"Sometimes, it just stops me from doing anything": A qualitative exploration of epilepsy management in people with intellectual disabilities and their carers

$\textit{Purpose}$: Epilepsy affects 1 in 5 people with an intellectual disability (ID), but little is known about their experiences of living with epilepsy. A qualitative study was conducted to investigate the impact and management of epilepsy in people with ID. $\textit{Materials and methods:}$ People with epilepsy and ID and their carers were invited to take part in semi-structured interviews. Eleven participants with ID and their carers were interviewed together, one participant with ID and their carer were interviewed separately, two interviews took place with the participant with ID only, and one interview took place with the carer only. The interviews were transcribed verbatim, coded, and analyzed thematically (dual independent coding for 30% of the transcripts). $\textit{Results:}$ Three themes emerged (participant characteristics, living with epilepsy, epilepsy management and information needs) which indicated the following: 1) diversity regarding health profiles, communication abilities, severity of epilepsy, perceived control of epilepsy, and support needs; 2) a reduction in severity and frequency of seizures for a sizeable proportion of participants through antiepileptic drugs; 3) the lifelong impact of epilepsy and related seizures on participants' activities and quality of life; 4) the perceived burden of epilepsy and difficulty managing the condition for a large proportion of participants; 5) high levels of satisfaction with epilepsy-related services and care; and 6) an overall lack of written accessible information about epilepsy. $\textit{Conclusions:}$ This study has highlighted a significant impact of epilepsy and related seizures on the daily lives and quality of life of people with ID. Although a sizeable proportion of participants and their carers considered their epilepsy to be well controlled, the majority reported difficulties managing epilepsy and minimizing its impact on their wellbeing. Excluding care staff and the support provided by epilepsy clinics, the participants had not accessed any adapted self-management or information resources about epilepsy

Understanding the Treatment Algorithm of Patients with Metastatic Pancreatic Neuroendocrine Neoplasms: A Single-Institution Retrospective Analysis Comparing Outcomes of Chemotherapy, Molecular Targeted Therapy, and Peptide Receptor Radionuclide Therapy in 255 Patients

Background The number of therapeutic options for patients with pancreatic neuroendocrine neoplasms (PNEN) has increased, but the optimal therapeutic algorithm has not been defined due to lack of randomised trials comparing different modalities. Methods We performed a retrospective study in patients with metastatic PNEN treated with ≥1 line of systemic therapy. The relationship between baseline characteristics, treatment type and time to treatment failure (TTF), time to progression (TTP) and overall survival (OS) was analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Results Two hundred and fifty-five patients with metastatic PNEN had 491 evaluable lines of therapy. Independent predictors of TTF included treatment type, Ki-67, tumour grade and chromogranin A. To reduce selection bias, a subgroup of 114 patients with grade 2 (G2) metastatic pancreatic neuroendocrine tumours (PNET) was analysed separately. These patients had received 234 lines of treatment (105 chemotherapy, 82 molecular targeted therapy, and 47 peptide receptor radionuclide therapy [PRRT]). In the G2 cohort, TTF and TTP were superior for PRRT compared with both chemotherapy and molecular targeted therapy. OS in the G2 cohort was also superior for those that had received PRRT compared with those that had not (median 84 vs 56 months; HR 0.55, 95%CI 0.31-0.98, p=0.04). Conclusions This study suggests that PRRT is associated with superior clinical outcomes relative to other systemic therapies for G2 metastatic PNET. Prospective studies are required to confirm these observations

Implementing an Evidence-Based COPD Hospital Discharge Protocol: A Narrative Review and Expert Recommendations

Discharge bundles, comprising evidence-based practices to be implemented prior to discharge, aim to optimise patient outcomes. They have been recommended to address high readmission rates in patients who have been hospitalised for an exacerbation of chronic obstructive pulmonary disease (COPD). Hospital readmission is associated with increased morbidity and healthcare resource utilisation, contributing substantially to the economic burden of COPD. Previous studies suggest that COPD discharge bundles may result in fewer hospital readmissions, lower risk of mortality and improvement of patient quality of life. However, evidence for their effectiveness is inconsistent, likely owing to variable content and implementation of these bundles. To ensure consistent provision of high-quality care for patients hospitalised with an exacerbation of COPD and reduce readmission rates following discharge, we propose a comprehensive discharge protocol, and provide evidence highlighting the importance of each element of the protocol. We then review care bundles used in COPD and other disease areas to understand how they affect patient outcomes, the barriers to implementing these bundles and what strategies have been used in other disease areas to overcome these barriers. We identified four evidence-based care bundle items for review prior to a patient’s discharge from hospital, including (1) smoking cessation and assessment of environmental exposures, (2) treatment optimisation, (3) pulmonary rehabilitation, and (4) continuity of care. Resource constraints, lack of staff engagement and knowledge, and complexity of the COPD population were some of the key barriers inhibiting effective bundle implementation. These barriers can be addressed by applying learnings on successful bundle implementation from other disease areas, such as healthcare practitioner education and audit and feedback. By utilising the relevant implementation strategies, discharge bundles can be more (cost-)effectively delivered to improve patient outcomes, reduce readmission rates and ensure continuity of care for patients who have been discharged from hospital following a COPD exacerbation

The combined diabetes and renal control trial (C-DIRECT) - a feasibility randomised controlled trial to evaluate outcomes in multi-morbid patients with diabetes and on dialysis using a mixed methods approach

Background: This cluster randomised controlled trial set out to investigate the feasibility and acceptability of the “Combined Diabetes and Renal Control Trial” (C-DIRECT) intervention, a nurse-led intervention based on motivational interviewing and self-management in patients with coexisting end stage renal diseases and diabetes mellitus (DM ESRD). Its efficacy to improve glycaemic control, as well as psychosocial and self-care outcomes were also evaluated as secondary outcomes. Methods: An assessor-blinded, clustered randomised-controlled trial was conducted with 44 haemodialysis patients with DM ESRD and ≥ 8% glycated haemoglobin (HbA1c), in dialysis centres across Singapore. Patients were randomised according to dialysis shifts. 20 patients were assigned to intervention and 24 were in usual care. The C-DIRECT intervention consisted of three weekly chair-side sessions delivered by diabetes specialist nurses. Data on recruitment, randomisation, and retention, and secondary outcomes such as clinical endpoints, emotional distress, adherence, and self-management skills measures were obtained at baseline and at 12 weeks follow-up. A qualitative evaluation using interviews was conducted at the end of the trial. Results: Of the 44 recruited at baseline, 42 patients were evaluated at follow-up. One patient died, and one discontinued the study due to deteriorating health. Recruitment, retention, and acceptability rates of C-DIRECT were generally satisfactory HbA1c levels decreased in both groups, but C-DIRECT had more participants with HbA1c < 8% at follow up compared to usual care. Significant improvements in role limitations due to physical health were noted for C-DIRECT whereas levels remained stable in usual care. No statistically significant differences between groups were observed for other clinical markers and other patient-reported outcomes. There were no adverse effects. Conclusions: The trial demonstrated satisfactory feasibility. A brief intervention delivered on bedside as part of routine dialysis care showed some benefits in glycaemic control and on QOL domain compared with usual care, although no effect was observed in other secondary outcomes. Further research is needed to design and assess interventions to promote diabetes self-management in socially vulnerable patients

Hypoglycaemia following upper gastrointestinal surgery: case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Hyperinsulinemic hypoglycemia is relatively recently recognized in persons undergoing bariatric surgery although knowledge and experience with this condition may not be commensurate with the number of such procedures being performed globally. This paper presents a novel case as an example of how such patients may present and how they may be investigated.</p> <p>Case Presentation</p> <p>A 69-year-old man was assessed 3 months post-fundoplication surgery for postprandial hypoglycaemia with neuroglycopenia that became progressively severe. A 72-h fast failed to show hypoglycaemia. During a clinic visit, the patient became confused and had a low plasma glucose, high plasma insulin, and high plasma C-peptide; symptoms were relieved with glucose. No tumours were visualized on CT, MRI, or endoscopic ultrasound. A total body Indium111-octreotide scan was negative. Selective arterial calcium stimulation showed a high insulin gradient in the splenic and superior mesenteric arteries, suggesting diffuse pancreatic beta cell hyperplasia. The patient declined pancreatic resection and recurrent symptomatic hypoglycaemia was successfully prevented with low dose octreotide.</p> <p>Conclusions</p> <p>Although increasingly recognized following bariatric surgery, this is the first reported development of NIPHS (non-insulinoma pancreatogenous hypoglycemia syndrome) following fundoplication surgery, as well as the first documented use of octreotide in post-operative NIPHS. Medical management may be an alternative to surgery for patients with this rare condition.</p

Mild Joint Symptoms Are Associated with Lower Risk of Falls than Asymptomatic Individuals with Radiological Evidence of Osteoarthritis

Osteoarthritis (OA) exacerbates skeletal muscle functioning, leading to postural instability and increased falls risk. However, the link between impaired physical function, OA and falls have not been elucidated. We investigated the role of impaired physical function as a potential mediator in the association between OA and falls. This study included 389 participants [229 fallers (≥2 falls or one injurious fall in the past 12 months), 160 non-fallers (no history of falls)], age (≥65 years) from a randomized controlled trial, the Malaysian Falls Assessment and Intervention Trial (MyFAIT). Physical function was assessed using Timed Up and Go (TUG) and Functional Reach (FR) tests. Knee and hip OA were diagnosed using three methods: Clinical, Radiological and Self-report. OA symptom severity was assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). The total WOMAC score was categorized to asymptomatic, mild, moderate and severe symptoms. Individuals with radiological OA and ‘mild’ overall symptoms on the WOMAC score had reduced risk of falls compared to asymptomatic OA [OR: 0.402(0.172–0.940), p = 0.042]. Individuals with clinical OA and ‘severe’ overall symptoms had increased risk of falls compared to those with ‘mild’ OA [OR: 4.487(1.883–10.693), p = 0.005]. In individuals with radiological OA, mild symptoms appear protective of falls while those with clinical OA and severe symptoms have increased falls risk compared to those with mild symptoms. Both relationships between OA and falls were not mediated by physical limitations. Larger prospective studies are needed for further evaluation

Conjugative Plasmids of Neisseria gonorrhoeae

Many clinical isolates of the human pathogen Neisseria gonorrhoeae contain conjugative plasmids. The host range of these plasmids is limited to Neisseria species, but presence of a tetracycline (tetM) determinant inserted in several of these plasmids is an important cause of the rapid spread of tetracycline resistance. Previously plasmids with different backbones (Dutch and American type backbones) and with and without different tetM determinants (Dutch and American type tetM determinants) have been identified. Within the isolates tested, all plasmids with American or Dutch type tetM determinants contained a Dutch type plasmid backbone. This demonstrated that tetM determinants should not be used to differentiate between conjugal plasmid backbones. The nucleotide sequences of conjugative plasmids with Dutch type plasmid backbones either not containing the tetM determinant (pEP5233) or containing Dutch (pEP5289) or American (pEP5050) type tetM determinants were determined. Analysis of the backbone sequences showed that they belong to a novel IncP1 subfamily divergent from the IncP1α, β, γ, δ and ε subfamilies. The tetM determinants were inserted in a genetic load region found in all these plasmids. Insertion was accompanied by the insertion of a gene with an unknown function, and rearrangement of a toxin/antitoxin gene cluster. The genetic load region contains two toxin/antitoxins of the Zeta/Epsilon toxin/antitoxin family previously only found in Gram positive organisms and the virulence associated protein D of the VapD/VapX toxin/antitoxin family. Remarkably, presence of VapX of pJD1, a small cryptic neisserial plasmid, in the acceptor strain strongly increased the conjugation efficiency, suggesting that it functions as an antitoxin for the conjugative plasmid. The presence of the toxin and antitoxin on different plasmids might explain why the host range of this IncP1 plasmid is limited to Neisseria species. The isolated plasmids conjugated efficiently between N. gonorrhoeae strains, but did not enhance transfer of a genetic marker

Differences in MEF2 and NFAT Transcriptional Pathways According to Human Heart Failure Aetiology

BACKGROUND:Ca(2+) handling machinery modulates the activation of cardiac transcription pathways involved in heart failure (HF). The present study investigated the effect of HF aetiology on Ca(+2) handling proteins and NFAT1, MEF2C and GATA4 (transcription factors) in the same cardiac tissue. METHODOLOGY AND PRINCIPAL FINDINGS:A total of 83 hearts from ischemic (ICM, n = 43) and dilated (DCM, n = 31) patients undergoing heart transplantation and controls (CNT, n = 9) were analyzed by western blotting. Subcellular distribution was analyzed by fluorescence and electron microscopy. When we compared Ca(+2) handling proteins according to HF aetiology, ICM showed higher levels of calmodulin (24%, p<0.01), calcineurin (26%, p<0.01) and Ca(2+)/Calmodulin-dependent kinase II (CaMKIIδ(b) nuclear isoform 62%, p<0.001) than the CNT group. However, these proteins in DCM did not significantly increase. Furthermore, ICM showed a significant elevation in MEF2C (33%, p<0.01), and GATA4 (49%, p<0.05); also NFAT1 (66%, p<0.001) was increased, producing the resultant translocation of this transcriptional factor into the nuclei. These results were supported by fluorescence and electron microscopy analysis. Whereas, DCM only had a significant increase in GATA4 (52%, p<0.05). Correlations between NFAT1 and MEF2C in both groups (ICM r = 0.38 and DCM r = 0.59, p<0.05 and p<0.01, respectively) were found; only ICM showed a correlation between GATA4 and NFAT1 (r = 0.37, p<0.05). CONCLUSIONS/SIGNIFICANCE:This study shows an increase of Ca(2+) handling machinery synthesis and their cardiac transcription pathways in HF, being more markedly increased in ICM. Furthermore, there is a significant association between MEF2, NFAT1 and GATA4. These proteins could be therapeutic targets to improve myocardial function

Learning environment associated with use of mixed mode delivery model among secondary business studies students in Singapore

At many teacher education institutes around the world, preservice teachers are empowered to use pedagogical tools and strategies that engage their students. We used a modified version of the Constructivist Learning Environment Survey (CLES) to evaluate the effectiveness of a pedagogical model known as the Mixed Mode Delivery (MMD) model in terms of the CLES’s five scales of personal relevance, uncertainty, critical voice, shared control and negotiation. Comparisons were made between 2,216 secondary school students taught by the preservice teachers in an MMD group and 991 students in a control group in terms of the relative magnitudes of the gap between the actual and preferred learning environment in students’ school classrooms. The findings supported the positive impact of using MMD in terms of students’ perceptions of their classroom environments for all CLES scales