How Different Are Threshold and Other Specified Feeding and Eating Disorders? Comparing Severity and Treatment Outcome

Background: Other Specified Feeding and Eating Disorders (OSFED) are characterized by less frequent symptoms or symptoms that do not meet full criteria for another eating disorder. Despite its high prevalence, limited research has examined differences in severity and treatment outcome among patients with OSFED compared to threshold EDs [Anorexia Nervosa (AN), Bulimia Nervosa (BN), and Binge Eating Disorder (BED)]. The purpose of the current study was to examine differences in clinical presentation and treatment outcome between a heterogenous group of patients with OSFED or threshold EDs. Method: Patients with threshold EDs (AN = 42, BN = 50, BED = 14) or OSFED (n = 66) presenting for eating disorder treatment completed self-report questionnaires at intake and discharge to assess eating disorder symptoms, depression symptoms, impairment, and self-esteem. Results: At intake, OSFED patients showed lower eating concerns compared to patients with BN, but similar levels compared to AN and BED. The OSFED group showed higher restraint symptoms compared to BED, and similar restraint to AN and BN. Global symptoms as well as shape and weight concerns were similar between OSFED and threshold ED groups. There were no differences between diagnostic groups in self-esteem, depression scores, or symptom change from intake to discharge. Discussion: Our findings suggest that individuals with OSFED showed largely similar ED psychopathology and similar decreases in symptoms across treatment as individuals diagnosed with threshold EDs. Taken together, findings challenge the idea that OSFED is less severe and more resistant to treatment than threshold EDs

“I had no hope, I had no help at all”: Insights from a first study of fathers and recurrent care proceedings

This article presents data from the first large-scale study of fathers involved in repeat (or recurrent) care proceedings in England. The project complements important research on mothers and recurrence. It consisted of three elements: an analysis of population-level administrative data from the Child and Family Court Advisory and Support Service (CAFCASS), a survey of fathers in pre-proceedings and care proceedings, and a qualitative longitudinal (QL) study of recurrent fathers. Here we report findings from the survey and the QL study, offering an expanded definition and description of fathers and recurrence. Elsewhere, we reported that a significant number of fathers appear in recurrent care proceedings and that the majority return with the same partner. Alongside this, there is also a notable pattern of “missing” fathers demonstrated by the proportion of lone mothers reappearing before the court. Our survey indicates a certain profile of recurrent fathers, but also that recurrent fathers are not straightforwardly a homogenous group. We report on the significance of recurrent fathers’ early lives, on the phenomenon of enduring couple relationships and on the prevalence of issues affecting parenting, such as poor mental health, substance use and domestic abuse. Insights from the QL study in particular reveal legacies of harm, loss, and a lack of emotional and relational resources in childhood, which have debilitating and far-reaching consequences. We argue the importance of understanding the vulnerabilities of recurrent fathers and of challenging certain assumptions in child welfare and family justice practices. There is much to be learnt from existing services for recurrent mothers, but also a need for bespoke or adapted services that may be more responsive to particular circumstances of recurrent fathers and couples

Absolute risk and risk factors for stroke mortality in patients with end stage kidney disease (ESKD): population-based cohort study using data linkage

INTRODUCTION: People with end-stage kidney disease (ESKD) have up to 30-fold higher risk of stroke than the general population. OBJECTIVE: To determine risk factors associated with stroke death in the ESKD population. METHODS: We identified all patients with incident ESKD in Australia (1980-2013) and New Zealand (1988-2012) from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) registry. We ascertained underlying cause of death from data linkage with national death registries and risk factors from ANZDATA. Using a competing risks multivariable regression model, we estimated cumulative incidence of stroke and non-stroke deaths, and risk factors for stroke deaths (adjusted sub-HR, SHR). RESULTS: We included 60 823 people with ESKD. There were 941 stroke deaths and 33 377 non-stroke deaths during 381 874 person-years of follow-up. Overall, the cumulative incidence of stroke death was 0.9% and non-stroke death was 36.8% 5 years after starting ESKD treatment. The risk of stroke death was higher at older ages (SHR 1.92, 95% CI 1.45 to 2.55), in females (SHR 1.41, 95% CI 1.21 to 1.64), in people with cerebrovascular disease (SHR 2.39, 95% CI 1.99 to 2.87), with ESKD caused by hypertensive/renovascular disease (SHR 1.39, 95% CI 1.09 to 1.78) or polycystic kidney disease (SHR 1.38, 95% CI 1.00 to 1.90), with earlier year of ESKD treatment initiation (SHR 1.93, 95% CI 1.56 to 2.39) and receiving dialysis (transplant vs haemodialysis SHR 0.27, 95% CI 0.09 to 0.84). CONCLUSION: Patients with ESKD with higher risk of stroke death are older, women, with cerebrovascular disease, with hypertensive/renovascular or polycystic kidney disease cause of ESKD, with earlier year of ESKD treatment and receiving dialysis. These groups may benefit from targeted stroke prevention interventions

Antihypertensive Treatment for Kidney Transplant Recipients

Background: In some nontransplant populations, effects of different antihypertensive drug classes vary. Relative effects in kidney transplant recipients are uncertain. Objectives: To assess comparative effects of different classes of antihypertensive agents in kidney transplant recipients. Search strategy: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, conference proceedings and reference lists of identified studies were searched. Selection criteria: Randomised controlled trials of any antihypertensive agent applied to kidney transplant recipients for at least two weeks were included. Data collection and analysis: Data was extracted by two investigators independently. Study quality, transplant outcomes and other patient centred outcomes were assessed using random effects meta-analysis. Risk ratios (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, both with 95% confidence intervals (CI) were calculated. Stratified analyses and meta-regression were used to investigate heterogeneity. Main results: We identified 60 studies, enrolling 3802 recipients. Twenty-nine studies (2262 participants) compared calcium channel blockers (CCB) to placebo/no treatment, 10 studies (445 participants) compared angiotensin converting enzyme inhibitors (ACEi) to placebo/no treatment and seven studies (405 participants) compared CCB to ACEi. CCB compared to placebo/no treatment (plus additional agents in either arm as required) reduced graft loss (RR 0.75, 95% CI 0.57 to 0.99) and improved glomerular filtration rate (GFR), (MD, 4.45 mL/min, 95% CI 2.22 to 6.68). Data on ACEi versus placebo/no treatment were inconclusive for GFR (MD -8.07 mL/min, 95% CI -18.57 to 2.43), and variable for graft loss, precluding meta-analysis. In direct comparison with CCB, ACEi decreased GFR (MD -11.48 mL/min, 95% CI -5.75 to -7.21), proteinuria (MD -0.28 g/24 h, 95% CI -0.47 to -0.10), haemoglobin (MD -12.96 g/L, 95% CI -5.72 to -10.21) and increased hyperkalaemia (RR 3.74, 95% CI 1.89 to 7.43). Graft loss data were inconclusive (RR 7.37, 95% CI 0.39 to 140.35). Other drug comparisons were compared in small numbers of participants and studies. Authors' conclusions: These data suggest that CCB may be preferred as first line agents for hypertensive kidney transplant recipients. ACEi have some detrimental effects in kidney transplant recipients. More high quality studies reporting patient centred outcomes are required

Prognostic value of cardiac tests in potential kidney transplant recipients: a systematic review

Background: Whether abnormal myocardial perfusion scintigraphy (MPS), dobutamine stress echocardiography (DSE) or coronary angiography, performed during preoperative evaluation for potential kidney transplant recipients, predicts future cardiovascular morbidity is unclear. We assessed test performance for predicting all-cause mortality, cardiovascular mortality and major adverse cardiac events (MACE). Methods: We searched MEDLINE and EMBASE (to February 2014), appraised studies, and calculated risk differences and relative risk ratios (RRR) with 95% confidence intervals (95% CI) using random effects meta-analysis. Results: Fifty-two studies (7401 participants) contributed data to the meta-analysis. Among the different tests, similar numbers of patients experienced MACE after an abnormal test result compared with a normal result (risk difference: MPS 20 per 100 patients tested [95% CI, 0.11-0.29], DSE 24 [95% CI, 0.10-0.38], and coronary angiography 20 [95% CI, 0.08-0.32; P = 0.91]). Although there was some evidence that coronary angiography was better at predicting all-cause mortality than MPS (RRR, 0.69; 95% CI, 0.49-0.96; P = 0.03) and DSE (RRR, 0.72; 95% CI, 0.50-1.02; P = 0.06), noninvasive tests were as good as coronary angiography at predicting cardiovascular mortality (RRR, MPS, 0.89; 95% CI, 0.38-2.10; P = 0.78; DSE, 1.09; 95% CI, 0.12-10.05; P = 0.93), and MACE (RRR: MPS, 1.09; 95% CI, 0.64-1.86; P = 0.74; DSE, 1.56; 95% CI, 0.71-3.45; P = 0.25). Conclusions: Noninvasive tests are as good as coronary angiography at predicting future adverse cardiovascular events in advanced chronic kidney disease. However, a substantial number of people with negative test results go on to experience adverse cardiac events

Proteasomal Degradation of p53 by Human Papillomavirus E6 Oncoprotein Relies on the Structural Integrity of p53 Core Domain

The E6 oncoprotein produced by high-risk mucosal HPV stimulates ubiquitinylation and proteasome-dependent degradation of the tumour suppressor p53 via formation of a trimeric complex comprising E6, p53, and E6-AP. p53 is also degraded by its main cellular regulator MDM2. The main binding site of p53 to MDM2 is situated in the natively unfolded N-terminal region of p53. By contrast, the regions of p53 implicated in the degradation by viral E6 are not fully identified to date. Here we generated a series of mutations (Y103G, Y107G, T155A, T155V, T155D, L264A, L265A) targeting the central folded core domain of p53 within a region opposite to its DNA-binding site. We analysed by in vitro and in vivo assays the impact of these mutations on p53 degradation mediated by viral E6 oncoprotein. Whereas all mutants remained susceptible to MDM2-mediated degradation, several of them (Y103G, Y107G, T155D, L265A) became resistant to E6-mediated degradation, confirming previous works that pointed to the core domain as an essential region for the degradation of p53. In parallel, we systematically checked the impact of the mutations on the transactivation activity of p53 as well as on the conformation of p53, analysed by Nuclear Magnetic Resonance (NMR), circular dichroism (CD), and antibody probing. These measurements suggested that the conformational integrity of the core domain is an essential parameter for the degradation of p53 by E6, while it is not essential for the degradation of p53 by MDM2. Thus, the intracellular stability of a protein may or may not rely on its biophysical stability depending on the degradation pathway taken into consideration

Sex differences in mortality among binational cohort of people with chronic kidney disease: population based data linkage study

Objective To evaluate sex differences in mortality among people with kidney failure compared with the general population. Design Population based cohort study using data linkage. Setting The Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), which includes all patients receiving kidney replacement therapy in Australia (1980-2019) and New Zealand (1988-2019). Data were linked to national death registers to determine deaths and their causes, with additional details obtained from ANZDATA. Participants Of 82 844 people with kidney failure, 33 329 were female (40%) and 49 555 were male (60%); 49 376 deaths (20 099 in female patients; 29 277 in male patients) were recorded over a total of 536 602 person years of follow-up. Main outcome measures Relative measures of survival, including standardised mortality ratios, relative survival, and years of life lost, using general population data to account for background mortality (adjusting for country, age, sex, and year). Estimates were stratified by dialysis modality (haemodialysis or peritoneal dialysis) and for the subpopulation of kidney transplant recipients. Results Few differences in outcomes were found between male and female patients with kidney failure. However, compared with the general population, female patients with kidney failure had greater excess all cause deaths than male patients (female patients: standardised mortality ratio 11.3, 95% confidence interval 11.2 to 11.5, expected deaths 1781, observed deaths 20 099; male patients: 6.9, 6.8 to 6.9, expected deaths 4272, observed deaths 29 277). The greatest difference was observed among younger patients and those who died from cardiovascular disease. Relative survival was also consistently lower in female patients, with adjusted excess mortality 11% higher (95% confidence interval 8% to 13%). Average years of life lost was 3.6 years (95% confidence interval 3.6 to 3.7) greater in female patients with kidney failure compared with male patients across all ages. No major differences were found in mortality by sex for haemodialysis or peritoneal dialysis. Kidney transplantation reduced but did not entirely remove the sex difference in excess mortality, with similar relative survival (P=0.83) and years of life lost difference reduced to 2.3 years (95% confidence interval 2.2 to 2.3) between female and male patients. Conclusions Compared with the general population, female patients had greater excess deaths, worse relative survival, and more years of life lost than male patients, however kidney transplantation reduced these differences. Future research should investigate whether systematic differences exist in access to care and possible strategies to mitigate excess mortality among female patients

How typhoons trigger turbidity currents in submarine canyons

Intense turbidity currents occur in the Malaylay Submarine Canyon off the northern coast of Mindoro Island in the Philippines. They start in very shallow waters at the shelf break and reach deeper waters where a gas pipeline is located. The pipeline was displaced by a turbidity current in 2006 and its rock berm damaged by another 10 years later. Here we propose that they are triggered near the mouth of the Malaylay and Baco rivers by direct sediment resuspension in the shallow shelf and transport to the canyon heads by typhoon-induced waves and currents. We show these rivers are unlikely to generate hyperpycnal flows and trigger turbidity currents by themselves. Characteristic signatures of turbidity currents, in the form of bed shear stress obtained by numerical simulations, match observed erosion/deposition and rock berm damage patterns recorded by repeat bathymetric surveys before and after typhoon Nock-ten in December 2016. Our analysis predicts a larger turbidity current triggered by typhoon Durian in 2006; and reveals the reason for the lack of any significant turbidity current associated with typhoon Melor in December 2015. Key factors to assess turbidity current initiation are typhoon proximity, strength, and synchronicity of typhoon induced waves and currents. Using data from a 66-year hindcast we estimate a ~8-year return period of typhoons with capacity to trigger large turbidity currents