Randomized controlled studies evaluating Topiramate, Botulinum toxin type A, and mABs targeting CGRP in patients with chronic migraine and medication overuse headache: A systematic review and meta-analysis.

BACKGROUND: This systematic review focuses on chronic migraine patients with medication overuse headache using, respectively, topiramate, botulinum toxin type A, and human monoclonal antibodies targeting calcitonin gene-related peptide or its receptor. METHODS: A systematic search was conducted in the databases CENTRAL, MEDLINE, Embase and Web of Science until May 2022. We included randomized controlled trials reporting the outcomes of change in monthly headache/migraine days, ≥50% response rates and change in medication overuse status. Studies were excluded if response rates were not reported. Risk of bias assessment was performed using the Cochrane RoB2 tool. The quality of evidence for outcomes across included studies was evaluated according to the five factors outlined in Cochrane GRADE approach. FINDINGS: The initial search resulted in 1599 records. Following screening, 10 studies met our inclusion criteria, while seven studies with sufficient data were included in the meta-analysis. Studies assessing Botulinum toxin type A included 1139 patients and showed a mean reduction in headache frequency by 1.92 days per month compared to placebo (-1.92; 95% CI -2.68 to -1.16). Studies assessing human monoclonal antibodies included 1982 patients, and showed significant positive effect compared to placebo for all measured outcomes. The overall odds ratio for the ≥50% response rate was 2.90 (95% CI, 2.23 to 3.78). No significant difference was observed in the frequency of adverse effect for both Botulinum toxin type A and low dose of human monoclonal antibodies compared to placebo. There is currently insufficient evidence to determine the impact of topiramate in chronic migraine patients with medication overuse headache. INTERPRETATION: Botulinum toxin type A and human monoclonal antibodies targeting calcitonin gene-related peptide receptor were beneficial in reducing monthly migraine days and ≥50% response rate, but uncertainties remained for Botulinum toxin type A regarding response rate. The effect size for human monoclonal antibodies was greater with relatively lower drop-out rate. High-quality randomized trials are required to evaluate the effect of topiramate in chronic migraine patients with medication overuse headache.

Thiopurines prevented surgical recurrence in patients with Crohn's disease after intestinal resection: Strategy based on risk stratification.

BACKGROUND AND AIM: Thiopurines (TPs) are effective in reducing clinical and endoscopic recurrence in postoperative patients with Crohn's disease (CD). However, whether TPs could prevent surgical recurrence (SR) remains unknown. We aimed to explore whether TPs could prevent SR and identify risk factors associated with SR. METHODS: This was a retrospective cohort study of 246 postoperative patients with CD. Cox proportional hazard model was used to identify risk factors for SR. Patients were stratified according to the presence of risk factors. RESULTS: A total of 50 (20.3%) patients suffered SR after a mean follow up of 54.3±46.4 months. Multivariable analysis showed independent risk factors for SR were penetrating disease behavior (HR 8.628; 95% CI 1.573-47.341; P = 0.01), ileocolonic disease location (HR 2.597; 95% CI 1.047-6.445; P = 0.04) and isolated upper gastrointestinal disease (UGID) location (HR 5.082; 95% CI 1.496-17.267; P = 0.009). However, use of TPs after surgery significantly reduced the risk of SR (HR 0.120; 95% CI 0.063-0.231; P < 0.001). When stratifying patients according to risk factors, there was no statistical difference of SR between patients treated or not by TPs (P = 0.08) in low-risk group (n = 46). However, in high risk group (n = 200), patients with TPs use had a lower risk of SR than those without TPs (HR 0.093; 95% CI 0.048-0.178; P < 0.001). CONCLUSIONS: Penetrating disease behavior and ileocolonic/isolated (UGID) location were associated with SR in CD patients. TPs use was beneficial in decreasing risk for SR in CD patients at high risk.

Cerebral Thrombosis: A Neurogenetic Approach.

Cerebral venous thrombosis (CVT) is a severe multifactorial condition with various clinical manifestations that may include headache, papilledema, seizures, focal deficits, coma and death. The mortality rate of untreated CVT is up to 50%, but it drops to 10% when CVT is properly treated. Prevention of CVT is feasible through healthy lifestyle, genetic counseling, molecular genetic analysis for common thrombophilia-related mutations, and prophylactic anticoagulative medication.

Modelling canine leishmaniasis spread to non-endemic areas of Europe.

Expansion of sandflies and increasing pet travel have raised concerns about canine leishmaniasis (CanL) spread to new areas of Europe. This study aimed to estimate the probability of CanL introduction and persistence following movements of infected dogs. Stochastic modelling was used to estimate the probabilities of (1) CanL infection during travels or imports of infected dogs (P inf and P infCA, respectively), (2) CanL persistence in a dog network with sandflies after introduction of an infected dog (P per), and (3) persistence in a CanL-free region (P per region) for N dogs moving between endemic and free regions. Different mitigation measures (MMs) were assessed. P inf [7.8%, 95% predictive interval (PI) 2.6-16.4] and P per (72.0%, 95% PI 67.8-76.0) were reduced by use of repellent, vaccine, prophylactic medication, and insecticide, in decreasing order of effectiveness. Testing and exclusion of positive dogs was most effective in reducing P per region for a small N. The spread of CanL to CanL-free areas with sandflies is thus likely, but can be reduced by MMs.

Medication overuse headache.

BACKGROUND: Medication overuse headache (MOH) affects between 1% and 2% of the general population but is present in up to 50% of patients seen in headache centers. There are currently no internationally accepted guidelines for treatment of MOH. METHODS: A review of the current literature on MOH treatment and pathophysiology. RESULTS: We conclude that headache frequency can be reduced to episodic headache in more than 50% of the patients by simple detoxification and information. Approximately half the patients will not have need for prophylactic medication after withdrawal. Pain perception is altered in patients with MOH but can be restored to a baseline pattern, indicating a reversible mechanism in the central sensitization leading to chronic pain. The great comorbidity with depression and anxiety could be a consequence of the altered serotonin metabolism indicating a reversible and potentially treatable condition. CONCLUSION: Increased focus on MOH is extremely important, as MOH both can and should be treated and prevented. MOH is thus a diagnosis that should be considered in all chronic headache patients as the very first step in their management strategy. In the general population, prevention campaigns against MOH are essential to minimize chronic pain disability.

Cluster headache: conventional pharmacological management.

Cluster headache pain is very intense, usually increases in intensity very rapidly from onset, and attacks are often frequent. These clinical features result in significant therapeutic challenges. The most effective pharmacological treatment options for acute cluster attack include subcutaneous sumatriptan, 100% oxygen, and intranasal zolmitriptan. Subcutaneous or intramuscular dihydroergotamine and intranasal sumatriptan are additional options. Transitional therapy is applicable mainly for patients with high-frequency (>2 attacks per day) episodic cluster headache, and options include short courses of high-dose oral corticosteroids, dihydroergotamine, and occipital nerve blocks with local anesthetic and steroids. Prophylactic therapy is important both for episodic and chronic cluster headache, and the main options are verapamil and lithium. Verapamil is drug of first choice but may cause cardiac arrhythmias, and periodic electrocardiograms (EKGs) during dose escalation are important. Many other drugs are also in current use, but there is an insufficient evidence base to recommend them.

Strategies for the prevention of postoperative recurrence of Crohn's disease.

AIM: To review the optimal strategy to prevent recurrence of Crohn's disease (CD) after surgery, with particular emphasis on the risk factors that predict postoperative recurrence, methods of monitoring for recurrence and medications used to prevent postoperative recurrence. METHOD: MEDLINE and the Cochrane Library were searched for clinical trials and meta-analyses that studied postoperative recurrence and prophylactic medications in CD. RESULTS: The most significant factor that predicted postoperative recurrence was patient smoking status. Smokers had an increased risk of recurrence (odds ratio = 2.15; 95% confidence interval (CI) = 1.42-3.27). Similarly, perforating CD appeared to be associated with a higher recurrence rate compared with nonperforating CD (hazard ratio = 1.50; 95% CI = 1.16-1.93). The optimal monitoring strategy for postoperative recurrence has yet to be established. Nonetheless, ileocolonoscopy is considered to be the gold standard. Noninvasive imaging techniques including contrast ultrasonography and capsule endoscopy appear to be useful for postoperative monitoring. A number of meta-analyses found that mesalazine, nitroimidazole antibiotics and purine analogues (azathioprine/6-mercaptopurine) significantly reduced the risk of postoperative recurrence when compared with placebo. Additionally, recent randomized controlled trials have suggested that an early intervention with infliximab is likely to prevent recurrence after ileocolonic resection. Likewise, in prospective studies, biological therapy (infliximab/adalimumab) reduced clinical and endoscopic CD activity in patients with early endoscopic recurrence after surgery. CONCLUSION: Although additional evidence is necessary, endoscopic monitoring and treatment step-up should be used to prevent postoperative recurrence of CD.

Rationale and design of a phase II study to evaluate prophylactic treatment of dacomitinib-induced dermatologic adverse events in epidermal growth factor receptor-mutated advanced non-small cell lung cancer (SPIRAL-Daco study).

BACKGROUND: Dacomitinib is the first second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) to significantly improve overall survival in the patients of EGFR mutation-positive inoperable or postoperative recurrent non-small cell lung cancer (NSCLC). However, dermatologic adverse events (AEs) increase with dacomitinib treatment, and the management strategy for dermatologic AEs is crucial. In particular, a proactive strategy has become desirable in clinical practice settings. We designed a trial to assess a proactive strategy for dermatologic AEs associated with dacomitinib treatment. METHODS: This is a single-arm, prospective, open-label, multicenter, phase II trial. Patients with advanced NSCLC harboring EGFR-activating mutations will receive dacomitinib and prophylactic treatment as follows: minocycline, skin moisturizer, topical steroid, and sunscreen. Treatment will be continued until progressive disease or any of the discontinuation criteria are met. The primary endpoint is the incidence of dermatologic AEs (≥ grade 2) in the first 8 weeks of dacomitinib treatment. Secondary endpoints are the proportion of dose reduction of dacomitinib, progression-free survival, and safety. DISCUSSION: We are conducting a phase II study to explore the preventive efficacy of prophylactic medication against dacomitinib-induced dermatologic AEs. TRIAL REGISTRATION: jRCTs071190015.

Prediction of intraoperative nausea and vomiting in caesarean delivery under regional anaesthesia.

Objectives This study aimed to predict patients who have caesarean operations under regional anaesthesia and are at risk for intraoperative nausea and vomiting (IONV), for ultimately prompting anaesthetists and surgeons to take preventive measures. Methods This was a retrospective study on 209 patients who had caesarean section under spinal-epidural combined regional anaesthesia. The relevant medical history, such as severe nausea and vomiting in the first trimester, smoking, a history of motion sickness, and premenstrual syndrome (PMS), were obtained from the patients' records and interviews. Results Patients who had a female neonate, a history of severe nausea and vomiting in the first trimester, and a history of PMS and motion sickness before pregnancy experienced a significantly higher rate of IONV. Smokers were less susceptible to IONV, but this was not significant. Conclusion This study shows that some factors in the medical history of a patient can help identify those who are more likely to suffer from IONV.

A novel prophylactic effect of furosemide treatment on autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).

The transgenic rat strain S284L-TG harbors the S284L mutant of the neuronal nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4), which is responsible for human autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). S284L-TG rats have epileptic seizure phenotypes during slow-wave sleep, similar to those in NFLE. We previously demonstrated that γ-aminobutyric acid (GABA)ergic action of these rats was suppressed before the onset of ADNFLE seizures, and that glutamate release in the epileptic focus lesion was increased at the onset of epilepsy. Here, mRNA analysis revealed that Cl(-)-accumulating Na-K-2Cl cotransporter 1 (NKCC1) levels were increased and Cl(-)-extruding K-Cl cotransporter 1 and 2 (KCC1 and KCC2) levels were decreased at the onset of ADNFLE seizures in S284L-TG rat frontal cortexes, which perturbed the GABAergic inhibitory system. The reversal potentials (EGABA) of GABAA receptor-mediated currents in cortical layer V pyramidal neurons of S284L-TG rats also changed their polarity from hyperpolarization to depolarization, and S284L-TG miniature excitatory postsynaptic currents (mEPSCs), but not miniature inhibitory postsynaptic currents (mIPSCs), significantly increased in both amplitude and frequency. Administration of 25mg/kg/day furosemide before, but not after, the onset of interictal discharges prevented idiopathic epileptic activity, reversed the depolarizing shift of EGABA and increased mEPSC amplitude to normal levels. These data indicate that early treatment with an agent that normalizes pathogenesis has a prophylactic effect on epilepsy. We propose a strategy for prophylactic medication against idiopathic epilepsy through the suppression of epileptogenesis and/or ictogenesis.