Increased incidence and unusual presentations of CMV disease in kidney transplant recipients after conversion to belatacept

Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4–68.5]) were converted to belatacept (median of 11.5 months [2.5–37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R− CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls [2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR <30 ml/min; cumulative incidences were 18.4 and 5.2/100 p-y, respectively. CMV diseases under belatacept were atypical, with late-onset disease (24/40 patients [60%]), high CMV seropositivity (27/40, 67%), increased severe and tissue-invasive disease rates (gastrointestinal involvement in 32/40 [80%]) and life-threatening diseases (4/40 [10%]). These findings should stimulate further research to secure the use of belatacept as a valuable rescue therapy in KTRs.     

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.     

Physical attractiveness of boys with gender identity disorder

University students blind to group status rated boys with gender identity disorder and clinical control boys regarding their physical attractiveness. Ratings were made of the face and upper torso from photographs taken at the time of clinical assessment ( age, 8.1 years). On all five adjectives (attractive, beautiful, cute, handsome, and pretty), boys with gender identity disorder were judged to be more attractive than were the clinical control boys. Attractiveness correlated with extent of behavioral femininity in the clinical control group, but not in the group of boys with gender identity disorder. The extent to which the group differences in attractiveness were due to objective, structural differences in facial attractiveness vs. socially created, or subjective, processes is discussed.A version of this article was presented at the meeting of the International Academy of Sex Research, Sigtuna, Sweden, August 1990.     

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.     

Social HMOs and Other Capitated Arrangements for Children with Special Health Care Needs

Objective: Children with special health care needs are increasingly enrolling in managed care arrangements. However, existing managed care organizations, including traditional HMOs, are often poorly suited for caring for this population. In the adult health care area, new managed care entities, called Social HMOs (S/HMO) and Programs for the All-inclusive Care for the Elderly (PACE), have been created to integrate health and health-related services for chronically ill and disabled adults. We describe these models and assess their potential for serving children with special health care needs. Method: We reviewed the literature on managed care for children with special health care needs and evaluation findings from the S/HMO and PACE models for the elderly. Results: Evaluations of the S/HMO and PACE models have yielded mixed findings. Some of the more positive accomplishments include lower use and expenditures for long-term care services compared to other demonstration projects, greater integration of primary care physicians in decision making concerning long-term care, and improved management of transitions between care levels. On the negative side, start-up has been slow, prospective members have been hesitant to enroll, intermittent and sometimes frequent operating deficits have emerged, no discernible positive effects on health or social outcomes are apparent, and no significant overall savings have emerged. Conclusions: With mixed results so far, caution is required in applying these or similar models for vulnerable child populations. However, given the inadequacies of traditional managed care for this population, we believe experimentation with new models of care that integrate health and health-related services is important. Such experimentation should be fostered only to the extent that the models are carefully designed and then implemented in a manner that protects the interests of children with special health care needs.     

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.     

Four-contrast defecography: Pelvic “floor-oscopy”

PURPOSE: This study was designed to determine the accuracy of physical examination (as judged by four-contrast defecography) for women with pelvic floor relaxation disorders. METHODS: Sixty-two women (mean age, 59 years) who had obstructed defecation or constipation, vaginal prolapse, urinary difficulty, or pelvic pain underwent four-contrast defecography. Oral, vaginal, bladder, and rectal contrast were administered selectively and fluoroscopy was performed. Radiographic findings were compared with physical examination diagnosis. RESULTS: Four-contrast defecography changed the diagnosis in 46 patients (75 percent); 26 percent of presumed cystoceles, 36 percent of enteroceles, and 25 percent of rectoceles were not present on defecography. Defecography also revealed unsuspected coexisting defects in addition to known abnormalities detected on physical examination. In contrast, when physical examination was negative for these defects, 63 percent of patients were found to have cystoceles, 46 percent to have enteroceles, and 73 percent to have rectoceles on four-contrast defecography. The discovery of Grade 2 or 3 unsuspected abnormalities was significant, especially so for enteroceles. For posterior vaginal eversions extending to or past the introitus, physical examination was accurate in only 61 percent. Physical examination of large anterior defects was more accurate, with 74 percent of patients being correctly diagnosed. CONCLUSIONS: Physical examination diagnosis of pelvic floor relaxation disorders is frequently inaccurate, especially for large vaginal eversions. Four-contrast defecography improves diagnostic accuracy, helps to identify all pelvic floor defects before surgery, and can assist with planning the correct operative approach.     

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