Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU): Trial Satisfaction and Attitudes towards Future Clinical Trials.

BACKGROUND: Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU). METHODS: We developed an anonymous, participant satisfaction survey tailored to participants enrolled in the DIAN-TU-001 double-blind clinical trial of solanezumab or gantenerumab and requested that all study sites share the survey with their trial participants. A total of 194 participants enrolled in the trial at 24 study sites. We utilized regression analysis to explore the link between participants' clinical trial experiences, their satisfaction, and their willingness to participate in upcoming trials. RESULTS: Survey responses were received over a sixteen-month window during 2020-2021 from 58 participants representing 15 study sites. Notably, 96.5% of the survey respondents expressed high levels of satisfaction with the trial, 91.4% would recommend trial participation, and 96.5% were willing to enroll again. Age, gender, and education did not influence satisfaction levels. Participants reported enhanced medical care (70.7%) and pride in contributing to the DIAN-TU trial (84.5%). Satisfaction with personnel and procedures was high (98.3%). Respondents had a mean age of 48.7 years, with most being from North America and Western Europe, matching the trial's demographic distribution. Participants' decisions to learn their genetic status increased during the trial, and most participants endorsed considering future trial participation regardless of the DIAN-TU-001 trial outcome. CONCLUSION: Results suggest that DIAN-TU-001 participants who responded to the survey exhibited high motivation to participate in research, overall satisfaction with the clinical trial, and willingness to participate in research in the future, despite a long trial duration of 4-7 years with detailed annual clinical, cognitive, PET, MRI, and lumbar puncture assessments. Implementation of features that alleviate barriers and challenges to trial participation is like to have a high impact on trial satisfaction and reduce participant burden.

Trail Making Test: Normative data for the Latin American Spanish-speaking pediatric population.

OBJECTIVE: To generate normative data for the Trail Making Test (TMT) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 3,337 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the TMT as part of a larger neuropsychological battery. The TMT-A and TMT-B scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age on both scores, such that as children needed less time to complete the test while they become older. TMT-A scores were affected by age2 for all countries except, Cuba, Guatemala, and Puerto. TMT-B scores were affected by age2 for all countries except, Guatemala and Puerto Rico. Models indicated that children whose parent(s) had a MLPE >12 years of education needed less time to complete the test compared to children whose parent(s) had a MLPE ≤12 years for Mexico and Paraguay in TMT-A scores; and Ecuador, Mexico, Paraguay, and Spain for TMT-B scores. Sex affected TMT-A scores for Chile, Cuba, Mexico, and Peru, in that boys needed less time to complete the test than girls. Sex did not affect TMT-B scores. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate approach to interpret the TMT in pediatric populations.

[Evolution of stress in families of children with attention deficit hyperactivity disorder]. / Evolución del estrés familiar en niños con trastorno por déficit de atención con hiperactividad.

INTRODUCTION: The objective of this study was to assess the evolution of stress in families of children and adolescents who start psychopharmacological treatment after being diagnosed with attention deficit hyperactivity disorder (ADHD), and the ability to detect this change using the FSI (Family Strain Index) questionnaire. METHODOLOGY: Forty eight (48) specialists in child-adolescent psychiatry or neuropediatrics included 429 families of children diagnosed with ADHD, represented by the father, mother or guardian of the child. In the baseline visit, and at two and four months, the intensity of the symptoms of ADHD was evaluated using the abbreviated Conners scale, and family stress was evaluated using the FSI questionnaire. RESULTS: The following was observed: a) an improvement in the overall FSI score and in all its dimensions (P<.001); b) an improvement in the intensity of the symptoms of hyperactivity (Conners, P<.0001); c) good agreement between these two scales at two months (R-intraclass 0.825, P<.0001) and at four months of follow-up (R-intraclass 0.784, P<.0001). Ninety seven point nine percent (97.9%) of the children or adolescents (420) received treatment with modified-release methylphenidate. CONCLUSIONS: There was a significant relationship between the positive evolution of symptoms in children with ADHD and the reduction of family stress, as evaluated by the FSI questionnaire, after starting psychopharmacological treatment. This study showed a great sensitivity to change in the clinical situation of patients with ADHD, evaluated through the stress it produces on its families. It is recommended to use this questionnaire as an indirect measurement of the repercussions of the disorder on the environment of the child with ADHD in terms of family stress.

Stroke incidence and risk factors in Havana and Matanzas, Cuba.

INTRODUCTION: Cerebrovascular disease is the third-leading cause of death and the second-leading cause of disability and dementia. OBJECTIVE: Determine stroke incidence and risk factors in a population of adults aged 65 and over in Cuba (Havana and Matanzas). MATERIAL AND METHODS: This prospective longitudinal study, completed between April 2008 and Abril 2011, re-evaluated 2916 elderly adults with an average follow-up time of 4 years. Cases included 2316 living subjects and 600 verbal autopsies. Study variables were age, sex, educational level, self-reported health, and description of chronic diseases and substance abuse. Laboratory tests included genotyping APOE. Stroke was diagnosed based on the World Health Organization definition. We calculated the global incidence rate for stroke, broken down by sex, age group, and risk factors for incident stroke. RESULTS: Stroke incidence was 786.2 in 100000 persons/year (95% CI: 672.3-906.4). History of alcohol consumption (HR: 3.5; 95% CI: 3.3-3.7), dementia (HR: 3.0; 95% CI, 1.6-5.5) and male sex (HR: 1.8; 95% CI, 1.2-2.8) were shown to be risk factors for incident stroke. CONCLUSIONS: Stroke incidence was similar to rates reported in developed countries and lower than that in low- to middle-income countries. Given that diabetes mellitus, heart disease, arterial hypertension, smoking, APOE4, etc. are associated with higher mortality rates, they will require separate analysis in a study of stroke risk factors.

Percutaneous lavage as primary treatment for infected pancreatic necrosis.

BACKGROUND: The classic treatment of infected pancreatic necrosis (IPN) is surgical debridement and drainage. This study reviews our experience with nonoperative percutaneous catheter drainage and serial lavage as primary treatment in patients with IPN. STUDY DESIGN: Between 1993 and 2009, a prospective nonselected series of 63 consecutive patients with microbiologically confirmed IPN were enrolled with the intent of treating them nonoperatively, and they were retrospectively analyzed. Catheters were placed percutaneously in the interventional radiology (IR) suite, and were used to lavage and debride the necrosis 1-3 times per week. The lavages continued on an outpatient basis by IR, and the catheters were removed with disease resolution. RESULTS: One patient rapidly became unstable and had to be taken primarily for open debridement. In the remaining 62 patients, 57 survived, for an overall mortality rate of 8%. Fifty patients were treated solely with percutaneous lavage, and 47 survived. Mean hospital length of stay was 61 days, ranging from 6 to 190 days. Mean length of outpatient treatment was 42 days, ranging from 3 to 180 days. Mean number of lavages was 21, ranging from 11 to 75. Eleven patients (18%) deteriorated during percutaneous treatment and required laparotomy, and 9 of these survived. One patient treated percutaneously resolved his sepsis but had a persistent pancreatic fistula and was managed with pancreaticojejunostomy. CONCLUSIONS: Percutaneous catheter drainage and serial lavage are an effective alternative to open surgical debridement in patients with IPN. Overall survival is excellent, and most patients avoid the morbidity of open debridement. A minority of patients deteriorate, but most of those can be salvaged with open drainage.

A phase I study of chemoembolization with cisplatin, thiotepa, and lipiodol for primary and metastatic liver cancer.

Thirty patients with primary hepatocellular carcinoma or liver metastases were entered into a program of chemoembolization with cisplatin, lipiodol, and escalating doses of thiotepa. Doses of cisplatin were 100/m2, and thiotepa doses ranged from 9 mg/m2 to 24 mg/m2. Two of three patients with ocular melanoma had partial responses in the liver metastases for 3+ and 16 months. In patients with either hepatocellular carcinoma (15 patients) or primary cholangiocarcinoma of the liver (three patients), there were two partial responses, for 22 and 33 months. Five patients had minor responses: four with a 40% reduction in tumor and one with a mixed response. There were four early deaths, which involved sepsis in two patients, respiratory failure in one, and acute myocardial infarction in one. Otherwise, toxicity was tolerable and reversible and included abdominal pain and transient elevation of serum creatinine, bilirubin, and transaminases. Less common toxicities included ototoxicity and peripheral neuropathy. Chemoembolization of the liver with cisplatin, thiotepa, and lipiodol can produce responses, but toxicity can be significant. The recommended starting phase II dose for future studies is thiotepa 24 mg/m2 and cisplatin 100 mg/m2.

ACE inhibition scintigraphy in the management of hypertension in children.

Angiotensin converting enzyme (ACE) inhibition scintirenography was performed to help establish the diagnosis and plan treatment of renovascular hypertension (RVH) in 57 hypertensive pediatric patients, 33 infants and 24 children older than 1 year. In 16 of 33 hypertensive infants, ACE inhibition scintirenography established the diagnosis of RVH from renal ischemia (due to aortic or renal arterial thrombi). Two scintigraphic criteria were used for the diagnosis of RVH: criterion I, ischemic and damaged kidney (a non-functioning kidney on or off ACE inhibition) and criterion II, ischemic but not damaged kidney (ACE inhibition induced deterioration of function of the kidney). When criterion I was present and the contralateral kidney was normal, ACE inhibitors could be used for treatment of hypertension without deterioration of renal function; kidneys satisfying criterion I eventually involuted or manifested growth arrest and frequently caused persistent RVH, even after resolution of the thrombus, requiring nephrectomy. When criterion II was present bilaterally, or it was associated with criterion I contralaterally, the use of antihypertensive drugs other than ACE inhibitors was necessary in order to prevent renal insufficiency or failure from ACE inhibitors. However, kidneys with criterion II showed normal growth and, following retraction or dissolution of the aortic thrombus, hypertension resolved. In 2 of 24 hypertensive children older than 1 year, the test was diagnostic of branch renal artery stenosis; RVH was cured by selective angioplasty. ACE inhibition scintirenography is useful in the evaluation and planning of treatment in children with hypertension and may predict the outcome of therapy and ultimate renal function.

Fibrous lesion of the distal femur associated with angular deformity.

Unilateral femoral angulation is uncommon. We describe two children with unilateral progressive distal femoral varus and limb-length discrepancy. These deformities were associated with a fibrous lesion involving the medial aspect of the distal femoral metaphysis. Both patients were 15 to 16 months old. In both, the deformity was progressive, resulting in excisional biopsy and osteotomy. The gross and microscopic appearance of both lesions was similar, and the histology was dense fibrous connective tissue. The patients' femoral alignment was maintained at follow-up of a minimum of 16-36 months. The etiology of these lesions is unknown; they are associated with progressive deformity and appear to respond well to surgical intervention.

Percutaneous catheter-directed debridement of infected pancreatic necrosis: results in 20 patients.

PURPOSE: To evaluate the usefulness of transcatheter debridement of infected pancreatic necrosis. MATERIALS AND METHODS: Transcatheter debridement was performed on 20 patients who ranged in age from 20 to 78 years during the 8-year study period. All patients had infected pancreatic necrosis and were hemodynamically stable. Necrosis was defined as nonenhancing pancreatic tissue, as seen on contrast-enhanced computed tomography (CT). Infection was suspected clinically and documented by cultures of the pancreatic fluid at its initial drainage. Debridement was performed in multiple sessions in close succession (duration, 30-120 minutes; mean, 60 minutes) via large-bore catheters with enlarged side holes. Debris was removed with use of suction catheters, stone baskets, and copious amounts of lavage fluid. RESULTS: All patients underwent successful catheter debridement. Success was determined by clinical course, as well as lesion appearance, at fluoroscopy and CT. Patients underwent 7-32 (average, 17) episodes of debridement and stayed 0-36 days (average, 9 days) in the intensive care unit, 13-118 days (average, 42 days) on the regular floor, and spent 0-98 days (average, 32 days) with the catheters as an outpatient. No deaths occurred. CONCLUSION: Percutaneous catheter-directed debridement is a safe and effective treatment and it can be used as the primary means of treatment for the hemodynamically stable patient with infected pancreatic necrosis.

Pictorial essay: thoracic cardiovascular complications of acquired immunodeficiency syndrome.

Patients with acquired immunodeficiency syndrome frequently develop complications of cardiac, pericardial, and thoracic vascular origin. The purpose of this pictorial essay is to review the most common etiologic and diagnostic imaging findings of these diseases. Patients with acquired immunodeficiency syndrome often demonstrate enlargement of the cardiac silhouette on the chest radiograph. While the cause of this finding may be clinically evident, the authors share cases in which chest computed tomography, echocardiography, and nuclear medicine studies better reveal the nature of underlying cardiac and pericardial abnormalities. Thoracic vascular complications, including pulmonary hypertension, pulmonary thromboembolism, and the sequelae of indwelling venous catheters, are also addressed.

Cost effectiveness of intraoperative autotransfusion in total hip arthroplasty surgery.

The purpose of this study was to analyze the cost effectiveness of the cell saver in reducing homologous blood transfusion requirements in patients undergoing primary total hip arthroplasties. In patients who had predonated autologous blood, the addition of the cell saver neither reduced the homologous blood requirements nor the percentage of patients exposed to banked blood. In patients without predonated autologous blood, the cell saver decreased the percentage of patients exposed to banked blood by 40% and decreased the mean homologous transfusion requirement from 2.6 to 1.5 units per patient (p < 0.05). The cell saver became cost effective when 3 units of blood were salvaged. Because the cell saver reclaimed a mean of 453 ml (approximately 2 units), it was not cost effective. This analysis is confounded by the risk of exposure to blood borne potentially life-threatening pathogens. In patients undergoing elective primary hip arthroplasty, the availability of predonated autologous blood obviates the need for expensive intraoperative blood salvage techniques. If an adequate volume of autologous blood cannot be procured preoperatively, or if the clinician suspects excessive intraoperative bleeding, then using the cell saver may be justified.

Arthroscopically assisted placement of a supracondylar intramedullary nail: operative technique.

The use of retrograde interlocking intramedullary nails has been described for the treatment of selected supracondylar fractures. A medial parapatellar incision and arthrotomy with its attendant morbidity is generally used for nail placement. Although a closed technique of nail placement has been described, the risks of damaging intra-articular structures with a blind approach have precluded the widespread use of this method. In this article, we present a simple, arthroscopically assisted method for the retrograde intramedullary nailing of supracondylar femoral fractures. This technique affords the potential benefits of intramedullary fixation of these fractures while avoiding the morbidity and complications associated with an arthrotomy. Potential benefits over the standard placement using an arthrotomy include earlier ambulation and soft tissue healing, decreased risk of damage to the knee joint, earlier convalescence with decreased hospitalization time, and better cosmesis.

A phase I study of chemoembolization with cisplatin and lipiodol for primary and metastatic liver cancer.

Twenty patients with either unresectable primary hepatocellular carcinoma or hepatic metastases were entered into a chemoembolization program with cisplatin and lipiodol; 19 patients were evaluable for response. Doses of cisplatin ranged from 40 to 100 mg/m2. Toxicity was tolerable and reversible and included abdominal pain, transient elevation in serum creatinine, serum bilirubin, and serum transaminases. Less common side effects include fever, ascites or pleural effusion, and hiccups. Two of four patients with ocular melanoma had partial responses. Duration of response was 10 and 11 months. Among 8 patients with unresectable hepatoma, 2 patients had partial response for 10+ and 13 months, 2 had minor response for 2 months and 4+ months, 1 patient had stable disease for 5+ months, and 3 patients failed to respond. Of the six colon cancer patients treated, one had a partial response in the liver, but developed progressive nodal disease, and another patient had a partial response for 3 months. Chemoembolization of the liver with cisplatin and lipiodol is feasible and doses of cisplatin at least 100 mg/m2 are tolerable. Antitumor activity in metastatic ocular melanoma is encouraging but requires further study.

Fatal massive hemoptysis secondary to intralobar sequestration.

We report the case of a 29-year-old woman who died of massive hemoptysis due to hemorrhage from an intralobar pulmonary sequestration into the tracheobronchial tree. The sequestration had been diagnosed in childhood but had been managed nonoperatively. This case emphasizes the need for early surgical treatment of pulmonary sequestration.

Characterization of a cell-type-restricted negative regulatory activity of the human granulocyte-macrophage colony-stimulating factor gene.

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the proliferation and maturation of normal myeloid progenitor cells and can also stimulate the growth of acute myelogenous leukemia (AML) blasts. GM-CSF is not normally produced by resting cells but is expressed by a variety of activated cells including T lymphocytes, macrophages, and certain cytokine-stimulated fibroblasts and endothelial cells. Production of GM-CSF by cultured AML cells has been demonstrated, and GM-CSF expression by normal myeloid progenitors has been postulated to play a role in myelopoiesis. We have investigated the regulation of expression of GM-CSF in AML cell lines, and our results demonstrate the presence of a strong constitutive promoter element contained within 53 bp upstream of the cap site. We have also identified a negative regulatory element located immediately upstream of the positive regulatory element (within 69 bp of the cap site) that is active in AML cell lines but not T cells or K562 CML cells. Competition transfection and mobility shift studies demonstrate that this activity correlates with binding of a 45-kDa protein.

Equipment malfunction in common hand surgical procedures. Complications associated with the pneumatic tourniquet and with the application of casts and splints.

Pneumatic tourniquets and plaster of Paris splints and casts are the hallmarks of hand surgery, firmly entrenched as an adjunct in the routine treatment of upper extremity disorders. Because they are usually employed with a comparative degree of safety and because they are relatively simple devices from a technologic perspective. Little is written about them in the scientific literature. In this paper we extensively review their historical developments, physiologic effects, and common complications, and we attempt to provide a rationale for their safe and effective use.

CT appearance of uterine leiomyomas.

Uterine leiomyomas, commonly known as fibroids, are one of the most common pelvic tumors found in women. Ultrasonography is the primary modality for evaluating leiomyomas. However, frequently these tumors are not accompanied by symptoms, and they are found incidentally during computed tomographic (CT) examinations performed for other indications. Because leiomyomas may first be noted on CT scans, radiologists should become familiar with their characteristic appearance. The authors describe the CT findings of uterine leiomyomas and their secondary changes, including cystic degeneration, calcification, infection, necrosis, fatty degeneration, and sarcomatous degeneration.