Speeding up beta-blockade prior to coronary CT angiography: can we predict the dose of intravenous metoprolol required to achieve target heart rate in a given patient?

AIM: To evaluate the use and safety of intravenous (IV) metoprolol in a cohort of patients undergoing coronary computed tomographic angiography (CCTA) at a university hospital, and in particular, to establish if the minimum dose required to achieve the target heart rate (HR) in a given patient can be predicted from the baseline HR. MATERIALS AND METHODS: Patients undergoing CCTA at a tertiary centre between January 2015 and May 2018, with baseline HR ≥60 bpm requiring IV metoprolol, were identified retrospectively from the database. Patients with a contraindication to beta-blockade or an indication for CCTA other than coronary disease were excluded. HR at baseline and at the time of scanning were recorded, together with the total dose of IV metoprolol administered. RESULTS: Of 625 patients identified, 330 (52.8%) achieved HR ≤60 with IV metoprolol. Patients who achieved target HR had lower baseline HR. They received a lower radiation exposure due to tight prospective gating and a lower tube voltage. The lower quartile dose of metoprolol administered was 5 mg for patients with baseline HR <65 beats per minute (bpm), but 10 mg for HR 65-74 bpm, and ≥20 mg for higher HRs. There were no cases of symptomatic bradycardia/hypotension. CONCLUSION: Patients with a resting HR of ≥60 bpm can reasonably be given an initial minimum dose of 5-20 mg metoprolol IV before CCTA, with additional doses as required.

Stereoselective synthesis of dispiro heterocycles by [3 + 2] cycloaddition of azomethine ylides with a thiazolo[3,2-a]indole derivative.

A green one pot three component [3 + 2] cycloaddition of a thiazolo[3,2-a]indole derivative (generated by the reaction of thieno[2,3-b]indole-2,3-dione and dimethyl acetylenedicarboxylate) with isatin derived azomethine ylides is reported here. An eco-friendly acetyl choline iodide-ethylene glycol (ACI/EG)-mediated deep eutectic solvent system was adopted for the reaction. Spiropyrrolidine oxindoles incorporating multiple stereocenters were obtained in a highly diastereoselective manner in excellent yields.

Maximizing the clinical benefit of high-pitch, single-heartbeat CT coronary angiography in clinical practice.

AIM: To prospectively analyse the occurrence of right coronary artery (RCA) artefact and assess its relationship with patient heart rate (HR) and HR variability (HRV) in order to determine the most appropriate parameters for high-pitch cardiovascular computed tomography (CT) acquisition, minimize the likelihood of artefact, and maximize the clinical benefit in consecutive clinical high-pitch CT coronary angiography (CA) examinations. MATERIALS AND METHODS: One hundred and seventy-three patients undergoing high-pitch CTCA were prospectively assessed for the presence of RCA artefact. Median and maximum HR and the difference in predicted and actual acquisition HR (HR difference, HRD) were correlated from the electrocardiograms recorded at the time of acquisition. RESULTS: Sixty-six percent of the cohort was male, with a median age of 54 (range 16-84 years). There were 53 cases of RCA artefact (30.6%); 26 (49.1%) of these required further imaging to fully delineate the RCA. Of the 53 cases with artefact, 81.1% affected the distal RCA and 18.9% were more proximal. Gender was not associated with an increased likelihood of the artefact (p = 0.14). RCA artefact decreased by 2% with each year of increasing age (p = 0.04). When compared with a reference HR of >70 beats/min, univariate analysis demonstrated RCA artefact significantly increased with both increasing median and maximum HR, whilst the incidence of RCA artefact increased for all HRD >1, with a greater likelihood of artefact with increasing HRD. CONCLUSION: The present results highlight the importance of optimizing patient HR in order to reduce the likelihood of RCA artefact. In addition to aggressive HR control to a median HR of ≤60 beats/min, the present results suggest limiting high-pitch acquisition to patients with HR variability of <3 beats/min. Therefore, use of beta-blockers is of crucial importance to both reduce HR and HR variability to optimize use of high-pitch single-heartbeat CTCA.

Point-of-care utrasound use over six-month training period in Rwandan district hospitals

Introduction: Point-of-care ultrasound (POCUS) is an effective diagnostic technology in resource-limited settings. There is increasing interest in introducing ultrasound training in such environments, but few reports describing long-term follow-up and impact of a POCUS program in a resource-limited setting. We introduced a POCUS program in Rwanda, and sought to determine the number and type of ultrasounds performed, the impact of a remote quality assurance (QA) program, and the effect of POCUS on patient management. Methods: Seventeen Rwandan physicians underwent a ten-day training course in POCUS in Kigali, Rwanda. Post-course, participants tracked the ultrasounds they performed using a cloud-based storage system, recorded clinical impressions,and received periodic QA with on-site proctoring over a six-month follow-up. Remote QA to evaluate image quality was performed by five emergency ultrasound fellowshiptrained clinicians. Images were graded on a scale of 0­4. (0=no meaningful image, 2= adequate, 4= outstanding). Trainees also documented how POCUS changed clinical management. Results: Over six months, 1158 ultrasounds were performed and logged by fifteen participants at eleven regional hospitals. 590(50.9%) had matched images and interpretations available for review. Abdominal ultrasound was the most frequently performed application (19.7%), followed by liver (14.6%), obstetrics (14.5%), renal (12.4%),and spleen (11%). Across all applications, the mean score was 2.5 (SD± 0.11, 95% confidence interval, 2.39­2.54). Ultrasound result in a management change in 84% of cases. Major changes in management related to medication choice (42.4%), admission (30%), transfer to a higher level of care (28.1%), and performance of procedures (23.3%). Conclusions: During this six-month training program in Rwanda, participants used POCUS for a range of applications. The remote QA process captured 51% of ultrasounds performed. Of scans with QA, the average score was adequate to good. POCUS routinely changed clinical management. This study demonstrates the impact of POCUS in a resource-limited setting

Skin prick testing and peanut-specific IgE can predict peanut challenge outcomes in preschoolchildren with peanut sensitization.

BACKGROUND: The rise in peanut allergy is a source of considerable burden in the community. A growing number of preschoolchildren have been identified as peanut sensitized in the course of investigation of other allergic conditions. Although many have never knowingly ingested peanuts and their clinical reactivity is not known, it has been common practice to place these children on avoidance diets for many years. OBJECTIVE: To determine the utility of skin prick tests (SPT) and fluorescent-enzyme immunoassays (FEIA) for identifying either peanut allergy or tolerance in preschoolchildren with peanut sensitization. METHODS: Forty-nine preschoolchildren (<5 years of age) with peanut sensitization (SPT ≥ 2 mm or peanut-specific IgE ≥ 0.35 kU/L) but unknown clinical reactivity had graded open peanut challenges reaching a total of 11 g. A positive challenge was defined as an objective IgE-mediated reaction during challenge or the 2-h observation. RESULTS: Forty-nine percent (24/49) of children had positive challenges. An SPT of >7 mm on the day of challenge predicted a positive challenge with a sensitivity of 83% and a negative predictive value (NPV) of 84%. An FEIA of >2.0 kU/L showed a sensitivity of 79% and an NPV of 80%. Predicting challenge outcome from a combination of SPT and FEIA (SPT >7 and/or FEIA >2 is positive) increased sensitivity to 96% and NPV to 95%. CONCLUSION AND CLINICAL RELEVANCE: At least half of preschoolchildren with peanut sensitization and no antecedent history of peanut ingestion can tolerate peanuts. A SPT<7 mm and FEIA<2 kU/L identify children most likely to tolerate peanut, with only a 5% likelihood of failing an oral challenge. This study assists clinicians considering challenges in very young peanut-sensitized children.

Derivation and validation of a sensitive IMA cutpoint to predict cardiac events in patients with chest pain.

OBJECTIVES: In patients with acute chest pain, we derived a cutpoint for ischaemia-modified albumin (IMA) and prospectively validated this cutpoint to predict 30-day major adverse cardiac events (MACEs). METHODS: We prospectively recruited a derivation cohort (18-month period) to establish a serum IMA cutpoint targeting 80% sensitivity. This was followed by a prospective validation cohort study of emergency department patients with acute chest pain at two university hospitals over a 3-month period. A MACE was defined as myocardial infarction, revascularisation or death at 30-day follow-up. RESULTS: In the derivation cohort of 151 patients, the IMA cutpoint that achieved 80% sensitivity for MACEs was 75 KU/litre. The sensitivity was prospectively validated in 171 patients consecutively enrolled, of whom 106 underwent multiple-biomarker analysis (19.8% MACE rate, 81% sensitivity of IMA). Furthermore, IMA by itself (81%, p<0.01) and in combination with initial highly sensitive cardiac troponin T (hsTnT) (90%, p<0.001) had significantly higher sensitivity than initial hsTnT (29%) for prediction of MACEs. CONCLUSIONS: We prospectively validated the sensitive IMA cutpoint of 75 KU/litre with 80% sensitivity for MACEs in patients with acute chest pain. Our data suggest that IMA alone and in combination with initial hsTnT are more sensitive than the initial hsTnT for MACEs.

Masticatory stress, orbital orientation and the evolution of the primate postorbital bar.

A postorbital bar is one of a suite of derived features which distinguishes basal primates from their putative sister taxon, plesiadapiforms. Two hypotheses have been put forward to explain postorbital bar development and variation in circumorbital form: the facial torsion model and visual predation hypothesis. To test the facial torsion model, we employ strain data on circumorbital and mandibular loading patterns in representative primates with a postorbital bar and masticatory apparatus similar to basal primates. To examine the visual predation hypothesis, we employ metric data on orbit orientation in Paleocene and Eocene primates, as well as several clades of visual predators and foragers that vary interspecifically in postorbital bar formation.A comparison of galago circumorbital and mandibular peak strains during powerful mastication demonstrates that circumorbital strains are quite low. This indicates that, as in anthropoids, the strepsirhine circumorbital region is excessively overbuilt for countering routine masticatory loads. The fact that circumorbital peak-strain levels are uniformly low in both primate suborders undermines any model which posits that masticatory stresses are determinants of circumorbital form, function and evolution. This is interpreted to mean that sufficient cortical bone must exist to prevent structural failure due to non-masticatory traumatic forces. Preliminary data also indicate that the difference between circumorbital and mandibular strains is greater in larger taxa.Comparative analyses of several extant analogs suggest that the postorbital bar apparently provides rigidity to the lateral orbital margins to ensure a high level of visual acuity during chewing and biting. The origin of the primate postorbital bar is linked to changes in orbital convergence and frontation at smaller sizes due to nocturnal visual predation and increased encephalization. By incorporating in vivo and fossil data, we reformulate the visual predation hypothesis of primate origins and thus offer new insights into major adaptive transformations in the primate skull.

Preemptive epidural analgesia and recovery from radical prostatectomy: a randomized controlled trial.

CONTEXT: Preemptive analgesia can decrease the sensitization of the central nervous system that would ordinarily amplify subsequent nociceptive input, but a clear demonstration of its clinical efficacy is necessary for it to become a routine component of acute pain therapy. OBJECTIVE: To determine the impact of preemptive epidural analgesia on postoperative pain and other clinically important outcome variables after radical retropubic prostatectomy. DESIGN AND SETTING: A block randomized double-blind clinical trial lasting 20 months at a single academic medical center. PATIENTS: A total of 100 generally healthy and neurologically intact patients scheduled for radical retropubic prostatectomy for the treatment of prostate cancer in whom an epidural catheter for treating postoperative pain was to be placed prior to the induction of general anesthesia. INTERVENTIONS: Epidural bupivacaine, epidural fentanyl, or no epidural drug was administered prior to induction of anesthesia and throughout the entire operation, followed by aggressive postoperative epidural analgesia for all patients. MAIN OUTCOME MEASURES: Daily pain scores during hospitalization and pain scores obtained 3.5, 5.5, and 9.5 weeks after hospital discharge. RESULTS: The patients who received epidural fentanyl or bupivacaine prior to surgical incision (preemptive analgesia) experienced 33% less pain while hospitalized (P=.007). Pain scores in those receiving preemptive analgesia were significantly lower at 9.5 weeks (P=.02), but were not significantly different at 3.5 or 5.5 weeks. At 9.5 weeks, 32 (86%) of 37 patients receiving preemptive analgesia were pain-free compared with 9 (47%) of 19 control patients (P=.004). Patients receiving preemptive analgesia were more active 3.5 weeks after surgery (P=.01), but not at 5.5 or 9.5 weeks. CONCLUSIONS: Even in the presence of aggressive postoperative pain management, preemptive epidural analgesia significantly decreases postoperative pain during hospitalization and long after discharge, and is associated with increased activity levels after discharge.

Respiratory status and allergy nine to 10 years after acute bronchiolitis.

In order to evaluate further the relationship between acute bronchiolitis in infancy and subsequent respiratory problems, children prospectively followed up from the time of their admission to hospital were reviewed along with a group of matched controls recruited at the previous five and a half year assessment. Sixty one index children and 47 controls took part. The groups were well matched for age, height, parental smoking, and social class. Although the prevalence of respiratory symptoms had fallen when related to the previous review, there remained an excess of coughing (48 and 17% in index and control children respectively; odds ratio 4.02) and wheezing (34 and 13% in index and control children respectively; odds ratio 3.59). Bronchodilator therapy was used by 33% of index children compared with 3% of controls. Lung function tests revealed no significant differences in the measurements of lung growth-for example, forced vital capacity, functional residual capacity, and total lung capacity-but the index children had significant reductions in measurements of airways obstruction-for example, forced expiratory volume in one second, maximum expiratory flow at 75, 50 and 25% of vital capacity, and airways resistance. Family history and personal skin tests showed no excess of atopy in the index group. This study supports the claim that the excess respiratory symptoms after acute bronchiolitis are not due to familial or personal susceptibility to atopy.

Inhaled budesonide for chronic wheezing under 18 months of age.

The role of budesonide in controlling chest symptoms in infants was assessed. It was administered from a metered dose inhaler into a large volume spacer (Nebuhaler) with attached Laerdal mask. Twenty nine infants were recruited into a double blind crossover trial. Five defaulted. The remaining 24 (mean age 11 months) were assessed for the tolerance of the device, adverse effects, treatment failures, parental opinion, and daily symptom and treatment records. Twenty tolerated the modified Nebuhaler. One developed meningitis on placebo. Two experienced exacerbations on placebo. Eleven of 18 parents whose children completed the maximum treatment preferred budesonide to placebo and one preferred placebo. Mean symptom scores on budesonide were better than on placebo for the 15 children with complete symptom records. Fewer bronchodilator doses were used while taking budesonide. Our findings indicate that budesonide given in this way is an effective treatment for infants who may need prophylaxis for their wheezing.

The effect of menses and use of catamenial products on cervical carriage of Staphylococcus aureus.

Cervical specimens for culturing for Staphylococcus aureus were obtained during menstruation and at midcycle from 40 users of tampons and twelve users of pads. Nine women (two users of pads and seven users of tampons) were colonized by S. aureus. Colonization rates of the cervix were similar for users of tampons and users of pads (18% and 17%, respectively). S. aureus was isolated more frequently during menstruation (17%) than at midcycle (5.8%). Six women had positive menstrual cultures without a positive midcycle culture, whereas no women had positive midcycle cultures and negative menstrual cultures. These observations indicate a significant (p less than 0.05) association of menses with staphylococcal colonization of the cervix.

Bacterial flora of the vagina during the menstrual cycle: findings in users of tampons, napkins, and sea sponges.

The recent association of menstruation, tampon use, and staphylococcal infection with toxic shock syndrome led us to study the association of menstruation and catamenial product use with changes in vaginal flora. Cultures of the cervical os were obtained in midcycle and during menstruation from 12 women who used napkins and 40 women who used tampons. Staphylococcus aureus was found during midcycle and menstruation in three women, during menstruation alone in six, and during midcycle alone in none, indicating a significant association of S. aureus with menstruation (p = 0.04). No difference was found in the rate of S. aureus colonization during menstruation in tampon users (18%) and napkin users (17%). In a similar study, cultures were taken for S. aureus and other aerobic bacteria from 58 tampon users and 25 users of sea sponges. Staphylococcal colonization was found to be increased during menstruation in both groups. Among the cultures done during menstruation, those from users of sea sponges were found to have significantly higher colonization rates with S. aureus, Escherichia coli and other Enterobacteriaceae. The association of sea sponges with a high rate of S. aureus colonization suggests that they are not an alternative to tampons for women seeking to decrease the risk of toxic shock syndrome.

Risk factors for staphylococcal toxic-shock syndrome.

Fifty-two cases of toxic-shock syndrome that occurred in January 1, 1976 through August 31, 1980, were reported to the Utah State Health Department between February 1 and August 31, 1980. The annual attack rate for Utah based on a six-month surveillance period was 14.4 per 100,000 women ages 12-49 years. All cases were in women who had onset of illness within two days of menses. Potential risk factors were investigated with a case-control study utilizing 29 women hospitalized with toxic-shock syndrome and 91 neighborhood female controls. Nine of the 29 (31%) women reported recurrences of similar illness. Use of tampons (p = 0.012) and use of a single brand of tampon-Rely-during the month of illness (p less than 0.005, RR =6.11) were associated with a significantly increased risk of acquiring toxic-shock syndrome. More controls were sexually active than women who had toxic-shock syndrome (p less than 0.05, RR - 0.277). This epidemiologic investigation of toxic-shock syndrome in menstrual-age women has identified tampons generally and a single brand specifically as significant risk factors in acquiring toxic-shock syndrome.

Transient pseudoleukocytosis caused by cryocrystalglobulinemia.

A patient with Sjögren's syndrome and cryoglobulinemia was found to have pseudoleukocytosis when a leukocyte count was performed on an electronic particle counter. This apparent increase in the leukocyte count was found to be caused by spontaneous crystallization of the cryoglobulin. Further studies showed that this phenomenon was transient. Disappearance of the spontaneous crystal formation without a change in the level of cryoglobulin suggests the possibility of an interaction between the cryoglobulin and a plasma component. Factors affecting spontaneous crystallization of cryoglobulins and the laboratory as well as the clinical implications of pseudoleukocytosis are discussed.