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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.
A detailed investigation of a glauconite bed within the Late Cretaceous Bryozoan Limestone Formation of the Bagh Group in central India, as well as the study of existing records, reveals the existence of a ‘glauconitic sea’ along the margins of the Palaeo-Tethys Ocean during the Late Cretaceous Epoch. The authigenic green mineral formed abundantly on shallow seafloors unlike in its modern, deep-sea counterpart. We present an integrated petrographical, geochemical and mineralogical investigation of the glauconite within Late Cretaceous transgressive deposits to highlight its unique geochemistry with moderate Fe2O3 and high Al2O3, SiO2, MgO as well as K2O contents. X-ray diffractional parameters identify the ‘evolved to high evolved’ nature of the glauconite while Mössbauer spectroscopic study reveals the dominance of Fe3+ compared to Fe2+ in the atomic structure. The rare earth elements (REE) pattern of glauconite reveals moderate light-REE/heavy-REE (LREE/HREE) fractionation and weak negative Eu anomaly. The Ce anomaly of the glauconite indicates a sub-oxic diagenetic condition. We propose that Late Cretaceous glauconites formed within a shallow marine depositional setting across the Tethyan belt because of enhanced supply of K, Si, Al, Fe, Mg cations through continental weathering under the extant greenhouse climate.
Working memory (WM) deficits are seen as a core deficit in schizophrenia, implicated in the broad cognitive impairment seen in the illness. Here we examine the impact of WM storage of a single item on the operation of other cognitive systems.
We studied 37 healthy controls (HCS) and 43 people with schizophrenia (PSZ). Each trial consisted of a sequence of two potential target stimuli, T1 and T2. T1 was a letter presented for 100 ms. After delays of 100–800 ms, T2 was presented. T2 was a 1 or a 2 and required a speeded response. In one condition, subjects were instructed to ignore T1 but respond to T2. In another condition, they were required to report T1 after making their speeded response to T2 (i.e. to make a speeded T2 response while holding T1 in WM).
PSZ were dramatically slowed at responding to T2 when T1 was held in WM. A repeated measures ANOVA yielded main effects of group, delay, and condition with a group by condition interaction (p's < 0.001). Across delays, the slowing of the T2 response when required to hold T1 in memory, relative to ignoring T1, was nearly 3 times higher in PSZ than HCS (633 v. 219 ms).
Whereas previous studies have focused on reduced storage capacity, the present study found that PSZ are impaired at performing tasks while they are successfully maintaining a single item in WM. This may play a role in the broad cognitive impairment seen in PSZ.
Congenital complete tracheal rings are usually associated with pulmonary slings. We report a rare association of congenital complete tracheal rings with hypoplastic left heart variant. A term infant with diagnosis of a mildly hypoplastic mitral valve, unicuspid aortic valve, and moderately hypoplastic aortic arch with severe coarctation underwent a hybrid procedure initially. Upon failing extubation attempts, complete tracheal rings were seen on direct laryngoscopy. The combination of the lesions resulted in a poor outcome. In patients with failure of extubation post-cardiac surgery, a diagnosis of complete tracheal rings should be included in the differential and a direct laryngoscopy should be considered.
Exposure to the endocrine disruptor bisphenol A (BPA) is ubiquitous and associated with health abnormalities that persist in subsequent generations. However, transgenerational effects of BPA on metabolic health are not widely studied. In a maternal C57BL/6J mice (F0) exposure model using BPA doses that are relevant to human exposure levels (10 μg/kg/day, LowerB; 10 mg/kg/day, UpperB), we showed male- and dose-specific effects on pancreatic islets of the first (F1) and second generation (F2) offspring relative to controls (7% corn oil diet; control). In this study, we determined the transgenerational effects (F3) of BPA on metabolic health and pancreatic islets in our model. Adult F3 LowerB and UpperB male offspring had increased body weight relative to Controls, however glucose tolerance was similar in the three groups. F3 LowerB, but not UpperB, males had reduced β-cell mass and smaller islets which was associated with increased glucose-stimulated insulin secretion. Similar to F1 and F2 BPA male offspring, staining for markers of T-cells and macrophages (CD3 and F4/80) was increased in pancreas of F3 LowerB and UpperB male offspring, which was associated with changes in cytokine levels. In contrast to F3 BPA males, LowerB and UpperB female offspring had comparable body weight, glucose tolerance and insulin secretion as Controls. Thus, maternal BPA exposure resulted in fewer metabolic defects in F3 than F1 and F2 offspring, and these were sex- and dose-specific.
Hardy’s uncertainty principle for the Gabor transform is proved for locally compact abelian groups having noncompact identity component and groups of the form
is a compact group having irreducible representations of bounded dimension. We also show that Hardy’s theorem fails for a connected nilpotent Lie group
which admits a square integrable irreducible representation. Further, a similar conclusion is made for groups of the form
is a discrete group.
The possible association between teat morphometric traits and subclinical mastitis (SCM) in dairy buffaloes was studied. Teat morphometric parameters, i.e. teat shape (bottle, conical, cylindrical, and others), teat-end shape (flat, round, and pointed), teat length (TL), teat diameter (TD), and teat-end to floor distance were measured before milking, but after proper milk let-down, in clinically healthy buffaloes (47 Murrah and 34 Nili-Ravi breeds). Subclinical mastitis was defined on the basis of bacteriology and somatic cell count (SCC) of quarter foremilk samples. A high proportion of cylindrical teats (40%) and pointed teat-ends (64·4%) was observed. Hind teats were longer and thicker than fore teats (P < 0·05). A significant breed effect was found with respect to teat shape, length and diameter (P < 0·05). Teats were mostly cylindrical (43·3 vs. 35·4%) and conical (34·2 vs. 30·8%) shaped, smaller (mean 8·2 vs. 9·5 cm) and thinner (mean 3·3 vs. 3·6 cm) in the Murrah breed compared with the Nili-Ravi breed. Teats that had ‘other’ shapes and were longer, wider, and placed closer to the floor were more associated with SCM (P < 0·05). Mean SCC was significantly higher (P < 0·05) in Nili-Ravi buffaloes, teat shapes classified as ‘others’, and quarters with SCM. Teat morphometric traits seem to be associated with indicators of udder health in buffaloes, thus, their inclusion in breeding programmes for selection against undesirable dairy type traits may be of value in reducing susceptibility to intramammary infections in Indian buffaloes.
To compare combined conventional Freer medialisation and controlled synechiae, performed for middle meatal access (during the initial steps of functional endoscopic sinus surgery) and post-operative middle turbinate medialisation, with basal lamella relaxing incision, the latter of which is a single step for achieving both middle meatal access and post-operative medialisation. The study also compared the effects of controlled synechiae and basal lamella relaxing incision on post-operative olfaction.
A randomised prospective study was performed on 52 nasal cavity sides (32 patients). Only basal lamella relaxing incision was performed in one group, and both conventional medialisation and controlled synechiae were performed in the other. Intra-operative and post-operative photography was used to measure the middle meatal area. A pocket smell test was used to assess olfaction.
There were no significant differences in operative middle meatal access and post-operative medialisation of the middle turbinate. Post-operative olfaction was affected more in the combined conventional medialisation and controlled synechiae group, compared to the basal lamella relaxing incision group, but this finding was not statistically significant.
Basal lamella relaxing incision is an effective single-step technique for achieving adequate middle meatal access and post-operative medialisation, with no significant effect on olfaction.
To evaluate the predictive ability of mid-upper arm circumference (MUAC) for detecting severe wasting (weight-for-height Z-score (WHZ) <−3) among children aged 6–59 months.
Rural Uttar Pradesh, India.
Children (n 18 456) for whom both WHZ (n 18 463) and MUAC were available.
The diagnostic test accuracy of MUAC for severe wasting was excellent (area under receiver-operating characteristic curve = 0·933). Across the lower range of MUAC cut-offs (110–120 mm), specificity was excellent (99·1–99·9 %) but sensitivity was poor (13·4–37·2 %); with higher cut-offs (140–150 mm), sensitivity increased substantially (94·9–98·8 %) but at the expense of specificity (37·6–71·9 %). The optimal MUAC cut-off to detect severe wasting was 135 mm. Although the prevalence of severe wasting was constant at 2·2 %, the burden of severe acute malnutrition, defined as either severe wasting or low MUAC, increased from 2·46 to 17·26 % with cut-offs of <115 and <135 mm, respectively. An MUAC cut-off <115 mm preferentially selected children aged ≤12 months (OR=11·8; 95 % CI 8·4, 16·6) or ≤24 months (OR=23·4; 95 % CI 12·7, 43·4) and girls (OR=2·2; 95 % CI 1·6, 3·2).
Based on important considerations for screening and case detection in the community, modification of the current WHO definition of severe acute malnutrition may not be warranted, especially in the Indian context.
Arterial switch operation has become the standard of care for d-transposition of great arteries and has excellent short- and long-term outcomes. We report the case of a newborn with a diagnosis of d-transposition of great arteries with intact ventricular septum and a low-risk coronary artery anatomy who developed coronary artery vasospasm while coming off bypass following arterial switch operation in the operating room. The coronary artery spasm led to severe biventricular dysfunction and need for extracorporeal membranous oxygenation support. Despite extracorporeal membranous oxygenation and inotropic support, there was no improvement in the left ventricular function, and cardiac transplantation was performed after 8 days. The explanted heart showed extensive infarction of both ventricles. Both the coronary ostei were patent with no evidence of thrombus, suggesting coronary artery vasospasm rather than embolus or thrombus formation. This is the first case of coronary artery vasospasm in a neonate with d-transposition of great arteries leading to cardiac transplantation. We speculate that early identification of patients who are at a high risk for coronary vasospasm and prophylactic or timely infusion of papaverine directly into the coronary arteries may be beneficial in this condition.
This study analysed the association between menopause, menarche and number of live births using cross-sectional primary data for 75 post-menopausal rural women from Shimla in the Indian state of Himachal Pradesh. The mean/median ages at menarche of the 75 women were 14.23/14 years, and those at menopause 45.35/45 years. There were no significant differences in these values between women in the age groups 40–55 and 56–65 years. Age at menopause was found to be significantly associated with age at menarche and maternal age at birth of the first and last child, but not with menopausal symptom severity score. The majority of the 75 post-menopausal women (70.7%) had very mild or no menopausal symptoms. Three principal components were identified that explained 72.43% of the underlying variation in menopausal symptoms.