Clinical features associated with ADB-BUTINACA exposure in patients attending emergency departments in England.

OBJECTIVE: Synthetic cannabinoid receptor agonists (SCRA) are commonly encountered new psychoactive substances. Here we report the recent detection of ADB-BUTINACA in samples from patients attending United Kingdom emergency departments with toxicity after suspected drug misuse and describe the associated clinical features. METHODS: Consenting adults (≥16 y) presenting to participating hospitals with toxicity after suspected drug misuse have been included in the Identification Of Novel psychoActive substances (IONA) study since March 2015. Demographic and clinical features are recorded and blood and/or urine samples analysed using high-resolution accurate mass liquid chromatography-mass spectrometry. RESULTS: By December 2021, analytical data were available for 1279 IONA participants and ADB-BUTINACA was detected in at least one sample from 10 (9 males, age range 16-51 median 45 years), all presenting since February 2021. Smoking 'spice' was reported by four patients, two had ingested edible "cannabis" gums and four reported heroin use (2 intravenous, 1 smoked, 1 route not known). Co-use of pregabalin (oral) and crack cocaine (smoked) were also reported. In 3 cases ADB-BUTINACA was the only substance detected, while in seven other substances of misuse were also detected including other SCRA, opioids, benzodiazepines cocaine and pregabalin. Clinical features reported in these 2 groups respectively included reduced level of consciousness (3/3, 6/7), agitation (0/3, 4/7), tachycardia (0/3, 3/7), seizures (1/3, 1/7), hallucinations (1/3, 1/7), hypotension (1/3, 1/7). Metabolic acidosis (1/3, 0/7) and respiratory acidosis (1/3, 0/7), All 10 patients recovered with supportive care, including intubation and ventilation for one case. The median length of hospital stay was 19 h (range 2.6-131 h). CONCLUSIONS: ADB-BUTINACA has recently emerged as a drug of misuse in England. Clinical features of toxicity are consistent with those of other SCRA and include reduced level of consciousness, respiratory and/or metabolic acidosis, seizures, confusion and hallucinations.

A prospective multicentre observational study of adverse iatrogenic events and substandard care preceding intensive care unit admission (PREVENT).

We examined the current incidence, type, severity and preventability of iatrogenic events associated with intensive care unit admission in five hospitals in England. All unplanned adult admissions to intensive care units were prospectively reviewed over a continuous six-week period. In the week before admission, 76/280 patients (27%) experienced 104 iatrogenic events. The majority of iatrogenic events were categorised as medical (37%), drug (17%) or nursing events (17%). Seventy-seven per cent of the events were considered preventable and 80% caused or contributed to admission. Eleven events were thought to have contributed to a patient's death. The mean (SD) age of patients who had an event was greater (63 (21) years) than those who had not (57 (19) years, p = 0.023), and they had a longer median (IQR [range]) intensive care stay, 4 (1-8 [0-29]) days vs 3 (1-5 [0-20]) days, respectively, p = 0.043.

Overlooking the abdominal X-ray --the peril of ascariasis.

A young child presented with intermittent bowel obstruction. The abdominal X-ray was not closely examined, and a contrast study was performed that demonstrated multiple tubular filling defects indicative of worms. The patient was treated accordingly. Reviewing the abdominal X-ray demonstrated numerous serpigenous, tubular, soft-tissue densities in gas-filled bowel loops.

Effects of storage at -20 degrees C on ischaemia-modified albumin results.

BACKGROUND: Ischaemia-modified albumin (IMA) is being studied as a new marker for reversible ischaemia in patients presenting with possible cardiac chest pain. The conditions under which samples are stored prior to analysis may be critical in influencing the analytical result and hence the cut-off used in any particular study. METHODS: Sixty-eight samples taken during a study assessing the performance of IMA for risk stratification in patients presenting with possible cardiac chest pain were analysed both within 2.5 h of collection and after periods of storage at -20 degrees C. RESULTS: Samples stored at -20 degrees C yielded IMA values on average 3 units higher than those analysed within 2.5 h (mean 90.5 vs. 87.5; P < 0.00001). A Bland-Altman plot showed that the difference was not concentration dependent. CONCLUSIONS: These results indicate that decision cut-offs will be influenced by conditions of sample storage prior to IMA analysis, and that these should be stated in detail for each study.

The PRIMA study: presentation ischaemia-modified albumin in the emergency department.

OBJECTIVES: To investigate the diagnostic accuracy of presentation ischaemia-modified albumin (IMA), in addition to cardiac troponin I (TnI), as a strategy to rapidly ascribe low risk to patients with chest pain attending an emergency department, and to determine whether IMA has the potential to reduce transit time in emergency departments. METHODS: A prospective observational study was carried out in two emergency departments (belonging to the John Radcliffe Hospital, Oxford, UK; and the Frenchay Hospital, Bristol, UK) of similar size. Consecutive adult patients presenting with features of possible ischaemic cardiac chest pain and a normal electrocardiogram were eligible. The index test (measurement of IMA and TnI at presentation) and reference standard (delayed TnI measurement, taken at least 8 h after pain onset) were applied to all recruited patients. All clinicians were blinded to the results of the index test. Assays were carried out in a single laboratory using standard techniques. RESULTS: 399 patients were recruited; 277 patients had a result for both the index test and reference standard. The sensitivity was 97.6% (95% confidence interval (CI) 87.4 to 99.9), negative predictive value 97% (95% CI 84.2 to 99.9) and specificity 13.6% (95% CI 9.5 to 18.7). Sensitivity analysis showed similar findings in three alternative scenarios. Receiver operating characteristic analysis indicated that a different "cut-off" value for IMA would not improve the properties of the test. The median potential time saved (n = 268) was 6 h and 10 min. CONCLUSION: The diagnostic accuracy of presentation IMA in this study does not support its use as an effective risk stratification tool for patients with chest pain in the emergency department. The sensitivity is insufficiently high, with a small number of false negatives undermining the safety of the test. Frequent false positives produce a low specificity that limits the practical value of the test.

Home nocturnal hemodialysis in children.

OBJECTIVE: To describe the effect of home nocturnal hemodialysis (NHD) in North American children. STUDY DESIGN: Four teenagers underwent NHD for 8 hours, 6 to 7 nights/week, using either central venous lines or fistulae for periods of 6 to 12 months. Blood flow approximated 200 mL/min, and dialysate flow was 300 mL/min; the dialysate contained potassium and phosphate. The procedure was remotely monitored. RESULTS: The children had unrestricted diets and fluid allowance and did not require phosphate binders. Persistent relative hypotension developed in 2 of 4 children. Weekly Kt/V urea values were consistently >10; other biochemical measures varied. Quality of life and school attendance improved in 3 of 4 children. The workload and reported emotional burden of NHD was substantial. No significant complications occurred. Dialysate losses of calcium, phosphate and carnitine required supplementation. The annual cost per patient was dollar 64,000 Canadian, which represented a 27% savings compared with thrice weekly in-center hemodialysis. CONCLUSIONS: NHD is feasible in selected children, allows free dietary and fluid intake, and improves patient wellbeing. The burden on the family is substantial, and NHD requires support of a dedicated multidisciplinary team.

Electrocardiographic features of Wolff-Parkinson-White syndrome.

Wolff-Parkinson-White syndrome is not uncommon in the emergency department. Its early recognition and initial treatment allows rapid restoration to sinus rhythm. Prompt referral to cardiology is essential for risk stratification through electrophysiological studies.

The postsynaptic spectrin/4.1 membrane protein "accumulation machine".

An important aspect of the function of the membrane-associated cytoskeleton has been suggested to be to trap and retain selected transmembrane proteins at points on the cell surface specified by cell adhesion molecules. In the process, cell adhesion molecules are cross-linked to each other, and so junctional complexes are strengthened. In this short review, we will discuss recent advances in understanding the role of this "accumulation machine" in postsynaptic structures. Function in the brain depends on correct ordering of synaptic intercellular junctions, and in particular the recruitment of receptors and other apparatus of the signalling system to postsynaptic membranes. Spectrin has long been known to be a component of postsynaptic densities, and recent advances in molecular cloning indicate that beta spectrins at PSDs are all "long" C-terminal isoforms characterised by pleckstrin homology domains. Isoforms of protein 4.1 are also present at synapses. All four 4.1 proteins are represented in PSD preparations, but it is 4.1R that is most enriched in PSDs. 4.1R binds to several proteins enriched in PSDs, including the characteristic PSD intermediate filament, alpha-internexin. Both 4.1 and spectrin interact with ionotropic glutamate receptors (AMPA and NMDA receptors, respectively): 4.1 stabilises AMPA receptors on the cell surface. By linking these receptors to the cytoskeletal and cell adhesion molecules that specify glutamatergic synapses, the membrane protein accumulation machine is suggested to direct the formation of postsynaptic signalling complexes.

Mid-thoracic tenderness: a comparison of pressure pain threshold between spinal regions, in asymptomatic subjects.

Palpation for tenderness forms an important part of the manual therapy assessment for musculoskeletal dysfunction. In conjunction with other testing procedures it assists in establishing the clinical diagnosis. Tenderness in the thoracic spine has been reported in the literature as a clinical feature in musculoskeletal conditions where pain and dysfunction are located primarily in the upper quadrant. This study aimed to establish whether pressure pain thresholds (PPTs) of the mid-thoracic region of asymptomatic subjects were naturally lower than those of the cervical and lumbar areas. A within-subject study design was used to examine PPT at four spinal levels C6, T4, T6, and L4 in 50 asymptomatic volunteers. Results showed significant (P<0.001) regional differences. PPT values increased in a caudal direction. The cervical region had the lowest PPT scores, that is was the most tender. Values increased in the thoracic region and were highest in the lumbar region. This study contributes to the normative data on spinal PPT values and demonstrates that mid-thoracic tenderness relative to the cervical spine is not a normal finding in asymptomatic subjects.

Protein 4.1 in forebrain postsynaptic density preparations: enrichment of 4.1 gene products and detection of 4.1R binding proteins.

4.1 Proteins are a family of multifunctional cytoskeletal components (4.1R, 4.1G, 4.1N and 4.1B) derived from four related genes, each of which is expressed in the nervous system. Using subcellular fractionation, we have investigated the possibility that 4.1 proteins are components of forebrain postsynaptic densities, cellular compartments enriched in spectrin and actin, whose interaction is regulated by 4.1R. Antibodies to each of 4.1R, 4.1G, 4.1N and 4.1B recognize polypeptides in postsynaptic density preparations. Of these, an 80-kDa 4.1R polypeptide is enriched 11-fold in postsynaptic density preparations relative to brain homogenate. Polypeptides of 150 and 125 kDa represent 4.1B; of these, only the 125 kDa species is enriched (threefold). Antibodies to 4.1N recognize polypeptides of approximately 115, 100, 90 and 65 kDa, each enriched in postsynaptic density preparations relative to brain homogenate. Minor 225 and 200 kDa polypeptides are recognized selectively by specific anti-4.1G antibodies; the 200 kDa species is enriched 2.5-fold. These data indicate that specific isoforms of all four 4.1 proteins are components of postsynaptic densities. Blot overlay analyses indicate that, in addition to spectrin and actin, postsynaptic density polypeptides of 140, 115, 72 and 66 kDa are likely to be 4.1R-interactive. Of these, 72 kDa and 66 kDa polypeptides were identified as neurofilament L and alpha-internexin, respectively. A complex containing 80 kDa 4.1R, alpha-internexin and neurofilament L was immunoprecipitated with anti-4.1R antibodies from brain extract. We conclude that 4.1R interacts with the characteristic intermediate filament proteins of postsynaptic densities, and that the 4.1 proteins have the potential to mediate the interactions of diverse components of postsynaptic densities.

Rule compliance and peer sociability: a study of family process, school-focused parent-child interactions, and children's classroom behavior.

This study examined the associations among family processes (cohesion, control, and conflict), school-focused parent-child interactions (support and pressure about achievement), and the child's own characteristics (assertiveness, frustration tolerance, intellectual effectiveness, and self-esteem) as correlates of rule compliance and peer sociability in the classroom. The sample consisted of 161 Grade 4 and 151 Grade 7 children. Family processes and parent-child interactions about school issues were associated with children's personal characteristics, which, in turn, predicted children's rule compliance and peer sociability. Some differences were found between the 4th- and 7th-grade samples; however, many variables consistently predicted the same outcomes across grades.

Mechanism of action and the substrate-dependent pH maximum shift of the alpha-amylase of Bacillus coagulans.

The alpha-amylase of Bacillus coagulans is a saccharifying alpha-amylase which hydrolyses the disaccharide maltose [L. Keating, C. Kelly, and W. Fogarty, Biochem. Soc. Trans., 24 (1996) 44S]. The pH maximum for maltose hydrolysis is pH 5.0, differing from the pH maximum for starch hydrolysis which is pH 6.0. Studies using reducing end 14C-labeled maltooligosaccharides revealed a substrate-dependent pH maximum shift; hydrolysis of radiolabeled maltotriose (G3*) was maximal at pH 5.0 while the pH maximum for hydrolysis of radiolabeled maltopentaose (G5*) and maltohexaose (G6*) was pH 6.0. With maltotetraose (G4*) however, the pH maximum was pH 5.0-6.0. In addition, the bond cleavage pattern of G4* was dependent on pH. At pH 5.0, the pH maximum for maltose hydrolysis, the frequency of hydrolysis of the reducing end terminal bond of G4* was maximal. Determination of the pH maximum of the productive binding modes of the cleavage patterns of G3* to G6* illustrated the possible role of the occupation of subsite r + 2 in the pH control mechanism of B. coagulans alpha-amylase.

Improved harness crutch to reduce upper limb effort in swing-through gait.

A novel crutch, the harness crutch, is described which reduces loading on the arms during the swing phase of swing-through gait. The device was fabricated by attaching a modified mountaineering harness by two side straps, to modified axillary crutches. The harness crutch was compared with the saddle crutch, described by Taylor in 1883. The saddle crutch produced pressures in excess of 500 mmHg in the perineal area; no pressures were produced in this area with the harness crutch. Ischial pressures produced by both systems were similar. In six out of eight non-impaired subjects, significantly more force was transmitted to the harness crutch (an average 47% of body weight) than to the saddle crutch (an average 40% of body weight). A comparison of the oxygen cost of swing-through gait was made between the harness crutch and unmodified axillary crutches; with the harness crutch oxygen cost was significantly lower (p < 0.01) and there were no significant differences in speed and stride length.

The generality of individual differences in the estimation of size.

These two studies pursued the notion that there are individual differences of considerable generality in the extent to which individuals estimate the size of objects, including body image and physical objects such as a blank card. In the first study, 79 female undergraduate students estimated the width of their own bodies (head, shoulders, waist, and hips), the waist of a standard "real" person, the bodies of two life-size wooden figures, and three boxes. In the second study, 60 female undergraduate students estimated the width of their bodies, three boxes, and two blank cards. Errors in estimation, computed as the difference between estimate and true value divided by the true value, were obtained from all subjects. Correlations between body-image errors and all other errors in estimation were positive in both studies, except for one correlation of - .02. Factor analyses of the correlations between the error scores in each study indicated a substantial general factor, although some residual common variance remained. Results supported the proposition that individuals differ in a consistent fashion across a wide range of size-estimation situations.

Bioavailability of carbonyl iron: a randomized, double-blind study.

49 female blood donors with iron-deficiency anemia were treated with equal doses of iron either as carbonyl iron or ferrous sulfate in a randomized, double-blind fashion. The prevalence of side-effects was similar in the two groups. Mean values for hemoglobin concentration, mean corpuscular volume, corrected reticulocyte count, platelet count, serum iron, total iron-binding capacity, transferrin saturation or erythrocyte protoporphyrin did not differ significantly between the two groups throughout the study. After 16 weeks of therapy, the mean increase in hemoglobin iron was similar in both groups (p = 0.2). Estimates of net changes in total body iron suggested that the overall bioavailability of carbonyl iron was high, about 70% that of ferrous sulfate.

A study of confidential unit exclusion.

The effectiveness of the confidential unit exclusion (CUE) procedure recommended by the Food and Drug Administration has been questioned by the blood banking community. The purpose of this study was to determine whether donors were informing the blood center correctly regarding the disposition (transfuse or do not transfuse) of their donated blood. A letter explaining the confidential study and requesting permission to send the participant a questionnaire noting his or her self-exclusion choice was mailed to 230 donors who had chosen transfuse and 276 donors who had chosen do not transfuse. After consent was obtained, participants were sent a second packet and asked to indicate whether they had chosen correctly and, if not, to identify reasons for that incorrect choice. A seven-word terminology quiz made up of words from the CUE form was also enclosed. All participants who had chosen transfuse indicated that this was the correct choice. Approximately 50 percent of those who had chosen do not transfuse indicated that this was an incorrect choice; the most common reason was that "I was not paying attention." The most frequently misunderstood term was "confidential." Donors who chose do not transfuse had a significantly higher rate of error on the terminology quiz (p less than 0.01) than did those who chose transfuse.

Second fingerstick: a simple method to increase the blood supply.

Before blood donors are deferred because of a low hemoglobin determination by the copper sulfate procedure, they are routinely retested with a microhematocrit. The copper sulfate test and the microhematocrit usually are performed on blood samples taken from the same finger (or earlobe) puncture. We studied 201 male and female volunteer blood donors who failed the copper sulfate test to determine if more donors would be accepted for donation if blood from a second fingerpuncture, instead of the original fingerstick, was used for the microhematocrit determination. Venous blood samples were obtained to evaluate complete blood count and measures of iron status. The results indicated that the deferral rate was reduced by 46% using a fresh fingerpuncture for the microhematocrit determination. The iron status of the additional donors accepted on the basis of the second puncture was not significantly different from that of the donors accepted by the original fingerstick. We conclude that using a second fresh fingerpuncture for the microhematocrit determination after failing the copper sulfate test decreases the number of hematocrit deferrals and does not compromise the iron status of the additional donors.

Prevention of iron deficiency with carbonyl iron in female blood donors.

The effectiveness of elemental, nontoxic carbonyl iron in replacing iron lost at blood donation was examined. In a randomized double-blind design, 99 women, aged 18 to 40, were given placebo or low-dose carbonyl iron (100 mg orally) at bedtime for 56 days after phlebotomy. Compliance was equivalent for the two regimens. Mild side effects were slightly greater with carbonyl iron. At Day 56, estimated net iron absorption from therapy or diet, or both, was sufficient to replace iron in 85 percent of those receiving carbonyl iron but in only 29 percent of those taking placebo (p less than 0.001). The rates of deferral from repeat donation were 8 percent in the carbonyl iron group and 36 percent in the placebo group (p less than 0.01), and the positive predictive value of routine screening in identifying participants without iron deficiency was 83 versus 13 percent (p less than 0.01). It can be concluded that short-term carbonyl iron supplementation in female blood donors can replace the iron lost at phlebotomy, protect the women against iron deficiency, and enhance their ability to give blood.

Red blood cell mass in autologous and homologous blood units. Implications for risk/benefit assessment of autologous blood crossover and directed blood transfusion.

A prospective analysis of 300 consecutively collected homologous blood (HB) units from a regional blood center and an analysis of 188 consecutively collected autologous blood (AB) units from a community hospital was conducted. Analysis of the red blood cell (RBC) mass content of these blood units revealed that HB contained 13 percent more RBC than AB: 200 +/- 1.1 vs 177.1 +/- 1.1 mL, (m +/- SE), respectively (p less than 0.05). Of 174 AB units eligible for crossover by AABB criteria for RBC mass (greater than or equal to 154 mL), 35 (20%) were below the 95 percent confidence interval range for RBC mass of HB units collected; mean RBC mass of 300 HB units was 12 percent greater than that of 174 AB units (200.1 +/- 1.1 vs 178.9 +/- 0.9 mL, p less than 0.001) and 20 percent greater than that of the 35 AB units outside the 95 percent confidence interval (200.1 +/- 1.1 vs 161.2 +/- 0.5 mL, p less than 0.001). These findings indicate that an evaluation of the issues of AB crossover for HB transfusion should include a risk/benefit analysis of AB units with lower RBC mass. These findings also indicate that the proposed changes in AABB standards regarding directed donation (DD) should consider the reduced benefits of DD units with lower RBC mass in a risk/benefit analysis of this practice, and support retention of homologous donor standards for directed donors.