The course of mental health problems in children presenting with abdominal pain in general practice

Objective. To investigate the course of mental health problems in children presenting to general practice with abdominal pain and to evaluate the extent to which abdominal pain characteristics during follow-up predict the presence of mental health problems at 12 months' follow-up. Design. A prospective cohort study with one-year follow-up. Setting. 53 general practices in the Netherlands, between May 2004 and March 2006. Subjects. 281 children aged 4-17 years. Main outcome measures. The presence of a depressive problem, an anxiety problem, and multiple non-specific somatic symptoms at follow-up and odds ratios of duration, frequency, and severity of abdominal pain with these mental health problems at follow-up. Results. A depressive problem persisted in 24/74 children (32.9%; 95% CI 22.3-44.9%), an anxiety problem in 13/43 (30.2%; 95% CI 17.2-46.1%) and the presence of multiple non-specific somatic symptoms in 75/170 children (44.1%; 95% CI 36.7-51.6%). None of the abdominal pain characteristics predicted a depressive or an anxiety problem at 12 months' follow-up. More moments of moderate to severe abdominal pain predicted the presence of multiple nonspecific somatic symptoms at follow-up. Conclusions. In one-third of the children presenting to general practice for abdominal pain, anxiety and depressive problems persist during one year of follow-up. Characteristics of the abdominal pain during the follow-up period do not predict anxiety or depressive problems after one-year follow-up. We recommend following over time children seen in primary care with abdominal pain

Stroke types, risk factors, quality of care and outcomes at a Referral Hospital in Western Kenya

Background: The prevalence of stroke is increasing in sub-Saharan Africa due to increases in size of  aging population and stroke risk factors.We assessed risk factors, quality of care and outcomes of stroke to identify modifiable risk factors and areas of care that need improvement for better outcomes.Objectives: To describe the stroke types, risk factors, outcomes and stroke quality of care in a large academic medical centre hospital.Design: Hospital based retrospective study.Setting: Moi Teaching and Referral Hospital (MTRH), Eldoret, Kenya.Subjects: All patients >18 years admitted with a diagnosis of stroke as per the WHO definition and with a supporting brain imaging (CT scan/ MRI )were included in the study. Data abstracted from the files included demographic details, stroke subtype, stroke risk factors, inpatient stroke care quality  indicators(based on US Joint Commission stroke quality indicator definitions) and in hospital stroke  outcomes. Descriptive statistics was used to summarise the data.Results: A total of 155 patients had stroke between January 2010 and December 2014 of whom 42% were male, the median age was 61 (IQR: 49-72) years. Majority (73%) had hypertension. The prevalence of diabetes was 4%. Left hemiplegia/hemiparesis was the predominant presentation (50%). Haemorrhagic strokes were frequent (52%) with anterior circulation stroke comprising 97% of all strokes. Assessment of quality of care indicators showed that overall, 84% of the patients had a brain CT scan on day one of admission,93% had a GCS documented at admission, 32% were on statins and 3% were screened for dysphagia before oral intake. Among patients with ischaemic strokes; none underwent thrombolysis, 24% received DVT prophylaxis, 54% received statins, and 73% received anti-thrombotic therapy by hospital day two. In hospital mortalityoccurred in 43(27%)with a higher rate among haemorrhagic strokes (31%) compared to ischaemic stroke (24%)(p=0.364).Conclusion: Haemorrhagic stroke was the most common type of stroke admitted, hypertension was the predominant risk factor and most strokes involved the anterior circulation. In-hospital mortality was 27%.There were several opportunities to improve evidence-based quality of care indicators

In the beginning: Role of autonomy support on the motivation, mental health and intentions of participants entering an exercise referral scheme

Self-determination theory (Deci & Ryan, 2000, Intrinsic motivation and self-determination in human behaviour. New York: Plenum Publishing) highlights the impact autonomy supportive environments can have on exercise motivation and positive health outcomes. Yet little is known about whether differential effects occur as a function of which significant other is providing this support. Further, no research has examined the relationship between motivation and the social environment with participants’ mental health and intentions to be physically active before entering an exercise intervention. Study participants were 347 British adults who were about to start an exercise referral scheme. Regression analyses revealed that the effects of autonomy support on mental health and physical activity intentions differed as a function of who provided the support (offspring, partner or physician), with the offspring having the weakest effects. A structural model was supported, indicating that autonomy support and more autonomous regulations led to more positive mental health outcomes and stronger intentions to be physically active. Knowledge of the social environmental and personal motivation of those about to commence an exercise programme can provide important insights for professionals supporting such efforts

Pharmacological treatment for methamphetamine withdrawal: A systematic review and meta-analysis of randomised controlled trials

Issues: Cessation of methamphetamine use may result in a characteristic withdrawal syndrome, no medication has been approved for this indication. This systematic review aims to assess the efficacy of pharmacotherapy for methamphetamine withdrawal, the first comprehensive meta-analysis since 2008. Approach: MEDLINE (1966–2020), CINAHL (1982–2020), PsychINFO (1806–2020) and EMBASE (1947–2020) were systematically searched. Studies were included if they were randomised controlled trials (RCT) investigating pharmacological treatments for methamphetamine withdrawal, reviewing outcomes of treatment discontinuation, mental health outcomes, withdrawal symptoms (including craving) and patient safety. The relative risk (RR) and weighted mean difference (MD) were used to meta-analyse dichotomous and continuous data respectively, with 95% confidence intervals. Risk of bias and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments were conducted. Key Findings: Nine RCTs of six medications (n = 242 participants) met inclusion criteria, however, only six trials of four medications (n = 186) could be meta-analysed. Mean sample size across studies was 27 participants, and 88% of participants were male. The quality of evidence in this review varies from low to very low on GRADE assessments. Amineptine may reduce discontinuation rates (RR 0.22, 95% confidence interval [CI] 0.07, 0.72, p = 0.01), and improve global state (MD −0.49, 95% CI −0.80, −0.17), compared with placebo, however, this medication is no longer approved. No other medications improved any domain when compared with placebo. Due to lack of reporting safety profiles could not be established. Conclusions: There is insufficient evidence to indicate any medication is effective for the treatment of methamphetamine withdrawal. The poor quality of the evidence indicates a need for better powered, high-quality trials

Regulation of multiple angiogenic pathways by Dll4 and Notch in human umbilical vein endothelial cells.

The Notch ligand, Dll4, is essential for angiogenesis during embryonic vascular development and is involved in tumour angiogenesis. Several recent publications demonstrated that blockade of Dll4 signalling inhibits tumour growth, suggesting that it may constitute a good candidate for anti-cancer therapy. In order to understand the role of Dll4 at the cellular level, we performed an analysis of Dll4-regulated genes in HUVECs. The genes identified included several angiogenic signalling pathways, such as VEGF, FGF and HGF. In particular we identified downregulation (VEGFR2, placenta growth factor PlGF) of VEGF pathway components resulting in the overall effect of limiting the response of HUVEC to VEGF. However extensive upregulation of VEGFR1 was observed allowing continued response to its ligand PlGF but the soluble form of the VEGFR1, sVEGFR1 was also upregulated. PlGF enhanced tubulogenesis of HUVEC suggesting that downregulation of PlGF and upregulation of VEGFR1 including sVEGFR1 are important mechanisms by which Dll4 attenuates PlGF and VEGF signalling. Dll4-stimulated HUVECs had impaired ERK activation in response to VEGF and HGF indicating that Dll4 signalling negatively regulates these pathways. Dll4 expression reduced vessel sprout length in a 3D tubulogenesis assay confirming that Dll4 signalling inhibits angiogenesis. Altogether, our data suggest that Dll4 expression acts as a switch from the proliferative phase of angiogenesis to the maturation and stabilisation phase by blocking endothelial cell proliferation and allowing induction of a more mature, differentiated phenotype. The regulation of sVEGFR1 provides a novel mechanism for Dll4 signalling to regulate cells at distance, not just in adjacent cells

Resolution requirements for numerical simulations of transition

The resolution requirements for direct numerical simulations of transition to turbulence are investigated. A reliable resolution criterion is determined from the results of several detailed simulations of channel and boundary-layer transition

Patients’ experiences of lupus related foot problems : a qualitative investigation

Background: Systemic lupus erythematosus (SLE) can present with a variety of symptoms. Previous research has shown there is a high prevalence of lower limb and foot problems in patients with SLE associated with the musculoskeletal, vascular and neurological changes. Furthermore, there is a high prevalence of infections affecting the feet and a range of common skin and nail problems. However, it is not known how these foot problems impact upon people’s lives. Therefore, we aimed to explore this using a qualitative approach. Method: Following ethical approval, 12 participants were recruited who had a diagnosis of SLE, current and/or past experience of foot problems and were over 18 years in age. Following consent, interviews were carried out with an interpretivist phenomenological approach to both data collection and analysis. Results: Seven themes provide insight into: foot problems and symptoms; the impact of these foot problems and symptoms on activities; disclosure and diagnosis of foot problems; treatment of foot problems and symptoms; perceived barriers to professional foot care; unanswered questions about feet and foot care; and identification of the need for professional foot care and foot care advice. Conclusion: These participants tend to “self-treat” rather than disclose that they may need professional foot care. A lack of focus upon foot health within a medical consultation is attributed to the participant’s belief that it is not within the doctor’s role, even though it is noted to contribute to reduced daily activity. There is a need for feet to be included as a part of patient monitoring and for foot health management to be made accessible for people with SLE

APC-targeted proinsulin expression inactivates insulin-specific memory CD8+ T cells in NOD mice

Type 1 diabetes (T1D) results from T-cell-mediated autoimmune destruction of pancreatic β cells. Effector T-cell responses emerge early in disease development and expand as disease progresses. Following β-cell destruction, a long-lived T-cell memory is generated that represents a barrier to islet transplantation and other cellular insulin-replacement therapies. Development of effective immunotherapies that control or ablate β-cell destructive effector and memory T-cell responses has the potential to prevent disease progression and recurrence. Targeting antigen expression to antigen-presenting cells inactivates cognate CD8+ effector and memory T-cell responses and has therapeutic potential. Here we investigated this in the context of insulin-specific responses in the non-obese diabetic mouse where genetic immune tolerance defects could impact on therapeutic tolerance induction. Insulin-specific CD8+ memory T cells transferred to mice expressing proinsulin in antigen-presenting cells proliferated in response to transgenically expressed proinsulin and the majority were rapidly deleted. A small proportion of transferred insulin-specific Tmem remained undeleted and these were antigen-unresponsive, exhibited reduced T cell receptor (TCR) expression and H-2Kd/insB15-23 tetramer binding and expressed co-inhibitory molecules. Expression of proinsulin in antigen-presenting cells also abolished the diabetogenic capacity of CD8+ effector T cells. Therefore, destructive insulin-specific CD8+ T cells are effectively inactivated by enforced proinsulin expression despite tolerance defects that exist in diabetes-prone NOD mice. These findings have important implications in developing immunotherapeutic approaches to T1D and other T-cell-mediated autoimmune diseases

Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom

PURPOSE: Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care hospitals in the United Kingdom.\ud \ud PATIENTS AND METHODS: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed.\ud \ud RESULTS: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation.\ud \ud CONCLUSIONS: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.\ud \u

Reevaluation of the Value of Autoparasitoids in Biological Control

Autoparasitoids with the capacity of consuming primary parasitoids that share the same hosts to produce males are analogous to intraguild predators. The use of autoparasitoids in biological control programs is a controversial matter because there is little evidence to support the view that autoparasitoids do not disrupt and at times may promote suppression of insect pests in combination with primary parasitoids. We found that Encarsia sophia, a facultative autoparasitoid, preferred to use heterospecific hosts as secondary hosts for producing males. The autoparasitoids mated with males originated from heterospecifics may parasitize more hosts than those mated with males from conspecifics. Provided with an adequate number of males, the autoparasitoids killed more hosts than En. formosa, a commonly used parasitoid for biological control of whiteflies. This study supports the view that autoparasitoids in combination with primary parasitoids do not disrupt pest management and may enhance such programs. The demonstrated preference of an autoparasitoid for heterospecifics and improved performance of males from heterospecifics observed in this study suggests these criteria should be considered in strategies that endeavor to mass-produce and utilize autoparasitoids in the future