Assessment of the in vitro acaricidal activity of Bravecto® (fluralaner) and a proposed orange oil-based formulation vehicle for the treatment of Sarcoptes scabiei.

BACKGROUND: Sarcoptic mange is a serious animal welfare concern in bare-nosed wombats (Vombatus ursinus). Fluralaner (Bravecto®) is a novel acaricide that has recently been utilised for treating mange in wombats. The topical 'spot-on' formulation of fluralaner can limit treatment delivery options in situ, but dilution to a volume for 'pour-on' delivery is one practicable solution. This study investigated the in vitro acaricidal activity of Bravecto, a proposed essential oil-based diluent (Orange Power®), and two of its active constituents, limonene and citral, against Sarcoptes scabiei. METHODS: Sarcoptes scabiei were sourced from experimentally infested pigs. In vitro assays were performed to determine the lethal concentration (LC50) and survival time of the mites when exposed to varying concentrations of the test solutions. RESULTS: All compounds were highly effective at killing mites in vitro. The LC50 values of Bravecto, Orange Power, limonene and citral at 1 h were 14.61 mg/ml, 4.50%, 26.53% and 0.76%, respectively. The median survival times of mites exposed to undiluted Bravecto, Orange Power and their combination were 15, 5 and 10 min, respectively. A pilot survival assay of mites collected from a mange-affected wombat showed survival times of < 10 min when exposed to Bravecto and Orange Power and 20 min when exposed to moxidectin. CONCLUSIONS: These results confirm the acaricidal properties of Bravecto, demonstrate acaricidal properties of Orange Power and support the potential suitability of Orange Power and its active constituents as a diluent for Bravecto. As well as killing mites via direct exposure, Orange Power could potentially enhance the topical delivery of Bravecto to wombats by increasing drug penetration in hyperkeratotic crusts. Further research evaluating the physiochemical properties and modes of action of Orange Power and its constituents as a formulation vehicle would be of value.

Influence of vitamin D supplementation on growth, body composition, pubertal development and spirometry in South African schoolchildren: a randomised controlled trial (ViDiKids).

OBJECTIVE: To determine whether weekly oral vitamin D supplementation influences growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. DESIGN: Phase 3 double-blind randomised placebo-controlled trial. SETTING: Socioeconomically disadvantaged peri-urban district of Cape Town, South Africa. PARTICIPANTS: 1682 children of black African ancestry attending government primary schools and aged 6-11 years at baseline. INTERVENTIONS: Oral vitamin D3 (10 000 IU/week) versus placebo for 3 years. MAIN OUTCOME MEASURES: Height-for-age and body mass index-for-age, measured in all participants; Tanner scores for pubertal development, spirometric lung volumes and body composition, measured in a subset of 450 children who additionally took part in a nested substudy. RESULTS: Mean serum 25-hydroxyvitamin D3 concentration at 3-year follow-up was higher among children randomised to receive vitamin D versus placebo (104.3 vs 64.7 nmol/L, respectively; mean difference (MD) 39.7 nmol/L, 95% CI 37.6 to 41.9 nmol/L). No statistically significant differences in height-for-age z-score (adjusted MD (aMD) -0.08, 95% CI -0.19 to 0.03) or body mass index-for-age z-score (aMD -0.04, 95% CI -0.16 to 0.07) were seen between vitamin D versus placebo groups at follow-up. Among substudy participants, allocation to vitamin D versus placebo did not influence pubertal development scores, % predicted forced expiratory volume in 1 s (FEV1), % predicted forced vital capacity (FVC), % predicted FEV1/FVC, fat mass or fat-free mass. CONCLUSIONS: Weekly oral administration of 10 000 IU vitamin D3 boosted vitamin D status but did not influence growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov NCT02880982, South African National Clinical Trials Register DOH-27-0916-5527.

A Cross-Sectional, Multicentric, Disease-Specific, Health-Related Quality of Life Study in Greek Transfusion Dependent Thalassemia Patients.

The assessment of health-related quality of life (HRQoL) in thalassemia offers a holistic approach to the disease and facilitates better communication between physicians and patients. This study aimed to evaluate the HRQoL of transfusion-dependent thalassemia (TDT) patients in Greece. This was a multicentric, cross-sectional study conducted in 2017 involving 283 adult TDT patients. All participants completed a set of two QoL questionnaires, the generic SF-36v2 and the disease-specific TranQol. Demographic and clinical characteristics were used to predefine patient subgroups. Significant factors identified in the univariate analysis were entered into a multivariate analysis to assess their effect on HRQoL. The SF-36 scores of TDT patients were consistently lower compared to the general population in Greece. The mean summary score of TranQol was relatively high (71 ± 14%), exceeding levels observed in national surveys in other countries. Employment emerged as the most significant independent factor associated with better HRQoL, whereas age had the most significant negative effect. This study represents the first comprehensive QoL assessment of a representative sample of the TDT population in Greece. The implementation of TranQol allowed for the quantification of HRQoL in Greece, establishing a baseline for future follow-up, and identifying more vulnerable patient subgroups.

Family practice research in the African region 2020-2022.

BACKGROUND:  The African region produces a small proportion of all health research, including primary health care research. The SCOPUS database only lists the African Journal of Primary Health Care Family Medicine (PHCFM) and the South African Family Practice Journal (SAFP) in the field of family practice. AIM:  To review the nature of all original research (2020-2022) published in PHCFM and SAFP. SETTING:  African region. METHOD:  All 327 articles were included. Data were extracted into REDCap, using a standardised tool and exported to the Statistical Package for Social Sciences. RESULTS:  The median number of authors was 3 (interquartile range [IQR]: 2-4) and institutions and disciplines 1 (IQR: 1-2). Most authors were from South Africa (79.8%) and family medicine (45.3%) or public health (34.2%). Research focused on integrated health services (76.1%) and was mostly clinical (66.1%) or service delivery (37.9%). Clinical research addressed infectious diseases (23.4%), non-communicable diseases (24.6%) and maternal and women's health (19.4%). Service delivery research addressed the core functions of primary care (35.8%), particularly person-centredness and comprehensiveness. Research targeted adults and older adults (77.0%) as well as health promotion or disease prevention (38.5%) and treatment (30.9%). Almost all research was descriptive (73.7%), mostly surveys. CONCLUSION:  Future research should include community empowerment and multisectoral action. Within integrated health services, some areas need more attention, for example, children, palliative and rehabilitative care, continuity and coordination. Capacity building and support should enable larger, less-descriptive and more collaborative interdisciplinary studies with authors outside of South Africa.Contribution: The results highlight the strengths and weaknesses of family practice research in Africa.

Association between chiropractic spinal manipulation and cauda equina syndrome in adults with low back pain: Retrospective cohort study of US academic health centers.

BACKGROUND: Cauda equina syndrome (CES) is a lumbosacral surgical emergency that has been associated with chiropractic spinal manipulation (CSM) in case reports. However, identifying if there is a potential causal effect is complicated by the heightened incidence of CES among those with low back pain (LBP). The study hypothesis was that there would be no increase in the risk of CES in adults with LBP following CSM compared to a propensity-matched cohort following physical therapy (PT) evaluation without spinal manipulation over a three-month follow-up period. METHODS: A query of a United States network (TriNetX, Inc.) was conducted, searching health records of more than 107 million patients attending academic health centers, yielding data ranging from 20 years prior to the search date (July 30, 2023). Patients aged 18 or older with LBP were included, excluding those with pre-existing CES, incontinence, or serious pathology that may cause CES. Patients were divided into two cohorts: (1) LBP patients receiving CSM or (2) LBP patients receiving PT evaluation without spinal manipulation. Propensity score matching controlled for confounding variables associated with CES. RESULTS: 67,220 patients per cohort (mean age 51 years) remained after propensity matching. CES incidence was 0.07% (95% confidence intervals [CI]: 0.05-0.09%) in the CSM cohort compared to 0.11% (95% CI: 0.09-0.14%) in the PT evaluation cohort, yielding a risk ratio and 95% CI of 0.60 (0.42-0.86; p = .0052). Both cohorts showed a higher rate of CES during the first two weeks of follow-up. CONCLUSIONS: These findings suggest that CSM is not a risk factor for CES. Considering prior epidemiologic evidence, patients with LBP may have an elevated risk of CES independent of treatment. These findings warrant further corroboration. In the meantime, clinicians should be vigilant to identify LBP patients with CES and promptly refer them for surgical evaluation.

Notalgia Paresthetica Responding Positively to Chiropractic Spinal Manipulation: A Case Report.

Notalgia paresthetica (NP) is a chronic cutaneous neuropathy characterized by localized pruritus and pain, numbness, and/or paresthesia, often linked to degenerative cervicothoracic changes. Treatment options for NP are limited. This case report details a 54-year-old woman with a six-year history of right-sided periscapular pruritus and cervicothoracic discomfort who presented to a chiropractor upon referral with a prior diagnosis of NP. Prior topical treatments yielded minimal relief. Radiographs revealed degenerative spinal changes at C5/6 and C6/7 which correlated with her periscapular symptom distribution. The patient responded positively to chiropractic spinal manipulative therapy (SMT), focusing on the cervicothoracic region, coupled with myofascial release. Symptoms significantly improved after a single SMT session and resolved after a second session, with no pruritus returning over one-month follow-up. While this case highlights the potential benefits of SMT for NP, further research is needed to explore the effectiveness of this treatment.

Influence of vitamin D supplementation on bone mineral content, bone turnover markers, and fracture risk in South African schoolchildren: multicenter double-blind randomized placebo-controlled trial (ViDiKids).

Randomized controlled trials (RCTs) to determine the influence of vitamin D on BMC and fracture risk in children of Black African ancestry are lacking. We conducted a sub-study (n = 450) nested within a phase 3 RCT of weekly oral supplementation with 10 000 IU vitamin D3 vs placebo for 3 yr in HIV-uninfected Cape Town schoolchildren aged 6-11 yr. Outcomes were BMC at the whole body less head (WBLH) and LS and serum 25-hydroxyvitamin D3 (25(OH)D3), PTH, alkaline phosphatase, C-terminal telopeptide, and PINP. Incidence of fractures was a secondary outcome of the main trial (n = 1682). At baseline, mean serum 25(OH)D3 concentration was 70.0 nmol/L (SD 13.5), and 5.8% of participants had serum 25(OH)D3 concentrations <50 nmol/L. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI, 36.1 to 43.6) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI, -0.94 to -0.17). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI, -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI, -1.3 to 0.8) or serum concentrations of bone turnover markers. Fractures were rare among participants in the main trial randomized to vitamin D vs placebo (7/755 vs 10/758 attending at least 1 follow-up; adjusted odds ratio 0.70, 95% CI, 0.27 to 1.85). In conclusion, a 3-yr course of weekly oral vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC or serum concentrations of bone turnover markers. Fracture incidence was low, limiting power to detect an effect of vitamin D on this outcome.

Vitamin D­the "sunshine vitamin"­is essential for helping the body to absorb calcium from the diet, which is laid down in bone to improve its strength. There is a lack of clinical trials testing whether vitamin D supplements can improve bone content of calcium and other minerals, or reduce risk of bone fractures (broken bones) in children of Black African ancestry. We therefore conducted such a study, recruiting 1682 schoolchildren aged 6­11 yr living in Cape Town, South Africa. We found that a weekly dose of 10 000 international units (250 micrograms) of vitamin D3, given by mouth for 3 yr, was effective in boosting vitamin D levels in trial participants who received it. However, this did not have any effect on bone content of calcium and other minerals. Relatively few children experienced a broken bone during the study, so we were unable to say with confidence whether or not vitamin D supplements might affect this outcome.

Rosuvastatin as a Supplemental Treatment for the Clinical Symptoms of Nephropathia Epidemica: A Pilot Clinical Study.

Nephropathis epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS), is an acute zoonotic disease endemic in the Republic of Tatarstan. This study aimed to assess the impact of rosuvastatin on the clinical and laboratory results of NE. A total of 61 NE patients and 30 controls were included in this study; 22 NE patients and 7 controls received a daily dose of rosuvastatin (10 mg) for ten consecutive days. Serum samples were collected on days 1, 5, and 10 after admission to the hospital. These samples were analyzed to determine the levels of lipids, cytokines, and kidney toxicity markers. Our findings indicate that rosuvastatin reduced the duration of the second wave of fever and alleviated back pain and headache symptoms. Additionally, low-density lipoprotein cholesterol (LDL-C) serum levels were significantly decreased on days 5 and 10 upon rosuvastatin treatment. Furthermore, rosuvastatin decreased the levels of cytokines in the serum, particularly proinflammatory cytokines IL-1ß and IL-8. NE patients had significantly altered levels of the kidney toxicity markers albumin and osteopontin. The data from our study provide evidence supporting the therapeutic potential of rosuvastatin in NE cases.

Effect of ginger supplementation on the fecal microbiome in subjects with prior colorectal adenoma.

Ginger has been associated with a decreased incidence of colorectal cancer (CRC) through reduction in inflammatory pathways and inhibition of tumor growth. Recent pre-clinical models have implicated changes in the gut microbiome as a possible mediator of the ginger effect on CRC. We hypothesized that, in adults previously diagnosed with a colorectal adenoma, ginger supplementation would alter the fecal microbiome in the direction consistent with its CRC-inhibitory effect. Sixty-eight adults were randomized to take either ginger or placebo daily for 6 weeks, with a 6-week washout and longitudinal stool collection throughout. We performed 16S rRNA sequencing and evaluated changes in overall microbial diversity and the relative abundances of pre-specified CRC-associated taxa using mixed-effects logistic regression. Ginger supplementation showed no significant effect on microbial community structure through alpha or beta diversity. Of 10 pre-specified CRC-associated taxa, there were significant decreases in the relative abundances of the genera Akkermansia (p < 0.001), Bacteroides (p = 0.018), and Ruminococcus (p = 0.013) after 6-week treatment with ginger compared to placebo. Ginger supplementation led to decreased abundances of Akkermansia and Bacteroides, which suggests that ginger may have an inhibitory effect on CRC-associated taxa. Overall, ginger supplementation appears to have a limited effect on gut microbiome in patients with colorectal adenomas.

Projecting the Future Pediatric Subspecialty Workforce: Summary and Recommendations.

This article summarizes the findings of a Pediatrics supplement addressing the United States workforce for 15 pediatric subspecialties. It includes results from a microsimulation model projecting supply through 2040; growth is forecasted to be uneven across the subspecialties with worsening geographic maldistribution. Although each subspecialty has unique characteristics, commonalities include (1) the changing demographics and healthcare needs of children, including mental health; (2) poor outcomes for children experiencing adverse social drivers of health, including racism; and (3) dependence on other subspecialties. Common healthcare delivery challenges include (1) physician shortages for some subspecialties; (2) misalignment between locations of training programs and subspecialists and areas of projected child population growth; (3) tension between increasing subsubspecialization to address rare diseases and general subspecialty care; (4) the need to expand clinical reach through collaboration with other physicians and advanced practice providers; (5) the lack of parity between Medicare, which funds much of adult care, and Medicaid, which funds over half of pediatric subspecialty care; and (6) low compensation of pediatric subspecialists compared with adult subspecialists. Overall, subspecialists identified the lack of a central authority to monitor and inform child healthcare provided by pediatric subspecialists as a challenge. Future research on the pediatric subspecialty workforce and the children it serves will be necessary to ensure these children's needs are met. Together, these articles provide overarching and subspecialty-specific recommendations to improve training, recruitment, and retention of a diverse workforce, implement innovative models of care, drive policy changes, and advise future research.

Evaluating the liver abscess microbiota of beef cattle during a reduction in tylosin supplementation shows differences according to abscess size and fraction.

Liver abscesses (LA) resulting from bacterial infection in cattle pose a significant global challenge to the beef and dairy industries. Economic losses from liver discounts at slaughter and reduced animal performance drive the need for effective mitigation strategies. Tylosin phosphate supplementation is widely used to reduce LA occurrence, but concerns over antimicrobial overuse emphasize the urgency to explore alternative approaches. Understanding the microbial ecology of LA is crucial to this, and we hypothesized that a reduced timeframe of tylosin delivery would alter LA microbiomes. We conducted 16S rRNA sequencing to assess severe liver abscess bacteriomes in beef cattle supplemented with in-feed tylosin. Our findings revealed that shortening tylosin supplementation did not notably alter microbial communities. Additionally, our findings highlighted the significance of sample processing methods, showing differing communities in bulk purulent material and the capsule-adhered material. Fusobacterium or Bacteroides ASVs dominated LA, alongside probable opportunistic gut pathogens and other microbes. Moreover, we suggest that liver abscess size correlates with microbial community composition. These insights contribute to our understanding of factors impacting liver abscess microbial ecology and will be valuable in identifying antibiotic alternatives. They underscore the importance of exploring varied approaches to address LA while reducing reliance on in-feed antibiotics.

Efficacy of manual therapy for sacroiliac joint pain syndrome: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: This study examined the efficacy of manual therapy for pain and disability measures in adults with sacroiliac joint pain syndrome (SIJPS). METHODS: We searched six databases, including gray literature, on 24 October 2023, for randomized controlled trials (RCTs) examining sacroiliac joint (SIJ) manual therapy outcomes via pain or disability in adults with SIJPS. We evaluated quality via the Physiotherapy Evidence Database scale and certainty via Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Standardized mean differences (SMDs) in post-treatment pain and disability scores were pooled using random-effects models in meta-regressions. RESULTS: We included 16 RCTs (421 adults; mean age = 37.7 years), with 11 RCTs being meta-analyzed. Compared to non-manual physiotherapy (i.e. exercise ± passive modalities; 10 RCTs) or sham (1 RCT) interventions, SIJ manual therapy did not significantly reduce pain (SMD: -0.88; 95%-CI: -1.84; 0.08, p = 0.0686) yet had a statistically significant moderate effect in reducing disability (SMD: -0.67; 95% CI: -1.32; -0.03, p = 0.0418). The superiority of individual manual therapies was unclear due to low sample size, wide confidence intervals for effect estimates, and inability to meta-analyze five RCTs with a unique head-to-head design. RCTs were of 'good' (56%) or 'fair' (44%) quality, and heterogeneity was high. Certainty was very low for pain and low for disability outcomes. CONCLUSION: SIJ manual therapy appears efficacious for improving disability in adults with SIJPS, while its efficacy for pain is uncertain. It is unclear which specific manual therapy techniques may be more efficacious. These findings should be interpreted cautiously until further high-quality RCTs are available examining manual therapy against control groups such as exercise. REGISTRATION: PROSPERO (CRD42023394326).

Harnessing Fermentation May Enhance the Performance of Biological Sulfate-Reducing Bioreactors.

Biological sulfate reduction (BSR) represents a promising strategy for bioremediation of sulfate-rich waste streams, yet the impact of metabolic interactions on performance is largely unexplored. Here, genome-resolved metagenomics was used to characterize 17 microbial communities in reactors treating synthetic sulfate-contaminated solutions. Reactors were supplemented with lactate or acetate and a small amount of fermentable substrate. Of the 163 genomes representing all the abundant bacteria, 130 encode 321 NiFe and FeFe hydrogenases and all genomes of the 22 sulfate-reducing microorganisms (SRM) encode genes for H2 uptake. We observed lactate oxidation solely in the first packed bed reactor zone, with propionate and acetate oxidation in the middle and predominantly acetate oxidation in the effluent zone. The energetics of these reactions are very different, yet sulfate reduction kinetics were unaffected by the type of electron donor available. We hypothesize that the comparable rates, despite the typically slow growth of SRM on acetate, are a result of the consumption of H2 generated by fermentation. This is supported by the sustained performance of a predominantly acetate-supplemented stirred tank reactor dominated by diverse fermentative bacteria encoding FeFe hydrogenase genes and SRM capable of acetate and hydrogen consumption and CO2 assimilation. Thus, addition of fermentable substrates to stimulate syntrophic relationships may improve the performance of BSR reactors supplemented with inexpensive acetate.

Addition of Vitamin C Mitigates the Loss of Antioxidant Capacity, Vitality and DNA Integrity in Cryopreserved Human Semen Samples.

Cryopreservation of human spermatozoa is a necessity for males suffering from infertility who cannot produce fresh semen for insemination. However, current ART cryopreservation protocols are associated with losses of sperm motility, vitality and DNA integrity, which are thought to be linked to the induction of oxidative damage and the toxic properties of commercial cryoprotectants (CPAs). Preventing or mitigating these losses would be hugely beneficial to sperm survival during ART. Therefore, in this in vitro investigation, lipid peroxidation, production of reactive oxygen species, movement characteristics, antioxidant capacity, vitality, and DNA integrity were examined in semen samples both pre- and post-cryopreservation with CPA supplementation. The findings revealed a 50% reduction in antioxidant capacity with CPA addition, which was accompanied by significant increases in generation of reactive oxygen species and formation of lipid aldehydes. These changes were, in turn, correlated with reductions in sperm viability, motility and DNA integrity. Antioxidant supplementation generated bell-shaped dose-response curves with both resveratrol and vitamin C, emphasising the vulnerability of these cells to both oxidative and reductive stress. At the optimal dose, vitamin C was able to significantly enhance vitality and reduce DNA damage recorded in cryopreserved human spermatozoa. An improvement in sperm motility did not reach statistical significance, possibly because additional pathophysiological mechanisms limit the potential effectiveness of antioxidants in rescuing this aspect of sperm function. The vulnerability of human spermatozoa to reductive stress and the complex nature of sperm cryoinjury will present major challenges in creating the next generation of cryoprotective media.

Doxorubicin-Based Ionic Nanomedicines for Combined Chemo-Phototherapy of Cancer.

Synergistic combination therapy approach offers lots of options for delivery of materials with anticancer properties, which is a very promising strategy to treat a variety of malignant lesions with enhanced therapeutic efficacy. The current study involves a detailed investigation of combination ionic nanomedicines where a chemotherapeutic drug is coupled with a photothermal agent to attain dual mechanisms (chemotherapy (chemo) and photothermal therapy (PTT)) to improve the drug's efficacy. An FDA-approved Doxorubicin hydrochloride (DOX·HCl) is electrostatically attached with a near-infrared cyanine dye (ICG, IR783, and IR820), which serves as a PTT drug using ionic liquid chemistry to develop three ionic material (IM)-based chemo-PTT drugs. Carrier-free ionic nanomedicines (INMs) are derived from ionic materials (IMs). The photophysical properties of the developed combination IMs and their INMs were studied in depth. The phototherapeutic efficiency of the combination drugs was evaluated by measuring the photothermal conversion efficiency and singlet-oxygen quantum yield. The improved photophysical properties of the combination nanomedicines in comparison to their parent compounds significantly enhanced INMs' photothermal efficiency. Cellular uptake, dark and light toxicity studies, and cell death mechanisms of the chemo-PTT nanoparticles were also studied in vitro. The combination INMs exhibited enhanced cytotoxicity compared to their respective parent compounds. Moreover, the apoptosis cell death mechanism was almost doubled for combination nanomedicine than the free DOX, which is attributed to enhanced cellular uptake. Examination of the combination index and improved in vitro cytotoxicity results revealed a great synergy between chemo and PTT drugs in the developed combination nanomedicines.

Child Health and the Neonatal-Perinatal Medicine Workforce: 2020-2040.

In 2022, 3.7 million children were born in the United States, of whom ∼600 000 received care from a neonatologist. The dramatic growth of the neonatal-perinatal medicine (NPM) workforce from 375 in 1975 to 5250 in 2022 has paralleled exploding clinical demand. As newborn medicine continues to push the limits of gestational viability and medical complexity, the NPM workforce must advance in numbers, clinical capability, scientific discovery, and leadership. This article, as part of an American Board of Pediatrics Foundation-sponsored supplement that is designed to project the future of the pediatric subspecialty workforce, features a discussion of the NPM workforce's history and current status, factors that have shaped its current profile, and some plausible scenarios of the workforce's needs and configuration in the future. In the article, we use an analytical model that forecasts the growth trajectory of the neonatologist workforce from 2020 through 2040. The model uses recent data on the number of neonatologists and clinical work equivalents per 100 000 children and projects future workforce supply under several theoretical scenarios created by modifying key baseline parameters. The predictions of this model confirm the need for a greater sustainable clinical capacity of the NPM workforce. Several future trends indicate that there may be geographic shortages of neonatologists, similar to expected shortages in other pediatric subspecialties. We do not address what an appropriate target for workforce size should be with the model or this article because the current and projected geographic variability in the NPM workforce and risk-appropriate care suggest that a uniform answer is unlikely.

Engagement in Integrative and Nonpharmacologic Pain Management Modalities Among Adults with Chronic Pain: Analysis of the 2019 National Health Interview Survey.

Objective: To examine variables associated with engagement in (1) integrative health and medicine (IHM) and (2) nonpharmacologic modalities rather than opioids among United States adults with chronic pain. Methods: Using the 2019 National Health Interview Survey, we examined sociodemographic, pain, and mental health predictors of (1) the sum of IHM modalities (ie, chiropractic care, yoga/Tai Chi, massage, or meditation/guided imagery) used to manage pain and (2) exclusive engagement in nonpharmacologic pain management modalities (ie, IHM, a chronic pain self-management program, support groups, or physical, rehabilitative, occupational, or talk therapy) or opioids in the past 3 months. Results: Metropolitan residency, higher family income, higher education levels, increased number of pain locations, and increased frequency of pain limiting life/work activities were associated with increased odds of IHM engagement. Older age, male sex, non-Hispanic Black/African American race/ethnicity, and daily opioid use were associated with decreased odds of IHM engagement. Older age, male sex, and increased depressive symptoms were associated with decreases in the count of IHM modalities used to manage pain. Metropolitan residency, higher family income, and higher education levels were associated with increased odds of exclusive nonpharmacologic modality engagement. Older age and increasing frequency of pain limiting life/work activities were associated with decreased odds of exclusive nonpharmacologic modality engagement. Conclusions: We identified several contrasts between factors prevalent among individuals with chronic pain and factors associated with engagement in nonpharmacologic and IHM modalities. These results support efforts to address barriers to accessing these modalities among subpopulations of adults with chronic pain (eg, older adults, individuals identifying as Black/African American, rural residents, and those with lower levels of education and income).

Association between spinal manipulative therapy and lumbar spine reoperation after discectomy: a retrospective cohort study.

BACKGROUND: Patients who undergo lumbar discectomy may experience ongoing lumbosacral radiculopathy (LSR) and seek spinal manipulative therapy (SMT) to manage these symptoms. We hypothesized that adults receiving SMT for LSR at least one year following lumbar discectomy would be less likely to undergo lumbar spine reoperation compared to matched controls not receiving SMT, over two years' follow-up. METHODS: We searched a United States network of health records (TriNetX, Inc.) for adults aged ≥ 18 years with LSR and lumbar discectomy ≥ 1 year previous, without lumbar fusion or instrumentation, from 2003 to 2023. We divided patients into two cohorts: (1) chiropractic SMT, and (2) usual care without chiropractic SMT. We used propensity matching to adjust for confounding variables associated with lumbar spine reoperation (e.g., age, body mass index, nicotine dependence), calculated risk ratios (RR), with 95% confidence intervals (CIs), and explored cumulative incidence of reoperation and the number of SMT follow-up visits. RESULTS: Following propensity matching there were 378 patients per cohort (mean age 61 years). Lumbar spine reoperation was less frequent in the SMT cohort compared to the usual care cohort (SMT: 7%; usual care: 13%), yielding an RR (95% CIs) of 0.55 (0.35-0.85; P = 0.0062). In the SMT cohort, 72% of patients had ≥ 1 follow-up SMT visit (median = 6). CONCLUSIONS: This study found that adults experiencing LSR at least one year after lumbar discectomy who received SMT were less likely to undergo lumbar spine reoperation compared to matched controls not receiving SMT. While these findings hold promise for clinical implications, they should be corroborated by a prospective study including measures of pain, disability, and safety to confirm their relevance. We cannot exclude the possibility that our results stem from a generalized effect of engaging with a non-surgical clinician, a factor that may extend to related contexts such as physical therapy or acupuncture. REGISTRATION: Open Science Framework ( https://osf.io/vgrwz ).

Vitamin B6 and vitamin D deficiency co-occurrence in geriatric memory patients.

INTRODUCTION: Vitamin B6 and D levels are not assessed routinely in geriatric memory patients. This study examined vitamin levels to determine the potential effects on cognition. METHODS: A chart review was conducted of 203 consecutive patients over a 12-month period. Levels of vitamins B1, B6, B12, and D were obtained on the day of clinic to identify deficiencies. A mental status exam (Mini Mental State Examination [MMSE]) was also performed. RESULTS: One hundred sixty-seven patients had one or more vitamin levels obtained on the day of clinical evaluation. Vitamin B6 deficiency was the most common (37.5%), followed by vitamin D deficiency (36.8%). A chi-square test revealed significant co-occurrence of deficiency of vitamins B6 and D (p < 0.001). Vitamin B6 and D deficiencies were associated with lower MMSE scores (p < 0.05). DISCUSSION: Vitamin B6 and D deficiencies are common in geriatric patients. The coexistence of these vitamin deficiencies has a significant association with cognitive performance, indicating the clinical importance of monitoring and supplementation.

Hierarchical End Points in Prior Heart Failure Trials and the HEART-FID Trial.

BACKGROUND: Clinical trials in heart failure (HF) traditionally use time-to-event analyses focusing on death and hospitalization for HF. These time-to-first event analyses may have more limited abilities to assess the probability of benefiting from a therapy, especially if that benefit manifests as improved functional status rather than reduced risk of death or HF hospitalization. Hierarchical end points including clinical outcomes and patient status measures allow for ranked evaluation of outcomes in 1 metric assessing whether patients randomized to intervention or control are more likely to derive an overall benefit while also allowing more patients to contribute to the primary outcome. METHODS: We review the rationale for using hierarchical end points in HF trials, provide examples of HF trials that used this type of end point, and discuss its use in the HEART-FID trial (Randomized Placebo-Controlled Trial of Ferric Carboxymaltose as Treatment for Heart Failure With Iron Deficiency), the largest HF trial to date implementing a hierarchical end point analysis for the primary outcome. RESULTS: Using a hierarchical end point as the primary outcome allows for the inclusion of different types of outcomes in 1 ranked end point, making it possible to more holistically assess the potential utility of a new therapy on patient well-being and outcomes. CONCLUSIONS: Hierarchical end points assess the potential utility of a new therapy on patient well-being and outcome more holistically than time-to-first event analysis. Trials that would not have been feasible due to decreasing rates of death and hospitalization in the HF population can use hierarchical end points to successfully power studies to identify promising HF therapies. The HEART-FID trial used hierarchical end points to better determine the role of intravenous ferric carboxymaltose in patients with HF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037931.