cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.58020/53bk-jk73
title: Nonalcoholic Fatty Liver Disease (NAFLD) Adult Database

description: Nonalcoholic fatty liver disease (NAFLD) affects 10%-30% of the general U.S. population and can progress to significant fibrosis and cirrhosis. When nonalcoholic steatohepatitis (NASH) is present, the 5-year and 10-year survivals are estimated at 67% and 59%, respectively. The presence of NASH and early fibrosis is currently established only by liver biopsy; noninvasively determining who has NASH and who is at risk for progressing to cirrhosis remains challenging.

The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) was initiated by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in 2002 to conduct multicenter, collaborative studies on the etiology, contributing factors, natural history, complications, and treatment of NASH. To meet these goals, patients with the full spectrum of NAFLD or cryptogenic cirrhosis were enrolled in an observational Database study.

Comprehensive data, including demographics, medical history, symptoms, medication use, diet and exercise habits, and routine laboratory studies were collected on all patients at entry and at annual visits for up to 4 years after enrollment. Study questionnaires administered at enrollment and at selected follow-up visits included AUDIT; Block Food Questionnaire; Skinner Lifetime Drinking History, Physical Activity Questionnaire, Modifiable Activity Questionnaire; and the MOS 36-Item Short-Form Health Survey. Specimens were collected at selected time points during follow-up. If liver biopsies were obtained as part of routine patient care, they were scored using the NASH CRN NAFLD Activity Score (NAS) and fibrosis score.
DOI: 10.58020/pga7-2s51
title: Nortriptyline for Idiopathic Gastroparesis

description: Gastroparesis, a syndrome in which patients experience delayed gastric emptying, is characterized by symptoms such as nausea, vomiting, bloating, abdominal pain, and early satiety. Management of gastroparesis is limited by few effective treatments, many of which function by accelerating gastric emptying. Based on the hypothesis that some symptoms of gastroparesis arise because of neuropathic changes in enteric and sensory nerves, tricyclic antidepressants (TCAs) in low doses have been used as neuromodulators to treat refractory symptoms of nausea, vomiting, and abdominal pain, but there is little evidence to support this use. The Nortriptyline for Idiopathic Gastroparesis (NORIG) study is a multicenter, randomized, clinical trial that was designed by the Gastroparesis Clinical Research Consortium (GpCRC) to test whether treatment with nortriptyline, a TCA with reduced anticholinergic side effects, results in symptomatic improvement in patients with idiopathic gastroparesis. 

Individuals between the ages of 21 and 68 years old with moderate to severe symptoms of idiopathic gastroparesis for at least 6 months were enrolled. Participants were randomized to treatment with either nortiptyline or placebo. In both groups, dosing was escalated at 3-week intervals (10, 25, 50, 75 mg) up to 75 mg at 12 weeks. At follow-up study visits, which occurred every 3 weeks, symptom questionnaires were administered to assess gastrointestinal and psychological symptoms, quality of life, and TCA side effects. Electrogastrography (EGG) satiety tests and electrocardiography tests were also performed. Treatment was continued for 15 weeks, at which time study medication dose was tapered to zero with a final assessment at 18 weeks.  The primary outcome measure was a decrease from the patient’s baseline Gastroparesis Cardinal Symptom Index (GCSI) score of at least 50% on two consecutive 3 week GCSI assessments over 15 weeks of treatment. Secondary outcome measures included physiological assessments during satiety testing, clinical and psychological symptom scores, and adverse event rates.

Overall symptomatic improvement, as defined by the primary outcome measure, did not differ between the treatment groups: 23% on nortriptyline versus 21% on placebo. Additionally, treatment with nortriptyline showed no improvement in nausea, fullness/satiety, bloating, or quality of life measures. These findings suggest that TCAs may not be effective in the treatment of idiopathic gastroparesis.
DOI: 10.58020/j25s-h675
title: Novel Therapies to Treat Resistant Focal Segmental Glomerulosclerosis: Phase II Clinical Trial

description: Therapeutic interventions for the treatment of Focal Segmental Glomerulosclerosis Clinical (FSGS) have been widely reported. However, evidence-based treatment guidelines have not been developed because of the lack of controlled studies and the small number of participants included in most reports. The FSGS Clinical Trial (FSGS-CT) was a multi-center, prospective, controlled, open label randomized trial designed to determine if treatment with mycophenolate mofetil (MMF) in conjunction with pulse steroids is superior to treatment with Cyclosporine-A (CSA) in inducing remission from proteinuria over 12 months.  The rationale and background related to each of the drugs chosen to be a part of the FSGS-CT therapeutic interventions are outlined in the study protocol.
DOI: 10.58020/76yj-zb92
title: Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus

description: Type 1 diabetes (T1D) is an autoimmune disease. This means that the immune system (the part of the body which helps fight infections) mistakenly attacks and destroys the cells that produce insulin (islet cells found in the pancreas). As these cells are destroyed, the body's ability to produce insulin decreases. There is evidence suggesting that repeated oral administration of an autoantigen (the same protein that the immune system is reacting to) may introduce a protective immunity and cause the immune system to stop its attack. An earlier, large scale study was done to see if oral insulin could delay or prevent the development of T1D in relatives at risk for developing T1D. The overall results showed that for the entire study population, oral insulin did not delay or prevent T1D.

However, an analysis that was done after the conclusion of the trial suggested a potential beneficial effect in a subgroup of participants. The participants who seemed to benefit from oral insulin had higher levels of insulin autoantibodies which were directed against insulin itself (called mIAA). Eligible participants were randomized to receive either oral insulin (7.5 mg of recombinant human insulin crystals) or placebo daily.

All participants randomized into TrialNet 07 were seen at a study site for a follow-up evaluation, three and six months after randomization, and every six months thereafter. Participants were contacted by phone between six monthly clinic visits to assess changes in diabetes status, medication compliance, and adverse events. These phone contacts occurred approximately three months from the date of the previous clinic visit. At the study visits, participants underwent assessments of their insulin production, immunologic status, and overall health.
DOI: 10.58020/pmbk-jp54
title: Panoramic CIT Data

description: The CIT consortium conducted a total of 9 studies across North America (CIT02 through CIT08) and the Nordic region (CIT01). CIT08 was a long-term follow-up study for interested participants at the North American sites. The target population is individuals with type 1 diabetes, normal kidney function, and intractable hypoglycemia. All studies treated participants with up to 3 separate infusions of islets.

Non-Study Specific CIT data are available for request
DOI: 10.58020/hbe8-s748
title: Pediatric Acute Liver Failure

description: Acute liver failure (ALF) is a condition in which liver function rapidly deteriorates. ALF often affects young people and causes serious, and sometimes fatal, complications. Treatment of the disease is dependent upon its cause, which can be numerous factors. Because recovery from this disease is random, there is no way to predict how a patient will respond to treatment. Sometimes a liver transplant is required in order for a patient to make a full recovery. The mission of the Pediatric Acute Liver Failure (PALF) study is to develop methods to predict whether a child will require a life-saving procedure in order to recover from the illness.

Clinical, epidemiological, and outcome data on PALF patients will be collected and analyzed. The study group will also use the data to identify unrecognized mechanisms of liver injury that cause PALF. Acute liver failure leads to hepatic encephalopathy and cerebral edema, so patients will be invited to participate in neurocognitive testing to determine whether long-term neurocognitive function has been compromised. The prediction methods will vary and be influenced by age, diagnosis, multi-system organ failure, degree of encephalopathy, and coagulopathy level.
DOI: 10.58020/ejz3-6m22
title: Pegylated Interferon +/- Ribavirin for Children with HCV

description: Treatment of chronic hepatitis C in adults has evolved from alpha interferon (IFNα) alone to the combination of PEG-IFNα with ribavirin (RV). Recommendations for treatment for HCV infection in children have been derived from trials in adults, although the efficacy and safety of these therapies may be different in children. The Pediatric Study of Hepatitis C (PEDS-C) was conducted as a randomized, controlled trial to investigate the safety and efficacy of PEG-IFNα with and without RV in children and adolescents with chronic hepatitis C.  The primary objective of the PEDS-C study was to determine if the addition of RV to PEG-IFNα maximized outcome of therapy of children with chronic hepatitis C. 

Children and adolescents ages 5 to 18 years with documented chronic HCV infection were enrolled in the study. All participants were randomly assigned in a 1:1 ratio to receive either PEG-IFNα and RV or PEG-IFNα and placebo. PEG-IFNα was administered in a dose of 180 µg/1.73m2 body surface area subcutaneously once weekly to all subjects, and ribavirin was administered in a dose of 15 mg/kg orally twice daily to the appropriate treatment group. Patients without detectable HCV RNA at 24 weeks were continued on treatment for another 24 weeks, while those with detectable HCV RNA at 24 weeks were considered treatment failures.  The primary outcome measure was the proportion of subjects with a sustained virologic response, defined as non-detectable HCV RNA in plasma (<10 IU/ml) at least 24 weeks after stopping treatment. The secondary outcome measure was safety, assessed by vital signs, laboratory tests, and adverse events.

Results showed that therapy with PEG-IFNα plus RV was superior to PEG-IFNα plus placebo regardless of age, alanine aminotransferase (ALT) levels, and histologic severity. Additionally, there was little change in side effect profile with the addition of RV to PEG-IFNα. The study concluded that the combination of PEG-IFNα and RV is superior to PEG-IFNα alone as therapy for chronic hepatitis C in children and adolescents in both safety and efficacy.
DOI: 10.58020/djpt-4d91
title: Peritransplant Deoxyspergualin in Islet Transplantation in Type 1 Diabetes and Extended Follow Up after Islet Transplantation in Type 1 Diabetes

description: The CIT consortium conducted a total of 9 studies across North America (CIT02 through CIT08) and the Nordic region (CIT01). CIT08 was a long-term follow-up study for interested participants at the North American sites. The target population was individuals with type 1 diabetes, normal kidney function, and intractable hypoglycemia. All studies treated participants with up to 3 separate infusions of islets. The focus of CIT03 was to evaluate the investigational agent, deoxyspergualin. Subjects in CIT03 received rabbit anti-thymocyte globulin (ATG; basiliximab instead of ATG for the 2nd and 3rd transplants, if applicable), deoxyspergualin, etanercept, sirolimus, and low-dose tacrolimus in an open-label fashion.
DOI: 10.58020/p490-y092
title: Predicting Response to Standardized Pediatric Colitis Therapy

description: This multicenter open-label study was designed to evaluate the safety and efficacy of standardized initial therapy using either mesalamine or corticosteroids then mesalamine for the treatment of children and adolescents newly diagnosed with ulcerative colitis. The study investigated the hypothesis that response to the initial 4 weeks of therapy as well as specific clinical, genetic, and immune parameters determined during the initial course of therapy predicted severe disease as reflected by need for escalation of medical therapy or surgery. 

Participants were assigned to one of two initial therapeutic plans (mesalamine only or prednisone/liquid equivalent prednisolone followed by mesalamine) depending upon initial disease severity determined by the validated multi-dimensional Pediatric Ulcerative Colitis Activity Index (PUCAI). Biospecimens were obtained at diagnosis, and subsequently following the initiation of therapy at weeks 4, 12, and 52 (blood and stool at weeks 4 and 12; blood, stool, and colonic tissue at week 52). Follow-up clinic visits were conducted for a minimum of 1 year to a maximum of 5 years depending on when the participant enrolled. Adherence to mesalamine dosing was monitored using a state of the art electronic Medication Event Monitoring System (MEMS®).

The primary publication associated with the PROTECT study can be found here: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501846/">Clinical and Biological Predictors of Response to Standardised Paediatric Colitis Therapy: A Multicentre Inception Cohort Study</a>.
DOI: 10.58020/vj16-wz20
title: Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis Liver Disease

description: Cystic fibrosis is an inherited condition in which cell secretions are thick and sticky, instead of thin and slippery. The secretions obstruct passageways and ducts, leading to severe internal damage. Patients with cystic fibrosis sometimes develop advanced liver disease (CFLD). Hepatic cirrhosis can occur with CFLD, as a result of the inflammation and scarring caused by clogged bile ducts. 

PUSH is a prospective longitudinal study that aims to determine the utility of abdominal ultrasound to predict the development of cirrhosis in patients with cystic fibrosis. Participants will undergo abdominal ultrasound at enrollment and, based on the outcome, will be placed in one of four groups. Within a five year period subjects will undergo other sample collection procedures in addition to abdominal ultrasound. This study will also monitor the effects of cystic fibrosis on associated pulmonary and nutritional issues.
DOI: 10.58020/jg1j-3648
title: Preservation of Pancreatic Production of Insulin Through Immunosuppression

description: Type 1 diabetes (T1D) is a chronic, slowly progressive autoimmune disease characterized by the destruction of β-cells in the pancreas. Results from previous studies of T1D have suggested that an intervention that prolongs β-cell function would be expected to improve metabolic control and reduce complications in patients.  The Preservation of Pancreatic Production of Insulin Through Immunosuppression (TN02 MMF/DZB) trial was established by TrialNet, a network of 18 clinical centers that conducts research on T1D, to investigate the effects of immunosuppressive agents on the progression of β-cell destruction in patients with recent-onset T1D. The study was a randomized, multicenter, placebo-controlled clinical trial that sought to determine the efficacy of mycophenolate mofetil (MMF) alone or in combination with daclizumab (DZB) in preserving β-cell function.

Eligible patients aged 8-45 years with evidence of β-cell function who were affected with autoimmune T1D for less than 3 months were enrolled. Participants were randomized to receive MMF alone (with DZB placebo), MMF and DZB in combination, or control (MMF placebo and DZB placebo). Study visits were conducted to evaluate safety, including assessment of diabetes care, adverse events, and laboratory measurements to assess medication side effects. Participants were followed for 2 years. The primary outcome measure was the geometric mean difference between active- and placebo-treated subjects of the area under the stimulated C-peptide curve over the first 2 hours of a 4-hour mixed meal glucose tolerance test conducted at the 2-year visit. Secondary outcome measures included differences in A1C hemoglobin levels, insulin dose, hypoglycemic episodes, rates of infection, and adverse events over time. 

Results showed comparable rates of diminishing C-peptide levels between the MMF and MMF and DZB treatment groups and the control group. The study found no treatment benefit from either MMF alone or from the combination of MMF and DZB on the preservation of β-cell function in patients with recent-onset T1D.
DOI: 10.58020/bpbb-wy70
title: Program to Reduce Incontinence by Diet and Exercise

description: Epidemiological studies suggest that obesity is a strong risk factor for urinary incontinence (UI), and preliminary studies have suggested that weight loss may have a beneficial effect on urinary incontinence in obese women. The Program to Reduce Incontinence by Diet and Exercise (PRIDE) study was a multi-center (2 sites) randomized clinical trial conducted to examine the long term effects of a weight loss intervention on urinary incontinence in overweight and obese women. 

A total of 338 women with at least UI episodes per week and a body-mass index (BMI) between 25 and 50 were enrolled in the study. Participants were randomly assigned to an intensive 6-month behavioral weight-loss program (intervention group) or to a structured four-session education program (control group) and followed for 18 months. Following completion of the 6-month weight loss intervention, participants in the intervention group underwent a second randomization to a motivationally focused weight loss maintenance program or a standard skills-based maintenance approach. The secondary randomization allowed the comparison of two approaches to weight loss maintenance. Urinary incontinence was assessed with a 7-day voiding diary. Assessments were completed at 6, 12, and 18 months, and information was collected on height, weight, demographics, and medical history, including urinary  incontinence history. The primary outcome measure was the percentage change in the number of urinary incontinence episodes reported in the 7-day voiding diary at 6 months after randomization. Secondary outcome measures included the change in number of episodes of urge and stress urinary incontinence, participant satisfaction with incontinence treatment, and a standardized pad test to measure 24-hour involuntary urine loss. Longer term effects of the behavioral weight-loss program on UI were assessed at 12 and 18 months. 

Results showed that the comprehensive behavioral weight-loss program resulted in a significantly greater reduction in the frequency of self-reported UI episodes (mean weekly number of incontinence episodes) at 6 months as compared with the structured education program. Additionally, decreased stress incontinence episode frequency was maintained at 12 months with a trend toward continued reduction in total incontinence episode frequency. At 18 months, there were no statistically significant differences in the reduction of weekly incontinence episode frequency for stress or total urinary incontinence between the groups, despite a substantial difference in greater weight loss and participant satisfaction with improvements in UI in the intervention group. The study concluded that the behavioral weight loss intervention was more effective than an educational control program in decreasing stress-related UI through 12 months, although the benefits at 18 months were more limited.
DOI: 10.58020/f5qd-z817
title: RAND Interstitial Cystitis Epidemiology Study

description: The RAND Interstitial Cystitis Epidemiology Study (RICE) is an observational study that sought to develop a case definition for Bladder Pain Syndrome (BPS)/Interstitial Cystitis (IC) with known sensitivity and specificity and to estimate the prevalence of the condition, which at the time had never been done using a large-population model. BPS/IC, which is clinically diagnosed based on patient-reported symptoms, is a poorly understood condition that can cause significant disability.

 An expert panel developed a case definitions of BPS/IC based on a review of medical literature. This definition was tested on 599 adult women diagnosed with BPS/IC or other conditions characterized by pelvic symptoms. Testing revealed that no single epidemiological definition demonstrated both high sensitivity and high specificity, so two definitions were developed: one of high sensitivity/low specificity and one of low sensitivity/high specificity.
Using these two definitions, researchers then screened 96,995 US households to identify women who had bladder symptoms. Those with symptoms underwent a secondary, more intensive screening and were asked to provide more information regarding symptoms, medical history, medical treatments, impact on daily life, physical and mental health, and demographic information.  Multivariate modeling was used to construct population and non-response weights. Weighted data was used to calculate prevalence estimates for both definitions and estimate the number of women affected.
DOI: 10.58020/zk68-8r70
title: Randomized Intervention for Children with Vesico Ureteral Reflux

description: This multicenter, randomized, double-blind, placebo-controlled trial was designed to determine whether daily antimicrobial prophylaxis is superior to placebo in preventing recurrence of urinary tract infection (UTI) in children with vesicoureteral reflux (VUR). Patients were randomly assigned to treatment for 2 years with daily antimicrobial prophylaxis (trimethoprim-sulfamethoxazole) or placebo. The study was designed to recruit 600 children (approximately 300 in each treatment group. The protocol encouraged prompt evaluation of children with UTI symptoms and early therapy of culture-proven UTIs. It was expected that approximately 10% of children would have to discontinue study medication due to allergic reactions. Assuming a 20% placebo event rate and 10% non-adherence rate, the study had 83% power to detect an absolute 10% event rate in the antimicrobial prophylaxis group. If the placebo event rate was instead 25%, power was 97% to detect an absolute 10% event rate in the treated group, even if non-adherence were as high as 15%. The primary analysis is intention-to-treat with missing outcome data analyzed as UTI.