Testing for mechanistic interactions in long-term follow-up studies.
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ABSTRACT:
SUBMITTER: Lin JH
PROVIDER: S-EPMC4374952 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The link between infection with high-risk human papillomavirus (hrHPV) and cervical cancer has been clearly demonstrated. Virological end-points showing the absence of persistent HPV infection are now accepted as a way of monitoring the impact of prophylactic vaccination programs and therapeutic vaccine trials. This study investigated the use of urine samples, which can be collected by self-sampling at home, instead of cervical samples for follow-up of an HPV intervention trial. Eighteen initially HPV DNA-positive women participating in an HPV therapeutic vaccine trial were monitored during a three-year follow-up period. A total of 172 urine samples and 85 cervical samples were collected. We obtained a paired urine sample for each of the 85 cervical samples by recovering urine samples from six monthly gynaecological examinations. We performed a small pilot study in which the participating women used a urine collection device at home and returned their urine sample to the laboratory by mail. All samples were analyzed using quantitative real-time HPV DNA PCR. A good association (? value of 0.65) was found between the presence of HPV DNA in urine and a subsequent cervical sample. Comparisons of the number of HPV DNA copies in urine and paired cervical samples revealed a significant Spearman rho of 0.676. This correlation was superior in women with severe lesions. The HPV DNA results of the small pilot study based on self-collected urine samples at home are consistent with previous and subsequent urine and/or cervical results. We demonstrated that urine sampling may be a valid alternative to cervical samples for the follow-up of HPV intervention trials or programs. The potential clinical value of urine viral load monitoring should be further investigated.
| S-EPMC4881571 | biostudies-literature
Project description:ContextDespite tremendous interest in hypoparathyroidism, large cohort studies describing typical treatment patterns, laboratory parameters, and rates of complications are lacking.ObjectiveOur objective was to characterize the course of disease in a large cohort of hypoparathyroid patients.Design and settingWe conducted a chart review of patients with permanent hypoparathyroidism identified via a clinical patient data registry. Patients were seen at a Boston tertiary-care hospital system between 1988 and 2009.PatientsWe identified 120 patients. Diagnosis was confirmed by documented hypocalcemia with a simultaneous low or inappropriately normal PTH level for at least 1 yr. Mean age at the end of the observation period was 52 ± 19 (range 2-87) yr, and the cohort was 73% female.Main outcome measureWe evaluated serum and urine laboratory results and renal and brain imaging.ResultsWe calculated time-weighted average serum calcium measurements for all patients. The time-weighted average for calcium was between 7.5 and 9.5 mg/dl for the majority (88%) of patients. Using linear interpolation, we estimated the proportion of time within the target calcium range for each patient with a median of 86% (interquartile range 67-98%). Of those with a 24-h urine collection for calcium (n = 53), 38% had at least one measurement over 300 mg/d. Of those with renal imaging (n = 54), 31% had renal calcifications, and 52% of those with head imaging (n = 31) had basal ganglia calcifications. Rates of chronic kidney disease stage 3 or higher were 2- to 17-fold greater than age-appropriate norms.ConclusionsHypoparathyroidism and its treatment carry a large burden of disease. Renal abnormalities are particularly common.
| S-EPMC3513540 | biostudies-literature
Project description:PURPOSE: To assess the long-term follow-up results of laparoscopic pyeloplasty for ureteropelvic junction obstruction. MATERIALS AND METHODS: Sixty-five patients (mean age, 43.8 years) who underwent standard laparoscopic pyeloplasty by transperitoneal approaches were enrolled in this study. The chief complaint was flank pain (n=57 patients); the remaining cases were detected incidentally. Twenty-three patients had undergone previous abdominal surgeries, including open pyeloplasty and endopyelotomy. Mean stricture length was 1.06 cm. Grade 3/4 and 4/4 hydronephrosis was detected in 36 and 14 patients, respectively. An obstructive pattern was present on the renal scan in 53 patients (81.5%). RESULTS: Fifty-seven patients were treated with dismembered Anderson-Hynes pyeloplasty and eight patients with Fenger pyeloplasty. During the operation, crossing vessels were found in 27 patients (41.5%). Mean operating time was 159.42 minutes. Although there were no cases of open conversion, two patients with colon and spleen injuries were detected postoperatively. The mean starting time of postoperative ambulation and diet was 1.54 days and 1.86 days, respectively. Mean hospital stay was 8.09 days. Mean follow-up period was 36.5 months. Follow-up intravenous pyelography and renal scan showed improvements in 59 patients, and the radiologic success rate was 90.8%. Eight patients showed failure on radiologic or symptomatic evaluation, and the overall success rate was 87.7%. In the comparative analysis between the success and failure groups, drained amount was the only risk factor related to failure (554.41 mL. vs. 947.70 mL, p=0.024). CONCLUSIONS: Long-term follow-up results support laparoscopic pyeloplasty as the standard treatment for ureteropelvic junction obstruction. Drained amount is a risk factor for failure of the operation.
| S-EPMC4198764 | biostudies-literature
Project description:BackgroundPrognostic factors are lacking in cardiac sarcoidosis (CS), and the effects of immunosuppressive treatments are unclear.ObjectivesTo identify prognostic factors and to assess the effects of immunosuppressive drugs on relapse risk in patients presenting with CS.MethodsFrom a cohort of 157 patients with CS with a median follow-up of 7 years, we analysed all cardiac and extra-cardiac data and treatments, and assessed relapse-free and overall survival.ResultsThe 10-year survival rate was 90% (95% CI, 84-96). Baseline factors associated with mortality were the presence of high degree atrioventricular block (HR, 5.56, 95% CI 1.7-18.2, p = 0.005), left ventricular ejection fraction below 40% (HR, 4.88, 95% CI 1.26-18.9, p = 0.022), hypertension (HR, 4.79, 95% CI 1.06-21.7, p = 0.042), abnormal pulmonary function test (HR, 3.27, 95% CI 1.07-10.0, p = 0.038), areas of late gadolinium enhancement on cardiac magnetic resonance (HR, 2.26, 95% CI 0.25-20.4, p = 0.003), and older age (HR per 10 years 1.69, 95% CI 1.13-2.52, p = 0.01). The 10-year relapse-free survival rate for cardiac relapses was 53% (95% CI, 44-63). Baseline factors that were independently associated with cardiac relapse were kidney involvement (HR, 3.35, 95% CI 1.39-8.07, p = 0.007), wall motion abnormalities (HR, 2.30, 95% CI 1.22-4.32, p = 0.010), and left heart failure (HR 2.23, 95% CI 1.12-4.45, p = 0.023). After adjustment for cardiac involvement severity, treatment with intravenous cyclophosphamide was associated with a lower risk of cardiac relapse (HR 0.16, 95% CI 0.033-0.78, p = 0.024).ConclusionsOur study identifies putative factors affecting morbidity and mortality in cardiac sarcoidosis patients. Intravenous cyclophosphamide is associated with lower relapse rates.
| S-EPMC7500618 | biostudies-literature
Project description:Recall-by-genotype (RbG) studies conducted with population-based biobank data remain urgently needed, and follow-up RbG studies, which add substance to this research approach, remain solitary. In such studies, potentially disease-related genotypes are identified and individuals with those genotypes are recalled for consultation to gather more detailed clinical phenotypic information and explain to them the meaning of their genetic findings. Familial hypercholesterolemia (FH) is among the most common autosomal-dominant single-gene disorders, with a global prevalence of 1 in 500 (Nordestgaard et al., Eur. Heart J., 2013, 34 (45), 3478-3490). Untreated FH leads to lifelong elevated LDL cholesterol levels, which can cause ischemic heart disease, with potentially fatal consequences at a relatively early age. In most cases, the pathogenesis of FH is based on a defect in one of three LDL receptor-related genes-APOB, LDLR, and PCSK9. We present our first long-term follow-up RbG study of FH, conducted within the Estonian Biobank (34 recalled participants from a pilot RbG study and 291 controls harboring the same APOB, LDLR, and PCSK9 variants that were included in the pilot study). The participants' electronic health record data (FH-related diagnoses, lipid-lowering treatment prescriptions) and pharmacogenomic risk of developing statin-induced myopathy were assessed. A survey was administered to recalled participants to discern the impact of the knowledge of their genetic findings on their lives 4-6 years later. Significant differences in FH diagnoses and lipid-lowering treatment prescriptions were found between the recalled participants and controls (34 and 291 participants respectively). Our study highlights the need for more consistent lipid-lowering treatment adherence checkups and encourage more follow-up RbG studies to be performed.
| S-EPMC9343846 | biostudies-literature
Project description:The addition of adjuvant trastuzumab therapy for 1 year to standard chemotherapy significantly improved disease-free survival and overall survival versus chemotherapy alone in a number of pivotal early breast cancer studies. Here we review long-term follow-up data on the efficacy, cardiac safety, and general safety of trastuzumab in these pivotal studies. We also evaluate ongoing phase II/III adjuvant trials with newer HER2-targeted agents and the efficacy and safety of the recently developed subcutaneous (SC) formulation of trastuzumab in early breast cancer. Long-term follow-up data confirm the significant survival benefit afforded by the addition of trastuzumab to chemotherapy in patients with HER2-positive disease, with an acceptable safety profile. Long-term cardiac safety data suggest that the incidence of cardiac adverse events is maintained at a relatively low level with continued follow-up. At this present time, 1 year of trastuzumab treatment remains the standard of care in HER2-positive early breast cancer. Future adjuvant trastuzumab treatment strategies should focus on reducing cardiotoxicity, particularly in elderly patients, by identifying potential predictive biomarkers of cardiac dysfunction. Clinicians must also decide whether to omit trastuzumab in women who would achieve little benefit from treatment to avoid cardiotoxicity.
| S-EPMC5054055 | biostudies-literature
Project description:Alström syndrome is a clinically complex disorder characterized by progressive degeneration of sensory functions, resulting in visual and audiological impairment as well as metabolic disturbances. It is caused by recessively inherited mutations in the ALMS1 gene, which codes for a centrosomal/basal body protein. The purpose of this study was to investigate the genetic and clinical features of two Tunisian affected siblings with Alström syndrome. Detailed clinical examinations were performed including complete ophthalmic examination, serial audiograms and several biochemical and hormonal blood tests. For the molecular study, first genomic DNA was isolated using a standard protocol. Then, linkage analysis with microsatellite markers was performed and DNA array was used to detect known mutations. Subsequently, all ALMS1 exons were simultaneously sequenced for one affected patient with the TaGSCAN targeted sequencing panel. Finally, segregation of the causal variant was performed by Sanger sequencing. Both affected siblings had cone rod dystrophy with impaired visual acuity, sensorineural hearing loss and truncal obesity. One affected individual showed insulin resistance without diabetes mellitus. Other clinical features including cardiac and pulmonary dysfunction, hypothyroidism, hyperlipidemia, acanthosis nigricans, renal and hepatic dysfunction were absent. Genetic analysis showed the presence of a homozygous splice site mutation (c.10388-2A > G) in both affected siblings. Although Alström syndrome is relatively well characterized disease, this syndrome is probably misdiagnosed in Tunisia. Here, we describe the first report of Tunisian patients affected by this syndrome and carrying a homozygous ALMS1 mutation. The diagnosis was suspected after long-term clinical follow-up and confirmed by genetic testing.
| S-EPMC5335873 | biostudies-other
Project description:BACKGROUND:A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone. OBJECTIVES:To assess long-term effects of a psilocybin-facilitated smoking cessation program at ?12 months after psilocybin administration. METHODS:The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ?12 months, and related data on subjective effects of psilocybin. RESULTS:All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (?16 months) follow-up, with a mean interval of 30 months (range = 16-57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives. CONCLUSION:These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.
| S-EPMC5641975 | biostudies-literature
Project description:IntroductionThe glaucomas often co-exist with cataract. We previously reported a large trial of anti-scarring treatment in combined phacotrabeculectomy surgery. Long-term outcomes in an African population are extremely rarely reported. We present here the outcomes in IOP, acuity, bleb morphology and patient perceptions at 3-5-years post surgery.MethodsTanzanian patients with glaucoma and visually significant cataract underwent combined phacotrabeculectomy surgery. In November 2015 an attempt was made to contact all participants in the study inviting them for a repeat examination. All who attended were given a detailed examination. A semi-structured interview in Swahili was administrated to determine patient experience and satisfaction with the surgery.ResultsSixty-eight (23%) attended for repeat review in 2015. The mean time from original surgery was 4.5-years (range 2.3-6.6-years). Overall 53 (78%) had IOP?<?21?mm?Hg and 29 (43%) an IOP?<?16?mm?Hg at final follow-up. A flat bleb at 26 and 100 days was associated with failure by IOP criteria at 4.5-years post-operatively. A vascular bleb at those time points was not any more associated with late failure than a non-vascular bleb. A majority of patients were pleased with the surgery. The cost of surgery is high but it is a price patients were willing to pay. Nearly all patients (95%) would recommend the service to family and friends.DiscussionOwing to the small proportion reviewed, our conclusions are severely limited. Phacotrabeculectomy worked well in a majority of the reviewed population long-term and is accepted by a majority of these patients as worthwhile.
| S-EPMC6707322 | biostudies-literature
Project description:BackgroundTourette's Syndrome (TS) is a childhood-onset movement disorder marked by the chronic presence of motor and vocal tics. Research shows that tics associated with TS tend to fade in severity for some (but not all) affected youth, though psychiatric comorbidities that commonly accompany TS may be more persistent. The long-term outcomes of individuals with TS have not been well characterized.ObjectiveTo characterize long-term clinical outcomes of individuals with TS.MethodWe conducted a long-term (25-32 years) follow-up study of 45 patients with TS who presented to the Tourette's and Tic Disorders Clinic within the Department of Psychiatry at the University of California San Francisco Medical Center, which was staffed by the first author (Thomas L. Lowe, MD [T.L.L.]), between 1983 and 1990. Baseline data were obtained via chart review, and follow-up data were obtained by self-report surveys.ResultsParticipants generally reported good psychosocial functioning, attainment of significant social milestones (academic attainment, gainful employment, marriage), and high subjective quality of life. The vast majority of participants (82%) reported improvement in their tics over time, though a significant minority continued to experience at least mild tic-related impairment (26%-40%, depending on metric). Lifetime rates of attention deficit hyperactivity disorder (ADHD) and anxiety disorders, including obsessive-compulsive disorder, were greater than in the general US population. Robust predictors of follow-up outcomes were not found.ConclusionsThese findings reflect a positive overall long-term prognosis for individuals with TS. Providing information about this prognosis at the time of diagnosis may decrease distress in affected individuals and their families. Future studies using planned longitudinal designs that address potential confounds of survey nonresponse are needed to detail long-term outcomes of individuals with TS more precisely.
| S-EPMC6335508 | biostudies-literature