Nonspecific oral medications versus anti-calcitonin gene-related peptide monoclonal antibodies for migraine: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To compare calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) versus nonspecific oral migraine preventives (NOEPs). BACKGROUND: Insurers mandate step therapy with NOEPs before approving CGRP mAbs. METHODS: Databases were searched for class I or II randomized controlled trials (RCTs) comparing CGRP mAbs or NOEPs versus placebo for migraine prevention in adults. The primary outcome measure was monthly migraine days (MMD) or moderate to severe headache days. RESULTS: Twelve RCTs for CGRP mAbs, 5 RCTs for topiramate, and 3 RCTs for divalproex were included in the meta-analysis. There was high certainty that CGRP mAbs are more effective than placebo, with weighted mean difference (WMD; 95% confidence interval) of -1.64 (-1.99 to -1.28) MMD, which is compatible with small effect size (Cohen's d -0.25 [-0.34 to -0.16]). Certainty of evidence that topiramate or divalproex is more effective than placebo was very low and low, respectively (WMD -1.45 [-1.52 to -1.38] and -1.65 [-2.30 to -1.00], respectively; Cohen's d -1.25 [-2.47 to -0.03] and -0.48 [-0.67 to -0.29], respectively). Trial sequential analysis showed that information size was adequate and that CGRP mAbs had clear benefit versus placebo. Network meta-analysis showed no statistically significant difference between CGRP mAbs and topiramate (WMD -0.19 [-0.56 to 0.17]) or divalproex (0.01 [-0.73 to 0.75]). No significant difference was seen between topiramate or divalproex (0.21 [-0.45 to 0.86]). CONCLUSIONS: There is high certainty that CGRP mAbs are more effective than placebo, but the effect size is small. When feasible, CGRP mAbs may be prescribed as first-line preventives; topiramate or divalproex could be as effective but are less well tolerated. The findings of this study support the recently published 2024 position of the American Headache Society on the use of CGRP mAbs as the first-line treatment.

Effect of convalescent plasma transfusion on outcomes of coronavirus disease 2019: a meta-analysis with trial sequential analysis.

The aim of this review was to update evidence for benefit of convalescent plasma transfusion (CPT) in patients with coronavirus disease 2019 (COVID-19). Databases were searched for randomized controlled trials (RCT) comparing CPT plus standard treatment versus standard treatment only in adults with COVID-19. Primary outcome measures were mortality and need for invasive mechanical ventilation (IMV). Twenty-Six RCT involving 19,816 patients were included in meta-analysis for mortality. Quantitative synthesis showed no statistically significant benefit of adding CPT to standard treatment (RR = 0.97, 95% CI = 0.92 to 1.02) with unimportant heterogeneity (Q(25) = 26.48, p = .38, I2 = 0.00%). Trim-and-fill-adjusted effect size was unimportantly changed and level of evidence was graded as high. Trial sequential analysis (TSA) indicated information size was adequate and CPT was futile. Seventeen trials involving 16,083 patients were included in meta-analysis for need of IMV. There was no statistically significant effect of CPT (RR = 1.02, 95% CI = 0.95 to 1.10) with unimportant heterogeneity (Q(16) = 9.43, p = .89, I2 = 3.30%). Trim-and-fill-adjusted effect size was trivially changed and level of evidence was graded as high. TSA showed information size was adequate and indicated futility of CPT. It is concluded with high level of certainty that CPT added to standard treatment of COVID-19 is not associated with reduced mortality or need of IMV compared with standard treatment alone. In view of these findings, further trials on efficacy of CPT in COVID-19 patients are probably not needed.

Percutaneous Interventional Strategies for Migraine Prevention: A Systematic Review and Practice Guideline.

OBJECTIVE: To systematically evaluate the efficacy and effectiveness of percutaneous interventional treatments for prevention of migraine through a qualitative and (when possible) quantitative analysis. METHODS: An expert panel was asked to develop recommendations for the multidisciplinary preventive treatment of migraine, including interventional strategies. The committee conducted a systematic review and (when evidence was sufficient) a meta-analytic review by using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria and the modified Cochrane Risk of Bias analysis available in the Covidence data management program. Clinical questions addressed adults with migraine who should be offered prevention. Examined outcomes included headache days, acute medication use, and functional impairment. Acute management of migraine was outside the scope of this guideline. RESULTS: The committee screened 1,195 studies and assessed 352 by full text, yielding 16 randomized controlled trials that met the inclusion criteria. RECOMMENDATIONS AND CONCLUSIONS: As informed by evidence related to the preselected outcomes, adverse event profile, cost, and values and preferences of patients, onabotulinumtoxinA received a strong recommendation for its use for chronic migraine prevention and a weak recommendation against its use for episodic migraine prevention. Greater occipital nerve blocks received a weak recommendation for their use for chronic migraine prevention. For greater occipital nerve block, steroid received a weak recommendation against its use vs the use of local anesthetic alone. Occipital nerve with supraorbital nerve blocks, sphenopalatine ganglion blocks, cervical spine percutaneous interventions, and implantable stimulation all received weak recommendations for their use for chronic migraine prevention. The committee found insufficient evidence to assess trigger point injections in migraine prevention and highly discouraged the use of intrathecal medication.

The practice of regional anesthesia during the COVID-19 pandemic: an international survey of members of three regional anesthesia societies.

PURPOSE: To determine the preferences and attitudes of members of regional anesthesia societies during the COVID-19 pandemic. METHODS: We distributed an electronic survey to members of the American Society of Regional Anesthesia and Pain Medicine, Regional Anaesthesia-UK, and the European Society of Regional Anaesthesia & Pain Therapy. A questionnaire consisting of 19 questions was developed by a panel of experienced regional anesthesiologists and distributed by email to the participants. The survey covered the following domains: participant information, practice settings, preference for the type of anesthetic technique, the use of personal protective equipment, and oxygen therapy. RESULTS: The survey was completed by 729 participants from 73 different countries, with a response rate of 20.1% (729/3,630) for the number of emails opened and 8.5% (729/8,572) for the number of emails sent. Most respondents (87.7%) identified as anesthesia staff (faculty or consultant) and practiced obstetric and non-obstetric anesthesia (55.3%). The practice of regional anesthesia either expanded or remained the same, with only 2% of respondents decreasing their use compared with the pre-pandemic period. The top reasons for an increase in the use of regional anesthesia was to reduce the need for an aerosol-generating medical procedure and to reduce the risk of possible complications to patients. The most common reason for decreased use of regional anesthesia was the risk of urgent conversion to general anesthesia. Approximately 70% of the responders used airborne precautions when providing care to a patient under regional anesthesia. The most common oxygen delivery method was nasal prongs (cannula) with a surgical mask layered over it (61%). CONCLUSIONS: Given the perceived benefits of regional over general anesthesia, approximately half of the members of three regional anesthesia societies seem to have expanded their use of regional anesthesia techniques during the initial surge of the COVID-19 pandemic.

RéSUMé: OBJECTIF: Déterminer les préférences et les attitudes des membres des sociétés d'anesthésie régionale pendant la pandémie de COVID-19. MéTHODE: Nous avons distribué un sondage électronique aux membres de l'American Society of Regional Anesthesia and Pain Medicine, de Regional Anesthesia-UK et de l'European Society of Regional Anaesthesia & Pain Therapy. Un questionnaire composé de 19 questions a été élaboré par un panel d'anesthésiologistes régionaux d'expérience et distribué par courriel aux participants. Le sondage couvrait les domaines suivants : les renseignements sur les participants, les contextes de pratique, leur préférence quant au type de technique d'anesthésie, l'utilisation d'équipement de protection individuelle et l'oxygénothérapie RéSULTATS: Le sondage a été complété par 729 participants provenant de 73 pays différents, avec un taux de réponse de 20,1 % (729/3630) pour le nombre de courriels ouverts et de 8,5 % (729/8572) pour le nombre de courriels envoyés. La plupart des répondants (87,7 %) se sont identifiés comme anesthésiologistes (académique ou consultant) et pratiquaient l'anesthésie obstétricale et non obstétricale (55,3 %). Leur pratique de l'anesthésie régionale s'est étendue ou est demeurée inchangée, et seulement 2 % des répondants ont indiqué avoir diminué leur utilisation de cette pratique par rapport à la période pré-pandémique. Les principales raisons d'une augmentation de l'utilisation de l'anesthésie régionale étaient de réduire la nécessité d'une intervention médicale générant des aérosols et de réduire le risque de complications potentielles pour les patients. La raison la plus courante de diminution du recours à l'anesthésie régionale était le risque de conversion urgente à une anesthésie générale. Environ 70 % des intervenants ont utilisé des précautions en matière de propagation des aérosols lorsqu'ils procuraient des soins à un patient sous anesthésie régionale. La méthode d'administration d'oxygène la plus fréquemment utilisée était les canules nasales avec un masque chirurgical superposé (61 %). CONCLUSION: Compte tenu des avantages perçus de l'anesthésie régionale par rapport à l'anesthésie générale, environ la moitié des membres de trois sociétés d'anesthésie régionale semblent avoir élargi leur utilisation des techniques d'anesthésie régionale pendant la vague initiale de la pandémie de COVID-19.

Reliability of transcranial sonography for assessment of brain midline shift in adult neurocritical patients: a systematic review and meta-analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to determine the reliability of transcranial sonography as an alternative to computed tomography for evaluation of brain midline shift in adult neurocritical patients. EVIDENCE AQUISITION: The PubMed, EMBASE, Cochrane Library, Scopus and Web of Science databases were searched. Original studies evaluating brain midline shift in adult neurocritical patients using both transcranial sonography and computed tomography were eligible. Primary outcome measure was concordance between both methods as quantified in terms of concordance correlation coefficient. Secondary outcome measure was limits of agreement, defined as mean difference between sonography and computed tomography plus and minus 1.96 standard deviations. EVIDENCE SYNTHESIS: Twelve studies (574 patients, 689 examinations) were eligible. Ten studies (416 patients, 492 examinations) provided adequate data for evaluation of concordance. Pooling of effect sizes showed strong concordance between both methods (concordance correlation coefficient, 0.91; 95% CI, 0.87 to 0.94). Two missing studies were imputed and effect size was adjusted to 0.88 (95% CI, 0.81 to 0.93). Nine studies (442 patients, 571 examinations) provided adequate data for estimation of limits of agreement. Pooling of effect sizes showed a bias of -0.53 mm (95% limits of agreement, -1.22 to 0.16 mm). Four missing studies were imputed and bias was adjusted to -0.68 mm (95% limits of agreement, -1.31 to -0.04 mm). CONCLUSIONS: Transcranial sonography may serve as reliable alternative to computed tomography for evaluation of brain midline shift in adult neurocritical patients. Both methods have strong concordance with acceptably narrow limits of agreement.

Value of new ST-segment/T-wave changes for prediction of major adverse cardiac events after vascular surgery: a meta-analysis.

INTRODUCTION: The aim of this review is to examine current evidence on value of new ST-segment or T-wave changes for prediction of major adverse cardiac events (MACE) after vascular surgery. EVIDENCE ACQUISITION: We searched PudMed, EMBASE and Cochrane Library databases for studies examining the relation between new ST-segment elevation or depression or T-wave inversion and MACE following vascular surgery. MACE was defined as fatal or non-fatal myocardial infarction, cardiac death, unstable angina, cardiac arrest, congestive heart failure, ischemic pulmonary edema, major ventricular arrhythmia or complete heart block. EVIDENCE SYNTHESIS: Eight eligible studies involving 1083 patients were included in meta-analysis. There was heterogeneity across included studies with possibility of publication bias. New ST-segment/T-wave changes had an imputed risk ratio (RR) for MACE of 2.04 (95% CI: 0.87 to 4.78). The overall predictive value was good (area under receiver-operating characteristic curve, 0.85; 95% CI: 0.83 to 0.90) with a sensitivity of 0.61 (95% CI: 0.55 to 0.67), specificity of 0.75 (95% CI: 0.72 to 0.78), and diagnostic odds ratio (DOR) of 13.03 (95% CI: 8.25 to 20.57). Meta-regression identified age (P value <0.01) and duration of ECG surveillance (P value <0.01) as possible sources for observed heterogeneity in RR. Neither factor influenced the DOR (P value, 0.87 and 0.36, respectively). CONCLUSIONS: Current evidence suggests that in the setting of vascular surgery, new ST-segment/T-wave changes could serve as predictor of MACE with reasonable accuracy. Heterogeneity across studies, possibility of publication bias and paucity of eligible studies are potential limitations to these conclusions.

A Novel Technique of Saddle Rhizotomy Using Thermal Radiofrequency for Intractable Perineal Pain in Pelvic Malignancy: A Pilot Study.

BACKGROUND: The prevalence of pain in advanced pelvic cancer may reach up to 95%. Control of such pain is often difficult owing to a variety of neuroanatomical and functional peculiarities. Different modalities have been utilized to treat this pain including saddle chemical rhizolysis with the potential for jeopardizing the neural control of the sphincters. OBJECTIVE: The aim of this pilot study is to determine the feasibility of using selective thermal radiofrequency as an alternative to saddle chemical rhizolysis in patients with refractory perineal pain associated with pelvic malignancies. STUDY DESIGN: Pilot study. SETTING: Pain Relief Department of the National Cancer Institute, Cairo University. METHODS: Forty patients, 18 years of age or older, who had pelvic malignancy and were complaining of moderate or severe perineal pain not controlled with maximum tolerable doses of morphine sulfate for at least 4 weeks were randomly allocated to receive selective saddle rhizotomy using thermal radiofrequency ablation of S3 on one side and bilateral ablation of S4 and S5 (RF group, n = 20) or conventional chemical rhizotomy using hyperbaric 6% phenol in glycerin (Phenol group, n = 20). Patients were assessed for the intensity of pain, daily consumption of analgesics, functional improvement, overall patient satisfaction, degree of disability and occurrence of procedure-related side effects at 1,4, and 12 weeks. RESULT: The results were comparable in both groups regarding the control of pain and functional improvement. The incidence of specific procedure-related adverse outcomes was also equivalent for both interventions, although per-patient incidence of major complications was significantly higher in the phenol group. LIMITATION: Small sample size to demonstrate statistical significance of the relatively small frequency of events, and the patients could not be blinded to the intervention they received owing to the technical uniqueness of either intervention. CONCLUSION: Selective thermal radiofrequency ablation of the S3 root on one side, S4 root on both sides, and S5 roots could serve as a feasible alternative to conventional saddle rhizotomy using hyperbaric phenol. KEY WORDS: Perineal cancer pain, chemical rhizotomy, thermal radiofrequency.

Effect of therapeutic hypothermia on survival and neurological outcome in adults suffering cardiac arrest: a systematic review and meta-analysis.

INTRODUCTION: The aim of this review was to determine current evidence for the effect of therapeutic hypothermia (TH) on survival and neurological outcome in adults suffering cardiac arrest (CA). EVIDENCE AQUISITION: We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE and NLM databases from 2000 to 2017 using the following terms: hypothermia, cooling, therapeutic, cardiac arrest, resuscitation, cardiopulmonary, CPR. Studies were eligible if they compared TH versus normothermic management in adult humans sustaining CA. Randomized controlled trials (RCT), pilot studies and observational trials were included. EVIDENCE SYNTHESIS: Ten studies involving 3259 patients were included in meta-analysis. Pooling all eligible studies showed a favorable effect for TH on survival and neurological recovery. However, sensitivity analysis for RCTs showed no benefit on either outcome, while observational trials showed benefit for neurological recovery with just marginally significant benefit regarding survival. Studies including patients with shockable rhythms demonstrated benefit for both outcome measures, while those including patients with any rhythms demonstrated benefit for neurological recovery but not for survival. TH did not benefit patients with non-shockable rhythms. Trials using external cooling favored TH regarding survival and neurological outcome but those using systemic cooling with or without external cooling did not show such benefit. When the overall incidence of complications was pooled, there was a statistically significant shift in odds ratio favoring normothermic management over TH. CONCLUSIONS: Evidence from RCTs suggests TH does not improve survival or neurological outcome, while observational trials favor TH over normothermia. TH may be attended with higher risk for complications.

Risk Factors for Chronic Saphenous Neuralgia Following Coronary Artery Bypass Graft Surgery Utilizing Saphenous Vein Grafts.

OBJECTIVES: The aim of this trial was to determine risk factors for chronic saphenous neuralgia (SN) following harvesting of the great saphenous vein (GSV) for coronary artery bypass graft (CABG) surgery. METHODS: In a prospective observational trial, 526 patients with no history of chronic painful disorders or surgery in the lower limbs were followed up for 13 weeks after undergoing CABG surgery in which GSV grafts were used. The primary outcome measure was persistence of clinically significant pain of neuropathic type in the territory supplied by the saphenous nerve beyond 12 weeks after surgery. RESULTS: Eighty-one (15.4%) patients consistently had probable neuropathic pain of clinically significant severity throughout the follow-up period and were labeled as suffering from chronic SN. Multivariable binary logistic regression analysis showed that younger age (OR, 0.92; 95% CI, 0.88-0.95; P-value, < 0.0001), female gender (OR, 2.28; 95% CI, 1.21-4.29; P-value, 0.011), higher body mass index (OR, 1.25; 95% CI, 1.17-1.35; P-value, < 0.0001), diabetes mellitus (OR, 2.13; 95% CI, 1.13-4.01; P-value, 0.020), distal-to-proximal dissection of the GSV (OR, 7.28; 95% CI, 3.62-14.66; P-value, < 0.0001), and closure of the leg wound in two layers (OR, 3.28; 95% CI, 1.81-5.95; P-value, 0.0001) were independent risk factors for chronic SN. CONCLUSIONS: Chronic SN after CABG surgery utilizing GSV grafts is not uncommon. Risk factors identified in this trial are younger age, female gender, higher body mass index, diabetes mellitus, distal-to-proximal dissection of the GSV, and closure of the leg wound in two layers.

Early treatment with risperidone for subsyndromal delirium after on-pump cardiac surgery in the elderly: a randomized trial.

BACKGROUND: The aim of this randomized, parallel-arm trial was to study the effect of treating subsyndromal delirium with risperidone on the incidence of clinical delirium in elderly patients who underwent on-pump cardiac surgery. METHODS: One hundred one patients aged 65 yr or older who experienced subsyndromal delirium after on-pump cardiac surgery were randomized using a computer-generated list to receive 0.5 mg risperidone (n = 51) or placebo (n = 50) every 12 h by mouth. Patients were assessed at 8 h by a blinded observer using the Intensive Care Delirium Screening Checklist, and those scoring more than 3 were evaluated by a blinded psychiatrist to confirm delirium. Patients in either group who experienced delirium were treated according to the same algorithm. Initially, risperidone was administered and if symptoms were not controlled, haloperidol was administered. The primary outcome was the proportion of patients who experienced delirium in either group. RESULTS: Seven (13.7%) patients in the risperidone group experienced delirium versus 17 (34%) in the placebo group (P = 0.031) Competing-risks regression analysis showed that failure to treat subsyndromal delirium with risperidone was an independent risk factor for delirium (subhazard ratio, 3.83; 95% CI, 1.63-8.98; P = 0.002). Two (3.9%) patients in the risperidone group experienced extrapyramidal manifestations versus one (2%) in the placebo group (P = 1.0). CONCLUSION: Administration of risperidone to elderly patients who experienced subsyndromal delirium after on-pump cardiac surgery was associated with significantly lower incidence of delirium. Larger studies are required to determine whether early administration of risperidone during the subsyndromal phase of delirium would influence the clinical course of such patients.

Risk factors for new-onset persistent low-back pain following nonobstetric surgery performed with epidural anesthesia.

BACKGROUND: The aim of this trial was to identify risk factors for persistent low-back pain (LBP) of new onset following nonobstetric surgery performed with lumbar epidural anesthesia. METHODS: Four-hundred eighty-three patients with no history of LBP were screened for backache 2 days, 10 days, and 13 weeks after nonobstetric surgeries were performed with lumbar epidural anesthesia. Demographic data, details of epidural techniques, and operative data were compared in patients who developed back pain that persisted for 13 weeks with those patients who did not. Multivariate logistic regression analysis was performed to identify predictors of persistent LBP. RESULTS: Ten patients (2.1%) consistently experienced clinically significant LBP at 2 days, 10 days, and 13 weeks after surgery; they were labeled as having persistent LBP. Multivariate analysis showed that higher body mass index (P < 0.001), multiple attempts at epidural placement (P = 0.026), surgery in the lithotomy position (P = 0.013), and duration of surgery exceeding 2½ hrs (P = 0.025) were independent risk factors for persistent LBP. As much as 51% of variation in the outcome measure could be explained by the model (R = 0.51), which had an overall accuracy of 98.1%. CONCLUSIONS: Persistent LBP after nonobstetric surgery performed with lumbar epidural anesthesia is rather rare. Independent risk factors for this untoward outcome are higher body mass index, multiple trials at epidural placement, surgery in the lithotomy position, and operative time exceeding 2½ hrs. These results need to be validated by prospective trials using larger cohorts.

Warfarin for refractory chronic cluster headache: a randomized pilot study.

OBJECTIVE: To investigate the effect of low-intensity anticoagulation with warfarin on chronic cluster headache refractory to pharmacological management. BACKGROUND: Isolated case reports on induction of remission in patients with intractable chronic cluster headache upon institution of oral anticoagulant therapy do exist. Nonetheless, evidence from randomized controlled trials on the role of oral anticoagulants in cluster headache is lacking. METHODS: Thirty-four patients with refractory chronic cluster headache were randomized to receive warfarin or placebo for 12 weeks. Warfarin was administered to achieve an international normalized ratio between 1.5 and 1.9. After a washout period of 2 weeks, patients were crossed over from 1 treatment to the other. Status of cluster headache was assessed during both treatment periods. The primary outcome measure was the occurrence of remission lasting ≥4 weeks. RESULTS: Seventeen (50%) patients underwent remission for ≥4 weeks during the warfarin period vs 4 (11.8%) patients during the placebo period (P = .004). This was associated with absolute risk reduction of 0.38 (95% CI = 0.18-0.58), and number needed to treat of 2.6 (95% CI = 1.7-5.5). The Kaplan-Meier curves for occurrence of remission had a hazard ratio of 5.26 (95% CI = 2.13-13.03, P = .0003). Frequency, duration, and intensity of cluster attacks were all significantly lower during treatment with warfarin (P < .01). CONCLUSION: In patients with refractory chronic cluster headache, low-intensity anticoagulation with warfarin was associated with significantly higher incidence of remission and less impact of headache on patients' lives compared with placebo.