Remote intervention engagement and outcomes in the Clinical Trials in Organ Transplantation in Children consortium multisite trial

Remote interventions are increasingly used in transplant medicine but have rarely been rigorously evaluated. We investigated a remote intervention targeting immunosuppressant management in pediatric lung transplant recipients. Patients were recruited from a larger multisite trial if they had a Medication Level Variability Index (MLVI) ≥2.0, indicating worrisome tacrolimus level fluctuation. The manualized intervention included three weekly phone calls and regular follow-up calls. A comparison group included patients who met enrollment criteria after the subprotocol ended. Outcomes were defined before the intent-to-treat analysis. Feasibility was defined as ≥50% of participants completing the weekly calls. MLVI was compared pre- and 180 days postenrollment and between intervention and comparison groups. Of 18 eligible patients, 15 enrolled. Seven additional patients served as the comparison. Seventy-five percent of participants completed ≥3 weekly calls; average time on protocol was 257.7 days. Average intervention group MLVI was significantly lower (indicating improved blood level stability) at 180 days postenrollment (2.9 ± 1.29) compared with pre-enrollment (4.6 ± 2.10), p = .02. At 180 days, MLVI decreased by 1.6 points in the intervention group but increased by 0.6 in the comparison group (p = .054). Participants successfully engaged in a long-term remote intervention, and their medication blood levels stabilized. NCT02266888.     

Understanding the financial impact of a diagnosis of young onset dementia on individuals and families in the United Kingdom: Results of an online survey

Although literature on postdiagnostic support for people affected by young onset dementia acknowledges financial concerns, this topic has remained underresearched. The aim of this study was to explore the financial impact of a diagnosis of young onset dementia on individuals and families. An online survey, comprising binary yes/no, multiple-response and open-ended questions, was codesigned with people living with young onset dementia. The survey was promoted via networks and online platforms. Data were collected from August to October 2019. Survey respondents across the United Kingdom (n = 55) who had received a diagnosis of young onset dementia were aged between 45 and 64, were at different stages of dementia and had been diagnosed with thirteen different types of dementia. Of the 55 respondents, 71% (n = 39) had received assistance from family members when completing the survey. The main financial impact of a diagnosis of young onset dementia resulted from premature loss of income and reduced and often deferred pension entitlements. In some cases, care-costs became unaffordable. Lack of clarity of processes and procedures around needs assessments, carers' assessments and financial assessments by different organisations resulted in some families having to ask for legal advice and, in some cases, involved lengthy appeal processes. Future research needs to involve Adult Social Care and Third Sector organisations to help codesign and test financial management interventions to support people affected by this progressive health condition.     

Renal functional reserve in children with reduced renal mass: study by two dietary periods

It has been suggested that the renal functional reserve (RFR) defined by the rise in glomerular filtration rate (GFR) after a protein load could disappear in patients with severe nephron loss but with a normal GFR. This study compared, in 17 children, inulin clearance (C _in) measured by the plasma inulin plateau at the end of two 14-day randomized periods differing in protein intake: 100% (low protein, LP), or 200% (high protein, HP) of recommended dictary allowances (RDA). Diets were aimed at maintaining food habits and energy intake. Compliance was assessed by records of the last 3–4 days, an interview with the dietician and by urinary nitrogen measurements. Mean actual protein intake was 109% (56%–139%) RDA for the LP period and 220% (163%–319%) RDA for the HP period.C _in did not change in 14 children with GFR below (n=7) or within (n=7) the normal range.C _in was higher in the HP period than in the LP period (+32, 50, 63%) in 3 children who had a 50% (single kidneys) or a 25% (sclerosed glomeruli) nephron loss. Non-responding children had a GFR below 105 ml/min per 1.73 m². Nephron loss (70% sclerosed glomeruli) was estimated in only 1 child with no RFR. The results suggest that GFR measurement after prolonged dietary stimulation could help in evaluating the severity of nephron loss in children with normal or borderline GFR. The prognostic value of this test has to be confirmed by long-term follow-up.     

Study of the Complex Between the Contrast Agent lobitridol (Xenetix®) and Elastase (PPE): A Model for Hydrophobic Site Protection in Drug-Protein Interactions

Purpose. The concept of Hydrophilic Sphere Stabilization, or Hydrophobic Shielding, has been postulated in the synthesis of biocompatible contrast agents in vascular imaging. To improve the safety of these polyiodinated agents, interactions with protein hydrophobic sites in biomacromolecules should be kept as low as possible. In order to evaluate the level of interactions with proteins, we have selected the serine proteinase Elastase, in presence of Iobitridol (Xenetix^®), as a model. Methods. The complex between Iobitridol and Pancreatic Porcine Elastase was investigated by X-ray diffraction techniques, on saturated monocrystals, using the synchrotron radiation at 0.98. Results. In contrast to Iohexol, which displays several interactions including one in the active site, Iobitridol is unable to interact directly with elastase. Only one partially occupied site is found in between two molecules of the crystal packing. Conclusions. The validation of the 'hydrophobic shielding' concept, which was at the origin of the design of the Iobitridol molecule, has been proven to be an essential feature in minimizing in vivo protein interactions.     

Internal derangements of the shoulder: decision tree and cost-effectiveness analysis of conventional arthrography, conventional MRI, and MR arthrography

Purpose. In a patient with internal derangement of the shoulder, the diagnostic method of choice is controversial. Conventional arthrography can diagnose most rotator cuff tears accurately; however, in many institutions MR arthrography is usually necessary to diagnose labral tears. We utilized decision tree methodology to compare the cost- effectiveness of conventional arthrography and conventional MRI with a hypothetical algorithm in which a patient underwent arthrography, performed with admixed gadolinium, which if negative, was followed by MRI. Design. The use of double-contrast arthrography alone, conventional MRI alone, and gadolinium-enhanced MRI used as an adjunct to conventional arthrography were modeled for the diagnosis of full-thickness rotator cuff tears (RCT), partial RCTs, labral tears, and the absence of cuff/labral tears using decision analysis methodology. English language medical publications were searched to determine the base probabilities for the accuracy of the diagnostic tests. The outcome utilities ranged from –1 to +1 to reflect the value of correct diagnostic evaluation. Charges for diagnostic tests and appropriate surgical treatments were based on 1997 Medicare reimbursement rates for professional fees and hospital charges in an outpatient setting. Sensitivity analyses were performed to evaluate the effects of uncertainty regarding the prevalence of each disease state and the accuracy of several diagnostic tests. Results. In the base-case analysis, the average effectiveness of double-contrast arthrography alone, MRI alone and arthrography selectively followed by MRI were 0.6610, 0.6715, and 0.7204, respectively. The average costs for each of these strategies were $1090, $2033, and $2339, respectively. Conclusion. Arthrography performed with admixed diluted gadolinium, which if negative is immediately followed by MRI, was somewhat more expensive than conventional MRI. However, because of much greater effectiveness, cost-effectiveness was significantly higher for our proposed algorithm. Conventional arthrography without gadolinium, although less expensive, had severely limited effectiveness. Received: 4 June 1999 Revision requested: 6 August 1999 Revision received: 30 August 1999 Accepted: 1 September 1999     

Risk Factors for Bladder Tumors in Spinal Cord Injury Patients

Purpose

We evaluated risk factors for the development of bladder tumors in spinal cord injury patients.

Materials and Methods

A retrospective review was done of all bladder tumors at 1 institution with matched controls for 7 years.

Results

We identified 17 malignant and 2 benign tumors. Indwelling bladder catheters and a history of bladder stones were statistically significant risk factors. Four patients with negative biopsies underwent repeat biopsy due to suspicious cytology and cancer was found.

Conclusions

An indwelling urinary catheter and a history of bladder stones are statistically significant risk factors. Cytology and biopsy are complementary in the evaluation of urothelial malignancy in this population. A high index of suspicion and thorough evaluation are needed in spinal cord injury patients.     

Diffusion of information about genetic risk within families

Recent developments in genetics are likely to exacerbate the ethical issues in clinical practice, especially with regard to privacy and disclosure of genetic information. To evaluate the behaviour of patients with respect to transmitting carrier information, we undertook a survey of 283 families with a balanced chromosomal rearrangement as a model. In these families, 1816 relatives were considered at risk and 806 of them were karyotyped (44.4%). The percentage of karyotypes performed is significantly related to the number of living children of the index couple, the reason for referral, the nature of the anomaly, the training of the counsellor and the age of the index case. This study shows the limits of the screening of at risk individuals within families, based on the willingness of the patients, and addresses practical and ethical issues around family disclosure in medical genetics.     

A randomized trial comparing 35Gy in ten fractions with 60Gy in 30 fractions of cerebral irradiation for glioblastoma multiforme and older patients with anaplastic astrocytoma.

A randomized prospective clinical trial was conducted to compare conventional high dose radiotherapy with hypofractionated, short course radiotherapy in poor prognosis patients with high grade glioma. The primary endpoint was overall survival.     

AUTOPSY FINDINGS IN THE WOLCOTT-RALLISON SYNDROME

Wolcott-Rallison syndrome is a rare autosomal recessive condition characterized by diabetes mellitus arising in early infancy and multiple epiphyseal dysplasia. To date, nine cases have been described in the world literature. We report an affected girl who died at the age of 4 years and on whom a full autopsy was performed. In addition to neonatal diabetes mellitus and epiphyseal dysplasia, this child had mental retardation and recurrent episodes of self-limiting hepatic failure. Autopsy revealed severe pancreatic hypoplasia and markedly abnormal pancreatic histology, while histology of the bone was consistent with epiphyseal dysplasia. There was laryngeal stenosis and pulmonary hypoplasia. The heart was enlarged with mitral valve dysplasia and stenosis, left atrial dilatation, left ventricular hypertrophy, and endocardial fibroelastosis. Examination of the central nervous system showed arrhinencephaly and cerebellar cortical dysplasia. The liver showed minor histological abnormalities but no features were present to account for the recurrent hepatic failure. In addition to Wolcott-Rallison syndrome this child had a deletion at 15q11-12 in 65 of her cells.     

Evaluation of sexual misconduct complaints: The Oregon Board of Medical Examiners, 1991 to 1995

OBJECTIVE: In 1991 the Oregon Board of Medical Examiners initiated a separate category for the complaint of sexual misconduct. Investigated complaints of sexual misconduct brought to the Oregon Board of Medical Examiners were analyzed for the years 1991 to 1995 to serve as a baseline. Comparison was made to the Federation of State Medical Boards sexual misconduct data for 1991 and 1992.STUDY DESIGN: One hundred complaints brought against 80 licensees were evaluated by practitioner's degree, age group, sex, specialty, and disposition of complaints for the years 1991 to 1995. The allegations were classified into behavior categories of sexual impropriety, sexual transgression, and sexual violations.RESULTS: Sexual misconduct was the allegation in 5.9% of the complaints investigated for the study period. Oregon had more sexual misconduct complaints than the average reported to the Federation of State Medical Boards for the years 1991 and 1992. Most (72%) complaints came from the patients or their families. Two female physicians (2.4%) had sexual boundary complaints. Sexual misconduct complaints increased by a risk ratio of 1.44 with advancing age by decades. Allegations classified into behavior categories according to severity revealed 39% sexual impropriety, 31% sexual transgression, and 30% sexual violation. Reportable disciplinary actions occurred only with multiple allegations of sexual impropriety (6.5%) and for sexual transgression (27%) whereas sexual violation allegations often had one complainant but there were 54% reportable disciplinary actions. Family practice, obstetrics and gynecology, and psychiatry had the highest incidence of sexual misconduct complaints whereas psychiatry and obstetrics and gynecology had the highest incidence of reportable disciplinary actions. Twenty-five percent of the closed cases resulted in reportable disciplinary actions. This analysis is discussed in relationship to legal and ethical issues and the goal of zero tolerance.CONCLUSIONS: Oregon has a higher percentage of sexual misconduct complaints than the average for 42 states reporting to the Federation of State Medical Boards for the years 1991 and 1992. Analysis of the Oregon Board's experience for the study years will provide a baseline for future evaluation and as an educational resource for the Oregon Board of Medical Examiners and professional and specialty societies. Ethical standards, the reporting and investigative processes, and the legal framework are in place and lessen the incidence of sexual misconduct and work toward zero tolerance. (Am J Obstet Gynecol 1997;176:1340-8.)