Promotion of mental health in young adults via mobile phone app: study protocol of the ECoWeB (emotional competence for well-being in Young adults) cohort multiple randomised trials.

BACKGROUND: Promoting well-being and preventing poor mental health in young people is a major global priority. Building emotional competence (EC) skills via a mobile app may be an effective, scalable and acceptable way to do this. However, few large-scale controlled trials have examined the efficacy of mobile apps in promoting mental health in young people; none have tailored the app to individual profiles. METHOD/DESIGN: The Emotional Competence for Well-Being in Young Adults cohort multiple randomised controlled trial (cmRCT) involves a longitudinal prospective cohort to examine well-being, mental health and EC in 16-22 year olds across 12 months. Within the cohort, eligible participants are entered to either the PREVENT trial (if selected EC scores at baseline within worst-performing quartile) or to the PROMOTE trial (if selected EC scores not within worst-performing quartile). In both trials, participants are randomised (i) to continue with usual practice, repeated assessments and a self-monitoring app; (ii) to additionally receive generic cognitive-behavioural therapy self-help in app; (iii) to additionally receive personalised EC self-help in app. In total, 2142 participants aged 16 to 22 years, with no current or past history of major depression, bipolar disorder or psychosis will be recruited across UK, Germany, Spain, and Belgium. Assessments take place at baseline (pre-randomisation), 1, 3 and 12 months post-randomisation. Primary endpoint and outcome for PREVENT is level of depression symptoms on the Patient Health Questionnaire-9 at 3 months; primary endpoint and outcome for PROMOTE is emotional well-being assessed on the Warwick-Edinburgh Mental Wellbeing Scale at 3 months. Depressive symptoms, anxiety, well-being, health-related quality of life, functioning and cost-effectiveness are secondary outcomes. Compliance, adverse events and potentially mediating variables will be carefully monitored. CONCLUSIONS: The trial aims to provide a better understanding of the causal role of learning EC skills using interventions delivered via mobile phone apps with respect to promoting well-being and preventing poor mental health in young people. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective Mobile-health public health strategies for preventing poor mental health and promoting well-being. TRIAL REGISTRATION: ClinicalTrials.gov ( www.clinicaltrials.org ). Number of identification: NCT04148508 November 2019.

Evaluating the impact of two training interventions to improve diagnosis and case-management of malaria and pneumonia in Uganda.

We present an age-structured mathematical model of malaria and pneumonia to study the effect of two capacity-building interventions: Integrated Management of Infectious Diseases (IMID) and On-site Support Services (OSS). IMID leads to a reduction in malaria prevalence by more than 2·4% across the [0,5), [5,14) and [14,50) age groups. IMID + OSS reduces it by more than 16·0% across all age groups. IMID decreases pneumonia prevalence by more than 3·0% across all age groups while IMID + OSS decreases it by more than 1·0% across all age groups. The number of malaria and pneumonia deaths is reduced by 7·8% by IMID across all age groups and IMID + OSS decreases this number by 30·5% across all age groups, which translates to saving a life of a child per month. Prevalence of malaria-pneumonia for the [0,5) age group is 0·52% at baseline, and IMID and IMID + OSS reduce it by 6·6% and 23·6%, respectively. There is no change in incidence of malaria or pneumonia disease episodes. The results also indicate that triaging of children contributes more than 50% to the effect of the interventions in reduction of deaths and a range of 14-91% in reduction of disease cases.

Phase II trial of docetaxel, cisplatin and 5FU chemotherapy in locally advanced and metastatic penis cancer (CRUK/09/001).

BACKGROUND: Penis cancer is rare and clinical trial evidence on which to base treatment decisions is limited. Case reports suggest that the combination of docetaxel, cisplatin and 5-flurouracil (TPF) is highly active in this disease. METHODS: Twenty-nine patients with locally advanced or metastatic squamous carcinoma of the penis were recruited into a single-arm phase II trial from nine UK centres. Up to three cycles of chemotherapy were received (docetaxel 75 mg m(-2) day 1, cisplatin 60 mg m(-2) day 1, 5-flurouracil 750 mg m(-2) per day days 1-5, repeated every 3 weeks). Primary outcome was objective response (assessed by RECIST). Fourteen or more responses in 26 evaluable patients were required to confirm a response rate of 60% or higher (Fleming-A'Hern design), warranting further evaluation. Secondary endpoints included toxicity and survival. RESULTS: 10/26 evaluable patients (38.5%, 95% CI: 20.2-59.4) achieved an objective response. Two patients with locally advanced disease achieved radiological complete remission. 65.5% of patients experienced at least one grade 3/4 adverse event. CONCLUSION: Docetaxel, cisplatin and 5FU did not reach the pre-determined threshold for further research and caused significant toxicity. Our results do not support the routine use of TPF. The observed complete responses support further investigation of combination chemotherapy in the neoadjuvant setting.

Origin of a prenatal mosaic supernumerary neocentromeric derivative chromosome 13 determined by QF-PCR.

Neocentromeres are mitotically stable human derivative centromeres without alpha-satellite DNA which are able to provide stability to rearranged chromosome fragments that would otherwise be acentric and rapidly lost. A female fetus was found to be mosaic for a supernumerary marker chromosome: 47,XX,+mar[3]/46,XX[36]. The marker was identified by fluorescence in situ hybridization and G-band as an inversion duplication of 13q21→13qter, with a neocentromere present at 13q21, in approximately 9% of colonies examined. Parental blood karyotypes were normal. QF-PCR performed on blood samples from both parents and the second amniotic fluid sample showed evidence of a second maternal allele at markers D13S258 (13q21) and D13S628 (13q31-q32), indicating formation at maternal meiosis I/II. This is the first reported case where the detection and origin of a low-level mosaic prenatal neo(13) were confirmed by QF-PCR.

Ciliated hepatic foregut cysts in children.

Ciliated hepatic foregut cyst (CHFC) is a rare foregut developmental malformation usually diagnosed in adulthood; however, rare cases have been reported in the pediatric population. CHFC can transform into a squamous cell carcinoma resulting in death despite surgical resection of the isolated malignancy. We report the presentation, evaluation, and surgical management of a symptomatic 17-year-old girl found to have a 6.5 x 4.5 cm CHFC and suggest that all patients with suspected CHFC undergo prompt evaluation and complete cyst excision.

Os acromiale: population differences and their etiological significance.

The os acromiale is an accessory bone resulting from failure of the acromial apophysis to fuse to the scapula. It is a relatively frequent defect affecting 4-18% of most large skeletal series. The etiology of os acromiale is poorly understood, and two competing hypotheses have been proposed: (1) that the accessory bone represents a genetic defect, and (2) that it results from mechanical stress on the developing acromion. In order to assess the evidence for these two hypotheses, os acromiale frequencies from a South African cadaver sample (n = 494) were compared to frequencies from a medieval Danish archaeological sample (n = 532). The South African frequency (18.2%) was significantly higher than the medieval Danish frequency (7.7%, p < 0.0001). These results mirror those of another study comparing African- and Euro-Americans, and tend to support the genetic hypothesis. However, a left side bias (72%) was also found among the South Africans (p = 0.013), lending some support to the mechanical stress hypothesis. Sex and age biases were also examined but were not found. In order to further test the mechanical hypothesis, the medieval Danes were divided into groups of higher and lower socioeconomic status based upon cemetery type. Lower status individuals were presumed to have engaged in strenuous labor activities more often and at a younger age than higher status individuals. However, comparison of these two groups failed to demonstrate a significant frequency difference (p = 0.105). Based on the results of this study, it is suggested that a third etiology combining a genetic predisposition for os acromiale with mechanical stress as the proximate cause should also be considered.

Rolling-circle replication of a high-copy BPV-1 plasmid.

We investigated the replicating form of a bovine papillomavirus type 1 (BPV-1) deletion mutant by direct electron-microscopic analysis of low molecular weight cellular DNA fractions. The detection of viral plasmid DNA replication intermediates was facilitated by the isolation of a spontaneously transformed mouse cell subclone containing an unusually high viral genome copy number (approx. 1000 per cell), and by employing a slight modification of the Hirt fractionation procedure to reduce the level of contaminating linear chromosomal DNA fragments. We observed exclusively rolling-circle-type viral DNA replication intermediates, at a frequency of detection of approximately one replication intermediate per 200 monomeric circular viral DNA molecules. The demonstration of rolling-circles with longer-than-genome-length tails indicated that this high-copy viral plasmid was not subject to a strict once-per-cell-cycle mode of DNA replication. Our observations provide further evidence in favour of an alternative replication mode of the BPV-1 genome, and may help to explain earlier conflicting findings concerning the mechanism of stable BPV-1 plasmid copy-number-control.

Segregation properties of bovine papillomaviral plasmid DNA.

Essentially complete segregation of replication-competent BPV-1 plasmid DNA species was observed in daughter subclones derived from primary co-transformed C127 cell lines. Thus, whereas primary co-transformants retained both of two distinguishable co-transfected plasmid species, subcloning experiments revealed that morphologically transformed daughter subclones derived from such co-transformed cell lines contained only one species of viral plasmid DNA. Similar results were obtained with each of two conveniently marked replication and transformation-competent mutants: one with a linker-insertion in the viral upstream regulatory region, and one with a 260 base-pair deletion within the L2 (late) gene, which has no recognized role in plasmid replication or stability. Morphological revertant cell clones that contained no detectable viral plasmid DNA genomes were also isolated at a surprisingly high frequency from clonal wild-type BPV-1 transformed cell lines and from cell lines transformed by various BPV-1 mutants. Further co-transfection experiments were done with a combination of transformation-competent and transformation-defective BPV-1 genomes to investigate a possible role for a viral oncogene in plasmid persistence. In this case, elimination of the transformation-defective mutant was observed after the initial establishment of both input genomes as replicating plasmids in cell clones morphologically transformed by the transformation-competent viral mutant with an intact E5 oncogene. No cell subclones were isolated that contained only the transformation-defective mutant, implying that it was defective in long-term plasmid persistence. Our results indicate that there is significant randomization in the processes of replication and/or partitioning of the BPV-1 genome in mouse C127 cells, and, in combination with previous observations, also suggest that BPV plasmid persistence in C127 cell lines may be the result of a selective proliferative advantage conferred on virus-infected cells by viral oncogene-induced cell growth transformation.

Evidence for multiple vegetative DNA replication origins and alternative replication mechanisms of bovine papillomavirus type 1.

By following up the chance detection in the electron microscope of a DNA replication intermediate within a preparation of bovine papillomavirus (BPV-1) DNA isolated from purified virus particles, information was obtained about the mechanism of BPV-1 genome replication during the final stages of virus multiplication in naturally infected bovine wart tissue. The structure of viral replication intermediates was investigated by electron microscopic analysis of viral DNA linearized by digestion with restriction endonucleases which cleave the circular BPV-1 chromosome at defined sites. Both Cairns and rolling circle-type molecules were identified. Furthermore, replication eyes were widely distributed within the viral genome, indicating that vegetative BPV-1 DNA replication origins are largely uncoupled from previously described plasmid maintenance sequence elements.

Fulminant hepatic failure from primary hepatic lymphoma: successful treatment with orthotopic liver transplantation and chemotherapy.

Systemic lymphomas may involve the liver but rarely cause fulminant hepatic failure (FHF). Acute liver failure from primary hepatic lymphoma (PHL) is even less common with most patients succumbing to the sequelae of FHF before the correct diagnosis is made. We report a patient who underwent successful orthotopic liver transplant (OLT) and chemotherapy for FHF secondary to PHL. This previously-well male developed profound coagulopathy and encephalopathy 6 weeks after the onset of jaundice and fatigue. Workup failed to reveal the underlying cause of his liver failure and the patient soon required urgent OLT. Pathologic evaluation of his explanted liver revealed a malignant T-cell rich, large B-cell non-Hodgkin's lymphoma with widespread hepatocellular necrosis. The patient made an excellent clinical recovery and is undergoing CHOP-Rituxan chemotherapy. This scenario demonstrates that lymphoma should be considered in the differential diagnosis of FHF without clear etiology because of the potential for intervention with transplant and chemotherapy.

Vascular access in hemodialysis: issues, management, and emerging concepts.

This article (1) identifies the types of hemodialysis access, (2) summarizes the clinical standard of care for dialysis access grafts and fistulae, (3) describes the pathology and pathogenesis of venous stenosis in dialysis access grafts and fistulae, (4) tabulates avail-able therapies for hemodialysis vascular access dysfunction and speculates on the rea-sons for the lack of effective therapies, and (5) discusses the development and application of novel therapeutic interventions for this difficult clinical problem. The possibility that dialysis access grafts and fistulae could be the ideal clinical model for testing novel local therapies to block neointimal hyperplasia is discussed.

The presence and estrogen control of immunoreactive calbindin-D9k in the fallopian tube of the rat.

The present study was undertaken to localize and investigate the endocrine control of immunoreactive 9K calbindin-D9k in the fallopian tube (oviduct) of the rat. Rat fallopian tubes were excised with the uterus, immediately fixed by freeze-substitution, and processed for immunoperoxidase staining. Staining employed a rabbit antiserum against purified rat intestinal calbindin-D9k and the streptavidin-biotin technique. Calbindin-D9k immunoreactivity was localized to luminal epithelial cells of the fallopian tube of mature rats, with no staining observed in other tissue layers of the tube. Epithelial cells in both the isthmus and the ampulla were positive for calbindin-D9k. In weanling rats, which have little ovarian function but high levels of 1,25-dihydroxyvitamin D, no immunoreactive calbindin-D9k was observed in any part of the tube. However, after daily injections of estradiol (6 micrograms/day) for 3 days, intense staining was observed in the epithelial cells of the immature rat fallopian tube. Progesterone treatment (1 mg/day for 3 days) of immature rats had no effect on calbindin-D9k in fallopian tube. The lumen of the fallopian tube (oviduct) is the key location for fertilization, a process that requires a narrowly defined concentration of extracellular calcium. By analogy to the intestine, calbindin-D9k may play a role in the transcellular movement of calcium across the fallopian tube epithelium in the fallopian tube lumen.

External beam radiation attenuates venous neointimal hyperplasia in a pig model of arteriovenous polytetrafluoroethylene (PTFE) graft stenosis.

PURPOSE: Hemodialysis vascular access dysfunction is an enormous clinical problem that causes great morbidity and costs well over one billion dollars per annum. The vast majority of hemodialysis vascular access dysfunction occurs as a result of venous stenosis and thrombosis at the graft-vein anastomosis. At a cellular level, this venous stenosis is the result of venous neointimal hyperplasia (VNH). There are, unfortunately, no effective therapies for VNH. The purpose of this study was to assess the role of external radiation therapy in preventing VNH and venous stenosis. METHODS AND MATERIALS: Seven-centimeter polytetrafluoroethylene loop grafts were placed bilaterally between the femoral artery and vein of 12 Yorkshire Cross pigs. One side was treated with a single 16-Gy dose of external beam radiation with a linear accelerator, while the contralateral side served as an internal control. Swine were killed after 28 days, and the grafts were carefully dissected out and removed. Neointimal hyperplasia and luminal stenosis were then assessed morphometrically at the graft-vessel anastomoses. RESULTS: External beam radiation therapy significantly reduced the amount of luminal stenosis at the graft-vein anastomosis, with minimal local and systemic toxicity. CONCLUSIONS: External beam radiation therapy could be a useful and clinically relevant local treatment for venous stenosis in polytetrafluoroethylene dialysis grafts.

A prospective study of clozapine in treatment-resistant schizophrenic patients. I. Preliminary report.

Preliminary results of a non-blinded prospective study of the effect of clozapine on symptomatology and social function in 51 treatment-resistant schizophrenic patients are reported. The mean duration of treatment at the time of this report was 10.3 +/- 8.1 months, median 7.6 months. Overall, 3/51 patients (60.8%) showed at least a 20% decrease in total BPRS, a criterion of improvement in the study of Kane et al. (1988). Four of 51 (7.8%) had at least a 50% decrease in total BPRS. Improvements in both positive and negative symptoms were noted. Marked improvements in social function were noted within the first 6 months of treatment. Improvement was first noted at all time points, with only 45.2% of improvers being identified after 6 weeks of treatment. These results suggest a 6-12-month trial may be desirable before deciding to discontinue clozapine because of insufficient response. Higher total Brief Psychiatric Rating Scale (BPRS) score and higher ratings on the Paranoid Disturbance subscales of the BPRS were factors which discriminated clozapine responders from non-responders.

Clapping or percussion causes atelectasis in dogs and influences gas exchange.

We examined the effects of 10 min of lower lateral chest wall percussion with a mechanical percussor or hand clapping in groups of anesthetized, paralyzed, and ventilated supine dogs. Mechanical percussion was applied at 10-16 Hz and caused an esophageal pressure swing (delta Pes) of 10-17 cmH2O. Hand clapping was applied at 4-7 Hz and caused a delta Pes of 6-17 cmH2O. At necropsy there were large reddened areas on the lateral surface of the underlying lung as well as smaller reddened areas on the hilar surfaces of both lungs and on the lateral surface of the opposite lung. These reddened regions were demonstrated to be atelectatic by postmortem lung inflation (which caused the reddened areas to disappear) and by microscopic examination. Despite the atelectasis, gas exchange improved toward the end of the percussion or clapping period. In four dogs that were ventilated for an additional 20 min after percussion, there was a tendency for gas exchange initially to worsen and then to gradually improve.

Delusional and Psychotic Depression in Late Life Clinical Research Needs.

Psychotic depression in younger patients has been associated with an increased rate of suicide, refractoriness to somatic treatment, and overall poor prognosis. However, the public health and scientific significance of this disorder in older patients has received limited attention in the past two decades; the topic was excluded from the 1991 NIH Consensus Development Conference on the Diagnosis and Treatment of Depression in Late Life. To address this obvious need in the field, a special work-group of recognized experts met in a special NIMH workshop to review and discuss clinical issues and key research questions. This is a report of that workshop's proceedings.

A physician-pharmacist model for the surveillance of blood pressure in the community: a feasibility study.

Hypertension is poorly managed. Hospital-based pharmacists working with physicians have been shown to improve the rate of achievement of "target" blood pressure in selected patients. It is unknown if such schemes can operate in the community and to what extent they would attract volunteers with poorly managed blood pressure. We assessed the feasibility of pharmacists to provide community-based, open-access, blood pressure monitoring. In addition, we describe the blood pressure profile of the group in comparison to that of the 1994 Health Survey of England (HSE). Pharmacists from six pharmacies were trained to deliver the service. Adults living within the postal districts of the pharmacies were invited, through an advertising campaign, to volunteer to have their blood pressure measured. Blood pressure data and information on treatment for hypertension and/or diabetes were collected on 263 registrants. Patients were advised to have their blood pressure managed by the general practitioner immediately (category 1), re-measured within 2-3 months (category 2) or in 12 months time (category 3). The mean (s.d.) blood pressure of patients in categories 1 (n = 16), 2 (n = 117) and 3 (n = 130) was 186(16)/97(29), 151(13)/94(9) and 139(22)/86(13) mm Hg respectively; P < 0.001. Ninety-one patients (35%) were in receipt of antihypertensive therapy. Forty-five percent of the treated group had controlled blood pressure (<160/95 mm Hg) compared with 30% in the HSE dataset. A large proportion of known hypertensive patients with poor blood pressure control who had visited their general practitioner within the previous 6 months were detected by the pharmacist-led service. Pharmacists operating an open-access blood pressure monitoring service may be of value in improving the management of hypertension.

Unsuspected sphincter damage following childbirth revealed by anal endosonography.

Anal endosonography was performed in 62 consecutive patients with incontinence of flatus or faeces following obstetric trauma, and in 18 parous controls. Of the incontinent group, 90% had defects in the external sphincter, 65% in the internal sphincter and 44% disruption of the perineal body, compared with none of the controls. This triad of lesions is pathognomonic of obstetric trauma. Anal endosonography revealed a higher prevalence of sphincter damage than expected from anorectal physiology tests, and therefore has a role in screening patients following complicated or difficult deliveries.

The variation of position of the conus medullaris in an adult population. A magnetic resonance imaging study.

STUDY DESIGN: Sequential study of magnetic resonance images of the lumbar spine. OBJECTIVES: To determine the variation in position of the conus medullaris in a living adult population without spinal deformity. SUMMARY OF BACKGROUND DATA: Cadaveric studies have shown that the position of the conus medullaris in the adult most commonly is located at L1-L2. There have been several studies documenting the changing level of the conus throughout infancy and childhood, but there is no detailed study that documents the range of conus positions in a living adult population without spinal deformity. METHODS: The T1-weighted, midline, sagittal, spin-echo magnetic resonance imaging studies of 504 patients were assessed to identify the tip of the conus medullaris. This location was recorded in relation to the upper, middle, or lower third of the adjacent vertebral body or the adjacent intervertebral disc. RESULTS: The study group consisted of 231 men and 273 women with a mean age 46 years (range, 16-85 years). Most patients were being examined for low back pain. Patients with spinal deformity were excluded. The mean conus position was the lower third of L1 (range, middle third of T12 to upper third of L3). The variation in conus positions followed a normal distribution. No significant difference in conus position was seen between male and female patients or with increasing age. CONCLUSIONS: The distribution of conus location in a large adult population was shown to range from the middle third of T12 to the upper third of L3.