Patient-reported outcome measures for systemic lupus erythematosus: an expert Delphi consensus to guide implementation in routine care.

BACKGROUND: Systemic lupus erythematosus (SLE) may result in great impact on patients' quality of life, social relationships, and work productivity. The use of patient-reported outcome measures (PROMs) in routine care could help capture disease burden to guide SLE management and optimize disease control. We aimed to explore the current situation, appropriateness, and feasibility of PROMs to monitor patients with SLE in routine care, from healthcare professionals' and patients' perspectives. METHODS: A scientific committee developed a Delphi questionnaire, based on a focus group with patients and a literature review, including 22 statements concerning: 1) Use of PROMs in routine care (n = 2); 2) PROMs in SLE management (n = 13); 3) Multidisciplinary management of patients with SLE (n = 4), and 4) Aspects on patient empowerment (n = 3). Statements included in Sects. 2-4 were assessed from three perspectives: current use, appropriateness, and feasibility (with currently available resources). For each statement, panellists specified their level of agreement using a 7-point Likert scale. A consensus was reached when ≥ 70% of the panellists agreed (6,7) or disagreed (1,2) on each statement. RESULTS: Fifty-nine healthcare professionals and 16 patients with SLE participated in the Delphi-rounds. A consensus was reached on the value of PROMs to improve SLE management (83%) and the key role of healthcare professionals (77%) and the need for a digital tool connected to the electronic medical record (85%) to promote and facilitate PROMs collection. PROMs most frequently used in clinical practice are pain (56%), patient's global assessment (44%) and fatigue (39%), all on visual analogue scales. Panellists agreed on the need to implement multidisciplinary consultation (79%), unify complementary tests (88%), incorporate pharmacists into the healthcare team (70%), and develop home medication dispensing and informed telepharmacy programmes (72%) to improve quality of care in patients with SLE. According to panellists, patient associations (82%) and nurses (80%) are critical to educate and train patients on PROMs to enhance patient empowerment. CONCLUSIONS: Although pain, fatigue, and global assessment were identified as the most feasible, PROMs are not widely used in routine care in Spain. The present Delphi consensus can provide a road map for their implementation being key for SLE management.

Clinical predictors of therapeutic failure of occipital nerve stimulation in refractory chronic cluster headache.

BACKGROUND: Occipital nerve stimulation (ONS) is a treatment with evidence in refractory chronic cluster headache (CCH). However, the variable response rate and cost make it necessary to investigate predictors of response. METHODS: This is a cross-sectional study conducted through the review of medical records of CCH patients from six hospitals in Madrid. Epidemiological and clinical variables were compared between patients with ONS failure and the rest. ONS failure was defined as the need for device withdrawal or switch off because of lack of response or adverse events. RESULTS: From a series of 88 CCH, 26 (29.6%) underwent ONS surgery, of whom 13/26 (50.0%) failed because lack of response. ONS failure group had an earlier headache onset (mean ± SD) of 27.7 ± 6.9 vs. 36.7 ± 11.8 years, p = 0.026) and a higher smoking rate (100% vs. 42.9%, p = 0.006). Stational fluctuations (58.3% vs. 7.7%, p = 0.007) and nocturnal exacerbations (91.7% vs. 53.9%, p = 0.035) were more frequent in the ONS failure group as well. There was no difference between groups in diagnostic delay, years of evolution prior to surgery, mental illness, comorbidity with other headache disorders or chronic pain conditions or prior response to occipital nerves anesthetic blocks. CONCLUSIONS: Some clinical features such as an early debut, smoking and seasonal or circadian fluctuations could be related to failure of ONS in refractory CCH.

Prevalence of Myofascial Trigger Points in Isolated Idiopathic Cervical Dystonia: A Possible Contributor to Pain, Movement and Disability.

BACKGROUND: Myofascial trigger points (TrPs) are hypersensitive points located in a tight band of muscle that, when palpated, produce not only local pain but also referred (distant) pain. The role of TrPs in patients with cervical dystonia (CD) has not been investigated. OBJECTIVE: To identify the presence of TrPs in patients with isolated idiopathic CD and their association with pain. METHODS: Thirty-one patients (74.2% women; age: 61.2 years, SD: 10.1 years) participated. TrPs were explored in the sternocleidomastoid, upper trapezius, splenius capitis, levator scapulae, anterior scalene, suboccipital, and infraspinatus muscles. Clinical features of CD were documented as well as the presence of pain. The severity of dystonia and its consequences were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). RESULTS: The mean number of TrPs for each patient was 12 (SD:3), with no differences between patients with pain (n = 20) and those without pain (n = 11). Active TrPs were only found in patients with pain (mean: 7.5, SD:4). Latent TrPs were found in both groups but were more prevalent (P < 0.001) in patients without pain (mean: 11, SD:3.5) than in those with pain (mean: 5, SD:3.5). The number of active TrPs or latent TrPs was positively associated with the TWSTRS disability subscale and the TWSTRS total score. The number of active, but not latent, TrPs was associated with worse scores on the TWSTRS pain subscale. CONCLUSION: Active TrPs were present in patients with CD reporting pain, while latent TrPs were present in all CD patients, irrespective of their pain status. The numbers of active/latent TrPs were associated with disability. TrPs could act as pain generators in CD and also contribute to the involuntary muscle contractions characteristic of dystonia.

Sensitization-Associated Symptoms and Neuropathic-like Features in Patients with Cervical Dystonia and Pain.

Background: This exploratory study evaluated the presence of sensitization-associated and neuropathic-like symptoms and identified their association with pressure sensitivity, pain, and disability in patients with cervical dystonia (CD). Methods: Thirty-one patients with CD (74.2% women, age: 61.2 years, SD 10.1) participated. Data collected included clinical variables, the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), the Central Sensitization Inventory (CSI), the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI), as well as widespread pressure pain thresholds (PPTs). Results: Patients with CD with pain (n = 20, 64.5%) showed higher scores on the TWSTRS disability subscale and the CSI (p < 0.001), and lower PPTs (p < 0.05). Fifteen patients (15/31, 48%) showed sensitization-associated symptoms (CSI ≥ 40), whereas five of the patients with pain (5/20, 25%) exhibited neuropathic-like symptoms (S-LANSS ≥ 12). The CSI and S-LANSS were positively associated with the TWSTRS, HADS-A and HADS-D, and negatively associated with PPTs. HADS-D and S-LANSS explained 72.5% of the variance of the CSI (r2: 0.725), whereas CSI explained 42.3% of the variance of the S-LANSS (r2: 0.423). Conclusions: Pain is an important source of disability in CD, and may be a consequence of different mechanisms, including sensitization.

Can anticoagulation be withdrawn in APS patients after aPL negativization?

Long-term vitamin K antagonist (VKA) anticoagulation is the cornerstone of the management of subjects with thrombotic antiphospholipid syndrome (APS). Recent investigations have opened up new discussion points regarding the potential for stopping anticoagulant medication in patients with a history of thrombotic APS who no longer have detectable aPL (the so called aPL negativization). Despite the lack of unanimous agreement, some experts agreed on defining aPL negativization as the presence of two negative determinations, 1 year apart. What to do in order to optimize the management of these subjects with thrombotic APS when aPL turn negative is still a matter of debate. In this review, we aim to summarize the main evidence highlighting the magnitude of aPL negativizing among patients with APS and the features to keep in mind when considering (or not) stopping anticoagulation.

Real-world experience of OnabotulinumtoxinA treatment in female patients with chronic migraine: a qualitative study using in-depth interviews.

BACKGROUND: Chronic migraine (CM) causes great disability and affects an individual's quality of life. OnabotulinumtoxinA (OBT-A, Botox®) was the first prophylactic treatment specifically indicated for CM. The aim of this study was to describe the experiences of women with CM treated with OBT-A. MATERIALS AND METHODS: The study design is a qualitative descriptive study. A purposeful sampling of 30 women (mean age, 42.7; standard deviation, 10.6) who had received at least two administrations of OBT-A for CM (PREEMPT protocol) was performed. Data collection included in-depth interviews and researchers' field notes. A thematic analysis was carried out according to qualitative research guidelines. RESULTS: Five themes were identified: (a) A long way to go before Botox®, (b) First time hearing about the treatment and its expectations, (c) The administration of Botox®, (d) Treatment effects, and (e) Follow-up. Patients described a long history of treatment failures prior to the start of OBT-A treatment. Information about this migraine treatment came from the neurologist; following the information, patients had high expectations, including unrealistic expectations regarding the onset and duration of effect. They acknowledged fear of the injections and some discomfort due to the procedure. With treatment, participants reported better migraine control and an improvement in their quality of life. Follow-up had some barriers, such as delayed appointments for subsequent doses, but also strengths, such as effectiveness and few side effects. CONCLUSIONS: Qualitative research offers insight into how patients with CM experience treatment with OBT-A. Our results highlight some relevant aspects that should be considered when providing OBT-A treatment.

Women had unrealistic expectations regarding the onset and duration of OBT-A effect.With OBT-A treatment, women perceived better migraine control and improved quality of life.Follow-up had barriers, such as delayed appointments for subsequent doses.

Steroids in Lupus: Enemies or Allies.

Glucocorticoids are the gold standard treatment for reducing immune activation and inflammation in a wide range of inflammatory and systemic autoimmune diseases. Glucocorticoids have potent and fast actions that quickly relieve some symptoms and lower mortality in some life-threatening conditions, but they also have side effects that limit the duration of treatment and the dose used. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the involvement of numerous organs and systems and the production of autoantibodies. Most current treatments include the use of corticosteroids and immunosuppressive medications. Glucocorticoids in SLE have been classically used not only to induce remission or treat an acute situation but also as maintenance therapy. During the last decades, new approaches to managing SLE have emerged, but corticosteroids continue to be part of all therapeutic regimes. There is more and more evidence about the side effects related to the use (or abuse) of steroids and their relationship with the accrual damage. In this manuscript, we try to make a critical review of the published literature about the benefit and side effects/damage that can be attributed to the use of glucocorticoids.

Clinical-Pathological Characteristics of Renal Injuries Identify Different Clusters in Patients With Antiphospholipid Antibodies.

Introduction: Significant heterogeneity still exists in the nomenclature of renal involvement in antiphospholipid syndrome (APS). Methods: We applied a hierarchical cluster analysis to determine subgroups of patients according to clinical, laboratory, and renal histology characteristics in a cohort of subjects with confirmed antiphospholipid antibodies (aPL) positivity and biopsy proven aPL-related renal injuries. Kidney outcomes were then assessed at 12 months. Results: A total of 123 aPL-positive patients were included in the study (101 [82%] female, 109 [88.6%] with systemic lupus erythematosus [SLE], 14 (11.4%) with primary APS [PAPS]). Three clusters were identified. Twenty-three patients (18.7%) were included in the first cluster (cluster 1), characterized by a higher prevalence of glomerular capillary and arteriolar thrombi and fragmented red blood cells in the subendothelial space. Cluster 2 included 33 patients (26.8%) and showed a higher prevalence of fibromyointimal proliferative lesions as seen in hyperplastic vasculopathy. Cluster 3 was the largest (67 patients, mainly with SLE) and was characterized by higher prevalence of subendothelial edema, of both glomerular capillaries and arterioles. Conclusion: Three different clusters of patients with aPL and renal injuries emerged from our study as follows: the first, with the worst renal prognosis, was associated with features of thrombotic microangiopathy (TMA), thrombosis, triple aPL positivity and higher adjusted Global APS Score (aGAPSS) values; the second, characterized by hyperplastic vasculopathy with an intermediate prognosis, was seen more frequently in patients with cerebrovascular manifestations; and the third, more benign in terms of outcomes and with no overt association with thrombotic features, was characterized by endothelial swelling in concomitant lupus nephritis (LN).

Epicranial headaches part 2: Nummular headache and epicrania fugax.

BACKGROUND: Nummular headache and epicrania fugax are two primary headaches that fall under the heading of epicranial headaches. METHODS: This article reviews the epidemiological and clinical features of nummular headache and epicrania fugax, proposed pathogenic mechanisms and state-of-the-art management, according to the literature. RESULTS AND CONCLUSIONS: Nummular headache and epicrania fugax are generally viewed as rare headache disorders, but no population-based epidemiological data are available. Nummular headache is characterized by continuous or intermittent head pain, which remains circumscribed in a round or oval area of the scalp, typically one to six centimeters in diameter. Epicrania fugax manifests with brief paroxysms of pain that move along the surface of the head, following a linear or zigzag trajectory through different nerve territories. Nummular headache and epicrania fugax are mostly primary headaches, but some secondary cases have been reported. The pathogenesis of these headaches is not fully understood. Nummular headache could probably originate in epicranial tissues or adjacent intracranial structures, while the origin of epicrania fugax could be extracranial or intracranial. Diagnostic assessment requires careful examination of the symptomatic areas. Underlying disorders should be excluded by additional investigations, including neuroimaging and appropriate blood tests. No controlled clinical trials have been conducted in nummular headache or epicrania fugax. Analgesics and anti-inflammatory drugs, botulinum toxin and gabapentin are currently the most recommended treatment options for nummular headache. In epicrania fugax, the most used treatments are gabapentin, lamotrigine, and other antiseizure medications.

Headache as a COVID-19 onset symptom or Post-COVID symptom according to the SARS-CoV-2 Variant.

INTRODUCTION: COVID19 associated headaches are highly common and there is currently an unmet need to better understand their association with SARSCoV2 variants. Headaches are a prevalent symptom in the acute phase of COVID19 and are associated with a better prognosis and better immune response. They are also a relevant post-COVID symptom. AREAS COVERED: This article analyses the differences in the prevalence of headache as an onset symptom and in post-COVID headache among the different SARS-CoV-2 variants: the historical strain, Alpha, Delta and Omicron. The different pathophysiological mechanisms by which SARS-CoV-2 infection may cause headache are also discussed. EXPERT OPINION: The presence of headache at the acute phase is a risk factor for post-COVID headache, whereas a history of primary headache does not appear to be associated with post-COVID headache. The prevalence of headache as an onset symptom appears to be variable for the different SARS-CoV-2 variants, but current data are inconclusive. However, the current evidence also suggests that headache represents a prevalent symptom in the acute and post-infection COVID-19 phase, regardless of SARS-CoV-2 variant.

Upfront autologous haematopoietic stem-cell transplantation versus carfilzomib-cyclophosphamide-dexamethasone consolidation with carfilzomib maintenance in patients with newly diagnosed multiple myeloma in England and Wales (CARDAMON): a randomised, phase 2, non-inferiority trial.

BACKGROUND: Standard-of-care treatment for patients with newly diagnosed multiple myeloma is bortezomib-based induction followed by high-dose melphalan and autologous haematopoietic stem-cell transplantation (HSCT) and lenalidomide maintenance. We aimed to evaluate whether an immunomodulatory-free carfilzomib-based induction, consolidation, and maintenance protocol without autologous HSCT was non-inferior to the same induction regimen followed by autologous HSCT and maintenance. METHODS: CARDAMON is a randomised, open-label, phase 2 trial in 19 hospitals in England and Wales, UK. Newly diagnosed, transplantation-eligible patients with multiple myeloma aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 received four 28-day cycles of carfilzomib (56 mg/m2 intravenously on days 1, 2, 8, 9, 15, and 16), cyclophosphamide (500 mg orally on days 1, 8, and 15), and dexamethasone (40 mg orally on days 1, 8, 15, and 22; KCd), followed by peripheral blood stem cell mobilisation. Patients with at least a partial response were randomly assigned (1:1) to either high-dose melphalan and autologous HSCT or four cycles of KCd. All randomised patients received 18 cycles of carfilzomib maintenance (56 mg/m2 intravenously on days 1, 8, and 15). The primary outcomes were the proportion of patients with at least a very good partial response after induction and difference in progression-free survival rate at 2 years from randomisation (non-inferiority margin 10%), both assessed by intention to treat. Safety was assessed in all patients who started treatment. The trial is registered with ClinicalTrials.gov (NCT02315716); recruitment is complete and all patients are in follow-up. FINDINGS: Between June 16, 2015, and July 8, 2019, 281 patients were enrolled, with 218 proceeding to randomisation (109 assigned to the KCd consolidation group [99 of whom completed consolidation] and 109 to the HSCT group [104 of whom underwent transplantation]). A further seven patients withdrew before initiation of carfilzomib maintenance (two in the KCd consolidation group vs five in the HSCT group). Median age was 59 years (IQR 52 to 64); 166 (59%) of 281 patients were male and 115 (41%) were female. 152 (71%) of 214 patients with known ethnicity were White, 37 (17%) were Black, 18 (8%) were Asian, 5 (2%) identified as Mixed, and 2 (1%) identified as other. Median follow-up from randomisation was 40·2 months (IQR 32·7 to 51·8). After induction, 162 (57·7%; 95% CI 51·6 to 63·5) of 281 patients had at least a very good partial response. The 2-year progression-free survival was 75% (95% CI 65 to 82) in the HSCT group versus 68% (95% CI 58 to 76) in the KCd group (difference -7·2%, 70% CI -11·1 to -2·8), exceeding the non-inferiority margin. The most common grade 3-4 events during KCd induction and consolidation were lymphocytopenia (72 [26%] of 278 patients who started induction; 15 [14%] of 109 patients who started consolidation) and infection (50 [18%] of 278 for induction; 15 [14%] of 109 for consolidation), and during carfilzomib maintenance were hypertension (20 [21%] of 97 patients in the KCd consolidation group vs 23 [23%] of 99 patients in the HSCT group) and infection (16 [16%] of 97 patients vs 25 [25%] of 99). Treatment-related serious adverse events at any point during the trial were reported in 109 (39%) of 278 patients who started induction, with infections (80 [29%]) being the most common. Treatment-emergent deaths were reported in five (2%) of 278 patients during induction (three from infection, one from cardiac event, and one from renal failure) and one of 99 patients during maintenance after autologous HSCT (oesophageal carcinoma). INTERPRETATION: KCd did not meet the criteria for non-inferiority compared with autologous HSCT, but the marginal difference in progression-free survival suggests that further studies are warranted to explore deferred autologous HSCT in some subgroups, such as individuals who are MRD negative after induction. FUNDING: Cancer Research UK and Amgen.

Headache as a COVID-19 onset symptom and post-COVID-19 symptom in hospitalized COVID-19 survivors infected with the Wuhan, Alpha, or Delta SARS-CoV-2 variants.

OBJECTIVE: This study looked at differences in the presence of headache as an onset symptom of coronavirus disease 2019 (COVID-19) and as a post-COVID-19 symptom in individuals previously hospitalized owing to infection with the Wuhan, Alpha, or Delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). BACKGROUND: Headache can be present in up to 50% of individuals during the acute phase of SARS-CoV-2 infection and in 10% of subjects during the post-COVID-19 phase. There are no data on differences in the occurrence of headache in the acute- and post-COVID-19 phase according to the SARS-CoV-2 variants. METHODS: A cross-sectional cohort study was conducted. Unvaccinated subjects previously hospitalized for COVID-19 caused by the Wuhan (n = 201), Alpha (n = 211), or Delta (n = 202) SARS-CoV-2 variants were scheduled for a telephone interview 6 months after hospital discharge. Hospitalization data were collected from hospital medical records. RESULTS: The presence of headache as a COVID-19 onset symptom at hospitalization was higher in subjects with the Delta variant (66/202, 32.7%) than in those infected with the Wuhan (42/201, 20.9%; odds ratio [OR] 1.83, 95% confidence interval [CI] 1.17-2.88) or Alpha (25/211, 11.8%; OR 3.61, 95% CI, 2.16-6.01) variants. The prevalence of post-COVID-19 headache 6 months after hospital discharge was higher in individuals infected with the Delta variant (26/202, 12.9%) than in those infected with the Wuhan (11/201, 5.5%; OR 2.52, 95% CI 1.22-5.31) or Alpha (eight of 211, 3.8%; OR 3.74, 95% CI 1.65-8.49) variants. The presence of headache as a COVID-19 onset symptom was associated with post-COVID-19 headache in subjects infected with the Wuhan (OR 7.75, 95% CI 2.15-27.93) and Delta variants (OR 2.78, 95% CI 1.20-6.42) but not with the Alpha variant (OR 2.60, 95% CI 0.49-13.69). CONCLUSION: Headache was a common symptom in both the acute- and post-COVID-19 phase in subjects infected with the Wuhan, Alpha, and Delta variants but mostly in those infected with the Delta variant.

Nummular headache responsive to anti-calcitonin gene-related peptide monoclonal antibodies in a patient with migraine.

BACKGROUND: Nummular headache (NH) is defined by the presence of localized pain circumscribed to a round or elliptical area of the scalp, with a well-defined contour and a diameter of 1-6 cm. Although some evidence supports a peripheral mechanism, its etiopathogenesis remains unclear. CASE: We report the case of a 64-year-old man with high-frequency episodic migraine who has used topiramate, beta-blockers, flunarizine, and amitriptyline without effect. In the last 8 years he also had continuous pain in an oval area of the scalp, consistent with NH. Triptans were ineffective for this new pain, and preventive therapy with gabapentin and onabotulinumtoxinA in the painful area had no effect. NH remitted when the patient received monthly treatment with subcutaneous galcanezumab for his migraine. CONCLUSIONS: Monoclonal antibodies against calcitonin gene-related peptide (CGRP), in particular galcanezumab, might be an effective therapy in some patients with NH. CGRP may have a role in the etiopathogenesis of this headache, which warrants further investigation.

Reply to Ayuso García et al. Health Perception among Female COVID-19 Patients. Comment on "Fernández-de-las-Peñas et al. Female Sex Is a Risk Factor Associated with Long-Term Post-COVID Related-Symptoms but Not with COVID-19 Symptoms: The LONG-COVID-EXP-CM Multicenter Study. J. Clin. Med. 2022, 11, 413".

We have read with great interest the comment by Ayuso García et al [...].

Exploiting Meltable Protein Hydrogels to Encapsulate and Culture Cells in 3D.

There is a growing realization that 3D cell culture better mimics complex in vivo environments than 2D, lessening aberrant cellular behaviors and ultimately improving the outcomes of experiments. Chemically crosslinked hydrogels which imitate natural extracellular matrix (ECM) are proven cell culture platforms, but the encapsulation of cells within these hydrogel networks requires bioorthogonal crosslinking chemistries which can be cytotoxic, synthetically demanding, and costly. Capsular antigen fragment 1 (Caf1) is a bacterial, polymeric, fimbrial protein which can be genetically engineered to imitate ECM. Furthermore, it can, reversibly, thermally interconvert between its polymeric and monomeric forms even when chemically crosslinked within a hydrogel network. It is demonstrated that this meltable feature of Caf1 hydrogels can be utilized to encapsulate neonatal human dermal fibroblasts at a range of cell densities (2 × 105 -2 × 106  cells mL-1 of hydrogel) avoiding issues with chemical cytotoxicity. These hydrogels supported cell 3D culture for up to 21 d, successfully inducing cellular functions such as proliferation and migration. This work is significant because it further highlights the potential of simple, robust, Caf1-based hydrogels as a cell culture platform.

Sensory processing and adaptive behavior in Phelan-McDermid syndrome: a cross-sectional study.

Phelan-McDermid syndrome (PMS) is a genetic disorder caused by a mutation or deletion of the SHANK3 gene (chromosome 22q13.3), characterized by different sensory processing anomalies. The objective of this study is to expand and provide a detailed definition of the sensory profile of patients with PMS. The secondary objective was to examine the relationship between sensory patterns and adaptive behavior. A cross-sectional study was carried out among 51 Spanish patients with a confirmed genetic diagnosis of PMS. All the participants' parents completed the Short Sensory Profile-Spanish (SSP-S) and the Adaptive Behavior Assessment System II (ABAS-II). Correlational, multiple regression and hierarchical cluster analyses were performed. An atypical sensory profile was identified in almost 75% of PMS patients. Definite differences were found among scores; nonetheless, sub-threshold values were observed in tactile sensitivity, underresponsive/seeks sensation, auditory filtering, and low energy/weak sensory categories. Conceptual, social, and practical domains, as well as the General Adaptive Composite (GAC) of the ABAS-II showed extremely low scores (i.e., <70). Significant correlations were found (p<0.005) between SSP-S scores and the conceptual, social, practical, and GAC index of the ABAS-II, whereby higher SSP-S scores were associated with better skills and higher adaptive performance. The cluster analysis indicated that the group with the largest mutation size (7.23 Mb) showed the greatest sensory processing difficulties and very low adaptive skills. CONCLUSIONS: Patients with PMS show an atypical sensory profile, which correlates with limitations in general adaptive behaviors. WHAT IS KNOWN: • PMS sensory processing difficulties were associated with a pattern of underresponsive/seeks sensation, low energy/weak, and tactile hyporeactivity. • Sensory processing difficulties have been associated with limitations in the development of appropriate adaptive communication and interaction behaviors. WHAT IS NEW: • Sensory definite differences associated with tactile hyperreactivity, as well as significant effects of underresponsiveness/seeks sensation and auditory filtering categories on the adaptive abilities were found in SHANK3deletion patients. • Cluster analysis suggests that smaller mutation sizes were related to better sensory processing and higher adaptive skills, while patients with larger deletion sizes have greater adaptive difficulties and worse sensory processing skills.

Understanding the interaction between clinical, emotional and psychophysical outcomes underlying tension-type headache: a network analysis approach.

OBJECTIVE: Evidence supports that tension-type headache (TTH) involves complex underlying mechanisms. The current study aimed to quantify potential multivariate relationships between headache-related, psychophysical, psychological and health-related variables in patients with TTH using network analysis. METHODS: Demographic (age, height, weight), headache-related (intensity, frequency, duration, and headache-related disability), psychological and emotional (Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index), psycho-physical (pressure pain thresholds [PPTs] and myofascial trigger points) and health-related variables (SF-36 questionnaire) were collected in 169 TTH patients. Network connectivity analysis was unsupervised conducted to quantify the adjusted correlations between the modelled variables and to assess their centrality indices (i.e., the connectivity with other symptoms in the network and the importance in the modelled network). RESULTS: The connectivity network showed local associations between psychophysical and headache-related variables. Multiple significant local positive correlations between PPTs were observed, being the strongest weight between PPTs over the cervical spine and temporalis area ([Formula: see text]: 0.41). The node with the highest strength, closeness and betweenness centrality was depressive levels. Other nodes with high centrality were vitality and headache intensity. DISCUSSION: This is the first study applying a network analysis to understand the connections between headache-related, psychophysical, psychological and health-related variables in TTH. Current findings support a model on how the variables are connected, albeit in separate clusters. The role of emotional aspects, such as depression, is supported by the network. Clinical implications of the findings, such as developing TTH treatments strategies targeting these most important variables, are discussed.