Vertical trends, of up to threefold changes, were linked to strong temperature gradients at low-latitude sites. In contrast, temperature played a lesser role at mid- and high-latitude sites, where vertical trends may be set jointly by particle biochemistry, fragmentation and microbial ecophysiology. This deconstruction of the Martin curve reveals the underpinning mechanisms that drive microbially mediated POC flux attenuation across oceanic provinces.

How does health visiting in the first year of life vary by family characteristics? A longitudinal analysis of administrative data.

BACKGROUND: The health visiting service in UK promotes the health and wellbeing of families with young children and comprises a universal offer (three mandated contacts between birth and 12 months) and additional contacts based on need. We aimed to understand how the level of health visiting support received varies by family characteristics. METHODS: Using the Community Services Data Set linked to Hospital Episode Statistics, we identified 52 555 children in 10 local authorities with complete health visiting data for 12 months between April 2016 and March 2020. We analysed variation in health visiting contacts by deprivation, child ethnicity, maternal age, adversity and previous live births. RESULTS: 41 340/52 555 children (79%) received the universal service; 63% received ≥1 additional contact and 25% received ≥3 additional contacts. The likelihood of receiving ≥3 additional contacts was greatest for children whose mothers had a history of hospital admissions relating to mental health, violence, self-harm or substance misuse (adjusted relative risk = 1.55, 95% confidence interval 1.26-1.92). CONCLUSIONS: Most families received health visiting support in addition to the universal service. Policymakers and commissioners should consider how health visiting services can be expanded or targeted more effectively to ensure all families receive the support they need.