The inequity of education, health and care plan provision for children and young people with intellectual and developmental disabilities.

BACKGROUND: Children and young people (CYP) with intellectual and developmental disabilities (IDDs) have significant additional educational needs compared with the general population. In England, the government has established a system of education, health and care plans (EHCPs) to support children with special educational needs and disabilities, but disparities exist between the degree of need and the availability of support. We conducted a prospective UK national cohort study (IMAGINE) of children with rare pathogenic genomic variants, all of which are associated with IDD, to investigate associated neuropsychiatric risk. Subsequently, we obtained information from the UK's National Pupil Database on their educational progress through the state school system. We aimed to identify whether they had received EHCP provision and whether that support was associated with their family's socioeconomic status, region of domicile, ethnicity, sex, primary special educational needs (SEN) type, academic performance and mental health well-being. METHODS: We recruited 2738 CYP from England into the IMAGINE study between 2014 and 2019. The educational histories of the participants (6-28 years old, mean ± standard deviation = 14 ± 4 years, 56% male) were obtained from the Department for Education's National Pupil Database in 2021. Educational data included attainment scores from the Early Year Foundation Stage (<5 years) to key stage 4 (15-16 years). Each family was assigned an index of multiple deprivation (IMD) score based on their home address postcode. Parents or carers rated their child's emotional and behavioural adjustment on the Strengths and Difficulties Questionnaire (SDQ). The association between receiving an EHCP and the child's IMD score, eligibility for free school meals, English region of domicile, ethnicity, sex, primary SEN type, academic attainment and SDQ score was investigated. RESULTS: In this cohort, 78% of participants had received an EHCP. CYP living in the most deprived IMD deciles were substantially less likely to receive EHCP support than those in the least deprived decile, irrespective of their degree of intellectual developmental disability, academic performance or associated mental health problems. There were no sex differences. Children of Asian heritage were more likely to have been granted an EHCP than White children from equivalent IMD deciles. There were striking regional disparities. Participants living in London were significantly more likely to have been awarded an EHCP than participants living anywhere else in England, regardless of their IMD decile; those in the least deprived decile had almost 100% EHCP provision. CONCLUSIONS: This study found evidence for nationwide regional inconsistencies in the awarding of EHCP to CYP with significant intellectual impairments of known genetic aetiology. Disparities in funds available to education authorities could be a contributory factor. EHCP support was potentially influenced by how strongly a parent advocates for their child.

Lactobacillus-fermented milk products attenuate bone loss in an experimental rat model of ovariectomy-induced post-menopausal primary osteoporosis.

AIM: In this study, we investigated the anti-osteoporotic effect of two fermented milk products (FMPs) fermented by Lactobacillus plantarum A41 and Lactobacillus fermentum SRK414 on a rat model of ovariectomy-induced post-menopausal primary osteoporosis. METHODS AND RESULTS: The two Lactobacillus FMPs increased the bone volume and bone mineral density (BMD) in ovariectomized (OVX) rats, and normalized the bone biomarkers in the serum. Additionally, they altered the gene expression levels of bone-metabolism-related markers. Furthermore, the two Lactobacillus FMPs downregulated bone-apoptosis-related genes stimulated by ovariectomy. Interestingly, the Lactobacillus FMPs decreased the levels of inflammation markers in the serum, bone, ileum and colon of the rats. Gut bacterial populations were also affected upon FMP treatment due to increase in the abundance of the genus Lactobacillus and Faecalibacterium prausnitzii. CONCLUSIONS: Milk products fermented by L. plantarum A41 and L. fermentum SRK414 can exhibit anti-osteoporotic effects on post-menopausal osteoporosis via regulating the expression of bone-metabolism-related markers. SIGNIFICANCE AND IMPACT OF THE STUDY: The two Lactobacillus FMPs used in the study can be an ideal method that has its potential of treating post-menopausal osteoporosis instead of drug treatments.

Use of Terlipressin in an Elderly Patient With Moderate Aortic Valve Stenosis Accompanied by Episodic Atrial Fibrillation During Liver Transplantation: A Case Report.

Anesthesia for patients with moderate aortic stenosis accompanied by atrial fibrillation during high-risk surgery such as liver transplantation remains a challenge in maintaining control of heart rate and maintenance of cardiac output. The action of terlipressin on vasopressin receptors (mainly V1 receptors) leads to splanchnic vasoconstriction and is the key mechanism responsible for increasing systemic vascular resistance and reducing heart rate. We report successful anesthetic management using low-dose terlipressin infusion in an elderly patient who had moderate aortic stenosis with atrial fibrillation during urgent deceased-donor liver transplantation.

Effect of Perioperative Terlipressin on Postoperative Renal Function in Patients Who Have Undergone Living Donor Liver Transplantation: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Recent studies have shown the efficacy of terlipressin on postoperative renal function in patients who have undergone living donor liver transplantation (LDLT). OBJECTIVES: To evaluate the effect of perioperative terlipressin on postoperative renal function in patients who have undergone LDLT and to analyze the hemodynamic data during transplantation surgery. STUDY DESIGN: A meta-analysis. METHODS: We assessed the postoperative peak serum creatinine level and changes in the hemodynamic data (e.g. the mean arterial pressure, heart rate, and systemic vascular resistance). We collected randomized controlled trials from PubMed, EMBASE Drugs and Pharmacology, Cochrane Controlled Trials Register, and Cochrane Database on Systematic Reviews. Analysis was conducted using RevMan 5.2. Data from each trial were pooled and weighted by their mean differences and corresponding 95% confidence intervals (CI). A heterogeneity assessment was performed. RESULTS: Three trials (151 patients) were included. The difference in the mean (95% CI) peak serum creatinine (mg/dL) levels postoperatively was not significant between the intervention and control groups (weighted mean difference [WMD]: -0.27; CI: -0.55-0.01; P = .06). Terlipressin significantly decreased heart rate during the anhepatic phase (WMD: -6.58; 95% CI: -8.85 to -4.31; P < .00001) with a low heterogeneity (I(2) = 41%) and significantly decreased heart rate during the neohepatic phase (WMD: -9.82; 95% CI: -11.96 to -7.68; P < .00001), although the heterogeneity was high (I(2) > 50%). CONCLUSIONS: An intravenous infusion of terlipressin perioperatively for LDLT has no effect on the creatinine values postoperatively. Larger randomized controlled trials on terlipressin infusions during liver transplantation are needed.

Effects of propofol or desflurane on post-operative spirometry in elderly after knee surgery: a double-blind randomised study.

BACKGROUND: Intravenous or volatile agents reduce respiratory function, which can result in respiratory complications in geriatric patients. We hypothesised that there would be no differences in lung function between anaesthesia established using either drug. METHODS: Elderly patients were randomly assigned to receive either propofol with remifentanil (n = 48) or desflurane (DES) with remifentanil (n = 52) for knee surgery. Spirometry tests including forced expiratory volume in 1 s (FEV1 ), forced vital capacity (FVC), forced mid-expiratory flow (FEF25-75), and FEV1 /FVC ratio were performed preoperatively, and 30 min, 60 min, and 24 h after awakening. Emergence time and post-operative pain scores were also measured. RESULTS: Time to emergence was significantly longer in the propofol than in the DES group (17.0 vs. 12.5 min, P = 0.04). Post-operative FEV1 (1.6 or 1.4 l, P = 0.68 between groups) were significantly lower than preoperative values (2.1 or 2.0 l, P = 0.001 vs. post-operative values, respectively) in both groups. Reduced FEV1 lasted for 24 h after surgery (1.7 or 1.6 l, P = 0.001 vs. preoperative values, respectively). Post-operative FVC or FEF25-75 were lower than preoperative values. FEV1 /FVC ratio did not change during the study period in both groups. There was no difference in FEV1 , FVC, FEF25-75, FEV1 /FVC, and post-operative pain between the two anaesthetic techniques. CONCLUSIONS: Although there is a delay in awakening when using propofol, the effects of propofol on post-operative spirometry parameters are similar to those of DES when anaesthesia duration is approximately 3 h. Decreased respiratory parameters persisted up to 24 h after anaesthesia, irrespective of the choice of anaesthetic.

Antipruritic and antiemetic effect of epidural droperidol: comparative study between single and continuous epidural injection.

BACKGROUND AND OBJECTIVES: This study was designed to investigate whether single epidural droperidol or continuous epidural droperidol inhibit pruritus and postoperative nausea and vomiting induced by postoperative continuous epidural fentanyl administration, and to identify the optimal method of administering epidural droperidol. METHODS: 120 ASA I-II patients undergoing subtotal gastrectomy with general anaesthesia combined with epidural anaesthesia were randomly allocated into three groups: control (no droperidol), single injection (droperidol 2.5 mg) and continuous group (droperidol 2.5 mg 2 day(-1)). Postoperatively the frequency and severity of pruritus and postoperative nausea and vomiting in all groups were compared during 48 h. RESULTS: The frequency and severity of pruritus was significantly lower in both single injection and continuous groups than control group after epidural fentanyl administration (P < 0.05). The frequency and severity of postoperative nausea and vomiting was significantly lower in single injection group than control group after epidural fentanyl administration (P < 0.05). CONCLUSION: Epidural continuous droperidol is effective for reducing pruritus, and single epidural droperidol injection is effective for reducing pruritus and postoperative nausea and vomiting induced by postoperative continuous epidural fentanyl analgesia.

Preemptive effect of intravenous ketamine in the rat: concordance between pain behavior and spinal fos-like immunoreactivity.

BACKGROUND: The purpose of this study was to compare behavioral antinociceptive responses with spinal fos-like immunoreactivity (FLI) for a intravenous ketamine injection between pre vs. postformalin administration in rats. METHODS: Sprague-Dawley rats (250-300 g) were prepared to receive either saline or ketamine. All rats were randomly divided into three groups: control, pretreatment and post-treatment group. Formalin (5%) 100 microl was injected into the hindpaw. Pain related behavior and FLI in the lumbar spinal cord was examined. RESULTS: Flinches of phase 2 were 239.3 (22,8), 118.6 (7,5) (P < 0.05 vs. control and post-treatment group), and 186.7 (16,6) in the control, pre and, post-treatment groups, respectively. Fos-like immunoreactivity expression was significantly correlated with phase 2 flinching behavior (P < 0.001). CONCLUSION: Pretreatment with intravenous ketamine inhibits inflammatory pain behavior and FLI expression following a formalin injection in rats, suggesting that pretreatment of ketamine plays an important role in preemptive analgesia.

The effects of beta2 adrenoceptor gene polymorphisms on pressor response during laryngoscopy and tracheal intubation.

We investigated whether human beta2 adrenoceptor (beta2AR) gene polymorphisms are associated with the pressor response to laryngoscopy and tracheal intubation. Ninety-two patients undergoing elective surgery under general anaesthesia were enrolled into this study. Arterial systolic pressure, heart rate and rate pressure product were measured before induction of anaesthesia and 1 min following laryngoscopy and tracheal intubation. Genomic DNA was then used to identify the beta2AR-16 and beta2AR-27 genes using an allele-specific polymerase chain reaction method. Using multiple linear regression models, controlling for age, sex, weight, baseline blood pressure, heart rate and rate pressure product, we found that patients who possessed the glutamic acid homozygote of beta2AR-27 produced significantly greater changes in mean arterial pressure and rate pressure products than patients with the glutamine homozygote of beta2AR-27 (beta coefficient for mean blood pressure = 11.81, beta coefficient for pulse-pressure product = 8.76, both p-values = 0.023). These findings suggest that genetic variability in the human beta2AR gene polymorphisms may be associated with the pressor response to laryngoscopy and tracheal intubation.

Systemic, but not intrathecal, ketamine produces preemptive analgesia in the rat formalin model.

BACKGROUND: We investigated the antinociceptive effects of pre- or posttreatment of intrathecal or intravenous ketamine on formalin-induced pain behaviors. METHODS: Rats were divided into 4 groups of 7 rats each and 2 control groups (saline). Rats received ketamine 1 mg/kg intrathecally (i.t.) through a catheter either 15 min before or 5 min after formalin. In the other groups, they received ketamine 1 mg/kg intravenously (i.v.) through a catheter either 1 min before or 5 min after the formalin. Pain related behavior was quantified by counting the incidence of flinching of the injected paw for 60 min. Formalin induced a biphasic fliching (phase 1, 0-5 min; phase 2, 10-60 min after formalin injection) of injected paw. The inter-group (control, pre, and posttreatment groups) comparisons were performed separately for route of administration (i.t. or i.v.) and phase 1 and 2 using one-way ANOVA and Tukey test. RESULTS: Flinches of phase 1 were not different among the three i.t. groups. The total flinches of phase 2 were reduced by posttreatment with i.t. ketamine (P < 0.05); In contrast, i.v. ketamine was effective only when given as a pretreatment. Flinches of phase 1 and 2 were reduced by pretreatment with i.v. ketamine (P < 0.05). CONCLUSIONS: Intrathecal ketamine was an analgesic even when administered as a posttreatment, whereas intravenous ketamine produced effective preemption only when given as a pretreatment.

Pain after laparoscopic cholecystectomy: the effect and timing of incisional and intraperitoneal bupivacaine.

PURPOSE: To examine the combined preemptive effects of somatovisceral blockade during laparoscopic cholecystectomy (LC). METHODS: One hundred fifty-seven patients under general anesthesia receiving local infiltration and/or topical peritoneal local anesthesia were studied. Patients were randomized to receive a total of 150 mg (0.25% 60 mL) bupivacaine via periportal (20 mL) and intraperitoneal (40 mL with 1:200,000 epinephrine) administration of each. Group A received preoperative periportal bupivacaine before incision and intraperitoneal bupivacaine immediately after the pneumoperitoneum. Group B received periportal and intraperitoneal bupivacaine at the end of the operation. Group C (preoperative) and Group D (postoperative) received only periportal bupivacaine and Group E (preoperative) and Group F (post-operative) received only intraperitoneal bupivacaine. The control group received no treatment. Pain and nausea were recorded at one, two, three, six, nine, 12, 24, 36, and 48 hr postoperatively. RESULTS: Throughout the postoperative 48 hr, incisional somatic pain dominated over other pain localizations in the control group (P <0.05). The incisional pain of groups A, B, C and D was significantly lower than that of the control group in the first and second hours. The incisional pain of groups A and C was significantly lower than that of the control group in the first three hours. CONCLUSION: Incisional pain dominated during the first two post-operative days after LC. Preoperative somato-visceral or somatic local anesthesia reduced incisional pain during the first three post-operative hours. A combination of somato-visceral local anesthetic treatment did not reduce intraabdominal pain, shoulder pain or nausea more than somatic treatment alone. Preoperative incisional infiltration of local anesthetics is recommended.

Surgical treatment of digital ischemia occurred after radial artery catheterization.

Permanent ischemic injury of the hand after radial artery cannulation is rare, but several cases of thromboembolism after the cannulation leading to amputation of affected limb or digits have been reported. A 48-yr-old man undergoing spine surgery showed normal modified Allen's test and had no preoperative vascular disease. We inserted 20-G radial artery catheter for the continuous monitoring of the blood flow and serial blood sampling. There was no specific event during the operation and the catheter was removed immediately after the operation. The signs and symptoms of the circulatory impairment of the radial artery developed four days after the operation and aggravated thereafter. Through the angiographic study, we found the total occlusion of the radial artery and some of its branches. After an emergent surgical exploration of the radial artery for removal of the thrombus and vein graft for the defect of the artery on the 8th postoperative day, the ischemic signs and symptoms disappeared and the radial pulse was restored.

Effects of different concentrations and volumes of formalin on pain response in rats.

BACKGROUND: Formalin test is commonly used in animal model to assess injury-produced pain response. If the total amount of formaldehyde is fixed, its concentration and volume can be easily adjusted. We evaluated the effect of two sets of three solutions of formalin (one set of same dose of formaldehyde at different concentration and volume, i.e. 2.5%--100 microL, 5%--50 microL, 10%--25 microL, and another set of same volume but at different concentrations, i.e. 2.5%--100 microL, 5%--100 microL, and 10%--100 microL) on the injury-produced pain response in rat. METHODS: Male Sprague-Dawley rats weighing 250-300 g were used. Following injection of formalin (n = 8 in each group) or saline (n = 6, control), the flinching frequencies and time spent in licking or biting the injected hind-paw in the early phase 1 (0-5 min after injection) and the late phase 2 (20-60 min after injection) were recorded. Sham-injection rats (n = 5) underwent subcutaneous insertion of the needle, but no substance was injected. RESULTS: Flinching in phase 1 and 2 was more frequent in the 2.5%--100 microL and 5%--50 microL groups than in the control group (P < 0.05). Licking (or biting) time in phase 2 in all these three groups was longer than the control group (P < 0.05). In the groups of another set of three different solutions (2.5%--100 microL, 5%--100 microL, and 10%--100 microL), flinching in phase 1 and phase 2 was also more frequent than the control group (P < 0.05). Regarding lick behavior of another set, it occurred more frequently in 2.5%--100 microL group in phase 1 and in 2.5%--100 microL group as well as 5%--100 microL group in phase 2 than the control group (P < 0.05). CONCLUSIONS: The 10%--25 microL formalin produces fewer flinching responses than other concentrations. Flinching was a biphasic behavior which was more spontaneous and active than was licking. The volume of formalin was a more important factor than the concentration of formalin in the generation of the active biphasic flinching response in the rat model.

Comparative effects of diltiazem with enflurane or desflurane on myocardial contractility and heart rate in the isolated rat hearts.

BACKGROUND: The volatile anesthetics may reduce cardiac contractility by limiting both membrane Ca2+ entry and altering intracellular Ca2+ release. Additional pharmacological effects of calcium channel blockers could potentially enhance anesthetic-induced depression. The aim of this study was to compare the direct cardiac effects of enflurane and a new volatile anesthetic, desflurane, in combination with diltiazem on the isolated Sprague-Dawley rat heart. METHODS: After stabilization period isolated rat hearts (n = 40) were perfused with an oxygenated modified Krebs' solution at 55 mmHg equilibrated with 1, 2 and 3 MAC of enflurane (1.7, 3.4 and 5.1 vol% respectively) or desflurane (6, 12 and 18 vol% respectively) in combination with 100 ng/mL diltiazem at 36 degrees C. Isovolumetric left ventricular pressure (LVP), rate of change of ventricular pressure (dp/dt), spontaneous heart rate and coronary flow were measured. To examine the indirect metabolic effect due to autoregulation of coronary flow, O2 delivery (DO2), myocardial O2 consumption (MVO2) and percent O2 extraction (POE) were also monitored. RESULTS: Diltiazem plus enflurane or desflurane depressed LVP and dp/dt dose-dependently. Enflurane plus diltiazem significantly decreased heart rate more than desflurane plus diltiazem in a dose-dependent manner. Desflurane plus diltiazem significantly increased coronary flow more than enflurane plus diltiazem and oxygen delivery increased proportionally with coronary flow. But there were statistically insignificant dose-dependent increases in both groups. Myocardial oxygen consumption and percentage of oxygen extraction were also decreased dose-dependently in both groups. Bradydysrhythmia that accompanied atrioventricular dissociation occurred with diltiazem plus high enflurane or desflurane concentration at an incidence of 46% and 40% respectively. CONCLUSIONS: These in vitro results demonstrate that diltiazem plus enflurane or desflurane depresses left ventricular contractile function and diltiazem plus enflurane causes higher incidence of bradydysrhythmia more than equivalent levels of diltiazem plus desflurane.

Halothane effect on formalin-induced paw edema and flinching in rat.

The formalin test is a model of injury-produced inflammatory pain. Anesthetics, in clinically relevant concentrations, affect neutrophils and immune suppression. This study was to determine whether halothane reliably inhibits inflammatory reaction and formalin induced pain behavior or does not. Rats were exposed to 100% oxygen (control) or halothane, respectively for 30 min and then 24 hr later five percent formalin test was assessed. The base values of the paw's diameter were obtained earlier, and then formalin induced edema was assessed by measuring diameters of the injected paws at 5 min, 1 hr, 4 hr and 24 hr after the injection. Nociceptive behavior was quantified by counting the number of times with the paw flinched at 5 min intervals for 60 min. The diameters of edema in the halothane group lessened more than those in the oxygen group at 1 and 24 hr in each following of the injection (p<0.05). The rats pre-administered with oxygen or halothane were similar appearances in nociceptive behaviors. It suggests that halothane anesthesia might inhibit slightly the inflammatory reaction with the formalin-induced edema but might not inhibit the formalin-induced pain behavior in the event of pre-administration halothane 24 hr earlier before the formalin test of rat.

Improved isolation of a 50 kDa anorexigenic protein from rat urine.

In prior work, a 50 kDa protein was purified to homogeneity from rat urine. This protein reduces food intake when injected into rats and is the only natural substance other than satietin known to be effective for long (24 hour) time periods and which does not make animals ill. However, when attempts were made to repeat the purification, contamination appeared in the 50 kDa fraction. The present contribution documents successful reisolation of the 50 kDa anorexigen by an improved method. Reisolation involved Cibacron blue-Sepharose, DEAE-Sephacel and Sephacryl S-200 chromatography, and SDS disc preparatory electrophoresis. The reisolated 50 kDa anorexigen contains no detectable carbohydrate. Partially purified preparations of the 50 kDa anorexigen were fragmented with trypsin and proteinase K without loss of anorexigenic activity. It is concluded that the 50 kDa anorexigen may be reproducibly purified to homogeneity and may contain within its amino acid sequence a peptide which is the basis of its anorexigenic activity.