HIT‐6 and MIDAS as Measures of Headache Disability in a Headache Referral Population

(Headache 2010;50:383‐395) Objective.— The objective of this study was to compare the headache impact test (HIT‐6) and the migraine disability assessment scale (MIDAS) as clinical measures of headache‐related disability. Background.— The degree of headache‐related disability is an important factor in treatment planning. Many quality of life and headache disability measures exist but it is unclear which of the available disability measures is the most helpful in planning and measuring headache management. Methods.— We compared HIT‐6 and MIDAS scores from 798 patients from the Canadian Headache Outpatient Registry and Database (CHORD). Correlation and regression analyses were used to examine the relationships between the HIT‐6 and MIDAS total scores, headache frequency and intensity, and Beck Depression Inventory (BDI‐II) scores. Results.— A positive correlation was found between HIT‐6 and MIDAS scores (r = 0.52). The BDI‐II scores correlated equally with the HIT‐6 and the MIDAS (r = 0.42). There was a non‐monotonic relationship between headache frequency and the MIDAS, and a non‐linear monotonic relationship between headache frequency and the HIT‐6 (r = 0.24). The correlation was higher between the intensity and the HIT‐6 scores (r = 0.46), than MIDAS (r = 0.26) scores. Seventy‐nine percent of patients fell into the most severe HIT‐6 disability category, compared with the 57% of patients that fell into the most severe MIDAS disability category. Significantly more patients were placed in a more severe category with the HIT‐6 than with the MIDAS (McNemar chi‐square = 191 on 6 d.f., P < .0001). Conclusions.— The HIT‐6 and MIDAS appear to measure headache‐related disability in a similar fashion. However, some important differences may exist. Headache intensity appears to influence HIT‐6 score more than the MIDAS, whereas the MIDAS was influenced more by headache frequency. Using the HIT‐6 and MIDAS together may give a more accurate assessment of a patient's headache‐related disability.     

Efficacy and safety of rivaroxaban or fondaparinux thromboprophylaxis in major orthopedic surgery: findings from the ORTHO‐TEP registry

Summary. Background: Thromboprophylaxis with rivaroxaban (R) is superior to enoxaparin in patients undergoing major orthopedic surgery (MOS). However, rivaroxaban has never been directly compared with fondaparinux (F), which also shows superior efficacy over enoxaparin. The clinical impact of switching from fondaparinux to rivaroxaban thromboprophylaxis is unclear. Objectives: To evaluate the efficacy and safety of rivaroxaban or fondaparinux thromboprophylaxis in unselected patients undergoing MOS. Patients/Methods: This is a monocentric, retrospective cohort study in 5061 consecutive patients undergoing MOS at our centre, comparing rates of symptomatic VTE, bleeding and surgical complications, length of hospital stay and risk factors for VTE. Results: Rates of symptomatic VTE were 5.6% (F) and 2.1% (R; P < 0.001), with rates for distal DVT being 3.9 vs. 1.1% (P < 0.001). Rates of major VTE were numerically higher with fondaparinux (1.8 vs. 1.1%), but not statistically significant. Rates of severe bleeding (bleeding leading to surgical revision or death, occurring in a critical site, or transfusion of at least two units of packed red blood cells) were statistically lower with rivaroxaban compared with fondaparinux (2.9 vs. 4.9%; P = 0.010). The mean length of hospital stay was significantly shorter in the rivaroxaban group (8.3 days, 95% CI 8.1–8.5 vs. 9.3 days, 9.1–9.5; P < 0.001). Conclusion: Based on an indirect comparison of two consecutive cohorts, our data suggest that thromboprophylaxis with rivaroxaban is associated with less VTE and bleeding events than fondaparinux in unselected patients undergoing MOS. Prospective comparisons are warranted to confirm our findings.     

The design of venous thromboembolism prophylaxis trials: fondaparinux is definitely more effective than enoxaparin in orthopaedic surgery

The fondaparinux trials in venous thromboembolism (VTE) prevention after orthopaedic surgery have been subject to methodological criticisms recently summarised in this journal. These criticisms merit comments and corrections. Fondaparinux reduced the risk of VTE and of proximal deep-vein thrombosis by more than 55% compared with enoxaparin, based on the efficacy endpoint that supported the registration and use of low-molecular-weight heparins (LMWH) in all their prophylactic indications, an endpoint endorsed by international consensus statements and health authorities. Fondaparinux is the only antithrombotic agent that significantly reduced the rate of symptomatic VTE in a single orthopaedic surgery trial that was powered to detect this effect. In contrast to the paucity of data available on LMWH, the relationship between the timing of first administration and efficacy and safety has been well documented for fondaparinux. Fondaparinux used according to its approved regimen provides a simple, easy-to-use, effective and safe post-operative regimen for all orthopaedic surgery patients.     

The mind‐brain gap and the neuroscience‐psychiatry gap

A problem underlying the mind brain gap is the complex integration among the disciplines involved in it: neurosciences, clinical psychiatry and psychology, and philosophy of science. Research in neurosciences and clinical psychiatry requires a positioning in relation to some conceptual/philosophical aspects. These are related to the models of interrelationship of the brain and the mind, to explanatory approaches in psychiatry, and to conceptual issues such as dimensionality versus categories, symptoms versus disorders, and neurobiological correlates versus clinical determination of mental disorder. In this article, we try to address some of these issues that, if taken into account, could reduce the gap between psychiatrists and neuroscientists and turn the research in this area more profitable.     

Homogeneous antibody–angiopep 2 conjugates for effective brain targeting

Antibody-based therapy has shown great success in the treatment of many diseases, including cancers. While antibodies and antibody–drug conjugates (ADCs) have also been evaluated for central nervous system (CNS) disorders as well as brain tumors, their therapeutic efficacy can be substantially limited due to low permeability across the blood–brain barrier (BBB). Thus, improving BBB permeability of therapeutic antibodies is critical in establishing this drug class as a reliable clinical option for CNS diseases. Here, we report that, compared with a conventional heterogeneous conjugation, homogeneous conjugation of the synthetic BBB shuttle peptide angiopep-2 (Ang2) to a monoclonal antibody (mAb) provides improved binding affinity for brain microvascular endothelial cells in vitro and accumulation into normal brain tissues in vivo. In a mouse model, we also demonstrate that the homogeneous anti-EGFR mAb–Ang2 conjugate administered intravenously efficiently accumulates in intracranial tumors. These findings suggest that homogeneous conjugation of BBB shuttle peptides such as Ang2 is a promising approach to enhancing the therapeutic efficacy of antibody agents for CNS diseases.

Homogeneous conjugation of angiopep-2 to a monoclonal antibody improves binding affinity for brain microvascular endothelial cells and accumulation into brain tissues and tumors across the BBB.     

Shared decision‐making across the specialties: Much potential but many challenges

Shared decision‐making (SDM) is a collaborative process through which patients and clinicians work together to arrive at a mutually agreed‐upon treatment plan. The use of SDM has gathered momentum, with it being legally mandated in some areas; however, despite being a ubiquitously applicable intervention, its maturity in use varies across the specialties and requires an appreciation of the nuanced and different challenges they each present. It is therefore our aim in this paper to review the current and potential use of SDM across a wide variety of specialties in order to understand its value and the challenges in its implementation. The specialties we consider are Primary Care, Mental Health, Paediatrics, Palliative Care, Medicine, and Surgery. SDM has been demonstrated to improve decision quality in many scenarios across all of these specialties. There are, however, many challenges to its successful implementation, including the need for high‐quality decision aids, cultural shift, and adequate training. SDM represents a paradigm shift towards more patient‐centred care but must be implemented with continued people centricity in order to realize its full potential.     

The Fife hormone service for prostate cancer patients: a cost‐effective and patient‐centric model

Injectable hormone therapy is a key element of treatment for many patients with prostate cancer. In the UK, it is typically administered in primary care. In 2003, National Health Service (NHS) Fife rolled out an innovative service for these patients, in which responsibility was moved from primary care to a specialist nurse‐led service in secondary care. The initial rationale was based on cost savings, but a significant number of other advantages have subsequently been demonstrated. These include a simpler patient journey, improved continuity of care and reduced use of consultant time. Standards of care have also improved, with fewer missed appointments, better provision of patient support and rapid access to specialist physician care when needed. An audit of 377 of 542 patients currently treated within the service has provided supportive evidence for many of these advantages. The Fife service offers a cost‐effective model for locally provided nurse‐led care that could be applied to hormone therapy services for prostate cancer elsewhere in the UK, and to services for other cancers with large numbers of patients requiring long‐term management.     

Mometasone furoate: an effective anti‐inflammatory with a well‐defined safety and tolerability profile in the treatment of asthma

Inhaled corticosteroids (ICS) are recommended as a controller medication in the most recent Global Initiative for Asthma and the National Heart, Lung and Blood Institute guidelines. Mometasone furoate (MF) is an effective, well‐tolerated inhaled steroid and is indicated for the maintenance treatment of adult and adolescent patients (≥ 12 years) with persistent asthma. MF is approved for once or bid maintenance treatment of asthma (in patients previously receiving ICS or bronchodilators). Low systemic bioavailability and high relative binding affinity for the glucocorticoid receptor are properties of MF that allow for a favourable efficacy and tolerability profile. Inhaled MF has been shown to be an effective and well‐tolerated controller medication for those patients with mild, moderate or severe persistent asthma. MF has recently been approved by the US regulatory authorities for use in children (4–11 years). Future developments include the combination of MF with the long‐acting bronchodilators, formoterol and indacaterol, to provide additional options in the treatment of asthma.