To estimate whether prolapse severity is a major contributor to urinary incontinence severity, as measured by validated incontinence questionnaires.
We analyzed data from two large female stress ...urinary incontinence (SUI) surgical cohorts: the Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr) study (N=655) and the subsequent Trial of Mid-Urethral Slings (TOMUS) study (N=597). All participants completed a standardized baseline assessment including validated measures of symptom severity, quality of life, objective measures of urine loss (Urogenital Distress Inventory UDI, Medical, Epidemiologic, and Social Aspects of Aging questionnaire, Incontinence Impact Questionnaire, and pad test), as well as the Pelvic Organ Prolapse Quantification assessment. Groups were compared using the chi; test (categorical measures) or the one-way analysis of variance (continuous measures). Statistical significance was defined as P<.05.
The SISTEr and TOMUS samples were similar for many variables including age (52 and 53 years, respectively), nulliparity (9% and 12%), prior urinary incontinence (UI) surgery (14% and 13%), and prior hysterectomy (31% and 28%), but other differences necessitated separate analysis of the two cohorts. There was not a statistically significant difference in UDI scores according to prolapse stage in either study population. Patients with prior surgery for pelvic organ prolapse and SUI had more incontinence symptoms and were more bothered by their UI regardless of prolapse stage.
Prolapse stage is not strongly or consistently associated with incontinence severity in women who select surgical treatment of SUI. Prior pelvic organ prolapse and UI surgery is associated with worse UI severity and bother.
ClinicalTrials.gov, www.clinicaltrials.gov, NCT00064662 and NCT00325039.
II.
Fecal incontinence has a high prevalence in the older population, which cannot be explained by comorbidity or the anatomical or psychological changes of aging alone. Fecal incontinence leads to a ...high economic burden to the healthcare system and is an important cause of institutionalization. In addition, fecal incontinence is associated with shame, social isolation and reduced quality of life. The importance of identifying treatable causes in the frail elderly is strongly emphasized. It is recommended that an assessment of fecal incontinence should be implemented as part of an evaluation of older patients. Although there is a substantial evidence base to guide choice of implementation activities targeting healthcare professionals, little implementation research has focused on the care of older people nor involved care processes or care personnel. This study is based on the assumption that fecal incontinence among nursing home patients can be prevented, cured or ameliorated by offering care staff knowledge of best practice through a multifaceted educational program. The primary objective is to test the hypothesis that a multifaceted educational program for nursing home care staff on assessment and treatment of fecal incontinence reduces patients' frequency of fecal incontinence.
The study is a two-armed, parallel cluster-randomized controlled trial. Primary outcome is the frequency of fecal incontinence among patients. Sample size calculations resulted in a need for a total sample of 240 patients. Twenty nursing home units in one city in Norway will be recruited and allocated to intervention or control by an independent statistician using computer-generated tables. The intervention is a multifaceted educational program. Units in the control arm will provide care as usual. The intervention period is 3 months. Data will be collected at baseline, 3, and 6 months. Data will be analyzed using mixed effect models with the cluster treated as a random effect.
This study is the first randomized controlled trial specifically focusing on this neglected area. The result of the study will give evidence for best practice for continence care in nursing homes, and organizational advice concerning implementation strategies.
ClinicalTrials.gov: NCT02183740 , registered June 2014.
This study examined the relationship of childhood abuse, both physical and sexual, with subsequent lifetime depressive and anxiety disorders--depression or dysthymia, post-traumatic stress disorder ...(PTSD), and panic or generalized anxiety disorder (GAD)--among American Indians (AIs).
Three thousand and eighty-four AIs from two tribes--Southwest and Northern Plains--participated in a large-scale, community-based study. Participants were asked about traumatic events and family history, and were administered standard diagnostic measures of depressive/anxiety disorders.
Prevalence of childhood physical abuse was approximately 7% for both tribes. The Southwest tribe had higher prevalence of depressive and anxiety disorders, with rates of PTSD being the highest. Childhood physical abuse was significant in bivariate models of depressive/anxiety disorders, and remained so in the multivariate models.
Childhood physical abuse was a significant predictor of all disorder groups for males in both tribes except for panic/GAD for the Northern Plains tribe in multivariate models; females showed a more varied pattern. Childhood sexual abuse did not significantly differ for males and females, and was an independent predictor of PTSD for both tribes, controlling for childhood physical abuse and other factors, and was significant for the other disorder groups only in the Southwest. Additional covariates that increased the odds of depressive/anxiety disorder, were adult physical or sexual victimization, chronic illness, lifetime alcohol or drug disorder, and parental problems with depression, alcohol, or violence. Results provided empirical evidence of childhood and later life risk factors and expanded the population at risk to include males.
DNA binding by the ternary complex factor (TCF) subfamily of ETS‐domain transcription factors is tightly regulated by intramolecular and intermolecular interactions. The helix–loop–helix ...(HLH)‐containing Id proteins are trans‐acting negative regulators of DNA binding by the TCFs. In the TCF, SAP‐2/Net/ERP, intramolecular inhibition of DNA binding is promoted by the cis‐acting NID region that also contains an HLH‐like motif. The NID also acts as a transcriptional repression domain. Here, we have studied the role of HLH motifs in regulating DNA binding and transcription by the TCF protein SAP‐1 and how Cdk‐mediated phosphorylation affects the inhibitory activity of the Id proteins towards the TCFs. We demonstrate that the NID region of SAP‐1 is an autoinhibitory motif that acts to inhibit DNA binding and also functions as a transcription repression domain. This region can be functionally replaced by fusion of Id proteins to SAP‐1, whereby the Id moiety then acts to repress DNA binding in cis. Phosphorylation of the Ids by cyclin–Cdk complexes results in reduction in protein–protein interactions between the Ids and TCFs and relief of their DNA‐binding inhibitory activity. In revealing distinct mechanisms through which HLH motifs modulate the activity of TCFs, our results therefore provide further insight into the role of HLH motifs in regulating TCF function and how the inhibitory properties of the trans‐acting Id HLH proteins are themselves regulated by phosphorylation.
Burkholderia pseudomallei, the causative agent of melioidosis, is endemic to Southeast Asia and northern Australia. Clinical manifestations of the disease are diverse, ranging from chronic localized ...infection to acute septicaemia, with death occurring within 24-48 h after the onset of symptoms. Definitive diagnosis of melioidosis involves bacterial culture and identification, with results obtained within 3-4 days. This delayed diagnosis is a major contributing factor to high mortality rates. Rapid diagnosis is vital for successful management of the disease. This study describes the purification and evaluation of three recombinant antigenic proteins, BPSL0972, BipD and OmpA from B. pseudomallei 08, for their potential in the serodiagnosis of melioidosis using an indirect enzyme-linked immunosorbent assay (ELISA) method. The recombinant proteins were evaluated using 74 serum samples from culture-confirmed melioidosis patients from Malaysia, Thailand and Australia. In addition, 62 nonmelioidosis controls consisting of serum samples from clinically suspected melioidosis patients (n=20) and from healthy blood donors from an endemic region (n=18) and a nonendemic region (n=24) were included. The indirect ELISAs using BipD and BPSL0972 as antigens demonstrated poor to moderate sensitivities (42% and 51%, respectively) but good specificity (both 100%). In contrast, the indirect ELISA using OmpA as an antigen achieved 95% sensitivity and 98% specificity. These results highlight the potential for OmpA to be used in the serodiagnosis of melioidosis in an endemic area.
Adjuvant chemotherapy is widely used for breast cancer and is known to extend survival. Some clinicians seek a greater survival benefit by increasing the intensity of the dose, whereas others lower ...it to diminish toxicity.
The Cancer and Leukemia Group B (CALGB) conducted a randomized trial of different levels of doses and dose intensity (dose per unit of time) of adjuvant chemotherapy in 1572 women with node-positive, stage II breast cancer who were assigned to three treatment groups. One group received 400 mg of cyclophosphamide per square meter of body-surface area and 40 mg of doxorubicin per square meter once every 28 days and 400 mg of fluorouracil per square meter twice every 28 days, for six cycles. Another group received 50 percent higher doses of the three drugs (600 mg, 60 mg, and 600 mg, respectively) but for only four cycles, so that the total dose was identical in these two groups but the dose intensity was higher in the first. The third group of women received half the total dose used in the other two groups and at half the dose intensity used in the second group.
After a median of 3.4 years of follow-up, the women treated with a high or moderate dose intensity had significantly longer disease-free survival (P < 0.001) and overall survival (P = 0.004) than those treated with a low dose intensity, in three-way log-rank comparisons. However, the difference in survival between the two groups treated with a moderate or high dose intensity was not significant. These results are consistent with either a dose-response effect or a threshold level of the dose or dose intensity.
The doses of chemotherapy used to treat breast cancer, especially early breast cancer, should not be reduced if the maximal benefit is to be achieved.
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