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Urinary tract infections (UTIs) constitute one of the main complications in kidney recipients, increasing both morbidity and mortality. Due to the resurgence of antimicrobial resistance, new prophylactic approaches are being investigated. Nitrofurantoin is an antibiotic from the nitrofuran group that is effective against several Gram-negative and Gram-positive organisms; hence, there has been a resurgence in its prescription for treating MDR pathogens. Objectives: This study aims to assess the effectiveness of nitrofurantoin as an add-on to conventional therapy (amikacin + ceftriaxone or cefotaxime) for the treatment of urinary tract infections in kidney recipients. Methods: In a prospective cohort study, we included patients who received a kidney in a tertiary-care hospital. According to the intensive care specialist, group 1 patients were treated with the conventional prophylactic treatment plus nitrofurantoin as an add-on. Group 2 patients were treated only with the conventional prophylactic treatment. They were followed-up for 3 months, and the incidence of urinary tract infections was reported. Results: The UTI incidence for group 1 at 3 months was 20.6%, and for group 2, it was 20.0%; no statistical difference between treatments was observed (p = 0.9). The most commonly isolated pathogens were E. coli (28.5) and K. pneumonie (28.5%). The factor most associated with developing a UTI was female gender (aHR: 7.0; 95% IC 2.3–20.9, p < 0.001). Conclusions: In our cohort study, nitrofurantoin as an add-on in conventional therapy did not prove to be effective in preventing UTI development; therefore, other treatment options should be considered as a part of prophylactic treatment. [ABSTRACT FROM AUTHOR]

Summary This study aims to investigate the effects of oral and non‐oral migraine prophylaxis on subjective sleep quality in migraine patients with sleep problems. A bidirectional relationship between migraine and sleep is presumed, although this relationship is not fully clarified. Possibly, prophylactic treatment of migraine aiming at a reduction of migraine attack frequency can also positively affect the quality of sleep for patients with migraine with sleep problems. PubMed, Cochrane, Embase and CINAHL databases were searched in March 2022 for studies evaluating prophylactic treatment of migraine and the impact on perceived sleep quality (Pittsburgh Sleep Quality Index or Insomnia Severity Index). A systematic review using the McMaster Tool and a random‐effects meta‐analysis (effect size Cohen's d) were conducted. Seven studies were identified, including 989 participants, of which 844/989 (85.3%) female, with a mean (SD) age of 41.3 (12.1) years. In 6/7 (85.7%) studies, monthly migraine days improved (p < 0.002). Five out of six (83.3%) studies presented a relevant improvement in quality of sleep (p < 0.05), and one study reported a clinically meaningful improvement in the treatment group (Insomnia Severity Index change >7, in >50% of participants). The meta‐analysis showed a large effect size of 1.09 (95% confidence interval 0.57–1.62; overall p < 0.001; Cochran's Q < 0.0001) for migraine prophylaxis on improving sleep quality. In conclusion, prophylactic migraine treatment improves sleep quality in patients with migraine and sleep problems, as measured with self‐reported questionnaires Pittsburgh Sleep Quality Index and Insomnia Severity Index. Unfortunately, some included studies used prophylactic treatment that is not in current (international) guidelines. The evidence for this improvement in quality of sleep is strong, and seems a generic effect of migraine prophylaxis. [ABSTRACT FROM AUTHOR]

Incidence rates of human Campylobacter jejuni infections are progressively increasing globally. Since the risk for the development of post-infectious autoimmune diseases correlates with the severity of the preceding enteritis and campylobacteriosis treatment usually involves symptomatic measures, it is desirable to apply antibiotic-independent compounds to treat or even prevent disease. Given its health-promoting including anti-inflammatory properties carvacrol constitutes a promising candidate. This prompted us to test the disease-alleviating including immune-modulatory effects of carvacrol prophylaxis in acute murine campylobacteriosis. Therefore, human gut microbiota-associated IL-10−/− mice were orally challenged with synthetic carvacrol starting a week before C. jejuni infection and followed up until day 6 post-infection. Whereas carvacrol prophylaxis did neither affect gastrointestinal pathogen loads, nor the human commensal gut microbiota composition, it improved the clinical outcome of mice, attenuated colonic epithelial cell apoptosis, and dampened pro-inflammatory immune responses not only in the intestinal tract but also in extra-intestinal organs including the liver and the spleen. In conclusion, our preclinical placebo-controlled intervention study provides convincing evidence that oral carvacrol pretreatment constitutes a promising option to mitigate acute campylobacteriosis and in turn, to reduce the risk for post-infectious complications. [ABSTRACT FROM AUTHOR]

Background: The Headache Impact Test (HIT‐6) is an important patient‐reported outcome measure (PROM) in migraine prevention trials. Objectives: This study aimed to (i) assess the reliability and validity of the Arabic version of HIT‐6 in Arabic‐speaking patients experiencing migraine, and (ii) evaluate the responsiveness of HIT‐6 following migraine preventive therapy. Methods: In this prospective study, patients with migraine (n = 145) were requested to fill out a headache diary, the Arabic version of HIT‐6, and Migraine Disability Assessment Scale (MIDAS) at two time points (baseline and 3 months after initiation of prophylactic treatment). Some respondents (n = 73) were requested to fill out HIT‐6 again 1 week from the baseline for test–retest reliability. The intensity of migraine headache attacks was evaluated using the Visual Analogue Scale (VAS). An anchor‐based method was used to establish the minimal important change (MIC) value and responsiveness of HIT‐6. Results: The total scores of HIT‐6 were significantly correlated to a fair degree with MIDAS (r = 0.41), as well as VAS (r = 0.53), and monthly migraine days (r = 0.38) at the baseline while at the follow‐up (after 3 months), the correlations were of moderate degree with MIDAS scores (r = 0.62) and monthly migraine days (r = 0.60; convergent validity). Reliability estimates of the Arabic HIT‐6 were excellent (Cronbach's α = 0.91 at baseline and 0.89 at follow‐up). The average measure interclass correlation coefficient (ICC) value for the test–retest reliability was 0.96 (95% confidence interval = 0.94–0.98, p < 0.001). The HIT‐6 total score is sensitive to change, being significantly reduced after prophylactic treatment compared to before (effect size = 1.5, standardized response mean = 1.3). A reduction from baseline of 4.5 on HIT‐6 showed the highest responsiveness to predict improvement with an area under the curve equal to 0.66, sensitivity of 80%, specificity of 45%, and significance at 0.021. Changes in the HIT‐6 total score were positively correlated with changes in monthly migraine days (r = 0.40) and VAS scores (r = 0.69) but not with changes in the score of MIDAS (r = 0.07). Conclusion: The Arabic version of HIT‐6 is valid, reliable, and sensitive to detect clinical changes following migraine prophylactic treatment with a MIC of 4.5 points. Plain Language Summary: The Arabic version of the Headache Impact Test (HIT‐6) is a valid, reliable tool in measuring the impact of headache in culturally different Arabic‐speaking patients experiencing migraine. The Arabic version of HIT‐6 is sensitive to detect changes in headache‐related disability following migraine preventive therapy. A change of 4.5 points or more in the total score of the Arabic version of HIT‐6 following migraine preventive therapy represents a clinically important change. [ABSTRACT FROM AUTHOR]

Objective: Adherence to drug use; it is a crucial part of patient care and clinical briefing. Non-compliance with prescribed treatment regimens is an important and common behavioral health problem for treating chronic diseases. In our study, we aimed to investigate the rate of adherence to medication use in migraine patients taking prophylactic drugs, the factors affecting it, and the reasons for decreased compliance. Methods: Eighty patients diagnosed with migraine and using prophylactic treatment for migraine were included in the study. Detailed sociodemographic and clinical histories were obtained at the first interview. The scores obtained by applying the Beck Anxiety and Depression Inventory were recorded for each patient. The patients were evaluated with weekly visits for four weeks; adherence was examined using the tablet counting method. Results: In our study, 70% of our patients who received prophylactic drugs for migraine were non-compliant with the treatment; it was observed that the three most common causes were forgetting to take medication, drug side effects, and drug expiration. It was observed that low education level, being married, diet and exercise incompatibility, and high sleep problems, depression, and anxiety symptoms affected the adherence to prophylactic drug use in a statistically significant and negative way. Conclusion: To increase the patient's compliance with the treatment regimen, all potential barriers to compliance must be considered. Measures that consider the factors under the patient's control and the interaction between patient and physician and patient-health care will have the greatest impact on improving adherence. This will lead to better clinical outcomes and decrease morbidity and health expenditures. [ABSTRACT FROM AUTHOR]

Amphotericin B (AmB) has long stood as a cornerstone in the treatment of invasive fungal infections (IFIs), especially among immunocompromised patients. However, the landscape of antifungal therapy is evolving. New antifungal agents, boasting novel mechanisms of action and better safety profiles, are entering the scene, presenting alternatives to AmB's traditional dominance. This shift, prompted by an increase in the incidence of IFIs, the growing demographic of immunocompromised individuals, and changing patterns of fungal resistance, underscores the continuous need for effective treatments. Despite these challenges, AmB's broad efficacy and low resistance rates maintain its essential status in antifungal therapy. Innovations in AmB formulations, such as lipid complexes and liposomal delivery systems, have significantly mitigated its notorious nephrotoxicity and infusion-related reactions, thereby enhancing its clinical utility. Moreover, AmB's efficacy in treating severe and rare fungal infections and its pivotal role as prophylaxis in high-risk settings highlight its value and ongoing relevance. This review examines AmB's standing amidst the ever-changing antifungal landscape, focusing on its enduring significance in current clinical practice and exploring its potential future therapeutic adaptations. [ABSTRACT FROM AUTHOR]

The diterpenoid isosteviol is one of the stevia derivatives that have reported various activities. In mice inhaling isosteviol, OVA- and ACh-induced bronchial asthma showed a dose-dependent improvement of a decline in the expression of inflammatory cytokines and the infiltration of basophils. Compared with inhalation of budesonide 0.6 mg/kg, sensitized mice inhaling 1.0 mg/kg dosage of isosteviol performed a higher tolerate against the ACh stimulation. In behavior tests, the 1.0 mg/kg isosteviol nebulization reached almost 80% of the level of budesonide with regard to the ameliorative effects on depression-like behavior and improvement in sport ability. In addition, lung and systemic inflammation were markedly prevented by isosteviol with a dosage of more than 0.6 mg/kg, which exhibited limited expression of IL-1β and TNF-α, less infiltration of basophils in lung tissues, and a low level of systemic immunocytes, which showed in hematoxylin and eosin staining, RT-PCR, and ELISA results. On the other hand, none of the abnormal pathology was found in both peripheral and central organs of all the administration groups. Generally, this study implicated that the mechanism could involve effects of isosteviol inhalation on the suppression of IL-1β and TNF-α to restrict a systemic upsurge of immunocytes and infiltration into the lung that prevents the occurrence of depression-like behavior and hypokinesia. [ABSTRACT FROM AUTHOR]

The incidence of human Campylobacter jejuni infections is increasing worldwide. It is highly desirable to prevent campylobacteriosis in individuals at risk for severe disease with antibiotics-independent non-toxic compounds. Activated charcoal (AC) has long been used as an anti-diarrheal remedy. Here, we tested the disease-mitigating effects of oral AC versus placebo in human gut microbiota-associated (hma) IL-10−/− mice starting a week prior to C. jejuni infection. On day 6 post-infection, the gastrointestinal C. jejuni loads were comparable in both infected cohorts, whereas campylobacteriosis symptoms such as wasting and bloody diarrhea were mitigated upon AC prophylaxis. Furthermore, AC application resulted in less pronounced C. jejuni-induced colonic epithelial cell apoptosis and in dampened innate and adaptive immune cell responses in the colon that were accompanied by basal concentrations of pro-inflammatory mediators including IL-6, TNF-α, IFN-γ, and nitric oxide measured in colonic explants from AC treated mice on day 6 post-infection. Furthermore, C. jejuni infection resulted in distinct fecal microbiota shift towards higher enterobacterial numbers and lower loads of obligate anaerobic species in hma mice that were AC-independent. In conclusion, our pre-clinical placebo-controlled intervention study provides evidence that prophylactic oral AC application mitigates acute murine campylobacteriosis. [ABSTRACT FROM AUTHOR]

Introduction: Prophylactic treatment of hemophilia B with recombinant factor IX (rFIX) molecules with enhanced pharmacokinetics including rIX-FP (albutrepenonacog alfa; Idelvion©) and rFIXFc (eftrenonacog alfa; Alprolix©) have commonly been used in the clinic. In the absence of head-to-head comparative trials, the aim of this study was to estimate the efficacy of rIX-FP versus rFIXFc using matching-adjusted indirect comparisons (MAICs). Methods: MAIC analyses leveraged individual patient data from the PROLONG-9FP trial and published summary-level data from the B-LONG trial for subjects who received weekly prophylaxis regimens. Individual patient data were used to assign weights and balance subjects from PROLONG-9FP with subjects from B-LONG on baseline disease severity, age, prior FIX regimen, and body mass index (BMI). Six efficacy outcomes were analyzed including annualized bleeding rate (ABR), annualized spontaneous bleeding rate (AsBR), annualized joint bleeding rate (AjBR), and the proportion of subjects without bleeding events (for total, spontaneous, and joint bleeding events). Results: After adjustment for baseline disease severity, age, prior FIX regimen, and BMI, rIX-FP was associated with a statistically significant decrease in AsBR (rate ratio [RR] 0.42; 95% confidence interval [CI] 0.22, 0.82; P = 0.0107), and the proportion of patients without bleeding events (odds ratio [OR] 3.24; 95% CI 1.41, 7.45; P = 0.0057), spontaneous bleeding events (OR 3.47; 95% CI 1.56, 7.73; P = 0.0023), and joint bleeding events (OR 2.41; 95% CI 1.10, 5.26; P = 0.0274) compared with rFIXFc. Prophylactic treatment with rIX-FP was also associated with a numerically lower ABR (RR 0.75; 95% CI 0.32, 1.75; P = 0.5095) and AjBR (RR 0.82; 95% CI 0.37, 1.82; P = 0.6178). Conclusion: The MAICs demonstrated that weekly prophylaxis treatment of severe hemophilia B with rIX-FP resulted in favorable efficacy outcomes as compared to rFIXFc. These findings suggest rIX-FP may offer improved clinical benefits over rFIXFc. [ABSTRACT FROM AUTHOR]

Background: Objective: This study aims to compare the effectiveness and safety of ketamine, tramadol, and dexmedetomidine in the prophylactic treatment of shivering after spinal anesthesia. Methods: A randomized controlled trial was conducted involving 200 patients undergoing surgeries requiring spinal anesthesia. The participants were equally divided into three groups to receive either ketamine, tramadol, or dexmedetomidine as a prophylactic measure against shivering. The primary outcome measured was the incidence of shivering, while secondary outcomes included monitoring hemodynamic parameters and noting any adverse effects. Results: The incidence of shivering was significantly lower in the dexmedetomidine group compared to the ketamine and tramadol groups. Hemodynamic parameters remained stable across all groups, with minimal and manageable side effects. Tramadol and ketamine were effective to a lesser extent but were associated with more side effects compared to dexmedetomidine. Conclusion: Dexmedetomidine demonstrates a higher efficacy and better safety profile in preventing shivering after spinal anesthesia compared to ketamine and tramadol. These findings suggest that dexmedetomidine can be considered a preferred choice for preventing shivering in patients undergoing surgeries with spinal anesthesia. Further studies are recommended to confirm these findings and explore long-term outcomes. [ABSTRACT FROM AUTHOR]

Human infections with the food-borne zoonotic enteropathogen Campylobacter jejuni are increasing globally. Since multi-drug resistant bacterial strains are further on the rise, antibiotic-independent measures are needed to fight campylobacteriosis. Given its anti-microbial and anti-inflammatory properties the polyphenolic compound resveratrol constitutes such a promising candidate molecule. In our present placebo-controlled intervention trial, synthetic resveratrol was applied perorally to human gut microbiota-associated (hma) IL-10-/- mice starting a week before oral C. jejuni infection. Our analyses revealed that the resveratrol prophylaxis did not interfere with the establishment of C. jejuni within the murine gastrointestinal tract on day 6 post-infection, but alleviated clinical signs of campylobacteriosis and resulted in less distinct colonic epithelial apoptosis. Furthermore, oral resveratrol dampened C. jejuni-induced colonic T and B cell responses as well as intestinal secretion of pro-inflammatory mediators including nitric oxide, IL-6, TNF-α, and IFN-γ to basal levels. Moreover, resveratrol application was not accompanied by significant shifts in the colonic commensal microbiota composition during campylobacteriosis in hma IL-10-/- mice. In conclusion, our placebo-controlled intervention study provides evidence that prophylactic oral application of resveratrol constitutes a promising strategy to alleviate acute campylobacteriosis and in consequence, to reduce the risk for postinfectious autoimmune sequelae. [ABSTRACT FROM AUTHOR]

Abstract Objective Novel disease-specific and mechanism-based treatments sharing good evidence of efficacy for migraine have been recently marketed. However, reimbursement by insurers depends on treatment failure with classic anti-migraine drugs. In this systematic review and meta-analysis, we aimed to identify and rate the evidence for efficacy of flunarizine, a repurposed, first- or second-line treatment for migraine prophylaxis. Methods A systematic search in MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov was performed for trials of pharmacological treatment in migraine prophylaxis, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Eligible trials for meta-analysis were randomized, placebo–controlled studies comparing flunarizine with placebo. Outcomes of interest according to the Outcome Set for preventive intervention trials in chronic and episodic migraine (COSMIG) were the proportion of patients reaching a 50% or more reduction in monthly migraine days, the change in monthly migraine days (MMDs), and Adverse Events (AEs) leading to discontinuation. Results Five trials were eligible for narrative description and three for data synthesis and analysis. No studies reported the predefined outcomes, but one study assessed the 50% reduction in monthly migraine attacks with flunarizine as compared to placebo showing a benefit from flunarizine with a low or probably low risk of bias. We found that flunarizine may increase the proportion of patients who discontinue due to adverse events compared to placebo (risk difference: 0.02; 95% CI -0.03 to 0.06). Conclusions Published flunarizine trials predate the recommended endpoints for evaluating migraine prophylaxis drugs, hence the lack of an adequate assessment for these endpoints. Further, modern-day, large‐scale studies would be valuable in re-evaluating the efficacy of flunarizine for the treatment of migraines, offering additional insights into its potential benefits.

Abstract Background Haemophilia A is a rare, hereditary haemorrhagic disease that manifests as induced spontaneous bleeding and leads to disability or premature death in severe cases. Prophylactic treatment is optimal for patients to prevent uncontrolled bleeding and reduce the severity of the injury. However, little is known about the use of prophylactic treatment among patients with haemophilia A in China, especially barriers that predispose them to low or non-adherence. In this study, we explore the barriers to the prophylactic treatment of patients with haemophilia A. Method We used personal interviews and focus groups to collect the data and analysed the data through thematic analysis. Purposive sampling was employed to recruit our participants. We continued recruiting participants until data saturation was reached from the thematic analysis. Ultimately, we obtained 37 participants, among whom 19 participated in personal interviews and 18 participated in focus groups (i.e., 3 focus groups with 6 participants each). Results Three themes and nine subthemes were identified from the thematic analysis. Nine subthemes (i.e., perceived barriers) emerged from the analysis, which were further clustered into three themes: (1) poor primary health care, (2) inadequate financial support, and (3) a lack of patient-centred care. Conclusion The findings presented in this descriptive qualitative study offer a unique view of Chinese patients with haemophilia A and their barriers to prophylactic treatment. Our findings not only provide an in-depth understanding of barriers to prophylactic treatment encountered by Chinese patients with haemophilia A but also address the urgent need to strengthen primary care, provide adequate financial support, and establish patient-centred care for these suffering patients.

Abstract Aim The prophylactic effect of negative‐pressure wound therapy against incisional surgical site infection after highly contaminated laparotomies has not been sufficiently explored. This study aimed to evaluate the prophylactic effect of negative‐pressure wound therapy against incisional surgical site infection after emergency surgery for colorectal perforation. Methods This nationwide, multicenter, retrospective cohort study analyzed data from the 48 emergency hospitals certificated by the Japanese Society for Abdominal Emergency Medicine. Patients who underwent an emergency laparotomy for colorectal perforation between April 2015 and March 2020 were included in this study. Outcomes, including the incidence of incisional surgical site infection, were compared between patients who were treated with prophylactic negative‐pressure wound therapy and delayed sutures (i.e., negative‐pressure wound therapy group) and patients who were treated with regular wound management (i.e., control group) using 1:4 propensity score matching analysis. Results The negative‐pressure wound therapy group comprised 88 patients, whereas the control group consisted of 1535 patients. Of them, 82 propensity score‐matched pairs (negative‐pressure wound therapy group: 82; control group: 328) were evaluated. The negative‐pressure wound therapy group showed a lower incidence of incisional surgical site infection [18 (22.0%) in the negative‐pressure wound therapy group and 115 (35.0%) in the control group, odds ratio, 0.52; 95% confidence interval, 0.30 to 0.92; p = 0.026]. Conclusions The prophylactic use of negative‐pressure wound therapy with delayed sutures was associated with a lower incidence of incisional surgical site infection after emergency surgery for colorectal perforation.

BackgroundChimeric antigen receptor T (CAR-T) cell immunotherapy is becoming one of the most promising treatments for hematological malignancies, however, complications such as cytokine release syndrome (CRS) seriously threaten the lives of patients. Interleukin 6(IL-6) monoclonal antibody is the common and useful treatment of CRS, however, it is not clear whether prophylactic use IL-6 monoclonal antibody before CAR-T therapy can reduce the incidence of CRS.PurposeThis study aims to systematically evaluate whether the prophylactic use of IL-6 monoclonal antibody can reduce the incidence of CRS.Data sources and methodsWe searched the PubMed, Embase, web of Science, and Cochrane Library databases for studies that reported the prophylactic use of IL-6 monoclonal antibody in the treatment of CRS-related complications of CAR-T cell immunotherapy before December 2022. The literature is screened according to the established inclusion and exclusion criteria, relevant data are extracted, and the quality of the literature is evaluated using the scale Cochrane bias risk assessment tool, and the Review Manager 5.3 is used to draw for related charts. Since the two experimental data only provide the median, the maximum and minimum values of the data, the mean and standard (Standard Deviation, SD) are calculated by this document Delai, and finally use Review Manager for data processing, and STATA software for supplementation.ResultsA total of 2 trials with a total of 37 participants were included in this study. Meta-analysis showed that compared with no use of IL-6 monoclonal antibody to prevent CRS, IL-6 monoclonal antibody was given to patients at 8 mg/kg one hour before CAR-T cell infusion, which reduced the incidence of CRS [RR: 0.41 95% confidence interval (0.20, 0.86) I[2] = 0.0% P = 0.338 z = −2.369 (p = 0.018)]. In subgroup analysis, compared with those who did not use IL-6 monoclonal antibody to prevent CRS, IL-6 monoclonal antibody was given to patients at 8 mg/kg one hour before CAR-T cell infusion, which reduced lactate dehydrogenase (LDH)[MD: −617.21, 95% confidence interval (−1104.41, −130.01) I[2] = 0% P = 0.88 Z = 2.48 (P = 0.01)], prophylactic use of IL-6 monoclonal antibody has a significant effect on reducing peak C-reactive protein (CRP) after CAR-T therapy [MD: −11.58, 95% confidence interval (−15.28, −7.88) I[2] = 0.0% P = 0.73 z = 6.14 (p < 0.00001)].ConclusionThe prophylactic use of IL-6 monoclonal antibody can significantly reduce the incidence of CRS complications after CAR-T therapy, can also reduce LDH vaule and peak CRP vaule after CAR-T therapy.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023487662, identifier CRD42023487662.

Introduction: Antiresorptive therapies are commonly utilized to mitigate and prevent skeletal-related-events in patients with metastatic osseous disease. However, limited data exists on the incidence or factors associated with prescription of antiresorptives or their effects on the incidence of pathologic fractures in patients with osseous metastatic disease. The aims of this study were to determine 1) the proportion of patients with osseous metastasis who receive antiresorptive therapy and sustain a pathologic fracture within 2-years of a new diagnosis, 2) factors associated with sustaining a pathologic fracture, and 3) factors are associated with the likelihood of receiving antiresorptive therapy. Methods: Between January 2010 and October 2021, 1,492,301 patients with a new diagnosis of osseous metastasis were captured in the Mariner dataset of the PearlDiver database. Patients were identified using International Classification of Disease (ICD) 10 codes for osseous metastasis. We excluded patients with a prior diagnosis of osseous metastasis and if they had less than two-years of follow-up. There were 696,459 patients (46.7 %) included for analysis. Of these patients, 63 % (N = 437,716) were over the age of 65, 46 % were women, and 5.6 % had Medicaid insurance. We identified patients who were prescribed antiresorptive therapy within 2-years of a new diagnosis of osseous metastasis. Cox proportional hazard ratio models were created to predict factors associated with 1) pathologic fracture and 2) receiving antiresorptive therapy within 2-years of a new diagnosis of osseous metastasis, respectively. Results: The incidence of antiresorptive therapy prescription was 7.7 % in our cohort. The incidence of pathologic fracture within 2-years of a new diagnosis was 7.3 %. The risk of sustaining a pathologic fracture was higher for patients aged 35–44 (HR 1.27 [95 % CI 1.08–1.51]; p = 0.004), those with primary kidney cancer (HR 1.78 [95 % CI 1.71–1.85]; p

Introduction: Cluster headache (CH) is a trigeminal autonomic cephalalgia characterized by attacks of severe unilateral pain associated with ipsilateral autonomic symptoms. Cluster headache attacks exhibit nocturnal predilection, and sleep disorders could be the first manifestation of an incipient cluster period. Sleep alterations in cluster headache patients may reflect the pivotal role of the hypothalamus, which is crucially involved in the pathophysiology of this primary headache. We describe the case of a patient affected by episodic cluster headache who experienced a sleep disorder after starting therapy with verapamil. Case presentation: A 47-year-old man was affected by episodic cluster headache, characterized by attacks of excruciating pain in the left orbital and temporal regions, associated with prominent ipsilateral vegetative symptoms. Headaches occurred during the night, with one or two nocturnal attacks appearing at 11.30-12 p.m. and 4-4.30 a.m. Preventive treatment with verapamil was started, with immediate pain relief. Later, he experienced consecutive nocturnal awakenings for a couple of weeks, always at the same time, without any pain or autonomic symptoms. He was not agitated and did not need to get out of bed; after the awakenings, he reported sleep disturbances with vivid dreams. Discussion and conclusion: This case represents the first description of recurrent cyclic nocturnal awakenings, without pain and autonomic symptoms, in a patient with episodic cluster headache during the active phase of a cluster bout. Nocturnal awakenings, started after the introduction of effective preventive therapy, might be an unusual formof "ghost attacks." After the beginning of prophylactic therapy, patients often describe mild pain or localized pressure in the same localization of CH attack. Similarly, the appearance of sleep disturbances, without any pain or vegetative symptoms, should be regarded as a warning sign of a still active cluster bout. Since these manifestations may influence therapeutic management, they should be carefully investigated. [ABSTRACT FROM AUTHOR]

Background: Haemophilia A is a rare, hereditary haemorrhagic disease that manifests as induced spontaneous bleeding and leads to disability or premature death in severe cases. Prophylactic treatment is optimal for patients to prevent uncontrolled bleeding and reduce the severity of the injury. However, little is known about the use of prophylactic treatment among patients with haemophilia A in China, especially barriers that predispose them to low or non-adherence. In this study, we explore the barriers to the prophylactic treatment of patients with haemophilia A. Method: We used personal interviews and focus groups to collect the data and analysed the data through thematic analysis. Purposive sampling was employed to recruit our participants. We continued recruiting participants until data saturation was reached from the thematic analysis. Ultimately, we obtained 37 participants, among whom 19 participated in personal interviews and 18 participated in focus groups (i.e., 3 focus groups with 6 participants each). Results: Three themes and nine subthemes were identified from the thematic analysis. Nine subthemes (i.e., perceived barriers) emerged from the analysis, which were further clustered into three themes: (1) poor primary health care, (2) inadequate financial support, and (3) a lack of patient-centred care. Conclusion: The findings presented in this descriptive qualitative study offer a unique view of Chinese patients with haemophilia A and their barriers to prophylactic treatment. Our findings not only provide an in-depth understanding of barriers to prophylactic treatment encountered by Chinese patients with haemophilia A but also address the urgent need to strengthen primary care, provide adequate financial support, and establish patient-centred care for these suffering patients. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy of memantine with that of valproate as a prophylactic treatment for episodic migraine within three months. The efficacy, safety, and response rate were evaluated. Methods: Prospective, randomized, double-blind, controlled clinical trial randomized participants were divided into two groups. The memantine group received memantine 10 mg twice daily, and the valproate group received valproate 500 mg twice daily. Results: Thirty-three patients participated in the study; 27 completed the treatment protocol, 14 in the memantine group, and 13 in the valproate group. The mean number of migraine attacks per month in the memantine group was 5.31 [standard deviation (SD) ± 1.54] initially and 0.93 (SD ± 1.49) at the end of treatment, noting a decrease of 4.21 (SD ± 1.76; P < 0.001). In the valproate group, the mean number of migraine attacks per month was 5.35 (SD ± 1.11) initially and 0.77 (SD ± 1.16) at the end of treatment, with a difference of 4.5 (SD ± 1.39; P < 0.001). All 27 patients had excellent response rates. Adverse effects were infrequent and mild in severity. Conclusions: A clinical trial compared the efficacy of memantine with that of valproate (first-line drug) as a prophylactic treatment. A significant reduction in attacks was noted in both drugs. Memantine could be a new preventive treatment option for migraine (ClinicalTrials.gov identifier: NCT04698525).

Abstract Background The Migraine in Poland study is the first large scale nationwide cross-sectional online survey of symptoms, approaches to management, treatment patterns, quality of life, and sociodemographic characteristics of the Polish migraine patients’ cohort, conducted from August 2021 to June 2022. Methods A cross-sectional online survey was designed based on the American Migraine Prevalence and Prevention (AMPP) Study. Participants were recruited through broad advertisement through various channels. The survey included questions allowing for the diagnosis of migraine without aura (MwoA) based on the third edition of the International Classification of Headache Disorders (ICHD-3). Moreover, the questionnaire assessed sociodemographic and headache features, comorbidities, consultation rates with medical professionals, as well as the use of abortive or preventive treatment, including non-pharmacological methods, psychological symptoms and the burden of migraine. Results A structured online questionnaire was submitted by 3225 respondents aged 13 to 80 (mean age 38.9, 87.1% women). In this group 1679 (52.7%) of participants fulfilled ICHD-3 diagnostic criteria for MwoA, which was in most cases (88.3%) confirmed by a medical professional in the past. In this group the average number of monthly headache days was 4.7, while 47.8% of participants had at least 4 migraine days per month. Mean Migraine Disability Assessment score was 42.65 (median 32). Among MwoA respondents, 1571 (93.6%) had consulted their headache with a medical professional in the past – mostly neurologists (n = 1450 (83.4%) and primary care physicians (n = 1393 (82.9%). In the MwoA cohort, 1553 (92.5%) of participants declared the current use of some form of treatment, although only 193 (11.5%) respondents were currently on preventive medications. The most prevalent comorbidities included: chronic rhinitis (37.1%), allergies (35.9%) and low blood pressure (26.9%). Anxiety (20.4%) and depression (21.3%) were highly prevalent among participants. Conclusions People with migraine in Poland face similar difficulties as their peers in other countries. Despite relatively high access to neurologist consultations and good diagnosis accuracy, migraine still poses diagnostic and therapeutic difficulties. In this context, migraine undertreatment in Polish population must be underlined, especially in context of high disease burden.

Abstract Objective The aim of this paper is to critically re-appraise the published trials assessing amitriptyline for migraine prophylaxis. Methods We report our methods and results following the Preferred Reporting Items for Systematic Reviews (PRISMA), by searching MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials of pharmacologic treatments for migraine prophylaxis. We included randomized trials that compared amitriptyline with placebo for migraine prophylaxis in adults. Our outcomes of interest were informed by the Outcome Set for preventive intervention trials in chronic and episodic migraine (COSMIG) and include the proportion of patients who experience a 50% or more reduction in migraine days per month, migraine days per month, and adverse events leading to discontinuation. We assessed risk of bias by using a modified Cochrane RoB 2.0 tool and the certainty of evidence by using the GRADE approach. Results Our search yielded 10.826 unique records, of which three trials (n = 622) were eligible for data synthesis and analysis. We found moderate certainty evidence that amitriptyline increases the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo (relative risk: 1.60 (95% CI 1.17 to 2.19); absolute risk difference: 165 more per 1,000 (95% CI 47 more to 327 more). We found moderate certainty evidence that amitriptyline increases the proportion of patients who discontinue due to adverse events compared to placebo (risk difference: 0.05 (95% CI 0.01 to 0.10); absolute risk difference: 50 more per 1,000 (95% CI 10 more to 100 more). Conclusions Our meta-analysis showed that amitriptyline may have a prophylactic role in migraine patients, however these results are far from robust. This warrants further large-scale research to evaluate the role of amitriptyline in migraine prevention.

Abstract Background Patients with cancer are at high risk for severe courses of COVID-19. Based on (pre-)clinical data suggesting a potential protective effect due to the immunomodulating properties of azithromycin, we have initiated a prospective randomized trial. Methods This randomized, single-center, single-blinded, placebo-controlled phase 2 trial included adult patients with cancer undergoing systemic treatment. Patients were 1:1 randomized to oral azithromycin (1500 mg once weekly for 8 weeks) or placebo. The primary endpoint was the cumulative number of SARS-CoV-2 infections 12 weeks after treatment initiation. Results In total, 523 patients were screened, 68 patients were randomized, and 63 patients received at least one dose of the study drug. Due to low acceptance and a lack of SARS-CoV-2 infections in the study cohort, the study was prematurely closed. With no reported grade III–IV possibly treatment-related adverse events, azithromycin was generally well tolerated. Overall survival (OS) rates after 12 months were 83.5% and 70.3% in the azithromycin and placebo group, respectively (p = 0.37). Non-SARS-CoV-2 infections occurred in 4/32 (12.5%) in the azithromycin and 3/31 (9.7%) in the placebo group (p = 1). No emergence of azithromycin-resistant S. aureus strains could be observed. According to treatment group, longitudinal alterations in systemic inflammatory parameters were detected for neutrophil/lymphocyte and leukocyte/lymphocyte ratios. Conclusion Although efficacy could not be assessed due to premature closure and low incidence of SARS-CoV-2 infections, azithromycin was associated with a favorable side effect profile in patients with cancer. As other prophylactic treatments are limited, SARS-CoV-2 vaccination remains a high priority in oncological patients. ClinicalTrials.gov registration number and date (dd/mm/yyyy): NCT04369365, 30/04/2020.

Post-traumatic stress disorder (PTSD) is a complex stress-related disorder induced by exposure to traumatic stress that is characterized by symptoms of re-experiencing, avoidance, and hyper-arousal. While it is widely accepted that brain regions involved in emotional regulation and memory—e.g., the amygdala and hippocampus—are dysregulated in PTSD, the pathophysiology of the disorder is not well defined and therefore, pharmacological interventions are extremely limited. Because stress hormones norepinephrine and cortisol (corticosterone in rats) are heavily implicated in the disorder, we explored whether preemptively and systemically antagonizing β-adrenergic and glucocorticoid receptors with propranolol and mifepristone are sufficient to mitigate pathological changes in synaptic plasticity, gene expression, and anxiety induced by a modified social defeat (SD) stress protocol. Young adult, male Sprague Dawley rats were initially pre-screened for anxiety. The rats were then exposed to SD and chronic light stress to induce anxiety-like symptoms. Drug-treated rats were administered propranolol and mifepristone injections prior to and continuing throughout SD stress. Using competitive ELISAs on plasma, field electrophysiology at CA1 of the ventral hippocampus (VH) and the basolateral amygdala (BLA), quantitative RT-PCR, and behavior assays, we demonstrate that our SD stress increased anxiety-like behavior, elevated long-term potentiation (LTP) in the VH and BLA, and altered the expression of mineralocorticoid, glucocorticoid, and glutamate receptors. These measures largely reverted to control levels with the administration of propranolol and mifepristone. Our findings indicate that SD stress increases LTP in the VH and BLA and that prophylactic treatment with propranolol and mifepristone may have the potential in mitigating these and other stress-induced effects. [ABSTRACT FROM AUTHOR]

In this paper, we present a mathematical model of the interaction between the human population and the vector (mosquito) population to study the stability of a malaria model in the presence of prophylactic treatment. This study is aimed at investigating the effect of the prophylactic treatment and the long-term dynamics of the solutions of the model. The graph-theoretic method was used to obtain the basic reproduction number (R0). We obtained the disease-free equilibrium for the model which is locally and globally asymptotically stable when the basic reproduction number is less than unity. Moreover, we showed that there exists a unique endemic equilibrium whenever R0 > 1, and the Lyapunov function was used to establish that the endemic equilibrium is globally asymptotically stable whenever R0 > 1. The simulations show the impact of prophylactic treatment on the population of infectious individuals and the findings of this study suggest that prophylactic treatment is an effective approach to reduce the transmission of malaria as prophylactic treatment reduces the population of infectious individuals. Further numerical simulations carried out conformed with the analytic results. [ABSTRACT FROM AUTHOR]

Introduction: The use of iodinated contrast media (ICM) can lead to thyrotoxicosis, especially in patients with risk factors, such as Graves' disease, multinodular goiter, older age, and iodine deficiency. Although hyperthyroidism may have clinically relevant effects, whether high-risk patients should receive prophylactic treatment before they are administered ICM is still debated. Aim of the study: We aimed to demonstrate the safety and efficacy of prophylactic treatment with sodium perchlorate and/or methimazole to prevent ICM-induced hyperthyroidism (ICMIH) in a population of high-risk cardiac patients. We ran a cost analysis to ascertain the most cost-effective prophylactic treatment protocol. We also aimed to identify possible risk factors for the onset of ICMIH. Materials and methods: We performed a longitudinal retrospective study on 61 patients admitted to a tertiary-level cardiology unit for diagnostic and/or therapeutic ICM-procedures. We included patients with available records of thyroid function tests performed before and after ICM were administered, who were at high risk of developing ICMIH. Patients were given one of two different prophylactic treatments (methimazole alone or both methimazole and sodium perchlorate) or no prophylactic treatment. The difference between their thyroid function at the baseline and 11-30 days after the ICM-related procedure was considered the principal endpoint. Results: Twenty-three (38%) of the 61 patients were given a prophylactic treatment. Thyroid function deteriorated after the administration of ICM in 9/61 patients (15%). These cases were associated with higher plasma creatinine levels at admission, higher baseline TSH levels, lower baseline FT4 levels, and no use of prophylactic treatment. The type of prophylaxis provided did not influence any onset of ICMIH. A cost-benefit analysis showed that prophylactic treatment with methimazole alone was less costly per person than the combination protocol. On multivariate analysis, only the use of a prophylactic treatment was independently associated with a reduction in the risk of ICMIH. Patients not given any prophylactic treatment had a nearly five-fold higher relative risk of developing ICMIH. Conclusion: Prophylactic treatment can prevent the onset of ICMIH in high-risk populations administered ICM. Prophylaxis is safe and effective in this setting, especially in cardiopathic patients. Prophylaxis with methimazole alone seems to be the most cost-effective option. [ABSTRACT FROM AUTHOR]

Aim: The prophylactic effect of negative‐pressure wound therapy against incisional surgical site infection after highly contaminated laparotomies has not been sufficiently explored. This study aimed to evaluate the prophylactic effect of negative‐pressure wound therapy against incisional surgical site infection after emergency surgery for colorectal perforation. Methods: This nationwide, multicenter, retrospective cohort study analyzed data from the 48 emergency hospitals certificated by the Japanese Society for Abdominal Emergency Medicine. Patients who underwent an emergency laparotomy for colorectal perforation between April 2015 and March 2020 were included in this study. Outcomes, including the incidence of incisional surgical site infection, were compared between patients who were treated with prophylactic negative‐pressure wound therapy and delayed sutures (i.e., negative‐pressure wound therapy group) and patients who were treated with regular wound management (i.e., control group) using 1:4 propensity score matching analysis. Results: The negative‐pressure wound therapy group comprised 88 patients, whereas the control group consisted of 1535 patients. Of them, 82 propensity score‐matched pairs (negative‐pressure wound therapy group: 82; control group: 328) were evaluated. The negative‐pressure wound therapy group showed a lower incidence of incisional surgical site infection [18 (22.0%) in the negative‐pressure wound therapy group and 115 (35.0%) in the control group, odds ratio, 0.52; 95% confidence interval, 0.30 to 0.92; p = 0.026]. Conclusions: The prophylactic use of negative‐pressure wound therapy with delayed sutures was associated with a lower incidence of incisional surgical site infection after emergency surgery for colorectal perforation. [ABSTRACT FROM AUTHOR]

Objective: The aim of this paper is to critically re-appraise the published trials assessing amitriptyline for migraine prophylaxis. Methods: We report our methods and results following the Preferred Reporting Items for Systematic Reviews (PRISMA), by searching MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials of pharmacologic treatments for migraine prophylaxis. We included randomized trials that compared amitriptyline with placebo for migraine prophylaxis in adults. Our outcomes of interest were informed by the Outcome Set for preventive intervention trials in chronic and episodic migraine (COSMIG) and include the proportion of patients who experience a 50% or more reduction in migraine days per month, migraine days per month, and adverse events leading to discontinuation. We assessed risk of bias by using a modified Cochrane RoB 2.0 tool and the certainty of evidence by using the GRADE approach. Results: Our search yielded 10.826 unique records, of which three trials (n = 622) were eligible for data synthesis and analysis. We found moderate certainty evidence that amitriptyline increases the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo (relative risk: 1.60 (95% CI 1.17 to 2.19); absolute risk difference: 165 more per 1,000 (95% CI 47 more to 327 more). We found moderate certainty evidence that amitriptyline increases the proportion of patients who discontinue due to adverse events compared to placebo (risk difference: 0.05 (95% CI 0.01 to 0.10); absolute risk difference: 50 more per 1,000 (95% CI 10 more to 100 more). Conclusions: Our meta-analysis showed that amitriptyline may have a prophylactic role in migraine patients, however these results are far from robust. This warrants further large-scale research to evaluate the role of amitriptyline in migraine prevention. [ABSTRACT FROM AUTHOR]

Background: The Migraine in Poland study is the first large scale nationwide cross-sectional online survey of symptoms, approaches to management, treatment patterns, quality of life, and sociodemographic characteristics of the Polish migraine patients’ cohort, conducted from August 2021 to June 2022. Methods: A cross-sectional online survey was designed based on the American Migraine Prevalence and Prevention (AMPP) Study. Participants were recruited through broad advertisement through various channels. The survey included questions allowing for the diagnosis of migraine without aura (MwoA) based on the third edition of the International Classification of Headache Disorders (ICHD-3). Moreover, the questionnaire assessed sociodemographic and headache features, comorbidities, consultation rates with medical professionals, as well as the use of abortive or preventive treatment, including non-pharmacological methods, psychological symptoms and the burden of migraine. Results: A structured online questionnaire was submitted by 3225 respondents aged 13 to 80 (mean age 38.9, 87.1% women). In this group 1679 (52.7%) of participants fulfilled ICHD-3 diagnostic criteria for MwoA, which was in most cases (88.3%) confirmed by a medical professional in the past. In this group the average number of monthly headache days was 4.7, while 47.8% of participants had at least 4 migraine days per month. Mean Migraine Disability Assessment score was 42.65 (median 32). Among MwoA respondents, 1571 (93.6%) had consulted their headache with a medical professional in the past – mostly neurologists (n = 1450 (83.4%) and primary care physicians (n = 1393 (82.9%). In the MwoA cohort, 1553 (92.5%) of participants declared the current use of some form of treatment, although only 193 (11.5%) respondents were currently on preventive medications. The most prevalent comorbidities included: chronic rhinitis (37.1%), allergies (35.9%) and low blood pressure (26.9%). Anxiety (20.4%) and depression (21.3%) were highly prevalent among participants. Conclusions: People with migraine in Poland face similar difficulties as their peers in other countries. Despite relatively high access to neurologist consultations and good diagnosis accuracy, migraine still poses diagnostic and therapeutic difficulties. In this context, migraine undertreatment in Polish population must be underlined, especially in context of high disease burden. [ABSTRACT FROM AUTHOR]

Background: Patients with cancer are at high risk for severe courses of COVID-19. Based on (pre-)clinical data suggesting a potential protective effect due to the immunomodulating properties of azithromycin, we have initiated a prospective randomized trial. Methods: This randomized, single-center, single-blinded, placebo-controlled phase 2 trial included adult patients with cancer undergoing systemic treatment. Patients were 1:1 randomized to oral azithromycin (1500 mg once weekly for 8 weeks) or placebo. The primary endpoint was the cumulative number of SARS-CoV-2 infections 12 weeks after treatment initiation. Results: In total, 523 patients were screened, 68 patients were randomized, and 63 patients received at least one dose of the study drug. Due to low acceptance and a lack of SARS-CoV-2 infections in the study cohort, the study was prematurely closed. With no reported grade III–IV possibly treatment-related adverse events, azithromycin was generally well tolerated. Overall survival (OS) rates after 12 months were 83.5% and 70.3% in the azithromycin and placebo group, respectively (p = 0.37). Non-SARS-CoV-2 infections occurred in 4/32 (12.5%) in the azithromycin and 3/31 (9.7%) in the placebo group (p = 1). No emergence of azithromycin-resistant S. aureus strains could be observed. According to treatment group, longitudinal alterations in systemic inflammatory parameters were detected for neutrophil/lymphocyte and leukocyte/lymphocyte ratios. Conclusion: Although efficacy could not be assessed due to premature closure and low incidence of SARS-CoV-2 infections, azithromycin was associated with a favorable side effect profile in patients with cancer. As other prophylactic treatments are limited, SARS-CoV-2 vaccination remains a high priority in oncological patients. ClinicalTrials.gov registration number and date (dd/mm/yyyy): NCT04369365, 30/04/2020. [ABSTRACT FROM AUTHOR]

Background: Cortical spreading depolarization, the cause of migraine aura, is a short-lasting depolarization wave that moves across the brain cortex, transiently suppressing neuronal activity. Prophylactic treatments for migraine, such as topiramate or valproate, reduce the number of cortical spreading depression events in rodents. Objective: To investigate whether cortical spreading depolarization with and without chronic treatment with topiramate or valproate affect the DNA methylation of the cortex. Methods: Sprague-Dawley rats were intraperitoneally injected with saline, topiramate or valproate for four weeks when cortical spreading depolarization were induced and genome-wide DNA methylation was performed in the cortex of six rats per group. Results: The DNA methylation profile of the cortex was significantly modified after cortical spreading depolarization, with and without topiramate or valproate. Interestingly, topiramate reduced by almost 50% the number of differentially methylated regions, whereas valproate increased them by 17%, when comparing to the non-treated group after cortical spreading depolarization induction. The majority of the differentially methylated regions lay within intragenic regions, and the analyses of functional group over-representation retrieved several enriched functions, including functions related to protein processing in the cortical spreading depolarization without treatment group; functions related to metabolic processes in the cortical spreading depolarization with topiramate group; and functions related to synapse and ErbB, MAPK or retrograde endocannabinoid signaling in the cortical spreading depolarization with valproate group. Conclusions: Our results may provide insights into the underlying physiological mechanisms of migraine with aura and emphasize the role of epigenetics in migraine susceptibility. [ABSTRACT FROM AUTHOR]

IntroductionCluster headache (CH) is a trigeminal autonomic cephalalgia characterized by attacks of severe unilateral pain associated with ipsilateral autonomic symptoms. Cluster headache attacks exhibit nocturnal predilection, and sleep disorders could be the first manifestation of an incipient cluster period. Sleep alterations in cluster headache patients may reflect the pivotal role of the hypothalamus, which is crucially involved in the pathophysiology of this primary headache. We describe the case of a patient affected by episodic cluster headache who experienced a sleep disorder after starting therapy with verapamil.Case presentationA 47-year-old man was affected by episodic cluster headache, characterized by attacks of excruciating pain in the left orbital and temporal regions, associated with prominent ipsilateral vegetative symptoms. Headaches occurred during the night, with one or two nocturnal attacks appearing at 11.30–12 p.m. and 4–4.30 a.m. Preventive treatment with verapamil was started, with immediate pain relief. Later, he experienced consecutive nocturnal awakenings for a couple of weeks, always at the same time, without any pain or autonomic symptoms. He was not agitated and did not need to get out of bed; after the awakenings, he reported sleep disturbances with vivid dreams.Discussion and conclusionThis case represents the first description of recurrent cyclic nocturnal awakenings, without pain and autonomic symptoms, in a patient with episodic cluster headache during the active phase of a cluster bout. Nocturnal awakenings, started after the introduction of effective preventive therapy, might be an unusual form of “ghost attacks.” After the beginning of prophylactic therapy, patients often describe mild pain or localized pressure in the same localization of CH attack. Similarly, the appearance of sleep disturbances, without any pain or vegetative symptoms, should be regarded as a warning sign of a still active cluster bout. Since these manifestations may influence therapeutic management, they should be carefully investigated.

IntroductionThe use of iodinated contrast media (ICM) can lead to thyrotoxicosis, especially in patients with risk factors, such as Graves’ disease, multinodular goiter, older age, and iodine deficiency. Although hyperthyroidism may have clinically relevant effects, whether high-risk patients should receive prophylactic treatment before they are administered ICM is still debated.Aim of the studyWe aimed to demonstrate the safety and efficacy of prophylactic treatment with sodium perchlorate and/or methimazole to prevent ICM-induced hyperthyroidism (ICMIH) in a population of high-risk cardiac patients. We ran a cost analysis to ascertain the most cost-effective prophylactic treatment protocol. We also aimed to identify possible risk factors for the onset of ICMIH.Materials and methodsWe performed a longitudinal retrospective study on 61 patients admitted to a tertiary-level cardiology unit for diagnostic and/or therapeutic ICM-procedures. We included patients with available records of thyroid function tests performed before and after ICM were administered, who were at high risk of developing ICMIH. Patients were given one of two different prophylactic treatments (methimazole alone or both methimazole and sodium perchlorate) or no prophylactic treatment. The difference between their thyroid function at the baseline and 11-30 days after the ICM-related procedure was considered the principal endpoint.ResultsTwenty-three (38%) of the 61 patients were given a prophylactic treatment. Thyroid function deteriorated after the administration of ICM in 9/61 patients (15%). These cases were associated with higher plasma creatinine levels at admission, higher baseline TSH levels, lower baseline FT4 levels, and no use of prophylactic treatment. The type of prophylaxis provided did not influence any onset of ICMIH. A cost-benefit analysis showed that prophylactic treatment with methimazole alone was less costly per person than the combination protocol. On multivariate analysis, only the use of a prophylactic treatment was independently associated with a reduction in the risk of ICMIH. Patients not given any prophylactic treatment had a nearly five-fold higher relative risk of developing ICMIH.ConclusionProphylactic treatment can prevent the onset of ICMIH in high-risk populations administered ICM. Prophylaxis is safe and effective in this setting, especially in cardiopathic patients. Prophylaxis with methimazole alone seems to be the most cost-effective option.

Abstract Background Despite guideline recommendations, the limited benefits and failure of prophylactic treatment in patients with migraine have been reported. This study aimed to estimate the incremental burden (i.e., healthcare resource use and cost) of disease in patients who received at least one prophylactic treatment compared to those who did not. Methods This study analyzed the Health Insurance Review and Assessment Service database, which covers the entire population of Korea from December 2014 to November 2019. We included adult patients with migraine (≥18 years) who had ≥1 claim with migraine diagnosis (G43) or received ≥1 prescription of triptan or ergotamine between December 2015 and November 2018. We defined two groups: (1) migraine patients who received at least one prophylactic treatment (prophylaxis group) and (2) migraine patients who never received prophylactic treatments (non-prophylaxis group). We performed propensity score matching to balance the baseline covariates between the two groups. In a matched cohort, we estimated healthcare resource use and costs in terms of outpatient visits, outpatient visits to neurologists, emergency department (ED) visits, and hospitalizations. Results After matching, 633,709 and 633,709 patients were identified in the prophylaxis and non-prophylaxis groups, respectively. The healthcare resource utilization was significantly higher in the prophylaxis group than in the non-prophylaxis group in terms of the number of outpatient visits (2.34 vs 1.70), outpatient visits to neurologists (2.23 vs 1.61), ED visits (1.07 vs 1.05), and hospitalizations (1.12 vs 1.09) (all P

Objective: To assess the prophylactic effect of anodal tDCS of the left motor cortex in patients with resistant chronic migraine (CM) and its long-term maintenance. Methods: In a patient-assessor blinded, sham-controlled trial, 36 patients were randomized to receive anodal tDCS (active group, n = 18) or sham tDCS (sham group, n = 18). The studied population was characterized by a previous failure of at least 3 classes of preventive drugs and a mean duration of migraine history of 26 years. The tDCS procedure consisted of an induction phase of 5 consecutive daily sessions (week 1) followed by a maintenance phase of 1 weekly session during the next 4 weeks and two bimonthly sessions in the next month, for a total of 11 sessions during 2 months. Anodal tDCS was delivered at 2 mA intensity for 20 min over the left motor cortex. The primary endpoint was the reduction in the monthly number of migraine attacks from baseline to each period of follow-up (months 1, 2, 3, 5) between the active and sham groups. Results: The monthly number of migraine attacks expressed as the percentage of reduction from baseline was significantly reduced in the active versus the sham group, from the end of first month (−21% ± 22 vs. −2% ±25, p = 0.019) to the end of follow-up (3-month post-treatment) (−32% ± 33 vs. −6% ±39, p = 0.011). At this time, the rate of responders, defined as a reduction of the monthly number of migraine attacks ≥30% from baseline, was significantly higher in the active group than in the sham group (50% vs. 14%, p = 0.043). Conclusion: Our results show a marked prophylactic effect of anodal tDCS of the left motor cortex in resistant CM extending several months after the stimulation period, and suggest that this neuromodulatory approach may be part of the prophylactic alternatives available for CM.

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to review the available evidence and provide expert advice regarding the diagnosis and management of cyclic vomiting syndrome. This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. This expert commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors who are experts in treating patients with cyclic vomiting syndrome. [ABSTRACT FROM AUTHOR]

Abstract Background Clinically, prophylactic anti-recurrence treatments for hepatocellular carcinoma (HCC) patients after radical surgery are extremely limited. Neoantigen based vaccine can generate robust anti-tumor immune response in several solid tumors but whether it could induce anti-tumor immune response in HCC and serve as a safe and effective prophylactic strategy for preventing postoperative HCC recurrence still remain largely unclear. Methods Personalized neoantigen vaccine was designed and immunized for 10 HCC patients with high risk of postoperative recurrence in a prime-boost schedule. The safety and immune response were assessed through adverse events, tissue sequencing, ELISpot, TCR sequencing. The clinical response was evaluated by recurrence-free survival (RFS) and personalized circulating tumor DNA (ctDNA) sequencing. Results In the 10 enrolled patients, no obvious adverse events were observed during neoantigen vaccinations. Until the deadline of clinical trial, 8 of 10 patients were confirmed with clinical relapse by imaging, the other 2 patients remained relapse-free. From receiving first neoantigen vaccination, the median RFS of 10 patients were 7.4 months. Among 7 patients received all planned neoantigen vaccinations, 5 of them demonstrated neoantigen-induced T cell responses and have significantly longer RFS after radical surgery than other 5 patients without responsive neoantigens or only with prime vaccination and propensity scores matching control patients (p = 0.035). Moreover, tracking personalized neoantigen mutations in ctDNA could provide real-time evaluation of clinical response in HCC patients during neoantigen vaccination and follow up. Conclusion Personalized neoantigen vaccine is proved as a safe, feasible and effective strategy for HCC anti-recurrence, and its progression could be sensitively monitored by corresponding neoantigen mutations in ctDNA, and thus provided solid information for individualized medicine in HCC. Trial registration This study was registered at Chinese Clinical Trial Registry; Registration number: ChiCTR1900020990 .

Abstract Background Erenumab, the first-in-class fully human monoclonal antibody targeting the calcitonin gene-related peptide receptor, was shown to be efficacious and safe for the prophylactic treatment of migraine in adults in randomized clinical trials. Large-scale, real-world evidence in multi-centre settings is still needed to confirm these results. Erenumab patient profiles outside clinical trials and physicians’ treatment patterns, as well as data from patients treated in Germany, a severely impacted population, are not published yet. Methods TELESCOPE was a multi-centre survey gathering real-world data from 45 German headache centres between July 2019 and December 2019. The project consisted of two parts. In the first part, treating physicians shared their experiences on current erenumab treatment with regard to patient profiles, treatment patterns and treatment responses. In the second part, a retrospective chart review was conducted of 542 migraine patients treated with erenumab for at least three months. Treatment responses focused on various aspects of patients’ quality of life. Results The analysis of 542 patients’ charts revealed that three-month treatment with erenumab significantly reduced monthly headaches, migraine and acute medication days. Furthermore, headache intensity and frequency were reduced in over 75 % and accompanying aura in 35 % of patients. The clinical global impression scale revealed a general improvement in 91 % of patients. According to the treating physicians’ professional judgement, 83 % of patients responded to erenumab and 80 % were satisfied with the treatment. Physicians evaluated restricted quality of life, the number of monthly migraine days and previous, prophylactic treatments as the main components of the current patient profile for monoclonal antibody recipients. Based on the assessment of physicians, erenumab reduced migraine symptoms in 65 % and increased quality of life in more than 75 % of their patients. Conclusions TELESCOPE confirms positive treatment responses with erenumab shown in clinical trials in a real-world multi-centre setting. The results show consistently positive experiences of physicians utilizing erenumab in clinical practice and underline that therapy with this monoclonal antibody is effective in migraine patients, particular in those, who have failed several prophylactic therapies.

Background: Lower limb ischemia-reperfusion injury (IRI-LL) is a common major complication of orthopedic surgery, especially in elderly patients. It has previously been demonstrated that folinic acid (FA) reduced IRI-LL damage in 3–4-month-old rats. This current work analyses the effect of FA in the prevention of IRI-LL in elderly animals. Methods: Forty-two 18-month-old male WAG/RijHsd rats were subjected to 3 h of ischemia. Eighteen animals received FA (2.5 mg/kg, ip) 20 min before the end of the ischemia period, while the other half received the same volume of saline solution. The animals were sacrificed after 3 h, 24 h, and 14 days of reperfusion for biochemical (tissue damage markers and electrolytes), histopathological studies of the gastrocnemius muscle and the daily assessment of the limb function by the Rota Rod test, respectively. Results: The administration of FA prior to the end of the ischemia period reduced the increase in LDH and CK observed in non-treated animals by 30–40% (p < 0.0001). When the histological sections were analyzed, FA was found to have reduced the number of damaged muscle fibers per field by 20% (60 ± 17.1 vs. 80.7 ± 16.4, p < 0.0001). The functional test revealed that FA also led to an improvement in the muscle function, assessed by the length of time that the animals kept running on the rod, compared to untreated animals. Conclusions: The administration of FA, prior to the end of the ischemic period, decreases the damage induced by IRI-LL, also achieving a faster recovery of mobility. [ABSTRACT FROM AUTHOR]

Background: There is a growing body of mitochondrial disorders that are associated with headaches, albeit only one of them is currently listed in the latest International Classification of Headache Disorders, 3rd edition (ICHD-3). Headache frequency and headache presentation can vary widely in this respective patient group. Acute and preventive migraine treatment can be quite challenging--the use of several established medications is often limited due to their side effects in the setting of mitochondrial dysfunction and multi-organ disease. Case presentation: Along with a review of the literature on treatment options in patients with mitochondrial disorders and migraine headaches, we present the case of a 23-year-old male with a homozygous mutation in the mitochondrial single-strand binding protein (SSBP1) with chronic migraine with aura. After failing several standard of care prophylactics due to either side effects or ineffcacy, he was successfully treated with a monoclonal anti-CGRP-antibody as a preventive migraine treatment. The monoclonal antibody was well tolerated and showed adequate effcacy with a sustained > 50% reduction in monthly headache days after 3 years of treatment. Conclusion: Migraine is often challenging to treat in patients with mitochondriopathy due to therapy-limiting comorbidities. Monoclonal CGRP-antibodies might be a safe treatment option in the prevention of migraine headaches in patients with a mitochondrial disorder. [ABSTRACT FROM AUTHOR]

Background & Aim: Treatment of Parkinson's disease (PD) has remained largely unchanged and focuses primarily on symptomatic relief through activation of dopaminergic pathways. Currently, there are no proven prophylactic approaches to the prevention of PD. This systematic review seeks to compare two separate compounds, metformin (MTF) and psilocybin, as potential prophylactic therapeutics against the development of PD., Methods: The authors conducted a systematic review focusing on primary studies that test these compounds on cell and animal models to determine if they might have any neuroprotective or neuroplastic effects., Results: The results of this review found that MTF may halt the progression of diseases such as PD through multiple mechanisms including reduced oxidative stress at the level of the mitochondria, thereby reducing α-synuclein related damage. Psilocybin, on the other hand, may increase repair of damaged neurons through psychoplastogenic activation of serotonergic pathways, particularly 5-HT 2A receptor activation, ultimately increasing the release of brain derived neurotropic factor (BDNF) and the reduction of α-synuclein accumulation., Conclusion: Implications of this study include a need for further research in off-label use of MTF as well as further research into serotonergic compounds such as psilocybin for the treatment and prevention of neurodegenerative diseases., Competing Interests: Declaration of competing interest No competing interests exist for the authors at this time., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Vestibular migraine is a relatively common syndrome characterized by the occurrence of vertigo and other vestibular symptoms, frequently -but not always- accompanied by migraine symptoms, such as headache, photophobia, and phonophobia., Areas Covered: The authors review the acute or abortive treatment during an attack and prophylactic treatment of vestibular migraines, including pharmacological and non-pharmacological options., Expert Opinion: Since its recognition as an independent clinical entity is recent, studies concerning its different treatment alternatives are still scarce, and the level of evidence of published studies is generally low. For acute treatment, although available data are conflicting, triptans are usually tried first. Neurostimulating devices can also be considered for acute treatment of vestibular migraine. Regarding the preventive treatment of vestibular migraine, based on the results of two randomized clinical trials and its pharmacological properties, flunarizine should be considered as the first treatment option. Second-line preventive treatments encompass propranolol, topiramate, venlafaxine, and valproic acid. Among non-pharmacological options, vestibular rehabilitation seems to be a sound prophylactic treatment option.

Hemiplegic migraine is a rare form of migraine characterized by aura with unilateral paralysis; however, studies on its treatment are limited. A 39-year-old man with migraine headaches and myofascial pain syndrome was referred to our hospital with transient right hemiplegia, after presenting to an outside emergency department with headache and right hemiplegia 2 days prior. Computed tomography, magnetic resonance imaging, and blood test results revealed no abnormalities. The symptoms resolved spontaneously; he was referred to our hospital. Based on the International Classification of Headache Disorders, Third Edition criteria, he was diagnosed with sporadic hemiplegic migraine. Propranolol was added to his regular regimen as prophylactic treatment, which resulted in reduction in his migraine frequency. Over the next 2 years, no recurrent paralysis occurred. Hemiplegic migraines should be considered in patients with migraine exhibiting transient hemiplegia without obvious intracranial abnormalities. Prophylactic treatment with propranolol could be effective in treatment of hemiplegic migraine., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Dental caries, the most prevalent chronic disease across all age groups, has a high prevalence, particularly among children. However, there is no specific and effective treatment for the prevention of caries in primary teeth (Pr.T.), which stems from a lack of knowledge regarding the basic nature of the tooth surface. Herein, we observed that the adhesion energies of the caries-related bacteria Streptococcus mutans and Streptococcus sanguinis to Pr.T were approximately 10 and 5.5 times higher than those to permanent teeth (Pe.T). A lower degree of mineralization and more hydrophilic characteristics of the Pr.T enamel account for this discrepancy. Accordingly, we proposed that the on-target modification of both hydroxyapatite and organic components on Pr.T by dual modification would render a sufficient hydration layer. This resulted in an approximately 11-time decrease in bacterial adhesion energy after treatment. In contrast, a single hydroxyapatite modification on Pe.T and young permanent teeth (Y.Pe.T) was sufficient to achieve a similar effect. Theoretical simulation further verified the rationality of the approach. Our findings may help understand the reason for Pr.T being caries-prone and provide references for treatment using resin restorations. This strategy offers valuable insights into daily oral hygiene and dental prophylactic treatment in children.

Abstract Background Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable localized episodes of edema, which is frequently managed with long-term prophylactic medications. Until recently, long-term prophylaxis has predominantly required regular intravenous or subcutaneous administration, however the recent approval of berotralstat (Orladeyo™) offers an orally administered prophylactic which may be associated with a lower burden of treatment compared to injectable options for some patients. Case presentation This report describes four participants in the APeX-S trial who transitioned from subcutaneously administered lanadelumab (Takhzyro®) to daily oral berotralstat for long-term HAE prophylaxis. Lanadelumab dosing continued after berotralstat commencement in all patients and was tapered before discontinuation in three of the four patients. No substantial increases in HAE attack rates were observed after the transition to berotralstat monotherapy. One patient experienced a treatment-related adverse event (dyspepsia), which was mild and self-resolving. Conclusions All four patients described in this case series successfully transitioned from lanadelumab to berotralstat monotherapy for long-term prophylaxis without significant complications and without the use of a complex transition protocol. The decision to transition to berotralstat monotherapy and how the transition should be achieved was discussed between patient and physician, ensuring that the comfort and perspectives of the patients were considered during the treatment transition. This report highlights the importance of individualization of HAE management plans to address both the disease and treatment burdens of HAE, and thus to provide the best possible quality of life for each patient.

BackgroundThere is a growing body of mitochondrial disorders that are associated with headaches, albeit only one of them is currently listed in the latest International Classification of Headache Disorders, 3rd edition (ICHD-3). Headache frequency and headache presentation can vary widely in this respective patient group. Acute and preventive migraine treatment can be quite challenging—the use of several established medications is often limited due to their side effects in the setting of mitochondrial dysfunction and multi-organ disease.Case presentationAlong with a review of the literature on treatment options in patients with mitochondrial disorders and migraine headaches, we present the case of a 23-year-old male with a homozygous mutation in the mitochondrial single-strand binding protein (SSBP1) with chronic migraine with aura. After failing several standard of care prophylactics due to either side effects or inefficacy, he was successfully treated with a monoclonal anti-CGRP-antibody as a preventive migraine treatment. The monoclonal antibody was well tolerated and showed adequate efficacy with a sustained > 50% reduction in monthly headache days after 3 years of treatment.ConclusionMigraine is often challenging to treat in patients with mitochondriopathy due to therapy-limiting comorbidities. Monoclonal CGRP-antibodies might be a safe treatment option in the prevention of migraine headaches in patients with a mitochondrial disorder.

Background: Despite guideline recommendations, the limited benefits and failure of prophylactic treatment in patients with migraine have been reported. This study aimed to estimate the incremental burden (i.e., healthcare resource use and cost) of disease in patients who received at least one prophylactic treatment compared to those who did not.Methods: This study analyzed the Health Insurance Review and Assessment Service database, which covers the entire population of Korea from December 2014 to November 2019. We included adult patients with migraine (≥18 years) who had ≥1 claim with migraine diagnosis (G43) or received ≥1 prescription of triptan or ergotamine between December 2015 and November 2018. We defined two groups: (1) migraine patients who received at least one prophylactic treatment (prophylaxis group) and (2) migraine patients who never received prophylactic treatments (non-prophylaxis group). We performed propensity score matching to balance the baseline covariates between the two groups. In a matched cohort, we estimated healthcare resource use and costs in terms of outpatient visits, outpatient visits to neurologists, emergency department (ED) visits, and hospitalizations.Results: After matching, 633,709 and 633,709 patients were identified in the prophylaxis and non-prophylaxis groups, respectively. The healthcare resource utilization was significantly higher in the prophylaxis group than in the non-prophylaxis group in terms of the number of outpatient visits (2.34 vs 1.70), outpatient visits to neurologists (2.23 vs 1.61), ED visits (1.07 vs 1.05), and hospitalizations (1.12 vs 1.09) (all P <  0.05). The estimated annual costs per patient were significantly higher in the prophylaxis group than in the non-prophylaxis group for outpatient (102.37 USD vs. 62.46 USD), neurology outpatient (141.80 USD vs. 120.30 USD), and ED visits (550.51 USD vs. 234.14 USD) and hospitalization (817.01 USD vs. 645.97 USD) (all P <  0.001).Conclusions: Migraine patients who received ≥1 prophylactic treatment had a higher burden of disease than migraine patients who received no prophylaxis. This indicates that despite migraine prophylaxis, the migraine-related disease burden remains high, and more efficient migraine prophylaxis strategies are needed. [ABSTRACT FROM AUTHOR]