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Studies have shown that people with intellectual disability (ID) show a greater severity of attention deficit hyperactivity disorder (ADHD) symptoms and atypical presentation, as well as having a greater risk of developing comorbidities, such as challenging behaviour, anxiety, tic disorders and sleep problems. It is estimated that 1.5% of patients with ID will have a clinical diagnosis of ADHD.
The aim of this audit was to find whether individuals with ID and ADHD, who are prescribed medication for ADHD are adequately monitored and reviewed in accordance with the ADHD medication prescription guidance by NICE and the Royal College of Psychiatrists (RCPsych).
This audit looked at ADHD medication prescription for the ID population within Greater Glasgow & Clyde NHS. This is the 6th audit cycle where electronic records (EMIS) were analysed between 28/9/19 to 09/10/20. (The 5th cycle data collection period ended on 28/9/19). We collected data on all patients aged over 18 years.
An audit tool was developed to find whether the following were documented; patient demographics, physical health monitoring, symptom severity, medication dosage, side effects, need for ongoing treatment and frequency of review. 100% of patients should have all components on the ADHD audit tool documented, as per NICE/ RCPsych prescription guidance.
32 patients were identified as being diagnosed with ADHD prescribed medication. One patient was impacted by the COVID-19 pandemic which meant that the required monitoring was not fully carried out. The age ranged from 18 to 56 years. 75% had mild intellectual disability, 19% had moderate and 6% had severe, with no cases of profound intellectual disability. Blood Pressure/pulse was recorded in 84% of patients. Height/weight/ BMI was recorded in 81% of patients. 97% of patients had ADHD symptom severity, medication dosage, side effects, need for ongoing treatment and frequency of review recorded.
There is further scope for improvement in the monitoring and documentation of physical health observations, however there was a significant improvement compared to the previous cycle of the audit. Other aspects of monitoring and documentation appear to be recorded in almost 100% of patients. This finding emphasises the challenges of physical health monitoring and compliance in psychiatry as a whole. We need to continue to encourage awareness and education around the physical health risks to our patients, not only due to their comorbidities but also as a result of the psychotropic medications we prescribe them.
Aortopulmonary window is a rare congenital heart defect. Left main coronary artery extrinsic compression by an enlarged pulmonary artery is a rare complication and a potential cause for chest pain and sudden cardiac death in patients with pulmonary hypertension. Here, we present the case of a 14-year-old boy with a large aortopulmonary window who was planned for a device closure, but during the procedure, he developed ST-T segment changes while the device was being deployed, and hence the procedure was abandoned. The boy subsequently underwent a successful surgical closure thereafter.
Several aspects of the coronavirus disease 2019 (COVID-19) pandemic remain ambiguous, including its transmission, severity, geographic, and racial differences in mortality. These variations merit elaboration of local patterns to inform wider national policies.
In a retrospective analysis, data of patients treated at a dedicated COVID hospital with moderate and severe illness during 8 wk of the pandemic were reviewed with attention to mortality in a competing risks framework.
A total of 1147 patients were hospitalized, and 312 (27.2%) died in hospital. Those who died were older (56.5 vs 47.6 y; P < 0.0001). Of these, 885 (77.2%) had tested positive on reverse transcriptase polymerase chain reaction (RT-PCR), with 219 (24.2%) deaths (incidence rate, 1.9 per 100 person-days). Median time from onset of symptoms to death was 11 days. A competing risks analysis for in-hospital death revealed an adjusted cause-specific hazard ratio of 1.4 for each decade increase in age.
This retrospective analysis provides broad patterns of disease presentation and mortality. Even COVID test-negative patients will receive treatment at dedicated facilities, and 33% presenting cases may die within the first 72 h, most with comorbid illness. This should be considered while planning distribution of services for effective health-care delivery
ABSTRACT IMPACT: This study advances our understanding of potentially key drivers in the early formation of pancreatic cancer, a disease with few treatment options and poor patient outcomes. OBJECTIVES/GOALS: Patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) have a 5-year survival rate of ˜9%. A key driver of poor patient outcomes is late-stage diagnosis. A better understanding of PDAC onset is needed. This study was developed to understand how extracellular vesicles may be involved in the early formation of PDAC. METHODS/STUDY POPULATION: Extracellular vesicles (EVs) were isolated from several human PDAC and normal pancreatic cell lines, using ultracentrifugation with filtration or size exclusion chromatography. We next treated normal pancreatic cell lines with cancer cell EVs (cEVs). Next generation sequencing was used to measure global gene expression changes after treatment. Validations were performed using qPCR and luciferase activity assays. Multi-omics characterization of EVs was accomplished using mass spectrometry based proteomics, metabolomics and lipidomics analysis. RESULTS/ANTICIPATED RESULTS: We found that normal cells upregulated a variety of stress response pathways in response to cEVs. Lipid synthesis was also severely downregulated in these cells. We further validated activation of the unfolded protein response (UPR) in normal cells treated with cEVs. Multi-omics characterization of cEVs identified several enriched proteins, lipids and metabolites which may play a role in the activation of the UPR. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results indicate that cEVs induce stress, and in particular the UPR, in normal pancreatic cells. Long-term UPR can impact a variety of cancer hallmarks. The UPR can mediate progression of pancreatic intraepithelial neoplasia (PanIN) to PDAC. Our results highlight a potential role for cEVs to alter the function of normal cells, aiding disease onset.
A 14-year-old girl admitted for corrective surgery for tetralogy of Fallot was found to have pulmonary arteriovenous malformations on pre-operative evaluation. In anticipation of a complicated postoperative course, percutaneous closure of the pulmonary arteriovenous malformations was undertaken first followed by a successful surgical outcome. Importance of this rare association and its clinical implication is hereby highlighted.
Maternal periconceptional undernutrition (PCUN) affected fetal pancreatic maturation in late gestation lambs and impaired glucose tolerance in 10-month-old sheep. To examine the importance of the timing of maternal undernutrition around conception, a further cohort was born to PCUN ewes [undernourished for 61 d before conception (PreC), 30 d after conception (PostC), or 61 d before until 30 d after conception (PrePostC)], or normally fed ewes (Control) (n = 15–20/group). We compared glucose tolerance, insulin secretion, and sensitivity at 36 months of age. We also examined protein expression of insulin signalling proteins in muscle from these animals and in muscle from a fetal cohort (132 d of gestation; n = 7–10/group). Adult PostC and PrePostC sheep had higher glucose area under the curve than Controls (P = 0.07 and P = 0.02, respectively), whereas PreC sheep were similar to Controls (P = 0.97). PostC and PrePostC had reduced first-phase insulin secretion compared with Control (P = 0.03 and P = 0.02, respectively). PreC was similar to Control (P = 0.12). Skeletal muscle SLC2A4 protein expression in PostC and PrePostC was increased 19%–58% in fetuses (P = 0.004), but decreased 39%–43% in adult sheep (P = 0.003) compared with Controls. Consistent with this, protein kinase C zeta (PKCζ) protein expression tended to be increased in fetal (P = 0.09) and reduced in adult (P = 0.07) offspring of all PCUN ewes compared with Controls. Maternal PCUN alters several aspects of offspring glucose homeostasis into adulthood. These findings suggest that maternal periconceptional nutrition has a lasting impact on metabolic homeostasis of the offspring.
Antimicrobial resistance is a major problem in India with limited understanding of whether this issue is related to systems, prescriber characteristics, patient characteristics, or diagnostic technologies. In our survey, most of the issues lie in the easy availability of antimicrobials and the lack of electronic storage of medical and microbiological records.
The pandemic of Coronavirus disease 2019 (COVID-19) is rapidly progressing, causing significant morbidity and mortality. Various antiviral drugs, anti-inflammatory drugs, and immunomodulators have been tried without substantial clinical benefits. The severe and critical cases of COVID-19 disease are characterised by gut microbiome dysbiosis, immune dysregulation, hyper-inflammation, and hypercytokinemia (cytokine storm). Therefore, the strategies which target these pathophysiological processes may be beneficial. Probiotics are one such strategy that exerts beneficial effects by manipulation of the gut microbiota, suppression of opportunistic pathogens in the gut, decrease translocation of opportunistic organisms, activate mucosal immunity, and modulation of the innate and adaptive immune response. Probiotics are the potential candidates to be tested in moderate and severe cases of COVID-19 due to several beneficial effects, including easy availability, easy to administer, and safe, and economical to use.
Thermochemical interactions between calcium–magnesium–aluminosilicate (CMAS) glass and an environmental barrier coating of ytterbium disilicate (Yb2Si2O7) and ytterbium monosilicate (Yb2SiO5) were investigated. Top coats were deposited by plasma spray-physical vapor deposition onto silicon carbide substrates. CMAS powder was prepared as a glass and cast into a tape to yield a CMAS loading of ~29 mg/cm2. Samples were heat treated with CMAS at 1300 °C for 1–10 h or at 1400 °C for 1 h in air. Polished specimen cross-sections were characterized using scanning electron microscopy, X-ray diffraction, X-ray energy-dispersive spectroscopy, and transmission electron microscopy to evaluate resulting microstructures, phases, and compositions at CMAS/Yb2Si2O7 interfaces. Coatings exposed at 1300 °C—10 h and 1400 °C—1 h were fully infiltrated and compromised by CMAS. Dissolution of ytterbium silicate into molten CMAS followed by precipitation of cyclosilicate, silicocarnotite, and Yb2Si2O7 at 1300 °C and Yb2Si2O7 at 1400 °C enabled CMAS to effectively infiltrate top coats, rendering the predominantly Yb2Si2O7 coating ineffective at arresting molten CMAS degradation.
Aneurysm formation around the site of coarctation of aortic arch is a well-recognised complication of untreated coarctation and is associated with an increased risk of aortic rupture and mortality. We present a rare case in a teenage girl with the combination of significant aortic arch coarctation, a “cauliflower-like” saccular aneurysm, and stenosis at the origin of the left subclavian artery. She was successfully managed with a hybrid approach, which is a combination of an endovascular surgical repair (a bypass graft placement from left carotid artery to subclavian artery by a vascular surgeon) and a transcatheter covered stent placement across the stenosis and aneurysm. This case highlights the successful role of a hybrid approach in patient’s who present with a combination of coarctation of the aorta and aortic arch aneurysms. This approach avoids the conventional surgical aortoplasty, which carries a higher mortality and morbidity risk in teenage patients.
OBJECTIVES/GOALS: Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related deaths by 2030. Though many other cancers have seen improvements in patient survival rates, patients diagnosed with PDAC have a 5-year survival rate of only ~9%. A major contributor to decreased survival is late-stage diagnosis of the disease. New methods of early detection are urgently needed. Extracellular vesicles (EVs) are secreted from cells of all tissue types into the circulation. EVs play important roles in a variety of diseases. They have shown to promote cancer progression and they are being studied as potential biomarkers for disease diagnosis. The purpose of this study was to perform qualitative and quantitative characterization of small-molecule profiles of EVs derived from various pancreatic cancer (PC) and normal pancreas cell lines, to provide proof-of-concept for evaluating the efficacy of leveraging EVs as potential biomarkers of PDAC. METHODS/STUDY POPULATION: EVs were isolated from the conditioned media of six PC and two normal pancreas cell lines using differential ultracentrifugation with filtration. EV enrichment was validated using quantitative ELISA, immunoblot and transmission electron microscopy. Targeted liquid chromatography coupled to mass spectrometry (LC-MS/MS) and untargeted (UPLC-QTOF-MS) metabolomics were used to analyze the biochemical composition of EVs. RESULTS/ANTICIPATED RESULTS: The biochemical profile of PC EVs was found to be significantly different from the profiles of normal cell EVs. Interestingly, amino acids were downregulated in PC EVs as compared to normal cell EVs. However, PC EVs were enriched in lactate and malate. PC EVs also had significant upregulation in other small molecules such as xanthosine, guanosine diphosphate and nicotinamide. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that the biochemical characterization of EVs using metabolomics has the potential to yield biomarkers which can delineate cancer cell-derived EVs from normal cell-derived EVs. Further work will test the clinical significance of these findings by similar analyses of plasma of PDAC patients. Furthermore, these profiles may be detectable before progression of the disease to late-stage PDAC, leading to the development of assays for earlier diagnosis in patients.
Analgesia in the prehospital setting is an extremely important, yet controversial topic. Ketamine, a N-methyl D-aspartate (NMDA) receptor antagonist, has been commonly used in the prehospital setting, including recommendations by the US Department of Defense and by the Royal Australian College of Pain Medicine, despite the paucity of high-level evidence.
Accordingly, a review of the literature was conducted using several electronic medical literature databases from the earliest available records to the time at which the search was conducted (October 2018).
The search strategy yielded a total of 707 unique papers, of which 43 were short-listed for full review, and ultimately, ten papers were identified as meeting all the relevant inclusion criteria. The included studies varied significantly in the prehospital context and in the means of administering ketamine. There was only low-grade evidence that ketamine offered a safe and effective analgesia when used as the only analgesic, and only low-grade evidence that it was as effective as alternative opioid options. However, there was moderate evidence that co-administration of ketamine with morphine may improve analgesic efficacy and reduce morphine requirement.
Overall, ketamine as a prehospital analgesic may be best used in combination with opioids to reduce opioid requirement. It is suggested that future studies should use a standardized approach to measuring pain reduction. Future studies should also investigate short-term side effects and long-term complications or benefits of prehospital ketamine.
The aim of study was to evaluate the pharmacotherapeutic efficacy of NDGA in experimental paradigm of depression i.e. olfactory bulbectomy (OB) specifically targeting kynurenine pathway.
Materials and method
Depression like behaviours was induced in OB mice and evaluated by assessment of various behavioural (olfactory deficit test, forced swim test, splash test, open field test, sucrose preference test), biochemical (catalase, reduced glutathione, SOD, nitrite, MAO-A, MDA, corticosterone), inflammatory cytokines (TNF- α, IL-1β, IL-6, IFN-γ) levels and alterations in delta sleep was recorded using EEG. Kynurenine pathway metabolites were determined in plasma and brain using HPLC method. After 14 days post-surgery, olfactory bulbectomized (OBX) mice were administered nordihydroguaiaretic acid (5 mg/kg, 10 mg/kg and 25 mg/kg) daily i.p.
We have developed a new HPLC method for simultaneous estimation of monoamines and kynurenine pathway metabolites in plasma and brain samples of mice. Chronic treatment with nordihydroguaiaretic acid significantly restored all behavioural, biochemical and neurochemical alterations in OBX mice and increase in quinolinic acid and decrease in kynurenic acid point out the neurodegeneration hypothesis of depression.
Nordihydroguaiaretic acid showed potent neuropharmacotherapeutic effect in OBX mice by virtue of its strong anti-oxidant, anti-inflammatory, anti-stress and by restoring quinolinic acid levels.
Bulimia Nervosa (BN) is an important cause of morbidity and mortality in hospitalized patients. While BN has been extensively studied in the past, the contemporary data for impact of BN on cost of hospitalization are largely lacking.
We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (HCUP-NIS) dataset between 1998-2011 using the ICD-9 codes. Severity of co-morbid conditions was defined by Deyo modification of Charlson co-morbidity index. Primary outcome was in-hospital mortality and secondary outcome was total charges for hospitalization. Using SAS 9.2, chi-square test, t-test and Cochran-Armitage test were used to test significance.
19,441 patients were analyzed. 94.13% were female and 5.87% male (P < 0.0001). 85.72% were white, 4.55% black and 9.73% of other race (P < 0.0001). Rate of hospitalization decreased from 1136.99/million to 802.47/million from 1998-2011. Overall mortality was 0.20% and mean cost of hospitalization was 15,496.82$. The in-hospital mortality reduced from 0.23% to 0.15% (P < 0.0001) and mean cost of hospitalization increased from 8,194.53$ to 22,547.86$. Total spending on BN related admissions have increased from $73.96 million/year to $139.93 million/year over the last decade.
While mortality has slightly decreased from 1998 to 2011, the cost has significantly increased from $73.96 million/year to $139.93 million/year, which leads to an estimated $65.97 million/year additional burden to US health care system. In the era of cost conscious care, preventing BN related Hospitalization could save billions of dollars every year. Focused efforts are needed to establish preventive measures for BN related hospitalization.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Anorexia Nervosa (AN) is an important cause of morbidity and mortality in hospitalized patients. While AN has been extensively studied in the past, the contemporary data for impact of AN on cost of hospitalization are largely lacking.
We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (HCUP-NIS) dataset between 1998-2011 using the ICD-9 codes for AN. Severity of co-morbid conditions was defined by Deyo modification of Charlson co-morbidity index. Primary outcome was in-hospital mortality and secondary outcome was total charges for hospitalization. Using SAS 9.2, chi-square test, t-test and Cochran-Armitage test were used to test significance.
28,150 patients were analyzed. 93.94% were female and 6.06% were male (P < 0.0001). 88.67% were white, 2.93% were black and 8.4% were of other race (P < 0.0001). Rate of hospitalization decreased from 1530/million to 1349.5/million from 1998-2011. Overall mortality was 0.78% and mean cost of hospitalization was 25,829.82$. The in-hospital mortality reduced from 0.95% to 0.44% (P < 0.0001) and mean cost of hospitalization increased from 11,956.55$ to 39,831.51$. Total yearly spending on AN related admissions increased from $145.33 million/year to $420.61 million/year.
While mortality has slightly decreased from 1998 to 2011, the cost has significantly increased from $145.33 million/year to $420.61 million/year, which leads to an estimated $275.28 million additional burden to the US health care system. In the era of cost conscious care, preventing AN related Hospitalization could save billions of dollars every year. Focused efforts are needed to establish preventive measures for AN related hospitalization.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Endoscopes provide a magnified view of the middle ear and visualisation of hidden areas. Otoendoscopes facilitate excellent visualisation of the round window niche during cochlear implantation.
To compare microscopic and endoscopic visualisation of the round window membrane during cochlear implantation in 20 patients.
Twenty patients who underwent cochlear implantation were included in the study. After maximum exposure of the round window, the accessibility of the round window membrane was graded according to the St Thomas Hospital classification, first by microscope and then by endoscope.
With the use of the endoscope, visualisation of the round window membrane improved in all the patients as compared to the microscope. The electrode array was inserted via a round window or extended round window approach in all but two cases; the latter cases required bony cochleostomy because of unfavourable anatomy.
The main benefit of endoscope-assisted cochlear implantation is improved visibility of the round window region.
Pompe disease is a type-II glycogen storage disease, and clinical manifestations include hypertrophic cardiomyopathy and generalised muscular hypotonia. Enzyme replacement therapy has proven to be effective in reversing the ventricular hypertrophy. The outcomes are variable depending on time to diagnosis and severity of the cardiac disease. We describe two contrasting cases of patients with infantile-onset Pompe disease. The first child was diagnosed late and had severe cardiac hypertrophy with respiratory decompensation and ventilator dependence and eventual death. The second case was diagnosed at birth with early initiation of therapy resulting in a good outcome. Our cases highlight the importance of early initiation of enzyme replacement therapy to improve clinical outcomes.
Antenatal exogenous glucocorticoids (ANG) are standard management for women at risk of preterm birth but are reputed to impair glucose tolerance in preterm offspring. We compared lambs born preterm (137 days gestation) following labour induced with exogenous glucocorticoids (G-Prem, glucocorticoid-induced preterm group), or with a progesterone synthesis inhibitor (NG-Prem, non-glucocorticoid-induced preterm group), with term-born lambs (Term; 149 days). We assessed glucose tolerance, insulin secretion and sensitivity at 4 and 10 months n = 11–14/group) and pancreatic and hepatic gene and protein expression at 4 weeks post-term (4 weeks; n = 6/group) and 12 months (12 months; n = 12–13/group). NG-Prem had higher plasma glucose concentrations than G-Prem, but not Term, at 4 months (Mean[SEM] mM: NG-Prem = 4.1[0.1]; G-Prem = 3.4[0.1]; Term = 3.7[0.1]; p = 0.003) and 10 months (NG-Prem = 3.9[0.1]; G-Prem = 3.5[0.1]; Term = 3.7[0.1]; p = 0.01). Insulin sensitivity decreased from 4 to 10 months, in NG-Prem but not in Term (Mean[SEM] µmol·ml−1·kg−1·min−1·ng−1, 4 vs. 10 months: NG-Prem = 18.7[2.5] vs. 9.5[1.5], p < 0.01; Term: 12.1[2.8] vs. 10.4[1.5], p = 0.44). At 12 months, β-cell mass in NG-Prem was reduced by 30% vs. G-Prem (p < 0.01) and 75% vs. Term (p < 0.01) and was accompanied by an increased β-cell apoptosis: proliferation ratio at 12 months. At 12 months, pancreatic glucokinase, igf2 and insulin mRNA levels were reduced 21%–71% in NG-Prem vs. G-Prem and 42%–80% vs. Term. Hepatic glut2 mRNA levels in NG-Prem were 250% of those in G-Prem and Term. Thus, induction of preterm birth without exogenous glucocorticoids more adversely affected pancreas and liver than induction with exogenous glucocorticoids. These findings do not support that ANG lead to long-term adverse metabolic effects, but support an effect of preterm birth itself.