"If you cannot measure it, you cannot improve it". Outcome measures in Duchenne Muscular Dystrophy: current and future perspectives.

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive neuromuscular disorder primarily affecting males, caused by mutations in the dystrophin gene. The absence of dystrophin protein leads to progressive skeletal muscle degeneration. Recent advances in the therapeutic landscape underscore the need to identify appropriate outcome measures to assess treatment efficacy in ambulant and non-ambulant DMD patients, across clinical and research settings.

Outcome measures in hemophilia: current and future perspectives.

Introduction: Hemophilia can detrimentally affect patients' quality of life and likelihood of survival. In the evolving landscape of therapies, the therapeutic gain of each treatment must be understood to accurately position it in the therapeutic armamentarium. Accordingly, appropriate outcomes must be measured with appropriate tools.

The complex landscape of DMD mutations: moving towards personalized medicine.

Duchenne muscular dystrophy (DMD) is a severe genetic disorder characterized by progressive muscle degeneration, with respiratory and cardiac complications, caused by mutations in the DMD gene, encoding the protein dystrophin. Various DMD mutations result in different phenotypes and disease severity. Understanding genotype/phenotype correlations is essential to optimize clinical care, as mutation-specific therapies and innovative therapeutic approaches are becoming available.

The good, the bad and the ugly of pain in haemophilia: Recent evidence on the epidemiology, molecular mechanisms and knowledge gaps preventing optimal treatment.

Introduction: Haemophilia is an inherited, X-linked blood clotting disorder caused by the deficiency of coagulation factors VIII (FVIII, haemophilia A) or IX (FIX, haemophilia B). Spontaneous bleeds are common in severe forms of haemophilia and can also occur in moderate and mild haemophilia. Severe or repeated bleeding at a joint can evolve into chronic haemophilic arthropathy, with functional damage of the joint, disability, and intense chronic articular pain.

Endometriosis and the diagnosis of different forms of migraine: an association with dysmenorrhoea.

Research Question: Women with endometriosis are frequently affected by headache. How many of these have a clear diagnosis of migraine? Are the different forms of migraine related to the phenotypes and/or characteristics of endometriosis?

Design: This was a prospective nested case-control study. A consecutive series of 131 women with endometriosis who attended the endometriosis clinic were enrolled and examined for the presence of headache.

Utilization patterns, cardiovascular risk, and concomitant serotoninergic medications among triptan users between 2008 and 2018: A gender analysis in one Italian region, Tuscany.

Objective: To describe the pattern of triptan use by gender in Tuscany, Italy, focusing on special user populations in which evidence on triptan safety is still not conclusive.

Background: Growing evidence supports the role of gender differences in migraine pathophysiology and treatment. However, gender impact on triptan real-word utilization has been poorly investigated.

The COVID-19 Pandemic Impact on the Outcome of Medically Assisted Reproduction Pregnancies.

Background: The impact of the Coronavirus Disease-2019 (COVID-19) pandemic on pregnancy is not well-understood. During the outbreak, the initial approach suggested by the major societies was to postpone all non-urgent assisted reproductive technology (ART) treatments. Nevertheless, the Italian Society of Fertility and Sterility and Reproductive Medicine considered ethically correct to proceed with ART treatments, as the infertility rate is increasing over time, with a consistent decline in the live birth rate.

Effectiveness of anti-CGRP monoclonal antibodies on central symptoms of migraine.

Background: Clinical trials and observational studies with anti-calcitonin gene-related peptide antibodies poorly investigated their impact on migraine prodromal and accompanying symptoms. This information might help deciphering the biologics' pharmacodynamic and provide hints on migraine pathogenesis. Herein, we report the effects of erenumab, fremanezumab and galcanezumab on attack prodromal and accompanying symptoms and on neurological and psychiatric traits.

Self-administered subcutaneous diclofenac sodium in acute migraine attack: A randomized, double-blind, placebo-controlled dose-finding pilot study.

Background: A novel formulation of diclofenac, complexed with hydroxypropyl-β-cyclodextrin (HPβCD) as a solubility enhancer, in a prefilled syringe for self-administered subcutaneous injection may overcome the limitations of acute migraine treatments administered by oral, rectal, intramuscular, or intravenous routes.

Methods: This multicentre, phase 2, double-blind, randomized, placebo-controlled, dose-finding pilot study evaluated the efficacy, safety and tolerability of three different doses (25/50/75 mg/1 mL) of subcutaneous diclofenac sodium in the treatment of an acute migraine attack in 122 subjects. The primary efficacy endpoint was the percentage of patients pain-free at 2 hours after the study drug injection.

Long-Term Effectiveness of Three Anti-CGRP Monoclonal Antibodies in Resistant Chronic Migraine Patients Based on the MIDAS score.

Background: Criteria, including clinical features and effective outcomes, for access and persistence of novel but costly treatments may vary between countries, thus affecting the health of patients. Monoclonal antibodies against the calcitonin gene-related peptide pathway (anti-CGRP mAbs) for migraine treatment are currently prescribed following strict criteria.

Objective: The aim was to assess the effectiveness and safety of three anti-CGRP mAbs (erenumab, galcanezumab, and fremanezumab) in consecutive resistant chronic migraine patients presenting at our Headache Center and the impact of criteria set by the Italian Medicines Agency to start and continue (achieving a ≥ 50% reduction in Migraine Disability Assessment [MIDAS] score) with treatment under the reimbursement program.

Predictors of sustained response and effects of the discontinuation of anti-calcitonin gene related peptide antibodies and reinitiation in resistant chronic migraine.

Background And Purpose: Guidelines for migraine prophylaxis suggest stopping medication after 6-12 months to reevaluate treatment appropriateness. The Italian Medicines Agency set a mandatory regulation to stop anti-calcitonin gene related protein (CGRP) pathway monoclonal antibody (anti-CGRP mAb) treatments for 3 months after 12 months of treatment. Herein, the effects of discontinuation and retreatment of anti-CGRP mAbs in resistant chronic migraine patients are assessed, evaluating predictive factors of sustained response.

Mental pain as a global person-centered outcome measure.

Background: Mental pain has been proposed as a global person-centered outcome measure. The aim of this cross-sectional study was to test an essential requisite of such a measure, namely that mental pain incorporates independent contributions from a range of discrete but disparate outcome measures.

Methods: Two hundred migraine patients were assessed concerning migraine disability, psychosomatic syndromes, mental pain, depression, anxiety, and psychosocial dimensions.

Time lost due to an attack - a novel patient-reported outcome measure for acute migraine treatments.

Objective: We propose a new outcome measure to assess the efficacy of migraine treatments translating the approach of the Global Burden of Disease studies from a societal to an individual level: Instead of calculating "years lived with disability", we suggest estimating "time lost due to an attack".

Methods: Time lost due to an attack is calculated by multiplying the duration and the degree of impaired functioning during an attack.

Results: Time lost due to an attack, different from other outcome measures, does not just focus on the short-term analgesic effects of treatments, but rather on the improvement of all migraine symptoms and restoration of functioning, also considering therapy-related impairment.

Position Paper on Post-Traumatic Headache: The Relationship Between Head Trauma, Stress Disorder, and Migraine.

Traumatic brain injury (mTBI) is a major public health concern, with mild TBI (mTBI) constituting the vast majority of the injuries. Post-traumatic headache (PTH) is one of the most frequent symptoms that follow a mTBI, occurring in isolation with a tension-type or migraine phenotype, or more often as part of a complex neurobehavioural array of symptoms. The existence of PTH as a separate entity from the primary headaches is still a matter of debate.

Medicines for headache before and during pregnancy: a retrospective cohort study (ATENA study).

Objective: To investigate headache treatment before and during pregnancy.

Background: Most headaches in pregnancy are primary disorders. Headaches are likely to ameliorate during pregnancy, although they may also begin or worsen.

Low-dose methadone for refractory chronic migraine accompanied by medication-overuse headache: a prospective cohort study.

Objectives: A refractory chronic migraine (RCM) accompanied by medication-overuse headache (MOH) is an extremely disabling disease. Evidence suggests that in selected patients, chronic opioids may be a valuable therapeutic option for RCM. The aim of the present study was to evaluate the effectiveness and safety of prophylaxis with low-dose methadone (LDM) in patients affected by RCM with continuous headache and MOH.

Persistent post-traumatic headache: a migrainous loop or not? The preclinical evidence.

Background: According to the International Classification of Headache Disorders 3, post-traumatic headache (PTH) attributed to traumatic brain injury (TBI) is a secondary headache reported to have developed within 7 days from head injury, regaining consciousness following the head injury, or discontinuation of medication(s) impairing the ability to sense or report headache following the head injury. It is one of the most common secondary headache disorders, and it is defined as persistent when it lasts more than 3 months.

Main Body: Currently, due to the high prevalence of this disorder, several preclinical studies have been conducted using different animal models of mild TBI to reproduce conditions that engender PTH.

Mental pain and pain-proneness in patients with migraine: results from the PAINMIG cohort-study.

Background: Pain has been qualified under four categories: nociception, perception of pain, suffering, and pain behaviors. Most of the literature on migraine has devoted attention to the first two. The aim of the present cohort study was to investigate patients with migraine enrolled at a tertiary care unit to study suffering and mental pain and identify potential risk factors for migraine.

Persistent post-traumatic headache: a migrainous loop or not? The clinical evidence.

Background: Headache is a common complication of traumatic brain injury. The International Headache Society defines post-traumatic headache as a secondary headache attributed to trauma or injury to the head that develops within seven days following trauma. Acute post-traumatic headache resolves after 3 months, but persistent post-traumatic headache usually lasts much longer and accounts for 4% of all secondary headache disorders.

Nummular headache: a gender-oriented perspective on a case series from the RegistRare Network.

Background: Nummular headache (NH) is a rare headache disorder characterized by a small, circumscribed painful area of the scalp. The description of many cases in the last years has supported its re-classification as a primary headache from the International Headache Society, moving it from its previous placement in the Appendix of the International Criteria of Headache Disorders.

Methods: Data were collected from a retro-prospective observational study about rare headaches promoted by the RegistRare Network, a collaborative group of seven Italian Headache Centres.

Criterion-related validity in a sample of migraine outpatients: the diagnostic criteria for psychosomatic research.

Objective: The Diagnostic Criteria for Psychosomatic Research (DCPR) are those of psychosomatic syndromes that did not find room in the classical taxonomy. More recently, the DCPR were updated, called DCPR-revised (DCPR-R). The present study was conducted to test the criterion-related validity of the DCPR-R.