Cohort Studies

Mitochondrial DNA depletion syndromes (MDSs) form a group of autosomal recessive disorders characterized by profoundly decreased mitochondrial DNA copy numbers in affected tissues. Three main clinical presentations are known: myopathic, encephalomyopathic and hepatocerebral. The first is associated with mutations in thymidine kinase 2 (TK2) and p53-induced ribonucleotide reductase B subunit (RRM2B); the second with mutations in succinate synthase A (SUCLA2) and B (SUCLG1); the third with mutations in Twinkle (PEO1), pol-γA (POLG1), deoxyguanosine kinase (DGUOK) and MPV17 (MPV17). In this work, we review the MDS-associated phenotypes and present our own experience of 32 MDS patients, with the aim of defining the mutation frequency of the known genes, the clinical spectrum of the diseases, and the genotype–phenotype correlations. Five of our patients carried previously unreported mutations in one of the eight MDS genes.

There are frequent applications for endoscopy in neurosurgery. However, endoscopic surgery in children has peculiar characteristics and is associated with different rates of success. In this study, the authors report on their experience with 134 consecutive endoscopy procedures performed in 126 patients<18 years of age. Between April 1993 and October 2007, 134 endoscopic procedures were performed in 126 children. Indications for surgery included brain tumors in 48 children, cystic lesions in 24, aqueductal stenosis in 23, various malformations in 20, hemorrhage and infarction in 6, and isolated ventricles in 5 children. In this long-term followup study, data were analyzed with respect to clinical and radiological success rates, as well as shunt dependence both in relation to lesion origin, and to the type of endoscopic procedure performed (endoscopic third ventriculostomy [ETV], septostomy, aqueductoplasty, or cystocisternostomy). Finally, the influence of patient age on the succ...

OBJECTIVE: To assess the impact of laser peripheral iridotomy (LPI) on forward-scatter of light and subjective visual symptoms and to identify LPI parameters influencing these phenomena. DESIGN: Cohort study derived from a randomized trial, using an external control group. PARTICIPANTS: Chinese subjects initially aged 50 or older and 70 years or younger with bilateral narrow angles undergoing LPI in 1 eye selected at random, and age- and gender-matched controls. METHODS: Eighteen months after laser, LPI-treated subjects underwent digital iris photography and photogrammetry to characterize the size and location of the LPI, Lens Opacity Classification System III cataract grading, and measurement of retinal straylight (C-Quant; OCULUS, Wetzlar, Germany) in the treated and untreated eyes and completed a visual symptoms questionnaire. Controls answered the questionnaire and underwent straylight measurement and (in a random one-sixth sample) cataract grading. MAIN OUTCOME MEASURES: Retina...

To evaluate the results of our method of surgical treatment of traumatic knee dislocation with injury to the posterolateral corner by use of a standardized protocol. Twenty-five consecutive patients presented with a grossly dislocated or reduced knee. Five of these patients were not included in this series. The remaining 20 patients were treated by primary arthroscopic reconstruction. The anterior cruciate ligament (ACL) was reconstructed using gracilis tendon reinforced with artificial ligament (Ligament Augmentation and Reconstruction System [LARS] ligament); the posterior cruciate ligament (PCL) was reconstructed with semitendinosus tendon and reinforced with LARS ligament; and the posterolateral corner was treated using the gracilis and semitendinosus tendons from the uninjured knee. Twenty patients returned for subjective and objective evaluation at a minimum of 24 months after surgery. Early mobilization through continuous and active exercise was started on the fourth day postoperatively. At a mean follow-up of 44 months, the mean Lysholm score was 90 points, the mean score on the survey of daily activities was 90 points, and the sports activities score on the knee outcome survey averaged 80 points. By the rating of Meyers et al. the results were excellent in 6 patients, good in 10 patients, fair in 3 patients, and poor in one patient. The final International Knee Documentation Committee (IKDC) rating was not normal in any knee. The mean loss of extension was 2° (range, 0° to 3°) and loss of flexion was 12° (range, 10° to 15°). By using the described method of arthroscopically assisted reconstruction of the cruciate ligaments and the posterolateral corner, 80% of the patients had good subjective results and functional stability, and according to the IKDC scale, 45% of knees were nearly normal, 45% were abnormal, and 10% were severely abnormal. No patient's rating returned to normal. Level IV, therapeutic case series.

Mitogen- and stress-activated kinases (MSKs) are important substrates of the mitogen-activated protein kinase (MAPK)-activated protein kinase family. MSK1 and MSK2 are both nuclear serine/threonine protein kinases, with MSK1 being suggested to potentially play a role in breast cancer cell proliferation, cell cycle progression, cell migration, invasion and tumour growth. The aim of the current study was to assess MSK1 protein expression in breast cancer tumour specimens, evaluating its prognostic significance. A large cohort of 1902 early stage invasive breast cancer patients was used to explore the expression of MSK1. Protein expression was examined using standard immunohistochemistry on tissue microarrays. Low MSK1 protein expression was associated with younger age (P = 0.004), higher tumour grade (P < 0.001), higher Nottingham Prognostic Index scores (P = 0.007), negative ER (P < 0.001) and PR (P < 0.001) status, and with triple-negative (P < 0.001) and basal-like (P &...

Peritonitis is caused most commonly by perforation of the hollow viscus and grave consequences of the dis-ease are attributed to the microbial infection of the perito-neal cavity. Factors predicting outcome in cases of perfo-ration peritonitis are well known and have been well ...

BACKGROUND: Clinical audit has been increasingly required for the accreditation process in every modern healthcare system. Data collection and analysis are excessively time-consuming in everyday practice. The primary aim of our study was to evaluate the ...

Rosacea is a chronic disease with a profound impact on quality of life. Although there are a range of treatments for its many manifestations, some cases are difficult to treat. Sbidian et al. show in this double-blind, randomized, placebo-controlled trial that low-dose isotretinoin can be effective in treating difficult-to-treat and frequently relapsing papulopustular rosacea.

Objective:To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples).Methods:Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks.Results:A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was ident...

Background and Purpose This study examined the interrater and intrarater reliability, concurrent validity, and criterion validity of the Tinetti Mobility Test (TMT) as a fall risk screening tool in individuals with Parkinson disease (PD). Subjects Thirty individuals with PD voluntarily participated in the study, and data from a retrospective review of 126 patient records were included. Methods Physical therapists and physical therapist students rated live and videotaped performances of the TMT. Tinetti Mobility Test scores were correlated with Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and comfortable gait speed. The ability of the TMT to accurately assess fall risk was determined. Results Interrater and intrarater reliability was good to excellent (intraclass correlation coefficient of >.80). Tinetti Mobility Test scores correlated with UPDRS motor scores (rs=−.45) and gait speed (rs=.53). The sensitivity and specificity of the TMT to identify fallers were...

This is an Accepted Article that has been peer-reviewed and approved for publication in the Journal of Diabetes, but has yet to undergo copy-editing and proof correction. Please cite this article as an “Accepted Article”; doi: 10.1111/j.1753-0407.2011.00115.x ... Comprehensive Risk ...

People who inject drugs (PWID) in Dar es Salaam, Tanzania, have an estimated human immunodeficiency virus (HIV) prevalence of 42%-50% compared with 6.9% among the general population. Extensive evidence supports methadone maintenance to lower morbidity, mortality, and transmission of HIV and other infectious diseases among PWID. In 2011, the Tanzanian government launched the first publicly funded methadone clinic on the mainland of sub-Saharan Africa at Muhimbili National Hospital. We conducted a retrospective cohort study of methadone-naive patients enrolling into methadone maintenance treatment. Kaplan-Meier survival curves were constructed to assess retention probability. Proportional hazards regression models were used to evaluate the association of characteristics with attrition from the methadone program. Overall, 629 PWID enrolled into methadone treatment during the study. At 12 months, the proportion of clients retained in care was 57% (95% confidence interval [CI], 53%-62%). Compared with those receiving a low dose (<40 mg), clients receiving a medium (40-85 mg) (adjusted hazard ratio [aHR], 0.50 [95% CI, .37-.68]) and high (>85 mg) (aHR, 0.41 [95% CI, .29-.59]) dose of methadone had a lower likelihood of attrition, adjusting for other characteristics. Older clients (aHR, 0.53 per 10 years [95% CI, .42-.69]) and female clients (aHR, 0.50 [95% CI, .28-.90]) had a significantly lower likelihood of attrition, whereas clients who reported a history of sexual abuse (aHR, 2.84 [95% CI, 1.24-6.51]) had a significantly higher likelihood of attrition. Patient retention in methadone maintenance is comparable to estimates from programs in North America, Europe, and Asia. Future implementation strategies should focus on higher doses and flexible dosing strategies to optimize program retention and strengthened efforts for clients at higher risk of attrition.

Objective.To report baseline and followup data on the first 438 patients with systemic sclerosis (SSc) included in the Belgian Systemic Sclerosis Cohort.Methods.According to LeRoy and Medsger’s classification, 73 patients with limited SSc (lSSc), 279 with limited cutaneous SSc (lcSSc), and 86 with diffuse cutaneous SSc (dcSSc) were included. History was collected and clinical examination, blood tests, and paraclinical investigations were repeated. The Disease Activity Score (DAS) and Disease Severity Score (DSS) of several organ systems were computed. An organ system was considered to demonstrate SSc if the corresponding DSS was ≥ 1.Results.At baseline, patients with dcSSc had more general, joint/tendon, muscle, gastrointestinal, and kidney involvement. Mean DLCO was below normal in patients with lSSc, indicating unsuspected lung involvement. Patients with anti-Scl-70 had more vascular, skin, joint/tendon, and lung involvement. Patients with anti-RNA polymerase III had more skin and...

Mental health outcomes for survivors of critical congenital heart disease (CHD) remain under-investigated. We sought to examine psychiatric disorders and psychosocial functioning in adolescents with single ventricle CHD and to explore whether patient-related risk factors predict dysfunction. This cohort study recruited 156 adolescents with single ventricle CHD who underwent the Fontan procedure and 111 healthy referents. Participants underwent comprehensive psychiatric evaluation including a clinician-rated psychiatric interview and parent- and self-report ratings of anxiety, disruptive behavior, including attention-deficit/hyperactivity disorder (ADHD), and depressive symptoms. Risk factors for dysfunction included IQ, medical characteristics, and concurrent brain abnormalities. Adolescents with single ventricle CHD had higher rates of lifetime psychiatric diagnosis compared with referents (CHD: 65%, referent: 22%; P < .001). Specifically, they had higher rates of lifetime anxie...

Low back pain (LBP) in children and adolescents was considered for many years to be rare and an indication of serious disease [1]. In the last two decades, epidemi-ological studies have shown that the prevalence of ... Ismail Bejia Nabiha Abid Kamel Ben Salem Mondher Letaief ...

This prospective cohort study examined the association between educational level and major causes of death in Japan.A baseline survey was conducted between 1988 and 1990 among 110,792 inhabitants of 45 areas aged 40–79 years. Follow-up surveys were conducted annually and causes of death were identified from death certificates. The analysis was restricted to 16,715 men and 23,284 women.During the follow-up period (377,139 person-years), 6628 deaths were recorded. Individuals with low levels of education had an increased overall risk of death [relative risk (RR) = 1.16, 95% confidence interval (CI): 1.08, 1.25, in men; RR = 1.26, 95% CI: 1.14, 1.39, in women], cancers (RR = 1.17, 95% CI: 1.04, 1.32, in men; RR = 1.10, 95% CI: 0.93, 1.30, in women), and death from external causes (RR = 1.81, 95% CI: 1.29. 2.54, in men; RR = 1.78, 95% CI: 1.18, 2.70, in women). Ischemic heart disease risk was marginally reduced in men with low levels of education (RR = 0.77, 95% CI: 0.58, 1.01).These results show that health inequalities exist in Japan, even though wealth inequalities are relatively low. Social and political initiatives will be needed to correct these inequities between different socioeconomic statuses.