"The healthcare system did fail me repeatedly": a qualitative study on experiences of healthcare among Canadian women with Cushing's syndrome.

BACKGROUND: As a rare endocrine disorder, Cushing's Syndrome (Cushing's) is characterized by numerous symptoms and a non-specific presentation, leading to a delay to diagnosis for patients with this disease. To date, research examining the lived experiences of patients with Cushing's in healthcare is absent in the literature. This preliminary inquiry into the healthcare experiences of women with Cushing's aimed to examine the utility of this line of inquiry to support the patient centered care of individuals with Cushing's. METHODS: Seven women from across Canada with endogenous Cushing's participated in the study. Semi-structured interviews were conducted examining participants' healthcare and body-related experiences with Cushing's. Results pertaining to healthcare experiences were analyzed for the current study using reflexive thematic analysis. RESULTS: Four themes emerged whereby women with Cushing's experienced (1) a lack of patient centered care, characterized by provider miscommunication and medical gaslighting; (2) a misunderstanding of their symptoms as related to weight gain; (3) weight stigma in healthcare encounters; and (4) a shift in their quality of care following diagnosis. CONCLUSIONS: The results highlight the importance of patient centered care as well as the negative impact of commonly reported barriers to patient centered care. Cushing's specific barriers to patient centered care may include weight stigma as well as the rare incidence of Cushing's. Further research is needed to better understand the healthcare experiences of people with Cushing's in Canada.

Association Between Vitamin D Insufficiency and Impaired Bone Density Among Adolescents With Perinatally Acquired HIV Infection.

Background: Stunting and pubertal delay are common among children growing up with human immunodeficiency virus (HIV) and are associated with bone and muscle impairments. We investigated factors associated with bone density and muscle function in adolescents living with HIV (ALWH). Methods: The VITALITY trial (PACTR202009897660297) investigated whether vitamin D and calcium supplementation improves musculoskeletal health among ALWH. A total of 842 ALWH aged 11-19 years, established on antiretroviral therapy (ART) for ≥6 months, were enrolled from HIV clinics in Zambia and Zimbabwe. Clinical history and examination were undertaken, and serum 25-hydroxyvitamin D3 (25[OH]D3) was measured. Dual-energy X-ray absorptiometry measured total-body-less-head bone mineral density adjusted for height (TBLH-BMDHT), and lumbar spine bone mineral apparent density (LS-BMAD) z scores. The association between a priori-defined covariates and musculoskeletal outcomes were investigated using baseline enrollment data and multivariable logistic regression. Results: TBLH-BMDHT  z scores were impaired (mean, -1.42 for male and -0.63 female participants), as were LS-BMAD z scores (mean -1.15 for male and -0.47 for female participants). In bivariate analysis, early pubertal stage, less physical activity, and older age at ART initiation were associated with lower TBLH-BMDHT  z scores. Younger age, early pubertal stage, and low socioeconomic status were associated with lower LS-BMAD z scores. Grip-strength-for-height and jump-power-for-height z scores were associated with lower TBLH-BMDHT and LS-BMAD z scores. Low dietary vitamin D and calcium were associated with lower adjusted TBLH-BMDHT  z scores. Lower 25(OH)D3 was associated with lower adjusted TBLH-BMDHT and LS-BMAD z scores. Conclusions: Deficits in bone density are common in ALWH. Vitamin D and calcium supplementation and promotion of exercise may improve musculoskeletal health among perinatally infected ALWH.

Suspension electrospinning of decellularized extracellular matrix: A new method to preserve bioactivity.

Decellularized extracellular matrices (dECM) have strong regenerative potential as tissue engineering scaffolds; however, current clinical options for dECM scaffolds are limited to freeze-drying its native form into sheets. Electrospinning is a versatile scaffold fabrication technique that allows control of macro- and microarchitecture. It remains challenging to electrospin dECM, which has led researchers to either blend it with synthetic materials or use enzymatic digestion to fully solubilize the dECM. Both strategies reduce the innate bioactivity of dECM and limit its regenerative potential. Herein, we developed a new suspension electrospinning method to fabricate a pure dECM fibrous mesh that retains its innate bioactivity. Systematic investigation of suspension parameters was used to identify critical rheological properties required to instill "spinnability," including homogenization, concentration, and particle size. Homogenization enhanced particle interaction to impart the requisite elastic behavior to withstand electrostatic drawing without breaking. A direct correlation between concentration and viscosity was observed that altered fiber morphology; whereas, particle size had minimal impact on suspension properties and fiber morphology. The versatility of this new method was demonstrated by electrospinning dECM with three common decellularization techniques (Abraham, Badylak, Luo) and tissue sources (intestinal submucosa, heart, skin). Bioactivity retention after electrospinning was confirmed using cell proliferation, angiogenesis, and macrophage polarization assays. Collectively, these findings provide a framework for researchers to electrospin dECM for diverse tissue engineering applications.

Impact of scheduled partial exchange transfusions on outcomes in pregnant patients with severe sickle cell disease: a retrospective study.

INTRODUCTION: The incidence of feto-maternal complications is high in women with sickle cell disease. The paucity of high-quality evidence has led to conditional recommendations for transfusional support in pregnant patients. This study aimed to assess if scheduled partial red cell exchanges impact pregnancy outcomes in sickle cell disease patients. METHODS: Forty-seven pregnancies were divided into two groups based on whether patients received scheduled partial red cell exchanges. Collected data included demographics, laboratory values, number of hospital visits, and prenatal/perinatal/postnatal outcomes. Data were analyzed using descriptive statistics, t-test, Chi-square and Fisher's exact tests, and binary regression. RESULTS: The mean age was 25.09 ± 4.39 years. Of 47 patients, 14 (29.8%) received scheduled red cell exchanges with 78.6% compliance with no evidence of alloimmunization. This procedure during pregnancy was associated with fewer admissions for pain crises (p=0.032), higher gestational age at delivery (p=0.007), and a lower incidence of neonatal intensive care admissions (p=0.011; odds ratio: 0.071; 95% confidence interval: 0.008-0.632). Logistic regression did not show any significant associations. CONCLUSIONS: Sickle cell disease patients with complications in previous pregnancies, including high hospitalization/admission rates and preterm deliveries, could benefit from scheduled partial red cell exchanges or simple transfusions. Further research is needed to guide clinical practice pertaining to transfusional support in pregnant patients with sickle cell disease.

Moving beyond mean heart dose: The importance of cardiac substructures in radiation therapy toxicity.

Normal tissue tolerance dose limits to the heart have been established to reduce the risk of radiation-induced cardiac disease (RICD). Dose constraints have been developed based on either the mean dose delivered to the whole heart (MHD) or the dose delivered to a specific volume, for example, volume of heart receiving equal to or greater than 30 Gy (V30). There is increasing evidence that the impact of thoracic radiation on cardiac morbidity and mortality has been underestimated. Consequently, there is a need to reduce the dose delivered to the heart in radical radiotherapy treatment planning. The pathophysiology of RICD may relate to dose to specific cardiac substructures (CS) rather than the traditionally observed MHD for common toxicities. The MHD or V30 Gy threshold dose rarely represents the true dose delivered to individual CS. Studies have shown the dose to specific areas may be more strongly correlated with overall survival (OS). With advances in modern radiotherapy techniques, it is vital that we develop robust, evidence-based dose limits for CS, to fully understand and reduce the risk of RICD, particularly in high-risk populations with cardiac risk factors. The following review will summarise the existing evidence of dose limits to CS, explain how dose limits may vary according to different disease sites or radiation techniques and propose how radiotherapy plans can be optimised to reduce the dose to these CS in clinical practice.

Epstein-Barr virus replication within differentiated epithelia requires pRb sequestration of activator E2F transcription factors.

Epstein-Barr virus (EBV) co-infections with human papillomavirus (HPV) have been observed in oropharyngeal squamous cell carcinoma. Modeling EBV/HPV co-infection in organotypic epithelial raft cultures revealed that HPV16 E7 inhibited EBV productive replication through the facilitated degradation of the retinoblastoma protein pRb/p105. To further understand how pRb is required for EBV productive replication, we generated CRISPR-Cas9 pRb knockout (KO) normal oral keratinocytes (NOKs) in the context of wild-type and mutant K120E p53. EBV replication was examined in organotypic rafts as a physiological correlate for epithelial differentiation. In pRb KO rafts, EBV DNA copy number was statistically decreased compared to vector controls, regardless of p53 context. Loss of pRb did not affect EBV binding or internalization of calcium-treated NOKs or early infection of rafts. Rather, the block in EBV replication correlated with impaired immediate early gene expression. An EBV infection time course in rafts with mutant p53 demonstrated that pRb-positive basal cells were initially infected with delayed replication occurring in differentiated layers. Loss of pRb showed increased S-phase progression makers and elevated activator E2F activity in raft tissues. Complementation with a panel of pRb/E2F binding mutants showed that wild type or pRb∆685 mutant capable of E2F binding reduced S-phase marker gene expression, rescued EBV DNA replication, and restored BZLF1 expression in pRb KO rafts. However, pRb KO complemented with pRb661W mutant, unable to bind E2Fs, failed to rescue EBV replication in raft culture. These findings suggest that EBV productive replication in differentiated epithelium requires pRb inhibition of activator E2Fs to restrict S-phase progression.IMPORTANCEA subset of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma is co-positive for Epstein-Barr virus (EBV). Potential oncogenic viral interactions revealed that HPV16 E7 inhibited productive EBV replication within the differentiated epithelium. As E7 mediates the degradation of pRb, we aimed to establish how pRb is involved in EBV replication. In the context of differentiated epithelium using organotypic raft culture, we evaluated how the loss of pRb affects EBV lytic replication to better comprehend EBV contributions to carcinogenesis. In this study, ablation of pRb interfered with EBV replication at the level of immediate early gene expression. Loss of pRb increased activator E2Fs and associated S-phase gene expression throughout the differentiated epithelium. Complementation studies showed that wild type and pRb mutant capable of binding to E2F rescued EBV replication, while pRb mutant lacking E2F binding did not. Altogether, these studies support that in differentiated tissues, HPV16 E7-mediated degradation of pRb inhibits EBV replication through unregulated E2F activity.

Spinal Cord Stimulation Improves Quality of Life for Patients With Chronic Pain-Data From the UK and Ireland National Neuromodulation Registry.

INTRODUCTION: Spinal cord stimulation (SCS) is a well-established treatment for chronic pain and is supported by numerous studies. However, some recent articles have questioned its efficacy. This article examines a cohort of >1800 patients with SCS from the UK and Ireland National Neuromodulation Registry. It is intended to provide a "real-world" assessment of efficacy and compare its effects with other procedures performed for painful indications. MATERIALS AND METHODS: Quality of life (QoL) data (EuroQoL five-level [EQ5D]) and demographic data were extracted from the National Neuromodulation Registry for all patients (N = 1811) who underwent SCS for chronic pain in 27 centers in the UK between February 2018 and July 2022. These were compared with data from the published literature for other commonly performed elective surgical procedures. RESULTS: The EQ5D utility index increased by a mean of 0.202 in the 1236 patients with paired pre- and postoperative utility scores. The median utility was 0.263 (interquartile range [IQR] = 0.384; n = 1811) preoperatively, whereas at six months after the operation, it was 0.550 (IQR = 0.396; n = 1025), p < 0.0001, Wilcoxon rank sum test. The median utility score at 12 months postoperation was 0.548 (IQR = 0.417; n = 970). There was no difference in utility scores at six months and 12 months after implantation (p = 0.15, Wilcoxon rank sum test). There was a significant improvement in QoL in all five domains of the five-level EQ5D tool at six months after baseline (p < 0.01, for all subcategories), and this was sustained at one year after implantation. The baseline utility was lower than in patients who underwent elective surgery for other painful conditions, and the absolute (and proportionate) increase in utility produced by SCS was greater than that achieved with most other interventions. CONCLUSIONS: SCS increases the QoL in patients requiring surgery for pain. Similar results were seen regardless of SCS indication. When comparing analogous data bases, SCS produces a greater percentage improvement in EQ5D utility than do many other elective surgical procedures for painful conditions, including spinal surgery and some joint replacements.

Alpha and theta oscillations on a visual strategic processing task in age-related hearing loss.

Introduction: Emerging evidence suggests changes in several cognitive control processes in individuals with age-related hearing loss (ARHL). However, value-directed strategic processing, which involves selectively processing salient information based on high value, has been relatively unexplored in ARHL. Our previous work has shown behavioral changes in strategic processing in individuals with ARHL. The current study examined event-related alpha and theta oscillations linked to a visual, value-directed strategic processing task in 19 individuals with mild untreated ARHL and 17 normal hearing controls of comparable age and education. Methods: Five unique word lists were presented where words were assigned high- or low-value based on the letter case, and electroencephalography (EEG) data was recorded during task performance. Results: The main effect of the group was observed in early time periods. Specifically, greater theta synchronization was seen in the ARHL group relative to the control group. Interaction between group and value was observed at later time points, with greater theta synchronization for high- versus low-value information in those with ARHL. Discussion: Our findings provide evidence for oscillatory changes tied to a visual task of value-directed strategic processing in individuals with mild untreated ARHL. This points towards modality-independent neurophysiological changes in cognitive control in individuals with mild degrees of ARHL and adds to the rapidly growing literature on the cognitive consequences of ARHL.

Effect of Mifepristone on Migration and Proliferation of Oral Cancer Cells.

Glucocorticoid receptor (GR) overexpression has been linked to increased tumour aggressiveness and treatment resistance. GR antagonists have been shown to enhance treatment effectiveness. Emerging research has investigated mifepristone, a GR antagonist, as an anticancer agent with limited research in the context of oral cancer. This study investigated the effect of mifepristone at micromolar (µM) concentrations of 1, 5, 10 and 20 on the proliferation and migration of oral cancer cells, at 24 and 48 h. Scratch and scatter assays were utilised to assess cell migration, MTT assays were used to measure cell proliferation, Western blotting was used to investigate the expression of GR and the activation of underlying Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signalling pathways, and immunofluorescence (IF) was used to determine the localisation of proteins in HaCaT (immortalised human skin keratinocytes), TYS (oral adeno squamous cell carcinoma), and SAS-H1 cells (squamous cell carcinoma of human tongue). Mifepristone resulted in a dose-dependent reduction in the proliferation of HaCaT, TYS, and SAS-H1 cells. Mifepristone at a concentration of 20 µM effectively reduced collective migration and scattering of oral cancer cells, consistent with the suppression of the PI3K-Akt and MAPK signalling pathways, and reduced expression of N-Cadherin. An elongated cell morphology was, however, observed, which may be linked to the localisation pattern of E-Cadherin in response to mifepristone. Overall, this study found that a high concentration of mifepristone was effective in the suppression of migration and proliferation of oral cancer cells via the inhibition of PI3K-Akt and MAPK signalling pathways. Further investigation is needed to define its impact on epithelial-mesenchymal transition (EMT) markers.

COVID-19 Public Health Restrictions and New Mothers' Mental Health: A Qualitative Scoping Review.

Public health restrictions to protect physical health during the COVID-19 pandemic had unintended effects on mental health, which may have disproportionately affected some potentially vulnerable groups. This scoping review of qualitative research provides a narrative synthesis of new mothers' perspectives on their mental health during COVID-19 pandemic restrictions through pregnancy to the postpartum period. Database searches in PubMed, CINAHL, and PsycINFO sought primary research studies published until February 2023, which focused on new mothers' self-perceived mental health during the pandemic (N = 55). Our synthesis found that new mothers' mental health was impacted by general public health restrictions resulting in isolation from family and friends, a lack of community support, and impacts on the immediate family. However, public health restrictions specific to maternal and infant healthcare were most often found to negatively impact maternal mental health, namely, hospital policies prohibiting the presence of birthing partners and in-person care for their infants. This review of qualitative research adds depth to previous reviews that have solely examined the quantitative associations between COVID-19 public health restrictions and new mothers' mental health. Here, our review demonstrates the array of adverse impacts of COVID-19 public health restrictions on new mothers' mental health throughout pregnancy into the postpartum period, as reported by new mothers. These findings may be beneficial for policy makers in future public health emergency planning when evaluating the impacts and unintended consequences of public health restrictions on new mothers.

Update: Vitamin D3 and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY trial): study protocol for a randomised placebo-controlled trial.

BACKGROUND: Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. This paper is an update to an already existing protocol that was previously published in Trials in 2022 and details changes in the trial outcomes. METHODS/DESIGN: We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D3 (20,000 IU) plus daily calcium carbonate (500 mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11-19 years taking ART for ≥ 6 months will be enrolled and followed up for 96 weeks. The primary outcome is DXA-measured total body less-head bone mineral density Z-score (TBLH-BMD) at 48 weeks and is an update to the previous primary outcome total body less-head bone mineral content adjusted for lean mass (TBLH-BMCLBM) Z-score. The primary outcome was updated to address the substantial differences in distributions of TBLH-BMCLBM Z-score between the two sites as a result of software differences of the DXA machines. Secondary outcomes are DXA-measured TBLH-BMD Z-score adjusted for height at 48 weeks a new secondary outcome, lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip-strength at 48 and 96 weeks, and TBLH-BMD Z-score at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function. DISCUSSION: This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual through childhood is critical for optimising adolescent and early adult bone health, and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR20200989766029. Registered on September 3, 2020. URL of trial registry record: https://pactr.samrc.ac.za TRIAL STATUS: Participant follow-up completed; data analysis ongoing.

Pim Kinase Inhibition Disrupts CXCR4 Signalling in Megakaryocytes and Platelets by Reducing Receptor Availability at the Surface.

A key step in platelet production is the migration of megakaryocytes to the vascular sinusoids within the bone marrow. This homing is mediated by the chemokine CXCL12 and its receptor CXCR4. CXCR4 is also a positive regulator of platelet activation and thrombosis. Pim-1 kinase has been shown to regulate CXCR4 signalling in other cell types, and we have previously described how Pim kinase inhibitors attenuate platelet aggregation to CXCL12. However, the mechanism by which Pim-1 regulates CXCR4 signalling in platelets and megakaryocytes has yet to be elucidated. Using human platelets, murine bone marrow-derived megakaryocytes, and the megakaryocyte cell line MEG-01, we demonstrate that pharmacological Pim kinase inhibition leads to reduced megakaryocyte and platelet function responses to CXCL12, including reduced megakaryocyte migration and platelet granule secretion. Attenuation of CXCL12 signalling was found to be attributed to the reduced surface expression of CXCR4. The decrease in CXCR4 surface levels was found to be mediated by rapid receptor internalisation, in the absence of agonist stimulation. We demonstrate that pharmacological Pim kinase inhibition disrupts megakaryocyte and platelet function by reducing constitutive CXCR4 surface expression, decreasing the number of receptors available for agonist stimulation and signalling. These findings have implications for the development and use of Pim kinase inhibitors for the treatment of conditions associated with elevated circulating levels of CXCL12/SDF1α and increased thrombotic risk.

Intracellular Flow Cytometry ("Phosphoflow") to Assess Signal Transduction in Rare Populations Such As Memory B Cell Subsets and Plasma Cells.

Intracellular flow cytometry is a powerful technique that can be used to interrogate signalling in rare cellular populations. The strengths of the technique are that massively parallel readouts can be gained from thousands of single cells simultaneously, and the assay is fast and relatively straightforward. This plate-based protocol enables different doses and different timepoints of stimulation to be assessed and has been optimized for rare B cell populations. Combining this technique with high-dimensional flow cytometry enables multiple signalling proteins to be measured with high confidence.

Exploring Experiences of People With Knee Osteoarthritis Who Received a Physiotherapist-Delivered Dietary Weight Loss and Exercise Intervention: A Mixed Methods Study.

OBJECTIVE: Explore the experiences of people with knee osteoarthritis (OA) who received a very low energy diet (VLED) and exercise program from a physiotherapist. METHODS: Mixed methods study involving questionnaires (n = 42) and semistructured interviews (n = 22) with randomized control trial participants with knee OA who had received a 6-month physiotherapist-delivered VLED weight loss and exercise intervention. Questionnaires measured participant satisfaction and perceptions about physiotherapist's skills/knowledge in delivery of the dietary intervention (measured on 5-7 point Likert scales). Interviews explored participant's experiences and were analyzed based on the principles of reflexive thematic analysis. RESULTS: Questionnaire response: 90%. Participants were satisfied with the program (95%), confident their physiotherapist had the required skills (84%) and knowledge (79%) to deliver the dietary intervention, felt comfortable talking to the physiotherapist about weight (74%), and would recommend others see a physiotherapist for the intervention they undertook (71%). The following four themes were developed from the interviews: (1) one-stop-shop of exercise and diet; (2) physiotherapist-delivered weight loss works (unsure initially; successfully lost weight); (3) physiotherapists knowledge and skills (exercise is forte; most thought physiotherapists had the necessary weight loss skills/knowledge, but some disagreed); and (4) physiotherapists have a role in weight loss (physiotherapists are intelligent, credible, and trustworthy; specific training in weight loss necessary). CONCLUSION: This study provides, to our knowledge, the first documented perspectives from people with OA who have received a physiotherapist-delivered weight loss intervention. Findings suggest physiotherapists may have a role in delivering a protocolized dietary intervention for some people with knee OA with overweight and obesity.

Longitudinal change in ultrasound-derived rectus femoris cross-sectional area in COPD.

Background: Skeletal muscle dysfunction is common in COPD. Ultrasound-derived rectus femoris cross-sectional area (RFCSA) is a radiation free, non-invasive measure of muscle bulk that relates to quadriceps strength in people with COPD. However, there are limited longitudinal data for RFCSA, and it is not known whether longitudinal change in RFCSA reflects change in quadricep strength, exercise capacity, lower limb function or muscle mass. We aimed to quantify longitudinal change in ultrasound-derived RFCSA and assess its relationship with change in quadriceps maximal voluntary contraction (QMVC), incremental shuttle walk test (ISWT), five-repetition sit-to-stand (5STS) and fat-free mass (FFM) over 12 months in people with COPD. Methods: We measured ultrasound-derived RFCSA, QMVC, ISWT, 5STS and FFM (measured by bioelectric impedance analysis) at baseline and 12 months in 169 people with stable COPD. Change was correlated using Pearson's or Spearman's coefficients. Results: Baseline characteristics: mean±sd age 70.4±9.4 years; FEV1 53.3±18.9% predicted. Over the course of 12 months mean RFCSA change was -33.7 mm2 (99% CI -62.6- -4.9 mm2; p=0.003) representing a mean±sd percentage change of -1.8±33.5%. There was a weak correlation between change in RFCSA and FFM (r=0.205, p=0.009), but not with change in QMVC, ISWT or 5STS. Conclusion: There is a statistically significant decrease in ultrasound-derived RFCSA over 12 months in people with stable COPD, but this decrease does not correlate with change in quadriceps strength, exercise capacity, FFM or lower limb function.

General population screening for type 1 diabetes using islet autoantibodies at the preschool vaccination visit: a proof-of-concept study (the T1Early study).

OBJECTIVE: Type 1 diabetes (T1D) screening programmes testing islet autoantibodies (IAbs) in childhood can reduce life-threatening diabetic ketoacidosis. General population screening is required to detect the majority of children with T1D, since in >85% there is no family history. Age 3-5 years has been proposed as an optimal age for a single screen approach. DESIGN: Capillary samples were collected from children attending their preschool vaccination and analysed for IAbs to insulin, glutamic acid decarboxylase, islet antigen-2 and zinc transporter 8 using radiobinding/luciferase immunoprecipitation system assays. Acceptability was assessed using semistructured interviews and open-ended postcard questionnaires with parents. SETTING: Two primary care practices in Oxfordshire, UK. MAIN OUTCOME MEASURES: The ability to collect capillary blood to test IAbs in children at the routine preschool vaccination (3.5-4 years). RESULTS: Of 134 parents invited, 66 (49%) were recruited (median age 3.5 years (IQR 3.4-3.6), 26 (39.4%) male); 63 provided a sample (97% successfully), and one participant was identified with a single positive IAb. Parents (n=15 interviews, n=29 postcards) were uniformly positive about screening aligned to vaccination and stated they would have been less likely to take part had screening been a separate visit. Themes identified included preparedness for T1D and the long-term benefit outweighing short-term upset. The perceived volume of the capillary sample was a potential concern and needs optimising. CONCLUSIONS: Capillary IAb testing is a possible method to screen children for T1D. Aligning collection to the preschool vaccination visit can be convenient for families without the need for an additional visit.

Assessment of the effect of gabapentin on blood pressure in cats with and without chronic kidney disease.

OBJECTIVES: The aim of the present study was to assess the effect of gabapentin on blood pressure (BP) in cats with and without chronic kidney disease (CKD). METHODS: A randomized, blinded, placebo-controlled crossover study was performed. A total of 29 cats were included: 13 cats with stable CKD (IRIS stage 2-4) and 16 apparently healthy cats (serum creatinine <1.6 mg/dl and urine specific gravity >1.035). The cats were evaluated twice, approximately 1 week apart, and BP (Doppler sphygmomanometry) was obtained 3 h after cats received either a single dose of gabapentin 10mg/kg PO or placebo. For each cat, BP readings were obtained at each visit using the same Doppler and sphygmomanometer unit, and the same cat holder and Doppler operator, in the same location. RESULTS: After administration of a single dose of gabapentin (10 mg/kg PO), BP was significantly lower (median 122 mmHg, range 82-170) than after administration of the placebo (median 150 mmHg, range 102-191; P = 0.001). In the CKD subgroup, BP was significantly lower after administration of gabapentin (median 129 mmHg, range 96-170) than after administration of the placebo (median 155 mmHg, range 102-191; P = 0.008). In the healthy cat subgroup, BP was significantly lower after administration of gabapentin (median 121 mmHg, range 82-139) than after administration of the placebo (median 137 mmHg, range 102-177; P = 0.002). The median change in BP was -12 mmHg (range -95 to 10) for healthy cats and -12 mmHg (range -43 to 21) for cats with CKD (no significant difference between subgroups). CONCLUSIONS AND RELEVANCE: Gabapentin may decrease arterial BP in cats with and without CKD and these findings should be taken into account when gabapentin is administered to patients in which measurement of BP is needed.