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Background Primary headache disorders are common and burdensome conditions. They are associated to several comorbidities, such as cardiovascular or psychiatric ones, which, in turn, contribute to the global burden of headache. The aim of this study is to provide a comprehensive description of the pooled prevalence of comorbidities of primary headache disorders using a meta-analytical approach based on studies published between 2000 and 2020. Methods Scopus was searched for primary research (clinical and population studies) in which medical comorbidities were described in adults with primary headache disorders. Comorbidities were extracted using a taxonomy derived from the Global Burden of Disease (GBD) study. We compared prevalence of comorbidities among headache sufferers against general population using GBD-2019 estimates, and compared comorbidities’ proportions in clinical vs. population studies, and by age and gender. Results A total of 139 studies reporting information on 4.19 million subjects with primary headaches were included: in total 2.75 million comorbidities were reported (median per subject 0.64, interquartile range 0.32–1.07). The most frequently addressed comorbidities were: depressive disorders, addressed in 51 studies (pooled proportion 23 %, 95 % CI 20–26 %); hypertension, addressed in 48 studies (pooled proportion 24 %, 95 % CI 22–26 %); anxiety disorders addressed in 40 studies (pooled proportion 25 %, 95 % CI 22–28 %). For conditions such as anxiety, depression and back pain, prevalence among headache sufferers was higher than in GBD-2109 estimates. Associations with average age and female prevalence within studies showed that hypertension was more frequent in studies with higher age and less females, whereas fibromyalgia, restless leg syndrome, and depressive disorders were more frequent in studies with younger age and more female. Conclusions Some of the most relevant comorbidities of primary headache disorders – back pain, anxiety and depression, diabetes, ischemic heart disease and stroke – are among the most burdensome conditions, together with headache themselves, according to the GBD study. A joint treatment of headaches and of these comorbidities may positively impact on headache sufferers’ health status and contribute to reduce the impact of a group of highly burdensome diseases.

Context Nonpharmacologic treatment, such as osteopathic manipulative therapy (OMTh; manipulative care provided by foreign-trained osteopaths) may be a beneficial complementary treatment for tension-type headache. However, to the authors’ knowledge, the benefit of OMTh in the management of tension-type headache has not been explored, especially chronic tension-type headache (CTTH). Objective To investigate the effectiveness of OMTh compared with traditional treatment in reducing pain intensity, frequency, and duration of CTTH, and to evaluate the objective postural measurement of the forward head posture (FHP) as an integral parameter in the assessment of the effects of OMTh and traditional management of CTTH. Methods Patients with CTTH were registered at the Headache Centre of Trieste in Italy. At the time of the study, none of the patients had been taking any headache prophylaxis in the past 3 months. A 3-month baseline period was recorded by all patients with an ad hoc diary. Patients were randomly placed in the test or control group using a simple randomization program in Excel (Microsoft). Patients in the OMTh group underwent a 3-month period of OMTh, and patients in the control group were treated with amitriptyline. Pain intensity, frequency, and duration of headaches, as well as FHP were analyzed. Results The study enrolled 10 patients (mean [SD] age, 42.6 [15.2] years) in the OMTh group and 10 patients (51.4 [17.3] years) in the control group. The final assessment of OMTh patients showed statistically significant changes in all headache parameters: pain intensity decreased from a mean (SD) score of 4.9 (1.4) to 3.1 (1.1) (P=.002); frequency decreased from 19.8 (6) to 8.3 (6.2) days per month (P=.002); and the duration of headaches decreased from 10 (4.2) to 6 (3) hours (P=.01). Significant improvement of all parameters was found in the control group as well: pain intensity decreased from a mean (SD) score of 5.9 (0.7) to 4.2 (1.75) (P=.03); frequency decreased from 23.4 (7.2) to 7.4 (8.7) days per month (P=.003); and duration decreased from 7.8 (2.9) to 3.6 (2.1) hours (P=.002). Forward head posture significantly improved in OMTh patients (P=.003). Conclusions Our data suggested that OMTh may be an effective treatment to improve headaches in patients with CTTH. Our results also suggest that OMTh may reduce FHP.

Introduction The purpose of the present study is to compare the effect of the physiotherapy to onabolulinumtoxin-A, and their combination, in relation to cervical and headache parameters in patients with chronic migraine. Methods This is an observational cohort study conducted by a headache center and a physiotherapy degree course on 30 patients with chronic migraine. The patients were distributed in three groups of treatments for three months: onabolulinumtoxin-A only, physiotherapy only, and onabolulinumtoxin-A plus physiotherapy. The patients were evaluated, before and after each treatment, using the following: the postural assessment software SAPO for the forward head posture; the CROM goniometer for the cervical range of motion; the Migraine Disability Assessment Score for headache parameters. Results After 3 months of each treatment, the scores obtained for the headache-related disability and the frequency of migraine decreased significantly for all groups, but the pain intensity scores changed significantly only in the onabolulinumtoxin-A (p = 0.01) and in the onabolulinumtoxin-A plus physiotherapy groups (p = 0.007). On the other hand, the forward head posture was reduced significantly in the physiotherapy (p = 0.002) and in the onabolulinumtoxin-A plus physiotherapy groups (p = 0.003). The cervical range of motion increased significantly in certain directions in the physiotherapy group and in the onabolulinumtoxin-A plus physiotherapy groups. Conclusions The physiotherapy improved the cervical parameters. The onabolulinumtoxin-A decreased pain intensity. As a consequence, it can be said that the combined treatment was more useful than a mono-therapy alone. From our results, it can be concluded that onabolulinumtoxin-A plus physiotherapy could be a good option in the management of chronic migraine.

Key points Age per se does not influence outcome in CLL patients on ibrutinib, whereas CIRS score is predictive of treatment management, PFS, and EFS.ECOG-PS and neutropenia resulted as the only baseline parameters affecting overall survival., Visual Abstract, Functional reserve of organs and systems is known to be relevant in predicting immunochemotherapy tolerance. Age and comorbidities, assessed by the cumulative illness rating scale (CIRS), have been used to address chemotherapy intensity. In the ibrutinib era, it is still unclear whether age, CIRS, and Eastern Cooperative Oncology Group performance status (ECOG-PS) retain their predictive role on treatment vulnerability. In this series of 712 patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib outside clinical trials, baseline ECOG-PS and neutropenia resulted as the most accurate predictors of treatment feasibility and outcomes. Age did not independently influence survival and ibrutinib tolerance, indicating that not age per se, but age-related conditions, may affect drug management. We confirmed the role of CIRS > 6 as a predictor of a poorer progression- and event-free survival (PFS, EFS). The presence of a severe comorbidity was significantly associated with permanent dose reductions (PDRs), not translating into worse outcomes. As expected, del(17p) and/or TP53mut and previous therapies affected PFS, EFS, and overall survival. No study so far has analyzed the influence of concomitant medications and CYP3A inhibitors with ibrutinib. In our series, these factors had no impact, although CYP3A4 inhibitors use correlated with Cox regression analysis, with an increased risk of PDR. Despite the limitation of its retrospective nature, this large study confirmed the role of ECOG-PS as the most accurate predictor of ibrutinib feasibility and outcomes, and importantly, neutropenia emerged as a relevant tool influencing patients’ vulnerability. Although CIRS > 6 retained a significant impact on PFS and EFS, its value should be confirmed by prospective studies.

There is a growing research interest towards the use of wireless IMU sensors to assess disability, monitor progress and provide feedback to patients on range of motion and movement performance during upper body rehabilitation. The quality of movement in patients with adhesive capsulitis and relative treatment efficacy has not yet been studied using inertial and magnetic sensors. The aim of this study was to investigate the possibility to quantitatively evaluate capsulate-related deficit versus healthy controls and to assess treatment efficacy by measurement of shoulder kinematic parameters with ISEO protocol using inertial and magnetic measurement system technology. We enrolled 6 patients with adhesive capsulitis (AC) who underwent the experimental assessment by using a set of wireless IMU sensors at the baseline (T0) and after the 15 one- hour individual sessions of physiotherapy (T1). The range of motion in elevation, abduction and the scapulo-humeral rhythm kinematic parameters were extracted from measurements performed in enrolled AC patients and in 7 healthy controls. The results of this preliminary study showed that proposed approach based on measurement of shoulder kinematic parameters with ISEO protocol using IMU wireless sensors can be useful in mobility deficit assessment of patients with adhesive capsulitis, as well as for monitoring of treatment efficacy and its further personalization.

Introduction: Chemoimmunotherapy has improved outcomes in chronic lymphocytic leukemia, yet it is not curative, with very high relapse rates, and is associated with a significant risk of toxicities. Moreover, patients with higher-risk genetic abnormalities continue to experience poorer outcomes and lower survival. Recently, novel targeted therapies have been developed to increase efficacy and reduce toxicity. Areas covered: Ibrutinib is an oral irreversible inhibitor of Bruton’s tyrosine kinase, a mediator of B-cell receptor signaling, which plays a vital role in various B-cell neoplasms. The drug has been approved for the treatment of several hematological malignancies, including chronic lymphocytic leukemia/small lymphocytic lymphoma, where large trials have shown outcomes never seen before even in high-risk patients. The safety profile appeared furthermore favorable, even in elderly and unfit patients. Expert opinion: Therapy with ibrutinib rarely provides MRD-negative complete remission; an indefinite maintenance is therefore needed, with the risk of developing adverse events (AE) or resistance resulting in treatment interruption or discontinuation. Novel, extremely promising, combination strategies, based on the association of ibrutinib with chemoimmunotherapy, anti-CD20 monoclonal antibody or other targeted agents, are currently being investigated, with the goal of achieving greater depth of remission, especially MRD-negativity, and removing the need for indefinite treatment.

Waldenstrom Macroglobulinemia is a rare lymphoproliferative disorder with distinctive clinical features. Diagnostic and prognostic charactrization in WM significantly changed with the discovery of two molecular markers: MYD88 and CXCR4. Mutational status of these latter influences both clinical presentation and prognosis and demonstrated therapeutic implications. Treatment choice in Waldemstrom disease is strictly guided by patients age and characteristics, specific goals of therapy, necessity for rapid disease control, risk of treatment-related neuropathy, disease characteristics, risk of immunosuppression or secondary malignancies and potential for future autologous stem cell transplantation. Therapeutic landscape has expanded during the last years and the approval of ibrutinib, the first drug approved for Waldenstrom Macroglobulinemia, represents an important step forward for a better management of the disease.

Ibrutinib represents a revolution in chronic lymphocytic leukemia treatment scenario providing results never seen before and offering an effective therapy even in high-risk patients with really poor outcome after chemoimmunotherapy. Thanks to longer updates, on one hand, ibrutinib has confirmed its efficacy continuing to show clinical benefits over time; on the other hand, resistance mechanisms are slowly emerging. Moreover, clinicians should be aware of ibrutinib-related side effects, paying attention to screen patients that could benefit more from the drug and try to prevent adverse events. While ibrutinib approval indication is expanding, high treatment costs will shortly require a selection of those who can really draw advantage from Bruton's tyrosine kinase inhibition and those who could continue to be treated with chemoimmunotherapy.