Comparative effectiveness of an individualized model of hemodialysis vs conventional hemodialysis: a study protocol for a multicenter randomized controlled trial (the TwoPlus trial).

BACKGROUND: Most patients starting chronic in-center hemodialysis (HD) receive conventional hemodialysis (CHD) with three sessions per week targeting specific biochemical clearance. Observational studies suggest that patients with residual kidney function can safely be treated with incremental prescriptions of HD, starting with less frequent sessions and later adjusting to thrice-weekly HD. This trial aims to show objectively that clinically matched incremental HD (CMIHD) is non-inferior to CHD in eligible patients. METHODS: An unblinded, parallel-group, randomized controlled trial will be conducted across diverse healthcare systems and dialysis organizations in the USA. Adult patients initiating chronic hemodialysis (HD) at participating centers will be screened. Eligibility criteria include receipt of fewer than 18 treatments of HD and residual kidney function defined as kidney urea clearance ≥3.5 mL/min/1.73 m2 and urine output ≥500 mL/24 h. The 1:1 randomization, stratified by site and dialysis vascular access type, assigns patients to either CMIHD (intervention group) or CHD (control group). The CMIHD group will be treated with twice-weekly HD and adjuvant pharmacologic therapy (i.e., oral loop diuretics, sodium bicarbonate, and potassium binders). The CHD group will receive thrice-weekly HD according to usual care. Throughout the study, patients undergo timed urine collection and fill out questionnaires. CMIHD will progress to thrice-weekly HD based on clinical manifestations or changes in residual kidney function. Caregivers of enrolled patients are invited to complete semi-annual questionnaires. The primary outcome is a composite of patients' all-cause death, hospitalizations, or emergency department visits at 2 years. Secondary outcomes include patient- and caregiver-reported outcomes. We aim to enroll 350 patients, which provides ≥85% power to detect an incidence rate ratio (IRR) of 0.9 between CMIHD and CHD with an IRR non-inferiority of 1.20 (α = 0.025, one-tailed test, 20% dropout rate, average of 2.06 years of HD per patient participant), and 150 caregiver participants (of enrolled patients). DISCUSSION: Our proposal challenges the status quo of HD care delivery. Our overarching hypothesis posits that CMIHD is non-inferior to CHD. If successful, the results will positively impact one of the highest-burdened patient populations and their caregivers. TRIAL REGISTRATION: Clinicaltrials.gov NCT05828823. Registered on 25 April 2023.

Symptom dimensions and cognitive-behavioural therapy outcome for pediatric obsessive-compulsive disorder.

OBJECTIVE: To examine whether obsessive-compulsive disorder (OCD) symptom subtypes are associated with response rates to cognitive-behavioural therapy (CBT) among pediatric patients. METHOD: Ninety-two children and adolescents with OCD (range = 7-19 years) received 14 sessions of weekly or intensive (daily psychotherapy sessions) family-based CBT. Assessments were conducted at baseline and post-treatment. Primary outcomes included scores on the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), remission status, and ratings on the Clinical Global Improvement (CGI) and Clinical Global Impression - Severity (CGI-Severity) scales. RESULTS: Seventy-six per cent of study participants (n = 70) were classified as treatment responders. Patients with aggressive/checking symptoms at baseline showed a trend (P = 0.06) toward improved treatment response and exhibited greater pre/post-treatment CGI-Severity change than those who endorsed only non-aggressive/checking symptoms. Step-wise linear regression analysis indicated higher scores on the aggressive/checking dimension were predictive of treatment-related change in the CGI-Severity index. Regression analysis with CY-BOCS score as the dependent variable showed no difference between OCD subtypes. CONCLUSION: Response to CBT in pediatric OCD patients does not differ substantially across subtypes.

Impacto del periodo de confinamiento por la pandemia COVID-19 en España sobre la salud y la atención recibida por los niños, niñas y jóvenes con discapacidad originada en la infancia / The impact of COVID-19 lockdown on the health and care of children and adolescents with a childhood-onset disability

Introducción Durante el periodo inicial del confinamiento por la COVID-19 se tomaron una serie de medidas de restricción que modificaron el día a día de la población. En este estudio se buscó conocer el impacto de este periodo en la salud física y mental de niños y jóvenes con discapacidad originada en la infancia, y de sus familias, y describir los cambios que se produjeron en el acceso a la educación y a los servicios de salud. Material y métodos Se realizó un estudio analítico observacional y transversal. Los datos se obtuvieron mediante una encuesta electrónica a través de una plataforma online realizada por la Academia Europea de Discapacidad Infantil. La encuesta incluyó preguntas sobre cuatro bloques temáticos: características sociodemográficas y de salud, impacto del confinamiento en la salud y bienestar, acceso a la educación y a los servicios de salud. Resultados Se obtuvieron 145 respuestas. El 45,5% de los niños y jóvenes eran totalmente dependientes. Se percibió un impacto sobre su salud física (54,5%), mental (47,6%) y sobre ambas (32%), mayores niveles de estrés (68,3%) y problemas de sueño (41,4%), así como una sobrecarga muy elevada en el 84,8% de los progenitores, sobre todo en familias de niños con mayor nivel de dependencia (p<0,001). El 55% de los niños y jóvenes no recibieron ningún tratamiento durante este periodo, ni siquiera remoto. Conclusiones El confinamiento afectó en gran medida la salud física y mental, así como a los servicios recibidos por los niños y jóvenes con discapacidad y sus familias (AU)

Introduction During the initial period of COVID-19 lockdown, restriction measures modified the day-to-day life of the population. This study sought to know the impact of this period on the physical and mental health of children and young people with disabilities originating in childhood, and their families, and to describe the changes that occurred in access to education and health services. Material and methods An observational and cross-sectional analytical study was carried out. The data were obtained by means of an electronic survey through an online platform carried out by the European Academy of Childhood Disability. The survey included questions on four thematic blocks: sociodemographic and health characteristics, impact of lock down on health and well-being, and access to education and health services. Results One hundred and forty-five responses were obtained. 45.5% of the children and young people were totally dependent. There was an impact on their physical (54.5%), mental health (47.6%) and both (32%), higher levels of stress (68.3%), and sleep problems (41.4%), as well as a high burden in 84.8% of parents, especially in families of children with a higher level of dependency (P=.00). 55% of children and young people did not receive any treatment during this period, not even remotely. Conclusions COVID lock down period greatly affected physical and mental health, as well as the services for children and young people with disabilities and their families (AU)

ALPs effective field theory and collider signatures.

We study the leading effective interactions between the Standard Model fields and a generic singlet CP-odd (pseudo-) Goldstone boson. Two possible frameworks for electroweak symmetry breaking are considered: linear and non-linear. For the latter case, the basis of leading effective operators is determined and compared with that for the linear expansion. Associated phenomenological signals at colliders are explored for both scenarios, deriving new bounds and analyzing future prospects, including LHC and High Luminosity LHC sensitivities. Mono-Z, mono-W, W-photon plus missing energy and on-shell top final states are most promising signals expected in both frameworks. In addition, non-standard Higgs decays and mono-Higgs signatures are especially prominent and expected to be dominant in non-linear realisations.

Acute haemodynamic effects of ibopamine and dopamine on isovolumic relaxation.

The effects of intraduodenal ibopamine (a new orally active inotropic agent claimed to have haemodynamic effects similar to dopamine) on isovolumic relaxation were monitored for 90 min in eight closed-chest anaesthetized dogs. Dopamine and epinine (ibopamine active metabolite) were also infused at graded doses. After 15 min, ibopamine (12 mg/kg) shortened the time constant of isovolumic relaxation, and increased stroke volume and mean aortic pressure. Peak positive dP/dt increased significantly only 10 min later. Heart rate did not change. Dopamine (10 micrograms/kg per min) similarly reduced the time constant, and increased stroke volume, mean aortic pressure, peak positive dP/dt and heart rate. Epinine (10 micrograms/kg per min) caused similar changes in peak positive dP/dt, stroke volume, mean aortic pressure, and accelerated time constant without raising the heart rate. Ibopamine and epinine therefore significantly improved the isovolumic relaxation phase, like dopamine, without however affecting the heart rate.

Haemodynamics at rest and under effort in chronic arteriovenous fistulae (AVFs).

Latero-lateral femoro-femoral arteriovenous fistulae (AVFs) were surgically created in mongrel dogs. After 7-9 months during which the dogs were trained on a treadmill, devices suitable for recording arterial pressure and aortic and coronary flow were chronically implanted. Haemodynamic parameters of the dogs were controlled either at rest or after effort, keeping AVFs open or manually closed. The results, when statistically processed, showed that haemodynamic changes induced by occlusion of AVFs at rest and under effort are similar from a qualitative point of view, but considerably more marked after muscular exercise. Under effort the shunt index calculated rose to a higher extent than cardiac output. The decrease in heart rate after AVFs occlusion was significantly correlated with flow in the fistulae. However, the Nicoladoni-Branham phenomenon ought to be used for indirect evaluation of the shunt flow.

Coronary blood flow and myocardial O2 consumption in hypertrophied cardiac muscle in dogs.

In dogs with experimental cardiac hypertrophy in resting conditions, coronary blood flow and myocardial O2 consumption increased proportionately to the cardiac mass; coronary flow and O2 consumption per gram of myocardium, therefore, ranged within normal values. The coronary reserve, neasured as the percentage increase in the coronary blood flow from rest till peak flow during reactive hyperaemia, was noticeably reduced, because it was partially utilized, even at rest, and consequently the possibility of an increase in flow after exercise or stress was diminished.

[Bipolar prosthesis in femoral neck fractures. Results and long-term acetabular tolerance of 36 bipolar arthroplasties]. / La prothèse intermédiaire dans les fractures du col du fémur. Résultats et tolérance cotyloïdienne à long terme de 36 arthroplasties intermédiaires.

The authors present the long-term results of 36 SEM cemented bipolar hip prostheses for femoral neck fractures with a mean observation time of 7.4 years. The objective was to study the acetabular tolerance of these prostheses comparing with Moore's and Thompson's conventional hemiarthroplasties. The average age of the patients was of 69 years. According to the Merle d'Aubigné's classification, clinical results were better than those results reported in the literature with conventional hemiarthroplasties. At long term, acetabular deteriorations were nevertheless frequent (41.6 per cent pinchings and 25 per cent protrusions), but with no clinical significative correlation. They seem to be favoured by technical errors (drilling, size of the cups) and acetabular morphology. The part of the intermediary joint's mobility is difficult to demonstrate and is far being univocal. The authors conclude, to the superiority of the bipolar hip prosthesis actually totalizable (long term clinical results and middle term acetabular tolerance) in comparison with the conventional hemiarthroplasties, and recommend the use of those implants in sub-capital displaced femoral neck fractures for elderly patients with no arthrosis.

A novel non-antibacterial, non-chelating hydroxypyrazoline derivative of minocycline inhibits nociception and oedema in mice.

BACKGROUND AND PURPOSE: Many in vitro and fewer in vivo studies have shown that tetracyclines present anti-inflammatory activity. We investigated if a novel non-antibacterial, non-chelating hydroxypyrazoline derivative of minocycline, 12S-hydroxy-1,12-pyrazolinominocycline (PMIN), also induced antinociceptive and anti-inflammatory effects. EXPERIMENTAL APPROACH: Antibacterial effects against a minocycline-sensitive Staphylococcus aureus strain were evaluated by applying a cylinder-plate agar diffusion technique. Antibacterial effects of diluted serum from mice pre-treated with minocycline or PMIN were also evaluated. Ca2+ binding activity was assessed by spectrophotometry. Formalin-induced nociceptive responses and carrageenan-induced paw oedema were evaluated in mice. The rota-rod apparatus was used to evaluate motor coordination. KEY RESULTS: Minocycline, but not PMIN, inhibited bacterial growth. Serum from mice treated with minocycline, but not with PMIN, also induced such an effect. The UV absorption spectrum of solutions of minocycline, but not those of PMIN, was markedly changed in the presence of Ca2+. Minocycline or PMIN inhibited both phases of formalin-induced nociception and carrageenan-induced paw oedema. It is unlikely that antinociception resulted from lack of motor coordination, as tetracycline did not impair the performance of mice on the rotating rod. CONCLUSIONS AND IMPLICATIONS: These results indicate that inhibition of nociception and oedema by tetracyclines is neither necessarily linked to antibacterial nor to Ca2+ chelating activities. This study supports the evaluation of the potential usefulness of PMIN in the treatment of painful and inflammatory diseases, as its lack of antibacterial and Ca2+ chelating activities might confer greater safety over conventional tetracyclines.