Rejected

Acute pain is common among patients requiring assistance from prehospital emergency medical services (EMS). Nonetheless, the undertreatment of pain in this context remains a frequent phenomenon. Timely and effective analgesia is a crucial feature in emergency medicine. To ensure analgesia provision, prehospital paramedics and nurses can administer analgesics via standard operating protocols or under a physician's remote supervision. Information about such protocols in Italian EMS is lacking.

Calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are new agents approved by the US Food and Drug Administration for preventive treatment of chronic migraine. Comparison between CGRPmAbs and previously approved Botulinum neurotoxin A (BoNT-A) will inform optimal preventive treatment of chronic migraine, but head-to-head trials are lacking. We therefore aimed to perform adjusted indirect comparison between CGRPmAbs and BoNT-A through a meta-analysis. OVID MEDLINE, EMBASE and the Cochrane central register of controlled trials, clinical registries, and government websites were searched from inception to September 2019. Randomized controlled trials comparing CGRPmAbs or BoNT-A with placebo in the preventive treatment of chronic migraine were included. The primary outcomes were headache days and migraine days measured at week 12. Data were synthesized by using a frequentist approach; and the treatments were ranked by P-score. We included 10 trials ( = 4,678) after screening 1049 candidates. Six trials were with low risk of bias. Fremanezumab had an effect similar to BoNT-A in the reduction of headache days at week 12 (standard mean difference [SMD] 0.08, 95%CI -0.55 to -0.7). Galcanezumab reduced more migraine days than BoNT-A at week 12 (SMD, -0.94, 95%CI -1.24 to -0.63); fremanezumab showed similar findings (SMD, -0.55, 95%CI -0.85 to -0.24). Galcanezumab and fremanezumab had better effect in mitigating headache impact at week 12. CGRPmAbs and BoNT-A had similar adverse event rate. CGRPmAbs and BoNT-A had similar effect in the preventive treatment of chronic migraine. BoNT-A might be preferentially selected owing to its cost-effectiveness profiles. Further studies with direct comparison of the two treatments are warranted.

Chronic migraine (CM) is often complicated by medication overuse headache (MOH) and psychiatric comorbidities that may influence the clinical outcome. This study aimed to investigate the relationship between psychiatric comorbidities and the effect of transcranial direct current stimulation (tDCS) in patients with CM with or without MOH. We recruited 16 consecutive CM patients who had an unsatisfactory response to at least three pharmacological preventive therapies. They were treated with anodal right-prefrontal and cathodal occipital tDCS (intensity: 2 mA, time: 20 min) three times per week for 4 weeks. All patients underwent a psychopathological assessment before and after treatment, and five of them were diagnosed with bipolar disorder (BD). After treatment, all the patients showed a significant decrease of severe and overall headache days per month. Despite having a higher migraine burden at baseline, patients with CM and BD showed a significantly greater reduction of severe headaches and psychiatric symptoms. Overall, tDCS seems to be effective in the treatment of CM patients with a poor response to different classes of pharmacological therapies, whereas BD status positively influences the response of migraineurs to tDCS.

Methylmercury (MeHg), the causal substrate in Minamata disease, can lead to severe and chronic neurological disorders. The main symptom of Minamata disease is sensory impairment in the four extremities; however, the sensitivity of individual sensory modalities to MeHg has not been investigated extensively. In the present study, we performed stimulus-response behavioral experiments in MeHg-exposed rats to compare the sensitivities to pain, heat, cold, and mechanical sensations. MeHg (6.7 mg/kg/day) was orally administered to 9-week-old Wistar rats for 5 days and discontinued for 2 days, then administered daily for another 5 days. The four behavioral experiments were performed daily on each rat from the beginning of MeHg treatment for 68 days. The pain sensation decreased significantly from day 11 onwards, but recovered to control levels on day 48. Other sensory modalities were not affected by MeHg exposure. These findings suggest that the pain sensation is the sensory modality most susceptive to MeHg toxicity and that this sensitivity is reversible following discontinuation of the exposure.

Why can we still not translate preclinical research to clinical treatments for acute strokes? Despite > 1000 successful preclinical studies, drugs, and concepts for acute stroke, only two have reached clinical translation. This is the translational block. Yet, we continue to routinely model strokes using almost the same concepts we have used for over 30 years. Methodological improvements and criteria from the last decade have shed some light but have not solved the problem. In this conceptual analysis, we review the current status and reappraise it by thinking "out-of-the-box" and over the edges. As such, we query why other scientific fields have also faced the same translational failures, to find common denominators. In parallel, we query how migraine, multiple sclerosis, and hypothermia in hypoxic encephalopathy have achieved significant translation successes. Should we view ischemic stroke as a "chronic, relapsing, vascular" disease, then secondary prevention strategies are also a successful translation. Finally, based on the lessons learned, we propose how stroke should be modeled, and how preclinical and clinical scientists, editors, grant reviewers, and industry should reconsider their routine way of conducting research. Translational success for stroke treatments may eventually require a bold change with solutions that are outside of the box.

This study focusses on identifying values and preferences of patients, caregivers and healthcare professionals who have dealt with lower limb amputation for no-option chronic limb threatening ischemia. No-option chronic limb threatening ischemia is defined as limb ischemia for which no treatment options exist and where lower limb amputation is necessary in the short term. The values and preferences identified in this study can help improve decision-making processes.

The purpose of this study was to determine if earlier age of first exposure to football is associated with worse brain health in middle-aged and older adult men who played high school football. Men from the United States, aged 35 and older, who reported playing high school football, completed a customized, online health survey via the Amazon Mechanical Turk (mTurk) platform. Survey items included physical, psychological, and cognitive symptoms over the past week and over the past year, sports participation history (including age of first exposure to football), medical history, and concussion history. Participants also completed the Patient Health Questionnaire-8 (PHQ-8) and the British Columbia Post-Concussion Symptom Inventory (BC-PSI). There were 186 men (age M = 51.78, SD = 10.93) who participated in high school football, and 87 (46.8%) reported football participation starting before the age of 12 and 99 (53.2%) reported football participation at or after the age of 12. Those who started playing football at an earlier age reported a greater number of lifetime concussions (M = 1.95, SD = 1.79) compared to those who started playing at age 12 or later (M = 1.28, SD = 1.52; U = 3,257.5, = 0.003). A similar proportion of men who played football before vs. after the age of 12 reported a lifetime history of being prescribed medications for depression, anxiety, chronic pain, headaches, or memory problems. When comparing men who played football before vs. after the age of 12, the groups did not differ significantly in their ratings of depression, anger, anxiety, headaches, migraines, neck or back pain, chronic pain, concentration problems, or memory problems over the past week or the past year. The two groups did not differ significantly in their ratings of current symptoms of depression (PHQ-8; U = 4,187.0, = 0.74) or post-concussion-like symptoms (BC-PSI; U = 3,944.0, = 0.53). Furthermore, there were no statistically significant correlations between the age of first exposure to football, as a continuous variable, and PHQ-8 or BC-PSI scores. This study adds to a rapidly growing body of literature suggesting that earlier age of first exposure to football is not associated with later-in-life brain health.

To explore the clinical efficacy of rhBNP in patients with acute myocardial infarction (AMI) and heart failure (HF).

Periodontitis is a chronic inflammatory disease associated with the formation of dysbiotic plaque biofilms and characterized by the progressive destruction of the alveolar bone. The transition from health to disease is characterized by a shift in periodontal immune cell composition, from mostly innate (neutrophils) to adaptive (T lymphocytes) immune responses. Resolvin E1 (RvE1) is a specialized pro-resolution mediator (SPMs), produced in response to inflammation, to enhance its resolution. Previous studies have indicated the therapeutic potential of RvE1 in periodontal disease; however, the impact of RvE1 in the microbial-elicited osteoclastogenic immune response remains uncharacterized . In the present study, we studied the impact of RvE1 on the gingival inflammatory infiltrate formation during periodontitis in a mouse model. First, we characterized the temporal-dependent changes of the main immune cells infiltrating the gingiva by flow cytometry. Then, we evaluated the impact of early or delayed RvE1 administration on the gingival immune infiltration and cervical lymph nodes composition. We observed a consistent inhibitory outcome on T cells -particularly effector T cells- and a protective effect on regulatory T cells (Tregs). Our data further demonstrated the wide range of actions of RvE1, its preventive role in the establishment of the adaptive immune response during inflammation, and bone protective capacity.

The aim of the present clinical trial is to evaluate the efficacy of kinesio taping on patients with chronic low back pain, when the exploration identifies skin/fascia mobilization as a factor that could modify the treatment effect. This study is a randomized controlled trial with intention-to-treat analysis. Sixty-two participants with chronic low back pain were therefore recruited from a tertiary referral hospital. Targeted kinesio taping, according to skin/fascia mobility exploration, was applied in the experimental group (17 female/13 male; 49.47 ± 11.15 years) once a week for four sessions. The control group (17 female/14 male; 48.87 ± 9.09 years) underwent a placebo taping application. At post-treatment time there was a statistically significant reduction both in disability (Roland-Morris Disability Questionnaire) and pain (Numeric Pain Rating Scale) in the experimental group (disability: -2.88, 95% confidence interval [CI] -4.56 to -1.21, P < .001; pain: -1.58, 95% CI -2.67 to -0.54 P = .001) and the control group (disability: -1.82, 95% CI -3.46 to -0.17 P = .025; pain: -1.30, 95% CI -2.32 to -0.28 P = .008). However, at six months, these changes only remained significant in the experimental group (disability: -2.95, 95% CI -4.72 to -1.18, P < .001; pain: -1.06, 95% CI -2.07 to -0.04, P < .05). As a conclusion, the application of targeted kinesio taping produced a significant reduction in pain and disability, at 4 weeks and at 6 moths follow-up, although there were no differences between groups at any measurement time point.