A novel likely pathogenic CLCN5 variant in Dent's disease.

BACKGROUND: The majority of cases of Dent's disease are caused by pathogenic variants in the CLCN5 gene, which encodes a voltage-gated chloride ion channel (ClC-5), resulting in proximal tubular dysfunction. We present three members of the same family and one unrelated paediatric patient with the same insertion-deletion CLCN5 variant. The identification of these patients and positive familial segregation led to the re-classification of this variant from one of unknown significance to one of likely pathogenicity. CASE PRESENTATION: A 41 year old male presented with end stage kidney failure, proteinuria and haematuria. Whole genome sequencing identified an insertion-deletion variant in CLCN5, resulting in a missense change (c.1744_1745delinsAA p.(Ala582Lys)). His brother and nephew, who both exhibited renal impairment, haematuria, proteinuria, glycosuria and nephrocalcinosis, were found to have the same variant. In addition, genetic testing of an unrelated paediatric patient who presented with proteinuria and hypercalciuria, demonstrated the same variant. CONCLUSIONS: The identification of this novel variant in four individuals with features of Dent's disease, has led to the re-classification of the variant to one of likely pathogenicity. As a result, our patients and any future patients with the same variant can be offered a likely diagnosis, without the need for kidney biopsy, and their family members can be offered genetic screening.

Analysis of COVID-19 Pandemic on Supplement Usage and Its Combination with Self-Medication within the State of Arkansas.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for the COVID-19 pandemic that can lead to severe respiratory distress requiring hospitalization and can be fatal. Media have reported that various dietary supplements (DS) or their combination with different medications can prevent infection or decrease disease severity. Here, we analyzed data collected from 15,830 patient follow-up telephone interviews from the University of Arkansas for Medical Sciences COVID-19 testing sites from March 15 to August 1, 2020. Within the REDCap database, we recorded patient demographics and DS and medication use. In total, data on DS and medication use was available for 8,150 study participants, of whom 21.9% and 4.1% reported using DS or medications, respectively, to either prevent or treat COVID-19. The majority of respondents were female (64%) and non-Hispanic whites (44.5%). Most individuals (64.5%) who took DS were younger than 50 years of age. Products such as vitamin C (1,013, 33.2%), multivitamins (722, 23.6%), and vitamin D (294, 9.6%) were the most commonly used DS among the responders. Analysis of the DS use and symptom scores association did not provide a strong evidence of beneficial health effects of DS. The results of this study demonstrate that a significantly higher proportion of study participants considered usage of DS to mitigate or prevent COVID-19-related symptoms compared to those who preferred medications. However, lack of observable health benefits associated with ingestion of DS suggests that more rigorous research is needed to substantiate the label claims.

Visual outcomes of primary versus secondary epiretinal membrane following vitrectomy and cataract surgery.

PURPOSE: To compare visual outcomes, incidence of cystoid macular edema (CME), and rate of repeat epiretinal membrane (ERM) surgery following phacovitrectomy for primary and secondary ERM. METHODS: Retrospective review of 178,856 cataract surgeries from 2003 to 2015. Eyes that underwent cataract surgery combined with ERM peel were included (n = 708). Eyes were divided into primary (n = 538) and secondary (n = 170) ERM groups. Patient demographics, visual acuity (VA), and postoperative CME were recorded. RESULTS: Patients with secondary ERM had worse preoperative VA, 0.9 ± 0.6 logMAR (20/160 Snellen equivalent) as compared to patients with primary ERM, 0.6 ± 0.3 (20/80), respectively (p < 0.0001). There was no difference between the secondary and primary ERM groups in postoperative vision (0.5 ± 0.4 logMAR vs. 0.5 ± 0.3; p = 0.9962) or proportion with VA ≥ 20/40 (46.4% vs. 43.1%; p = 0.6744) at 12-24 weeks. Postoperative CME was twice as likely in the secondary ERM group (16.5%) compared to the primary ERM group (7.8%) (p = 0.0018). There was no difference in the rate of repeat ERM surgery between the secondary ERM group (1.8%) and the primary ERM group (1.5%) (p = 0.7308). CONCLUSION: Eyes with secondary ERM had significant postoperative improvement in VA. They had worse preoperative VA and had a twofold increase in postoperative CME than primary ERM.

Time-dependent cognitive and somatic symptoms of depression as predictors of new cardiac-related events in at-risk patients: the UPBEAT-UK cohort.

BACKGROUND: Evidence suggests that somatic rather than cognitive depressive symptoms are risk factors for recurrent cardiac events in at-risk patients. However, this has never been explored using a time-dependent approach in a narrow time-frame, allowing a cardiac event-free time-window. METHODS: The analysis was performed on 595 participants [70.6% male, median age 72 (27-98)] drawn from the UPBEAT-UK heart disease patient cohort with 6-monthly follow-ups over 3 years. Depressive symptomatology was measured using the Patient Health Questionnaire-9 (PHQ-9) (four somatic, five cognitive items). New cardiac events (NCEs) including cardiac-related mortality were identified by expert examination of patient records. Analyses were performed using Cox proportional hazard models with delayed entry, with time-dependent depressive dimensions and covariates measured 12-18 months (median: 14.1, IQR: 3.5) prior to the event, with a 12-month cardiac event-free gap. RESULTS: There were 95 NCEs during the follow-up [median time-to-event from baseline: 22.3 months (IQR: 13.4)]. Both the somatic (HR 1.12, 95% CI 1.05-1.20, p = 0.001) and cognitive dimensions (HR 1.11, 95% CI 1.03-1.18, p = 0.004) were time-dependent risk factors for an NCE in the multi-adjusted models. Specific symptoms (poor appetite/overeating for the somatic dimension, hopelessness and feeling like a failure for the cognitive dimension) were also significantly associated. CONCLUSION: This is the first study of the association between depressive symptom dimensions and NCEs in at-risk patients using a time-to-event standardised approach. Both dimensions considered apart were independent predictors of an NCE, along with specific items, suggesting regular assessments and tailored interventions targeting specific depressive symptoms may help to prevent NCEs in at-risk populations.

Early Postoperative Complications and Factors Associated with Early vs Late Discharge of Patients Undergoing Colporrhaphy for Pelvic Organ Prolapse: A National Report.

INTRODUCTION: Pelvic organ prolapse is a highly prevalent condition that is commonly managed with surgical intervention. Our purpose was to determine associated factors and postoperative morbidity rates of early (≤1 day) vs late (>1 day) hospital discharge after outpatient colporrhaphy. METHODS: From the National Surgical Quality Improvement Program® database, 11,652 female patients who received colporrhaphy between 2005 and 2016 were identified; 3,728 were stratified into the early discharge group and 7,924 into the late discharge group. Patient characteristics, surgical data and 30-day postoperative complications were recorded, and variables were compared between groups. RESULTS: In comparison to the late discharge group, the early discharge group had a shorter mean operating time (p <0.001) and overall was less likely to suffer from 30-day morbidity (OR 0.67 [95% CI 0.55-0.82]), reoperation (OR 0.59 [95% CI 0.39-0.90]) or readmission (OR 0.40 [95% CI 0.26-0.90]). Factors independently associated with a lower likelihood of early discharge included age ≥55 years, higher body mass index, White race, current smoker, American Society of Anesthesiologists® classification IV/V and longer operating time. Increased likelihood of early discharge was associated with receiving colporrhaphy after 2012 and posterior colporrhaphy. CONCLUSIONS: Patients discharged from the hospital early had lower rates of postoperative morbidity than those discharged later. Early discharge was associated with procedures performed after 2012 and with isolated posterior colporrhaphy. Longer hospital stays were associated with longer operating times and older age, White race, obesity, comorbidities and history of smoking.

The OPTIMIZE patient- and family-centered, primary care-based deprescribing intervention for older adults with dementia or mild cognitive impairment and multiple chronic conditions: study protocol for a pragmatic cluster randomized controlled trial.

BACKGROUND: Most individuals with dementia or mild cognitive impairment (MCI) have multiple chronic conditions (MCC). The combination leads to multiple medications and complex medication regimens and is associated with increased risk for significant treatment burden, adverse drug events, cognitive changes, hospitalization, and mortality. Optimizing medications through deprescribing (the process of reducing or stopping the use of inappropriate medications or medications unlikely to be beneficial) may improve outcomes for MCC patients with dementia or MCI. METHODS: With input from patients, family members, and clinicians, we developed and piloted a patient-centered, pragmatic intervention (OPTIMIZE) to educate and activate patients, family members, and primary care clinicians about deprescribing as part of optimal medication management for older adults with dementia or MCI and MCC. The clinic-based intervention targets patients on 5 or more medications, their family members, and their primary care clinicians using a pragmatic, cluster-randomized design at Kaiser Permanente Colorado. The intervention has two components: a patient/ family component focused on education and activation about the potential value of deprescribing, and a clinician component focused on increasing clinician awareness about options and processes for deprescribing. Primary outcomes are total number of chronic medications and total number of potentially inappropriate medications (PIMs). We estimate that approximately 2400 patients across 9 clinics will receive the intervention. A comparable number of patients from 9 other clinics will serve as wait-list controls. We have > 80% power to detect an average decrease of - 0.70 (< 1 medication). Secondary outcomes include the number of PIM starts, dose reductions for selected PIMs (benzodiazepines, opiates, and antipsychotics), rates of adverse drug events (falls, hemorrhagic events, and hypoglycemic events), ability to perform activities of daily living, and skilled nursing facility, hospital, and emergency department admissions. DISCUSSION: The OPTIMIZE trial will examine whether a primary care-based, patient- and family-centered intervention educating patients, family members, and clinicians about deprescribing reduces numbers of chronic medications and PIMs for older adults with dementia or MCI and MCC. TRIAL REGISTRATION: NCT03984396. Registered on 13 June 2019.

Interprofessional identity development within a brief shadowing experience: An exploratory case study.

The Deans' Interprofessional Honors Colloquium (DIHC) is an honors-level interprofessional elective course that provides a seminar-based forum for students from eleven academic programs to explore the characteristics and implications of collaborative interprofessional practice around a contemporary health topic. This project-based course combines didactic presentations, interactive group learning, and an interprofessional shadowing experience with a corresponding written reflection paper. Ten semesters of Interprofessional Shadowing Reflections (n = 401) were studied via thematic and content analyses to examine the extent to which a brief interprofessional shadowing experience influenced interprofessional identity development. Interprofessional socialization framework was employed as a lens to refine themes and to track students' trajectory in developing a dual professional identity. This exploratory case study indicated that nearly all participants' reflections included content indicative of the second stage (interprofessional role learning) of the interprofessional socialization framework, and many progressed toward the third stage (dual identity development). Major themes included emergent role learning, increased differentiation among roles and care models, and increased appreciation for other professionals. The experience provided an opportunity for correction of misconceptions and improved understanding of the role and practice of other professions. Nearly all of the participating students (1) reflected on the benefits of interprofessional collaboration and (2) indicated a desire to work interprofessionally in the future, an early indication of dual identity formation. Findings indicated that the interprofessional shadowing experience and written reflection were highly valuable elements of the DIHC and provided a critical opportunity for interprofessional identity development.

Edoxaban Versus Warfarin in Patients With Atrial Fibrillation and History of Liver Disease.

BACKGROUND: Patients with liver disease have increased risk of thrombosis and bleeding but are typically excluded from trials of direct oral anticoagulant agents. OBJECTIVES: This study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), clinical efficacy and safety of edoxaban versus warfarin in patients with atrial fibrillation (AF) and history of liver disease. METHODS: ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction Study 48) was a randomized, double-blind trial comparing edoxaban with warfarin in patients with AF followed for 2.8 years. History of liver disease was defined as investigator-reported liver disease or >2-fold transaminase elevation at randomization. The primary efficacy and safety endpoints of stroke or systemic embolic event (SSEE) and major bleeding were assessed stratified by history of liver disease. PK/PD assessments of edoxaban included endogenous and extrinsic factor Xa activity and edoxaban concentration. RESULTS: Among 21,105 patients, 1,083 (5.1%) had a history of liver disease; they had a higher prevalence of many comorbidities. The adjusted risks of SSEE were similar (adjusted hazard ratio [HRadj]: 0.90; 95% confidence interval [CI]: 0.67 to 1.22; p = 0.50), but major bleeding was more common in patients with liver disease (HRadj: 1.38; 95% CI: 1.10 to 1.74; p = 0.005). There were no significant differences in PK/PD assessment of edoxaban in patients with versus without liver disease. The HRs for higher-dose edoxaban versus warfarin for SSEE were 0.86 (95% CI: 0.73 to 1.01) in patients without and 1.11 (95% CI: 0.54 to 2.30) with liver disease (p for interaction [pint] = 0.47), major bleeding 0.80 (95% CI: 0.70 to 0.91) in patients without and 0.91 (95% CI: 0.56 to 1.47) with liver disease (pint = 0.63). There were no significant differences in hepatic adverse events between the 2 treatment groups. CONCLUSIONS: Among patients with AF receiving oral anticoagulation, bleeding, but not thromboembolic events, was increased in patients with liver disease. A history of liver disease did not alter the relative efficacy and safety of edoxaban compared with warfarin. Hepatic adverse events were similar between edoxaban and warfarin.

A multi-dimensional approach to the relationship between insight and aggressiveness in schizophrenia: Findings from the FACE-SZ cohort.

BACKGROUND: Aggressiveness is a stigma frequently associated with schizophrenia. The role of insight as a risk factor of aggressiveness remains contradictory; mainly because single measures of these states mask their complexity and heterogeneity. METHODS: This study was conducted on 666 patients aged 15 and above with a DSM-IV-TR diagnosis of schizophrenia spectrum disorder, drawn from the French national network of schizophrenia expert center database. Collected data comprised socio-demographics and standardized psychiatric assessments. Aggressiveness was evaluated using the Buss-Perry Aggression Questionnaire and insight using the Scale to assess Unawareness of Mental Disorder (SUMD) and Birchwood Insight Scale (BIS). RESULTS: Hostility was the aggressiveness dimension the most strongly associated with SUMD insight dimensions. Patients aware of their illness were nearly twice as likely to show hostility than those seriously unaware (OR = 1.95, 95% CI.: 1.08-3.5), but not when further adjusting for depression. Similarly, those aware of the consequences of their illness and of their symptoms were more hostile. Patients moderately aware of illness consequences had a higher risk of both anger and physical aggressiveness than those unaware (OR = 2.63, 95% CI.: 1.42-4.86, OR = 2.47, 95% CI.: 1.33-4.60, respectively), even when adjusting for depression for anger. CONCLUSION: Our study confirms that a multi-dimensional approach to insight and aggressiveness is essential to understand the types of links between these clinical states. Insight may trigger the expression of an underlying hostile tendency, maybe via depression and self-stigmatisation. This should be taken into account in therapeutic approaches to improve insight.

Pimavanserin: Potential Treatment For Dementia-Related Psychosis.

Psychosis is common across dementia types with a prevalence of 20% to 70%. Currently, no pharmacologic treatment is approved for dementia-related psychosis. Atypical antipsychotics are frequently used to treat these disorders, despite significant safety concerns. Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved in the U.S. for treating hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Patients in the pimavanserin group experienced a significant (p=0.001) improvement in Scale for the Assessment of Positive Symptoms - Parkinson's disease (SAPS-PD) scores vs. placebo. In a subgroup analysis of patients with cognitive impairment (MMSE score ≥21 but ≤24), the observed improvement on the SAPS-PD with pimavanserin (N=50) was also significant (p=0.002) and larger than in the overall study population without an adverse effect on cognition. In a Phase 2 study with pimavanserin in Alzheimer's disease psychosis, pimavanserin significantly (p=0.045) improved psychosis at Week 6 vs. placebo on the NPI-NH Psychosis Score (PS). In a prespecified subgroup of patients with a baseline NPI-NH PS ≥12, a substantively larger treatment effect (p=0.011) was observed vs. participants with NPI-NH PS <12. The results of these studies in cognitively impaired patients with PDP provided the scientific foundation for an ongoing study of pimavanserin for treating patients with dementia-related psychosis associated with the most common neurodegenerative disorders. The study uses a relapse-prevention design with the endpoint of time-to-relapse of psychosis to evaluate the long-term efficacy and safety of pimavanserin as a potential treatment for hallucinations and delusions of dementia-related psychosis.

Shooting up? Analysis of 182 gunshot injuries presenting to a London major trauma centre over a seven-year period.

Introduction Metropolitan Police data, and those from the emergency department at a London major trauma centre show a resurgence in gun crime. The aim of this study was to collect data on all gunshot injuries over a seven-year period at South-East London's trauma hub. Materials and methods This was a retrospective observational study of all gunshot injuries between 1 January 2010 and 31 December 2016 at a London major trauma centre. Information regarding patient demographics, morbidity and mortality was collected. Data from the English indices of multiple deprivation were reviewed in relation to shooting locations and socioeconomic status in South-East London. Results A total of 182 patients from 939,331 emergency admissions presented with firearm injuries. Males comprised 178 (97.8%) victims and 124 (68.1%) were documented as being Black or Afro-Caribbean. The median age was 22 years. Some 124 (71.7%) victims were shot within a 4 km radius of the hospital. The mean indices of multiple deprivation decile ranking in shooting locations compared with non-shooting locations was 2.6 (± 0.1384) and 3.8 (± 0.1149), respectively. A total of 122 (67.0%) patients underwent specialist operative intervention and 111 (61.0%) suffered only superficial or musculoskeletal injuries. Six patients required emergency thoracotomies; three (50.0%) survived to discharge. The median length of stay was 4 days (interquartile range 2-9 days) and 35 (24.0%) were admitted to intensive care. Ten (5.5%) patients died. Discussion and conclusion Firearms injuries are increasing and place a significant burden on hospital resources. Care provided to gunshot victims has improved as a result of recent trauma management initiatives at South-East London's major trauma centre.

Oral Anticoagulation in Patients With Liver Disease.

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population.

Frequent attendance and the concordance between PHQ screening and GP assessment in the detection of common mental disorders.

OBJECTIVE: Frequent Attenders (FAs) have high rates of both common mental disorders (CMD) and physical disorders, partly justifying this service use behaviour. This study examines both case and non-case concordance between CMDs as estimated by a self-report screening questionnaire and as rated by the general practitioner (GP), in FAs compared to Other Attenders (OAs). METHODS: 2275 patients of an overlapping sample of 55 GPs from 2 surveys performed 10 years apart, completed in the waiting room the Patient Health Questionnaire (PHQ) and Client Service Receipt Inventory on 6-month service use. For each patient, the GP rated mental health on a 0-4 scale, with a clear indication that scores of 2 and above referred to caseness. PHQ-CMDs included major and other depressive, anxiety, panic, and somatoform disorders, identified using the original PHQ DSM-IV criteria-based algorithms. FA was defined as the top 10% of attenders in age, sex and survey-year stratified subgroups. RESULTS: FAs had higher rates of PHQ-CMDs (42% versus 23% for OAs, p < .0001). They reported more personal and social problems, disability and had higher GP-rated physical illness. Survey-day antidepressant/anxiolytic medication prescription was higher for FAs (p < .0001), with (p = .02) but also without a CMD (p < .0001). Both GP/PHQ case and non-case concordance differed between FAs and OAs, with a non-case concordance odds ratio of 0.5 (95% CI: 0.3-0.7, p = .001) for FAs compared to OAs. CONCLUSION: Despite a greater likelihood of GPs detecting CMDs in FAs, our findings suggest a potential risk of 'over-detection' of patients not reaching CMD threshold criteria among FAs.

Short-chain fatty acids induce tissue plasminogen activator in airway epithelial cells via GPR41&43.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease generally divided based on the presence or absence of nasal polyps (NPs). One of the features of NPs is excessive fibrin deposition, which is associated with down-regulation of tissue plasminogen activator (t-PA) in NPs. As t-PA is expressed in epithelial cells, and epithelium is readily accessible to topical therapies, identifying compounds that can mediate the induction of t-PA would be a potential new strategy for the treatment of NPs. OBJECTIVE: The objective of this study was to determine whether short-chain fatty acids (SCFAs) can induce t-PA in airway epithelial cells via their known receptors GPR41 and GPR43. METHODS: We performed immunohistochemistry (IHC) to determine whether receptors for SCFAs, known as G protein-coupled receptor 41/free fatty acid receptor 3 (GPR41/FFAR3) and GPR43/FFAR2, are expressed in nasal tissue. Primary normal human bronchial epithelial (NHBE) cells were stimulated with different concentrations of SCFAs to test induction of t-PA, which was analysed by expression of mRNA and protein. Mediation of responses by SCFA receptors was evaluated by specific receptor gene silencing with siRNA. RESULTS: Immunohistochemistry study revealed that airway epithelial cells expressed GPR41 and GPR43. Acetic acid, propionic acid, butyric acid and valeric acid significantly induced t-PA expression from two- to tenfolds. The strongest inducer of t-PA from NHBE cells was propionic acid; cells stimulated with propionic acid released t-PA into the supernatant in its active form. Gene silencing of GPR41 and GPR43 revealed that induction of t-PA by SCFAs was dependent upon both GPR41 and GPR43. CONCLUSIONS AND CLINICAL RELEVANCE: Short-chain fatty acids were shown to induce airway epithelial cell expression of t-PA via GPR41 and GPR43. Topical delivery of potent compounds that activate these receptors may have value by reducing fibrin deposition and shrinking nasal polyp growth.

[Ability of French General Practitioners to detect common mental disorders identified using the Patient Health Questionnaire: Has this changed with the introduction of gatekeeping and registration with a chosen doctor?] / Détection par le médecin généraliste des troubles psychiatriques courants selon l'auto-questionnaire diagnostique le Patient Health Questionnaire : dix ans après, le dispositif du médecin traitant a-t-il modifié la donne ?

OBJECTIVES: The general practitioner (GP) is the most frequently consulted health professional by patients with common mental disorders (CMD). Yet approximately half of cases are not detected by the GP. Many factors linked to the patient, the doctor and the health care system influence detection. For example, detection rates are higher when patients are better known to their GP. On the other hand, patients visiting a different GP for reasons of dissatisfaction with previous care are more likely to be detected on the survey-day. In France, a form of gatekeeping was introduced in 2005 to encourage patients to register with a doctor (most often a GP) of their choice (known as the Preferred Doctor), responsible for care coordination and referral if necessary to secondary care. Visiting a different GP, other than for non-avoidable reasons (for e.g. GP unreachable, patient on holiday), is still possible but financially sanctioned with lower reimbursement rates. We aimed to compare GP detection rates before and after the introduction of this gatekeeping scheme. Patient service use behaviour such as doctor-shopping and GP referral to secondary care were also compared. METHODS: Two cross-sectional surveys using the same study methods were carried out 10 years apart. In 2003, 46 GPs and 1151 patients participated (approximately 25 patients per GP), with a 32.7% GP participation rate. In 2013, 38 GPs participated (of which 29 had participated in the previous study, with a 85.3% "recapture" rate) and 1133 patients (approximately 30 patients per GP). Patient participation rates were 89.8% and 67%, respectively. Patients completed self-report questionnaires in the waiting room of which the DSM-IV diagnostic criteria Patient Health Questionnaire (PHQ) and an adapted version of the Client Service Receipt Inventory (CSRI) on contacts with health care services in the previous six months. For each patient, the GP completed a questionnaire giving his rating of psychiatric illness on a five-point scale with his/her diagnosis for cases, and action undertaken. RESULTS: Of the patients, 27% and 25.4% had a CMD according to the PHQ (defined as a diagnosis of minor or major depression, panic attack, anxiety or somatoform disorder) in 2003 and 2013 respectively. Corresponding detection rates were 51% and 52.6%. Rates were highest for threshold disorders: panic disorder (69.4% and 79.9% in 2003 and 2013, respectively), major depression (75% and 63.3% in 2003 and 2013, respectively) and other anxiety disorders (69.1% and 78.8% in 2003 and 2013, respectively). In 2003, the GPs declared seeing 15.5% for the first time on the survey-day, compared to 9.6% in 2013 (P=0.006). Doctor-shopping declined between the two studies, from 18.4% to 12.1% for practical and mostly unavoidable reasons, and from 9.8% to 4.2% for dissatisfaction reasons (P<0.0001). Referral to specialist doctors increased from 9.7% in 2003 to 14.7% in 2013 (P=0.014). In 2013, on the survey-day, 94.8% of patients had registered with a Preferred Doctor and 81.2% were seeing this Preferred Doctor. In 2003, 93.5% of patients declared having a usual GP and 79.9% were visiting this GP on the survey-day. CONCLUSIONS: This is one of the first studies to report data from two repeated surveys carried out before and after a change in the health service organisation, with data collected from both the patient and the GP. We report relatively high GP detection rates for the two periods, with about 50% of CMDs, including subsyndromic conditions, detected by the GP. Rates are considerably higher for the threshold disorders. The overall detection rate did not increase as expected between the two studies. Detection is a complex topic, involving issues such as the suitability of applying categorical DSM-IV criteria diagnoses to primary care, the relevance of detecting subthreshold conditions and the ability of cross-sectional studies to correctly assess the ability of GPs to recognise cases. The introduction of gatekeeping with the choice of a Preferred Doctor has led to a decline in the frequency of doctor-shopping, whatever its reason, with patients no doubt being better known to the GP. Yet it appears most patients had already chosen a GP they were loyal to before the scheme, with a similar proportion of patients consulting their chosen GP or Preferred Doctor on both survey-days in 2003 and 2013, suggesting the scheme may to some extent only have officialised what already existed with respect to having a usual GP. The French reform still allows for doctor-shopping which can be considered as a positive aspect of the scheme: patients either dissatisfied with previous care or needing to change GP are thus able to "test" and choose the doctor that best suits their needs.

Epidemiology of penetrating injuries in the United Kingdom: A systematic review.

INTRODUCTION: Penetrating injuries account for a significant number of deaths in the United Kingdom (UK) annually. Numerous articles have examined the epidemiology of penetrating trauma in various areas of the UK. This article aimed to systematically review the current literature and evaluate the incidence and mortality of penetrating injury according to region in the UK. METHODS: A systematic literature search was performed using MEDLINE® (1946 to June 2016), EMBASE® (1974 to June 2016), and PsycINFO® (1806 to June 2016) databases. The following keywords were used in combination with Boolean operators: "epidemiology", "incidence", "frequency", "pattern", "distribution"; "penetrating"; "injuries", "injury", "trauma"; "United Kingdom", "UK", "England", "Scotland", "Wales", "London". RESULTS: Eleven relevant studies were identified across five regions of the UK. Study periods ranged from 3 months to 16 years and encompassed between 343 and 127,191 patients. Relative incidence within individual studies ranged from 0.3% (Midlands) to 21.0% (London) and mortality ranged from 0.5% (London) to 15.4% (Midlands). The majority of patients were young males. DISCUSSION: An extensive range of incidence and mortality rates were observed between studies in all regions. This was largely dependent on the study population under review. London was found to have the highest incidence of penetrating injuries, however these studies tended to focus on populations of trauma patients. The high proportion of male victims may reflect the risk of becoming involved in gangs and violence. CONCLUSIONS: Our ambiguous results indicate the need for further work directed towards the epidemiology of penetrating injuries within regional trauma networks.

Association between lifetime headache and history of suicide attempts in the elderly.

BACKGROUND: Pain-related conditions have been reported to play a key role among risk factors for suicide. Headache in particular has been repeatedly associated with suicidal thoughts and behaviors. The aims of this study were: 1) to assess the association between lifetime headache (both non-migrainous headache and migraine) and lifetime suicide attempts (SA); 2) to differentiate, within subjects with lifetime SA, patients with and without lifetime headache in terms of socio-demographic and clinical features. METHODS: We studied 1965 subjects from a cohort of community-dwelling persons aged 65 years and over without dementia (the ESPRIT study), divided in two groups: those with (n=75), and those without a lifetime SA (n=1890). Logistic regression analyses were used to compare these groups according to lifetime headache status. RESULTS: After adjusting for gender, living alone, tobacco and alcohol consumption, and depressive, manic/hypomanic and anxiety disorders, lifetime headache frequency was significantly higher in subjects with a lifetime SA compared with controls (OR=1.92 [1.17-3.15]). Additionally, different factors were identified as being associated with lifetime SA in participants with lifetime headache (female gender, a lower level of high-density lipoprotein cholesterol, insomnia, lifetime major depression) versus participants without headache (glycemia and lifetime major depression). CONCLUSIONS: Lifetime headache was associated with lifetime SA. Subjects who are women and report the co-occurrence of headache and insomnia as well as lifetime major depression require higher attention and a careful screening for suicidal thoughts and behaviors.

Escherichia coli O78 isolated from septicemic lambs shows high pathogenicity in a zebrafish model.

The pathogenicity of Escherichia coli O78 strain K46, originally isolated from an outbreak of septicemia in neonatal lambs, was investigated in zebrafish embryo and murine models of infection. Its biofilm potential, cellulose production, and the expression of type 1 pili and curli fimbriae were measured by in vitro assays. The strain was highly pathogenic in the zebrafish embryo model of infection, where it killed all embryos within 24 h post inoculation (hpi) at doses as low as 1000 colony forming units. Zebrafish embryos inoculated with similar doses of commensal E. coli strains showed no signs of disease, and cleared the bacteria within 24 h. E. coli K46 colonized the murine gut at the same level as the uropathogenic E. coli (UPEC) reference strain CFT073 in CBA/J mice after oral inoculation, but infected the murine bladder significantly less than CFT073 after transurethral inoculation. Type 1 pili were clearly expressed by E. coli K46, while curli fimbriae and cellulose production were weakly expressed. The ability to produce biofilm varied in different growth media, but overall E. coli K46 was a poorer biofilm producer compared to the reference strain E. coli UTI89. In conclusion, the zebrafish lethality model provides further evidence that E. coli K46 is highly pathogenic and might be useful in future studies to identify bacterial virulence factors.