Subsegmental pulmonary embolism and anticoagulant therapy: the impact of clinical context.

BACKGROUND: Anticoagulation for subsegmental pulmonary embolism (SSPE) is controversial. AIM: To assess the impact of clinical context on anticoagulation and outcomes of SSPE. METHODS: We electronically searched computed tomography pulmonary angiogram reports to identify SSPE. We extracted demographic, risk factor, investigations and outcome data from the electronic medical record. We stratified patients according to anticoagulation and no anticoagulation. RESULTS: From 1 January 2017 to 31 December 2019, we identified 166 patients with SSPE in 5827 pulmonary angiogram reports. Of these, 123 (74%) received anticoagulation. Compared with non-anticoagulated patients, such patients had a different clinical context: higher rates of previous venous thromboembolism (11% vs 0%; P = 0.019), more recent surgery (26% vs 9%; P = 0.015), more elevated serum D-dimer (22% vs 5%; P = 0.004), more lung parenchymal abnormalities (76% vs 61%; P = 0.037) and were almost twice as likely to require inpatient care (76% vs 42%; P < 0.001). Such patients also had twice the all-cause mortality at 1 year (32% vs 16%). CONCLUSIONS: SSPE is diagnosed in almost 3% of pulmonary angiograms and is associated with high mortality, regardless of anticoagulation, due to coexistent disease processes rather than SSPE. Anticoagulation appears dominant but markedly affected by the clinical context of risk factors, alternative indications and illness severity. Thus, the controversy is partly artificial because anticoagulation after SSPE is clinically contextual with SSPE as only one of several factors.

Urgent care-seeking and injury severity for intimate partner violence during COVID-19: a Canadian retrospective chart review.

BACKGROUND: Early reports raised alarms that intimate partner violence (IPV) increased during the COVID-19 pandemic, but initial studies showed that visits to emergency departments (EDs) decreased. This study assessed the impact of the prolonged pandemic and its associated restrictions on both rates of urgent care-seeking and injury severity for IPV. METHODS: Data from the Kingston Health Sciences Centre's (KHSC) ED were utilized to compare IPV presentations during 'Pre-COVID' (December 17, 2018 - March 16, 2020) and 'COVID' (March 17, 2020 - June 16, 2021), as well as three periods of heightened local restrictions: 'Lockdown-1' (March 17 - June 12, 2020), 'Lockdown-2' (December 26, 2020 - February 10, 2021) and 'Lockdown-3' (April 8 - June 2, 2021). The primary outcomes were incidence rate of IPV visits and injury severity, which was assessed using the Clinical Injury Extent Score (CIES) and Injury Severity Score (ISS). RESULTS: A total of 128 individuals were included. This sample had mean age of 34 years, was comprised of mostly women (97%), and represented a variety of intimate relationship types. Some individuals presented multiple times, resulting in a total of 139 acute IPV presentations. The frequency of IPV visits during COVID was similar to the Pre-COVID time period (67 vs. 72; p = 0.67). Incidence rate was 13% higher during COVID, though this difference was non-significant (6.66 vs. 5.90; p = 0.47). IPV visit frequency varied across lockdown periods (11 in Lockdown-1, 12 in Lockdown-2 and 6 in Lockdown-3), with the highest incidence rate during Lockdown-2 (12.71). There were more moderate and severe injuries during COVID compared to Pre-COVID, but mean CIES was not statistically significantly different (1.91 vs. 1.69; p = 0.29), nor was mean ISS (11.88 vs. 12.52; p = 0.73). CONCLUSIONS: During the 15-months following the start of COVID-19, there were small, but non-significant increases in both incidence rate and severity of IPV presentations to the KHSC ED. This may reflect escalation of violence as pandemic restrictions persisted and requires further investigation.

Timing of native nephrectomy and kidney transplant outcomes in children.

BACKGROUND: No consensus exists on the optimal timing for native nephrectomy in pediatric kidney transplant recipients. Data comparing outcomes between recipients undergoing pretransplant nephrectomy (staged nephrectomy with subsequent transplant) and those undergoing nephrectomy simultaneously with the transplant are lacking. METHOD: We studied 32 pediatric kidney transplant recipients who underwent native nephrectomy at a single center from 01/01/2011 to 12/31/2016. We divided recipients into two groups based on the nephrectomy timing (simultaneous nephrectomy/transplant and staged nephrectomy). We used Wilcoxon rank-sum test, Fisher's exact test, and Kaplan-Meier methods to compare outcomes. RESULTS: Of 32 recipients, 20 underwent simultaneous and 12 underwent staged nephrectomy. Simultaneous recipients were younger (median (years): 2.0 vs 7.0; P = .049). Staged recipients were more likely to have proteinuria/hypoalbuminemia, whereas simultaneous recipients were more likely to have hydronephrosis/vesicoureteral reflux/urinary infections as nephrectomy indications (P = .06). Median prenephrectomy albumin for patients with nephrotic syndrome was significantly lower in staged recipients (median g/dL: 1.9 vs 3.8; P = .02). Total number of hospital days (including both procedures) was higher for staged recipients compared with simultaneous (one procedure) recipients (median (days): 17.0 vs 11.5; P = .05). We observed no difference in 5-year graft survival between the groups (95.0% vs 91.7%, P = .73). Patient survival was 100% in both groups over a median follow-up of 44.2 months. Surgical complications were similar between the groups. CONCLUSION: Staged and simultaneous native nephrectomy in pediatric kidney transplant recipients are associated with comparable outcomes.

De novo, deleterious sequence variants that alter the transcriptional activity of the homeoprotein PBX1 are associated with intellectual disability and pleiotropic developmental defects.

We present eight patients with de novo, deleterious sequence variants in the PBX1 gene. PBX1 encodes a three amino acid loop extension (TALE) homeodomain transcription factor that forms multimeric complexes with TALE and HOX proteins to regulate target gene transcription during development. As previously reported, Pbx1 homozygous mutant mice (Pbx1-/-) develop malformations and hypoplasia or aplasia of multiple organs, including the craniofacial skeleton, ear, branchial arches, heart, lungs, diaphragm, gut, kidneys, and gonads. Clinical findings similar to those in Pbx mutant mice were observed in all patients with varying expressivity and severity, including external ear anomalies, abnormal branchial arch derivatives, heart malformations, diaphragmatic hernia, renal hypoplasia and ambiguous genitalia. All patients but one had developmental delays. Previously reported patients with congenital anomalies affecting the kidney and urinary tract exhibited deletions and loss of function variants in PBX1. The sequence variants in our cases included missense substitutions adjacent to the PBX1 homeodomain (p.Arg184Pro, p.Met224Lys, and p.Arg227Pro) or within the homeodomain (p.Arg234Pro, and p.Arg235Gln), whereas p.Ser262Glnfs*2, and p.Arg288* yielded truncated PBX1 proteins. Functional studies on five PBX1 sequence variants revealed perturbation of intrinsic, PBX-dependent transactivation ability and altered nuclear translocation, suggesting abnormal interactions between mutant PBX1 proteins and wild-type TALE or HOX cofactors. It is likely that the mutations directly affect the transcription of PBX1 target genes to impact embryonic development. We conclude that deleterious sequence variants in PBX1 cause intellectual disability and pleiotropic malformations resembling those in Pbx1 mutant mice, arguing for strong conservation of gene function between these two species.

Differential clinical characteristics, management and outcome of delirium among ward compared with intensive care unit patients.

BACKGROUND: Delirium is common in hospitalised patients but its epidemiology remains poorly characterised. AIMS: To test the hypothesis that patient demographics, clinical phenotype, management and outcomes of patient with delirium in hospital ward patients differ from intensive care unit (ICU) patients. METHODS: Retrospective cohort of patients admitted to an Australian university-affiliated hospital between March 2013 and April 2017 and coded for delirium at discharge using the International Classification of Diseases System, 10th revision, criteria. RESULTS: Among 61 032 hospitalised patients, 2864 (4.7%) were coded for delirium. From these, we studied a random sample of 100 ward patients and 100 ICU patients. Ward patients were older (median age: 84 vs 65 years; P < 0.0001), more likely to have dementia (38% vs 2% for ICU patients; P < 0.0001) and less likely to have had surgery (24% vs 62%; P < 0.0001). Of ward patients, 74% had hypoactive delirium, while 64% of ICU patients had agitated delirium (P < 0.0001). Persistent delirium at hospital discharge was more common among ward patients (66% vs 17%, P < 0.0001). On multivariable analysis, age and dementia predicted persistent delirium, while surgery predicted recovery. CONCLUSIONS: Delirium in ward patients is profoundly different from delirium in ICU patients. It has a dominant hypoactive clinical phenotype, is preceded by dementia and is less likely to recover at hospital discharge. Therefore, delirium prevention, detection and goals of care should be adapted to the environment in which it occurs.

A review of the global distribution of Alexandrium minutum (Dinophyceae) and comments on ecology and associated paralytic shellfish toxin profiles, with a focus on Northern Europe.

Alexandrium minutum is a globally distributed harmful algal bloom species with many strains that are known to produce paralytic shellfish toxins (PSTs) and consequently represent a concern to human and ecosystem health. This review highlights that A. minutum typically occurs in sheltered locations, with cell growth occurring during periods of stable water conditions. Sediment characteristics are important in the persistence of this species within a location, with fine sediments providing cyst deposits for ongoing inoculation to the water column. Toxic strains of A. minutum do not produce a consistent toxin profile, different populations produce a range of PSTs in differing quantities. Novel cluster analysis of published A. minutum toxin profiles indicates five PST profile clusters globally. Some clusters are grouped geographically (Northern Europe) while others are widely spread. Isolates from Taiwan have a range of toxin profile clusters and this area appears to have the most diverse set of PST producing A. minutum populations. These toxin profiles indicate that within the United Kingdom there are two populations of A. minutum grouping with strains from Northern France and Southern Ireland. There is a degree of interconnectivity in this region due to oceanic circulation and a high level of shipping and recreational boating. Further research into the interrelationships between the A. minutum populations in this global region would be of value.

Endoscopic antireflux surgery leading to obstruction in pediatric renal transplant patients.

To describe a multicenter experience with management of ureteral obstruction after injection of Dx/HA for VUR in pediatric renal transplant patients. The records of all pediatric renal transplant patients who underwent Dx/HA injection for VUR and had subsequent obstruction were identified, and the management and outcomes were reviewed. Follow-up ranged from 1 to 10 years. There were four patients identified, all of whom had a history of rising creatinine, recurrent UTI, and increasing hydronephrosis which led to the diagnosis of high-grade VUR. Obstruction was diagnosed within 24-72 hours after injection in three patients. One patient was asymptomatic, and rising creatinine and hydronephrosis were noted 1 month after injection. One patient was managed expectantly, while three patients underwent ureteral stent placement. After the stent was removed, one patient went on to open reimplant due to delayed obstruction, the second patient with voiding dysfunction is currently managed with an indwelling ureteral stent and may require further definitive surgery, the third patient recovered, and the fourth is being observed. Our cases illustrate that despite initial successful management of the obstruction in some, delayed obstruction is possible and may necessitate open reimplant. It is imperative that these patients have close follow-up after Dx/HA.

Squamous cell carcinoma at bladder exstrophy site after early cystectomy.

Patients with bladder exstrophy-epispadias complex (BEEC) are at risk for bladder cancer, usually this presents as adenocarcinoma (Smeulders "BJU Int" 87:623-628, 2001). Squamous cell carcinoma (SCC) is rare, with only 13 documented case reports. This is a case of SCC in a 78-year-old man with BEEC who underwent cystectomy and ureterosigmoidostomy in childhood.

Systematic Review and Meta-Analysis of Policies and Interventions that Improve Health, Psychosocial, and Economic Outcomes for Young People Leaving the Out-of-Home Care System.

Young people who transition to adulthood from out-of-home care (OOHC) are more likely to experience a range of poorer outcomes relative to their same-age peers in the community. This systematic review assessed the effectiveness of policies or interventions (hereafter "interventions") aimed at improving housing, health, education, economic, and psychosocial outcomes for youth leaving OOHC (hereafter "care leavers"). Eleven databases of published literature were reviewed along with gray literature. Eligible studies used randomized or quasi-experimental designs and assessed interventions that provided support to care leavers prior to, during, or after they left OOHC. Primary outcomes were housing and homelessness, health and well-being, education, economic and employment, criminal and delinquent behavior, and risky behavior, while secondary outcomes were supportive relationships and life skills. Where possible, results were pooled in a meta-analysis. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Fourteen studies published in 27 reports were identified that examined independent living programs (ILPs) (n = 5), intensive support services (n = 2), coaching and peer support (C&PSP) (n = 2), transitional housing (n = 1), health information or coaching (n = 2), and extended care (n = 2). All but one study was conducted in the United States. Twenty small meta-analyses were undertaken encompassing ILPs and C&PSP, with two showing results that favored the intervention with certainty. The level of confidence in each meta-analysis was considered very low. A significant risk of bias was identified in each of the included studies. While some interventions showed promise, particularly extended care, the scope and strength of included evidence is insufficient to recommend any included approach.

Society for fetal urology recommendations for postnatal evaluation of prenatal hydronephrosis--will fewer voiding cystourethrograms lead to more urinary tract infections?

PURPOSE: There is no consensus on the extent and mode of postnatal imaging after a diagnosis of prenatal hydronephrosis. We validated the protocol of our practice, which parallels current Society for Fetal Urology (SFU) recommendations, in limiting voiding cystourethrogram, while examining its impact on the incidence of febrile urinary tract infections. A secondary goal was to examine predictors of postnatal intervention. MATERIALS AND METHODS: We evaluated a cohort of 117 infants with prenatal hydronephrosis and retrospectively reviewed outcomes. Excluded from study were 30 infants with anatomical abnormalities. Third trimester prenatal ultrasound was done to evaluate SFU grade, laterality and anteroposterior diameter. Cox proportional hazard model and chi-square analysis were used to assess predictors of resolution and surgical intervention. RESULTS: A total of 87 infants with a median followup of 33.5 months were included in analysis. Postnatal voiding cystourethrogram was done in 52 patients, of whom 7 had vesicoureteral reflux. In 6 infants (6.9%) a febrile urinary tract infection developed, which was diagnosed with a catheter specimen during followup. In 3 infants a urinary tract infection developed immediately after catheterization. Anteroposterior diameter 9 mm or greater and SFU grade 3 or greater independently predicted the need for postnatal intervention (p = 0.0014 and 0.001, respectively). CONCLUSIONS: With adherence to our protocol, voiding cystourethrogram was avoided in almost half of evaluated infants. No infant diagnosed with vesicoureteral reflux had a urinary tract infection. Catheterization was associated with a urinary tract infection in 50% of cases. An anteroposterior diameter of 9 mm or greater and a SFU grade of 3 or greater were associated with postnatal progression to surgery. Patients with a SFU grade of 4 progressed to surgical intervention at a faster rate than those with a grade of greater than 3.

Pressure-relieving interventions for treating diabetic foot ulcers.

BACKGROUND: Diabetes-related foot ulceration is a major contributor to morbidity in diabetes. Diabetic foot ulcers are partly a consequence of abnormal foot pressures and pressure relief is a widely used treatment for healing diabetes-related plantar foot ulcers, but the most effective method for healing is unclear. OBJECTIVES: To determine the effects of pressure-relieving interventions on the healing of foot ulcers in people with diabetes. SEARCH METHODS: For this update we searched the Cochrane Wounds Group Specialised Register (searched 2 November 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10); Ovid MEDLINE (1950 to October Week 4 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, October 31, 2012); Ovid EMBASE (1980 to 2012 Week 43); and EBSCO CINAHL (1982 to 1 November 2012). There were no restrictions based on language or publication status. SELECTION CRITERIA: Randomised controlled trials evaluating the effects of pressure-relieving interventions on the healing of foot ulcers in people with diabetes. DATA COLLECTION AND ANALYSIS: Data from eligible trials were extracted, and summarised using a data extraction sheet, by two review authors independently. MAIN RESULTS: Fourteen trials (709 participants) met the inclusion criteria for the review. One study compared two different types of non-removable casts with no discernable difference between the groups. Seven studies (366 participants) compared non-removable casts with removable pressure-relieving devices. In five of those studies non-removable casts were associated with a statistically significant increase in the number of ulcers healed compared with the removable device (RR 1.17 95% CI 1.01 to 1.36: P value = 0.04).Two studies (98 participants) found that significantly more ulcers healed with non-removable casts than with dressings alone. Achilles tendon lengthening combined with a non-removable cast in one study resulted in significantly more healed ulcers at 7 months than non-removable cast alone (RR 2.23; 95% CI 1.32 to 3.76). More ulcers remained healed at two years in this group (RR 3.41; 95% CI 1.42 to 8.18).Other comparisons included surgical debridement of ulcers; felt fitted to the foot; felted foam dressings and none of these showed a statistically significant treatment effect in favour of the intervention. AUTHORS' CONCLUSIONS: Non-removable, pressure-relieving casts are more effective in healing diabetes related plantar foot ulcers than removable casts, or dressings alone. Non-removable devices, when combined with Achilles tendon lengthening were more successful in one forefoot ulcer study than the use of a non-removable cast alone.

Problem-solving interventions and depression among adolescents and young adults: A systematic review of the effectiveness of problem-solving interventions in preventing or treating depression.

Problem-solving (PS) has been identified as a therapeutic technique found in multiple evidence-based treatments for depression. To further understand for whom and how this intervention works, we undertook a systematic review of the evidence for PS's effectiveness in preventing and treating depression among adolescents and young adults. We searched electronic databases (PsycINFO, Medline, and Cochrane Library) for studies published between 2000 and 2022. Studies meeting the following criteria were included: (a) the intervention was described by authors as a PS intervention or including PS; (b) the intervention was used to treat or prevent depression; (c) mean or median age between 13-25 years; (d) at least one depression outcome was reported. Risk of bias of included studies was assessed using the Cochrane Risk of Bias 2.0 tool. A narrative synthesis was undertaken given the high level of heterogeneity in study variables. Twenty-five out of 874 studies met inclusion criteria. The interventions studied were heterogeneous in population, intervention, modality, comparison condition, study design, and outcome. Twelve studies focused purely on PS; 13 used PS as part of a more comprehensive intervention. Eleven studies found positive effects in reducing depressive symptoms and two in reducing suicidality. There was little evidence that the intervention impacted PS skills or that PS skills acted as a mediator or moderator of effects on depression. There is mixed evidence about the effectiveness of PS as a prevention and treatment of depression among AYA. Our findings indicate that pure PS interventions to treat clinical depression have the strongest evidence, while pure PS interventions used to prevent or treat sub-clinical depression and PS as part of a more comprehensive intervention show mixed results. Possible explanations for limited effectiveness are discussed, including missing outcome bias, variability in quality, dosage, and fidelity monitoring; small sample sizes and short follow-up periods.

Intractable hemorrhagic cystitis after hematopoietic stem cell tranplantation--is there a role for early urinary diversion in children?

PURPOSE: Severe hemorrhagic cystitis is a major complication in the pediatric population undergoing hematopoietic stem cell transplantation. Percutaneous nephrostomy tube drainage as a treatment for severe hemorrhagic cystitis has rarely been investigated. We examined children undergoing hematopoietic stem cell transplantation for risk factors associated with severe hemorrhagic cystitis, as well as our experience with percutaneous nephrostomy tube placement as an adjunctive management strategy. MATERIALS AND METHODS: Using prospectively collected data from the Blood and Marrow Transplant Database at the University of Minnesota, we reviewed 40 pediatric patients with severe hemorrhagic cystitis from 1996 to 2010. Specific treatment for each patient was administered at the discretion of the attending physician and generally included bladder irrigation before bladder fulguration or percutaneous nephrostomy tube placement. A percutaneous nephrostomy tube was placed in 11 patients due to the intractable nature of the hemorrhagic cystitis. RESULTS: Of the 11 patients who underwent percutaneous nephrostomy tube drainage 5 (45%) had improvement of the hemorrhagic cystitis within 30 days and the same number had long-term resolution. Among the patients with long-term resolution hemorrhagic cystitis resolved an average of 12.4 days after percutaneous nephrostomy tube placement, and the tubes were removed an average of 8.8 weeks after placement. Through September 2011 mortality among patients with percutaneous nephrostomy tubes was 55% (6 of 11 patients), which was identical to the overall mortality in the severe hemorrhagic cystitis group (22 of 40). No death could be directly attributed to hemorrhagic cystitis or percutaneous nephrostomy tube placement. CONCLUSIONS: Placement of percutaneous nephrostomy tubes for treatment of severe hemorrhagic cystitis results in long-term improvement in intractable hemorrhagic cystitis, and is a safe and viable option for the majority of patients.

Spectrum of urodynamic abnormalities and renal function changes in adult men with non-neurogenic urinary retention.

INTRODUCTION: The purpose of this study was to identify abnormalities in bladder and renal function in men with urinary retention presumed to be due to BPH. METHODS: In this retrospective analysis, urodynamic studies (UDS) and renal function were evaluated. Bladder contractility and compliance and the severity of bladder outlet obstruction (BOO) were determined from urodynamics. Renal function (BUN, creatine, eGFR) was assessed prior to retention, at the time of presentation and after urodynamic evaluation. RESULTS: Of 87 patients with evaluable UDS, 48% did not demonstrate detrusor activity during testing while 52% showed some detrusor contractile activity. Of these, 23% did not have BOO. Diminished bladder compliance was detected in 56%. In the entire cohort, BUN, serum creatinine, and eGFR were significantly changed during retention but were restored after catheterization. In older patients (>75 years), BUN and creatinine during retention were significantly higher, and eGFR was significantly lower compared to younger patients, but renal function after catheterization was not different between age groups. No significant correlations were found between renal function measurements and bladder compliance or age. CONCLUSION: The urodynamic spectrum in men with urinary retention ranged from detrusor acontractility to varied degrees of contractility associated with outlet obstruction spanning from equivocal to severe. Moreover, prompt relief of retention restores renal function to baseline levels, regardless of age. This study indicates that prostatic obstruction may not be the only cause of urinary retention in adult men presumed to have BPH and illustrates the value of urodynamic assessment prior to potentially failure-prone surgical interventions.

Improving the quality of family meeting documentation in the ICU at the end of life.

Objective: Improve documentation quality of end-of-life family meetings in a tertiary intensive care unit (ICU). Design: Before-and-after interventional quality improvement project between October 2018 and February 2020 utilising an electronic pro-forma record. Setting: Australian, University affiliated, mixed medical-surgical 22 bed adult ICU. Participants: Patients who were admitted to the ICU for active management and subsequently died during that ICU admission. We enrolled 50 patients who died before and 50 patients after the introduction of the electronic family meeting pro-forma record. Intervention: Through collaboration with ICU medical and nursing staff, End-of-life Special Interest Group and Clinical Documentation Committee we developed the ICU Family Meeting Discussion Note as an electronic pro-forma record with multiple key fields of entry. Main outcome measures: Patient records were examined for the presence of documented details around patient's admission, family meetings and specific elements surrounding the patient's death. Results: The introduction of a pro-forma record markedly improved the quality of documentation of end-of-life care related family meetings. Documentation increased in recording hospital admission date/time (6% vs 84%), meeting location (14% vs 70%), the reason patients were absent from the meeting (34% vs 72%), the Medical Treatment Decision Maker (MTDM) (10% vs 44%), the patient's resuscitation status (22% vs 54%), and treatment options discussed (78% vs 94%) (p ⩽ 0.005 for all). Conclusion: Introducing an electronic pro-forma record to facilitate family meeting documentation increased the frequency of important recorded information. Further studies are required to assess whether documentation quality improvements are sustainable and whether they affect patient- or relative-centred outcomes.

The value of toxin profiles in the chemotaxonomic analysis of paralytic shellfish toxins in determining the relationship between British Alexandrium spp. and experimentally contaminated Mytilus sp.

Although phytoplankton is ubiquitous in the world's oceans some species can produce compounds that cause damaging effects in other organisms. These include the toxins responsible for paralytic shellfish poisoning, which, in UK waters, are produced by dinoflagellates from the Alexandrium genus. Within Great Britain (GB) a monitoring programme exists to detect this harmful genus as well as the Paralytic Shellfish Poisoning (PSP) toxins in the flesh of shellfish from classified production areas. The techniques used for toxin analysis allow for detailed analysis of the toxin profiles present in contaminated shellfish. It is possible to compare the toxin profiles of contaminated shellfish with the profiles from toxin producing algae and use this information to infer the causative microalgal species responsible for the contamination. This study sought to evaluate the potential for this process within the GB monitoring framework. Two species of toxic Alexandrium, A. catenella from Scotland and A. minutum from Southern England, were fed to mussels (Mytilus sp.) under controlled conditions. The toxin profile in mussels derived from feeding on each species independently, when mixed and when introduced sequentially was analysed and compared to the source algal cultures using K means cluster analysis. Toxin profiles in contaminated shellfish clustered with those of the causative algae and separately from one another during toxin accumulation and, where A. catenella was the sole toxin source, during depuration. During depuration after feeding with A. minutum and where mixed or sequential feeding was undertaken deviant toxin profiles were observed. Finally, data generated within this experimental study were compared to monitoring data from the GB official control programme. These data indicated that the causative algal species in sole source contaminations could be inferred from toxin profile analysis. This technique will be of benefit within monitoring programmes to enhance the value of data with minimal additional expense, where the toxin profiles of causative microalgae have been well described.

Protocol for a systematic review of policies, programs or interventions designed to improve health and wellbeing of young people leaving the out-of-home care system.

BACKGROUND: Relative to their counterparts in the general population, young people who leave, or transition out of, out-of-home (OOHC) arrangements commonly experience poorer outcomes across a range of indicators, including higher rates of homelessness, unemployment, reliance on public assistance, physical and mental health problems and contact with the criminal justice system. The age at which young people transition from OOHC varies between and within some countries, but for most, formal support ceases between the ages of 18 and 21. Programs designed to support transitions are generally available to young people toward the end of their OOHC placement, although some can extend beyond. They often encourage the development of skills required for continued engagement in education, obtaining employment, maintaining housing and general life skills. Little is known about the effectiveness of these programs or of extended care policies that raise the age at which support remains available to young people after leaving OOHC. This systematic review will seek to identify programs and/or interventions that improve outcomes for youth transitioning from the OOHC system into adult living arrangements. METHODS: This review will identify programs, interventions and policies that seek to improve health and wellbeing of this population that have been tested using robust controlled methods. Primary outcomes of interest are homelessness, health, education, employment, exposure to violence and risky behaviour. Secondary outcomes are relationships and life skills. We will search, from January 1990 onwards, MEDLINE, EMBASE, PsycINFO, ERIC, CINAHL, Cochrane CENTRAL, SocINDEX, Sociological Abstracts, Social Services Abstracts, NHS Economic Evaluation Database and Health Technology Assessment. Grey literature will be identified through searching websites and databases, e.g. clearing houses, government agencies and organisations known to be undertaking or consolidating research on this topic area. Two reviewers will independently screen all title and abstracts and full text articles with conflicts to be resolved by a third reviewer. Data extraction will be undertaken by pairs of review authors, with one reviewer checking the results of the other. If more than one study with suitable data can be identified, we plan to undertake both fixed-effects and random-effects meta-analyses and intend to present the random-effects result if there is no indication of funnel plot asymmetry. Risk of bias will be assessed using tools appropriate to the study methodology. Quality of evidence across studies will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. DISCUSSION: Previous reviews were unable to identify any programs or interventions, backed by methodologically rigorous research, that improve outcomes for this population. This review seeks to update this previous work, taking into account changes in the provision of extended care, which is now available in some jurisdictions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020146999.

Referral patterns for undescended testis: A 7 year comparative analysis of primary care providers.

INTRODUCTION: Cryptorchidism, or undescended testis (UDT), is identified in 1% of boys by one year of age and carries long term risks of infertility and testicular neoplasia. In 2014, the American Urological Association (AUA) released a guideline statement stating that patients with UDT should be referred to a urologist by 6 months of age in order to facilitate timely surgical correction. This study is the follow-up to a 2010 study assessing referral patterns to our university center from primary care providers. OBJECTIVE: In this new study, we aim to identify changes in referral patterns in response to the establishment of the 2014 AUA guidelines and to understand how our referring physicians stay abreast of current knowledge regarding UDT. STUDY DESIGN: A 9 question anonymous survey regarding UDT referral patterns was sent to providers who had previously referred a patient to our pediatric urology practice. The results were categorized by specialty and were compared to the similar survey from 2010. RESULTS: Surveys were sent to 500 physicians with 138 (27.6%) responses received. Less than half of respondents reported that they would refer a boy with unilateral or bilateral palpable UDT by 6 months of age (37.0% and 38.4% respectively). This was not significantly different than the 2010 survey (p = 0.68 and 0.27 respectively). Two-thirds of physicians would refer a patient with unilateral nonpalpable UDT within the recommended time frame (68.8%); this was also unchanged from 2010 (p = 0.87). There was an improvement in respondents who would refer immediately for bilateral nonpalpable testes from 49.8% in 2010 to 53.6% in 2017 (p = 0.01). Residency training was most commonly cited as the primary source of knowledge regarding UDT although 89.3% of respondents citing this were >5 years removed from residency training. DISCUSSION: Delayed referral patterns were reported by the majority of providers for palpable UDT and by greater than one-third of providers for nonpalpable UDT. There was minimal change in referral patterns between 2010 and 2017 despite the release of the AUA cryptorchidism guidelines in 2014. In both 2010 and 2017, residency training was identified as the primary source of knowledge regarding management of UDT. CONCLUSION: These findings suggest an unmet need for education regarding contemporary management of UDT for the primary care physicians in our community.

Outbreeding lethality between toxic Group I and nontoxic Group III Alexandrium tamarense spp. isolates: Predominance of heterotypic encystment and implications for mating interactions and biogeography.

We report the zygotic encystment of geographically dispersed isolates in the dinoflagellate species complex Alexandrium tamarense, in particular, successful mating of toxic Group I and nontoxic Group III isolates. However, hypnozygotes produced in Group I/III co-cultures complete no more than three divisions after germinating. Previous reports have suggested a mate recognition mechanism whereby hypnozygotes produced in co-cultures could arise from either homotypic (inbred) or heterotypic (outbred) gamete pairs. To determine the extent to which each occurs, a nested PCR assay was developed to determine parentage of individual hypnozygotes. The vast majority of hypnozygotes from pairwise Group I/III co-cultures were outbred, so that inviability was a result of hybridization, not inbreeding. These findings support the assertion that complete speciation underlies the phylogenetic structure of the Alexandrium tamarense species complex. Additionally, the ribosomal DNA (rDNA) copy numbers of both hybrid and single ribotype hypnozygotes were reduced substantially from those of haploid motile cells. The destruction of rDNA loci may be crucial for the successful mating of genetically distant conjugants and appears integral to the process of encystment. The inviability of Group I/III hybrids is important for public health because the presence of hybrid cysts may indicate ongoing displacement of a nontoxic population by a toxic one (or vice versa). Hybrid inviability also suggests a bloom control strategy whereby persistent, toxic Group I blooms could be mitigated by introduction of nontoxic Group III cells. The potential for hybridization in nature was investigated by applying the nested PCR assay to hypnozygotes from Belfast Lough, Northern Ireland, a region where Group I and III populations co-occur. Two hybrid cysts were identified in 14 successful assays, demonstrating that Group I and III populations do interbreed in that region. However, an analysis of mating data collected over an 18-year period indicated a leaky pre-mating barrier between ribosomal species (including Groups I and III). Whether the observed selectivity inhibits hybridization in nature is dependent on its mechanism. If the point of selectivity is the induction of gametogenesis, dissimilar ribotypes could interbreed freely, promoting displacement in cases where hybridization is lethal. If instead, selectivity occurs during the adhesion of gamete pairs, it could enable stable coexistence of A. tamarense species. In either case, hybrid inviability may impose a significant obstacle to range expansion. The nested PCR assay developed here is a valuable tool for investigation of interspecies hybridization and its consequences for the global biogeography of these important organisms.