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Objective: To determine variables associated with difficult clinical encounters., Patients and Methods: This was a cross-sectional study of 428 new patients evaluated from 2022 to 2023. Demographic, clinical, social (eg, missed appointments, prior felony conviction, prior pain physicians, medical assistance) and visit-related (eg, visit took longer than expected, difficulty communicating) information was recorded, supplemented by in-person history gathered by the trainee and attending whose demographic data were also recorded. Physicians independently rated the "difficulty" of the encounter on a 6-point Likert scale from 1 = very easy/pleasant, 2 = easy/pleasant, 3 = neutral/average, 4 = difficult, 5 = very difficult, to 6 = extremely difficult. A difficult encounter was a combined trainee and attending rating of one IQR above the median of 2.0±1.75., Results: Among 428 participants, mean ± SD age was 54.2±15.8 years and 261 (61.0%) were female. Attending gender, gender concordance, race and racial concordance, and years of physician experience were not associated with difficulty. In multivariable analysis, requesting opioids (P=.001), lengthier than expected visit (P<.001), hostile/demanding behavior (P=.003), refusal to try recommended treatment (P=.002), unrealistic expectations (P<0.001), and difficulty communicating (P=.02) were associated with difficult encounters., Conclusion: Most variables associated with physician impressions of difficult encounters were visit-related, suggesting some patient-related factors (eg, prior substance abuse, translator requirement) may be less relevant in pain patients. Future research should evaluate interventions designed to decrease the difficulty of encounters and determine their effect on patients and physicians., (Published by Elsevier Inc.)

Introduction: With increasing globalization and diversity, the intersection of immigration and language barriers can impact patient outcomes. This scope review aims to summarize current evidence on immigration and language barriers on pediatric surgical outcomes., Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Four databases were searched with Medical Subject Heading terms describing pediatric surgery, immigration, limited English proficiency (LEP), and refugees between 2000-2023. Four independent reviewers screened and analyzed texts for final inclusion., Results: Thirty-three studies were included. Ten studies described disease incidence and severity, finding that LEP, immigrant, and refugee patients were more likely to present with severe disease in appendicitis and traumatic injuries. five studies described pain management, finding patients with LEP received fewer pain assessments, waited longer for analgesia, and had more discrepancies in pain scores. Seventeen studies investigated treatment receipt and delay, finding that immigrants and patients with LEP had longer time to and reduced rates of treatment. Seventeen studies described surgical outcomes, finding that patients with LEP have longer length of stay and more postoperative emergency department visits but fewer follow-up appointments. In kidney transplants, patients with LEP and immigrants had worse outcomes, but these trends are not seen in immigrants from Europe. Overall, immigrants and refugees have higher rates of complications and mortality., Conclusions: Immigrants and patients with LEP and are more likely to present with advanced disease and severe injuries, receive inadequate pain management, experience delays in surgery, and suffer more complications. There is continued need to assess the impact of LEP and immigration on pediatric surgery outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Ambulatory Blood Pressure Monitoring (ABPM) is recommended for diagnosis and management of hypertension. We aimed to identify characteristics associated with physician action after receipt of abnormal findings., Methods: This was a retrospective cross-sectional analysis of patients 5-22 years old who underwent 24-h ABPM between 2003-2022, met criteria for masked or ambulatory hypertension, and had a pediatric nephrology clinic visit within 2 weeks of ABPM. "Action" was defined as medication change/initiation, lifestyle or adherence counseling, evaluation ordered, or interpretation with no change. Characteristics of children with/without 1 or more actions were compared using Student t-tests and Chi-square. Regression analyses explored the independent association of patient characteristics with physician action., Results: 115 patients with masked (n = 53) and ambulatory (n = 62) hypertension were included: mean age 13.0 years, 48% female, 38% Black race, 21% with chronic kidney disease, and 25% overweight/obesity. 97 (84%) encounters had a documented physician action. Medication change (52%), evaluation ordered (40%), and prescribed lifestyle change (35%) were the most common actions. Adherence counseling for medication and lifestyle recommendations were documented in 3% of encounters. 24-h, wake SBP load, and sleep DBP load were significantly higher among those with physician action. Patients with > 1 action had greater adiposity, SBP, and dipping. Neither age, obesity, nor kidney disease were independently associated with physician action., Conclusions: While most abnormal ABPMs were acted upon, 16% did not have a documented action. Greater BP load was one of the few characteristics associated with physician action. Of potential actions, adherence counseling was underutilized., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Introduction: The Holter bin method evaluates QT interval changes in the presence of heart rate changes without correcting the QT interval. However, the method does not allow time-matched comparisons, thus contradicting available guidance and good practice. We report a modification of the methods that allows time-matched comparisons without any heart rate correction., Methods and Results: The modified Holter bin method (a) finds matching baseline heart rates for each QT reading on treatment and (b) calculates ΔQT values from the QT intervals on baseline and on treatment that match in heart rates. The difference between ΔQT values on active treatment and placebo provides the ΔΔQT value. The method was compared with the individual correction method in the data of the mirabegron thorough QT study in which supratherapeutic doses of this β3-adrenoceptor agonist led to substantial heart rate changes. The modified Holter bin method reproduced closely the results obtained with the individual heart rate correction. At all time points of the mirabegron study, the differences between the mean ΔΔQT values by the Holter bin method and the individual correction method were below 1 millisecond. Compared to the individual correction, the Holter bin method led to slight increases in the standard deviations of ΔΔQT values, but these were on average below 0.25 millisecond., Conclusions: The Holter bin methodology can be modified to make it compatible with the available guidance and with good practice of clinical investigations. The results obtained with the modified Holter bin method are practically the same as with individualized heart rate corrected QT intervals. The close correspondence between the 2 methods demonstrates that the present possibilities of comparing QT interval duration in the presence of experiment-induced heart rate differences are not influenced by methodological artifacts., (© 2014 Wiley Periodicals, Inc.)

Purpose: Intra-ocular cytokine profiles were determined to study the immunological mechanisms of corneal graft opacification due to rejection and/or herpetic stromal keratitis (HSK)., Methods: Sera and aqueous humour (AH) were sampled shortly after the onset of corneal graft opacification, group I (n=18). In eyes with clear grafts, samples were taken 5 months after transplantation, group II (n=59). Samples of non-inflamed eyes, prior to cataract surgery, were used to determine baseline cytokine levels, group III (n=49). Total protein (TP) levels were measured with Bradford reagent and interleukin (IL)-6, IL-10, IL-4 and interferon (IFN)-gamma with ELISAs., Results: All patients who's corneal grafts showed clinical evidence of graft opacification due to rejection and/or HSK were sampled. In the AH-samples of group I, increased levels of TP were found in 60% (9/15), IL-6 in 79% (11/14), IL-10 in 39% (7/18) and IL-4 in none (0/12). IFN-gamma was detected in 19% (3/16), in the case of HSK only. In contrast, samples obtained from patients with clear grafts in group II showed increased levels of TP in 36% (20/55), IL-6 in 14% (8/57) and IL-10, IL-4 or IFN-gamma in none (n=58)., Conclusions: During corneal graft rejection and/or HSV-infection, increased levels of TP and IL-6 in AH confirmed anterior chamber inflammation with breakdown of the blood-aqueous barrier. Based on the data presented, cytokine patterns in the AH do not appear to distinguish corneal opacification due to graft rejection from that due to herpes keratitis.

The sensory neuropeptide, calcitonin gene-related peptide (alpha-CGRP), has been implicated in the pathogenesis of migraine headache. The present study aimed to evaluate the effects of intracarotid infusions of human alpha-CGRP (10, 30 and 100 pmol/kg.min; n = 8), as compared to that of saline (4 times; n = 8) on haemodynamics and blood flow distribution within the carotid circulation of the anaesthetized pig, using the radioactive microsphere method. Furthermore, the effects of antimigraine drugs, dihydroergotamine (100 micrograms/kg i.v.; n = 4) or sumatriptan (300 micrograms/kg i.v.; n = 4), on these parameters were studied in the presence of the infusion of the highest concentration of human alpha-CGRP. Additionally, putative positive inotropic responses to human alpha-CGRP (10(-9)-10(-7) M) were investigated in porcine isolated atrial and ventricular trabeculae. Human alpha-CGRP increased carotid artery blood flow and conductance dose-dependently, together with an enhancement in vascular pulsations. These effects were associated with a fall in systemic blood pressure with concomitant increases in heart rate and cardiac output. The increase in carotid blood flow was reflected by an increase in total capillary blood flow, predominantly to extracerebral tissues including the dura, whereas blood flow through arteriovenous anastomoses remained stable. Both dihydroergotamine and sumatriptan reduced carotid blood flow and its capillary fraction without affecting systemic vascular conductance. In tissues, these drugs reversed blood flow increases due to human alpha-CGRP in most extracerebral tissues, but failed to reduce dural blood flow. In porcine isolated atrial and ventricular trabeculae, noradrenaline (10(-8)-10(-5) M) increased force of contraction in a concentration-dependent manner. In contrast, human alpha-CGRP (10(-9)-10(-7) M) failed to increase force of contraction in atrial trabeculae (n = 6) and exerted only a moderate concentration-dependent positive inotropic effect in ventricular trabeculae (approximately 25% of the response to 10(-5) M noradrenaline, n = 10). These data indicate that human alpha-CGRP caused arteriolar dilatation together with a fall in blood pressure in the pig. The tachycardia may be reflex-mediated, but the peptide also exerts a moderate positive inotropic action on ventricular trabeculae. The fall in systemic arterial blood pressure and the marked increase in capillary blood flow most likely prevented the opening of arteriovenous anastomoses. Furthermore, the antimigraine drugs, dihydroergotamine and sumatriptan, were able to reverse blood flow changes induced by human alpha-CGRP in the porcine carotid circulation.

1. The role of nitric (NO) in the regulation of capillary and arteriovenous anastomotic blood flow was evaluated in the carotid circulation of the pig. For this purpose, the effect of intracarotid (i.c.) infusions of saline and two NO donors, nitroprusside sodium (NPR) and S-nitroso-N-acetylpenicillamine (SNAP) in concentrations of 3-100 micrograms min-1 was studied on systemic haemodynamics and carotid blood flow and its distribution in anaesthetized pigs with low arteriovenous anastomotic blood flow, by use of the radioactive microsphere method. 2. Apart from heart rate, which increased after both NPR and SNAP, no major changes in systemic haemodynamic variables were observed. In contrast to saline, both NPR and SNAP increased common carotid blood flow, vascular conductance and vascular pulsations dose-dependently. 3. The distribution of the carotid artery blood flow over capillary and arteriovenous anastomotic fraction remained stable after saline infusions. Both NPR and SNAP enhanced total capillary blood flow and conductance. In contrast to NPR, arteriovenous anastomotic blood flow and conductance were increased by SNAP. 4. At the tissue level, capillary blood flow increases following NPR or SNAP were reflected by an increase in both extracerebral and dural blood flow without changes in total brain blood flow. 5. These results indicate that both NO donors cause arteriolar dilatation together with enhanced vascular pulsations in the carotid circulation of the pig. Probably by way of a 'steal' phenomenon, this pronounced arteriolar dilatation limits the effect of NO donors on arteriovenous anastomoses. 6. The results of the present investigation support the contention that dilatation of intra- and extra cranial arteries and arteriovenous anastomoses leads to increased vascular pulsations, which (rather than increased blood flow) could, at least in part, be responsible for the headache caused by nitro vasodilators.

1. The role of nitric oxide (NO) biosynthesis in the regulation of blood flow through arteriovenous anastomoses was evaluated in the carotid circulation of the anaesthetized pig. For this purpose, the effect of intracarotid (i.c.) administration of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME: 0.1, 0.3 and 1.0 mg kg-1; n = 6) or saline (n = 6) was studied on the distribution of common carotid blood flow, using the radioactive microsphere method. 2. Apart from the highest dose, L-NAME caused no major changes in the systemic haemodynamic variables. Both cardiac output and systemic vascular conductance were reduced by L-NAME (1 mg kg-1), being reversed partly by L-arginine (100 mg kg-1, i.c.). In both groups, L-arginine slightly reduced mean arterial blood pressure. 3. Total common carotid artery blood flow as well as its distribution over the capillary and arteriovenous anastomotic fraction remained stable after saline injection. In contrast, L-NAME caused a dose-dependent decline in common carotid artery blood flow and conductance and this decline was confined entirely to its arteriovenous anastomotic part. 4. Subsequent intracarotid injection of L-arginine (100 mg kg-1) reversed the reduction in total carotid conductance almost completely and that in the arteriovenous anastomotic region partially. Additionally, L-arginine increased capillary conductance significantly in the L-NAME--as well as the saline-treated animals. 5. These results indicate that the L-arginine-NO pathway contributes little to the regulation of tissue perfusion in the porcine carotid circulation. In contrast, NO seems to play an important role in shunting arterial blood through arteriovenous anastomoses in the anaesthetized pig.

The potential ability of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1 to 10 mg/kg), to modulate blood pressure responses to 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT) and (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) (DOI) was studied in pithed rats. The hypotensive responses to 5-HT in the presence of ketanserin were augmented by L-NAME as well as by phenylephrine infusion, both of which themselves increased blood pressure. L-NAME also tended to prolong the duration of the response of 5-HT. Likewise, the hypotensive responses to 5-CT were potentiated. The magnitude of the hypertensive responses to 5-HT was unaffected by L-NAME or phenylephrine. However, in contrast to phenylephrine, L-NAME prolonged the duration of these responses. The magnitude and duration (middle dose only) of the hypertensive responses to DOI were augmented by L-NAME, but phenylephrine was ineffective. These results suggest that L-NAME increases blood pressure, probably by inhibiting the basal release of NO in animals with a low vascular tone. However, the hypotensive responses to 5-HT and 5-CT seem to be largely independent of NO release by the endothelium, but the hypertensive responses to 5-HT and DOI appear to be limited by the release of NO in the pithed rat.

1. The haemodynamic effects of NG-nitro-L-arginine methylester (L-NAME; 1, 3, 10 and 30 mg kg-1) and its potential ability to attenuate the hypotensive responses to acetylcholine (0.03, 0.1, 1.0 and 3.0 micrograms kg-1) have been investigated in anaesthetized rats and cats. 2. In the rat, L-NAME elicited a dose-dependent pressor effect increasing mean arterial blood pressure from the baseline value of 116 +/- 4 mmHg to a maximum of 156 +/- 6 mmHg with 30 mg kg-1. This increase in blood pressure could be only partly reversed by L-arginine (300 mg kg-1). However, the increase in blood pressure by lower doses (up to 10 mg kg-1) of L-NAME was effectively reversed by L-arginine (1000 mg kg-1). 3. In the cat, L-NAME did not significantly modify systemic haemodynamic variables (heart rate, mean arterial blood pressure, cardiac output, stroke volume or total peripheral resistance), when compared to the changes in saline-treated animals. Administration of L-arginine did not cause any significant effect in cats treated with L-NAME, but some decrease in heart rate and increases in cardiac output and stroke volume were observed in the saline-treated group. 4. With the lowest dose (1 mg kg-1), L-NAME did not affect tissue blood flows in the cat, but higher doses (3 and 30 mg kg-1) significantly reduced blood flows to the mesentery, stomach, spleen, intestines, lungs and the total liver. L-Arginine (300mgkg-1) injected into the control (saline-treated) animals resulted in a significant increase in blood flow to the heart, mesentery, lungs as well as the total liver, particularly its portal fraction. L-Arginine-induced increases in tissue blood flows (mesentery, kidneys, spleen, lungs, total liver and portal blood flow) in saline-treated animals were attenuated in animals treated with L-NAME.5. The acetylcholine-induced peak hypotensive response was not reduced in rats or cats by L-NAME. The duration of acetylcholine response was, however, attenuated in both species by L-NAME. Treatment with L-arginine (10-100mg kg- 1) did not change the acetylcholine-induced hypotension.6. The above results reveal a marked difference between the haemodynamic effects of L-NAME in rats and cats and suggest that in cats, unlike rats, the role of the L-arginine-NO pathway in the regulation of blood pressure is rather limited, although such a pathway may exist in several tissues. Furthermore, the hypotensive response to acetylcholine in both species seems to be mediated largely by NO-independent pathways.