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Prescription Trends and Clinical Decision‐Making in Neuropathic Pain Pharmacological Treatment: Results From a Cross‐Sectional Survey by the Spanish Pain Society
Get PDFBackground: Neuropathic pain (NP) is a complex chronic condition with limited therapeutic effectiveness. Despite multiple drug classes and international guidelines, real‐world adherence remains inconsistent, and data on prescribing practices among pain specialists is scarce. Methods: We conducted a nationwide cross‐sectional survey among members of the Spanish Pain Society in May 2025. A structured 62‐item questionnaire assessed prescribing habits, decision‐making criteria, guideline adherence, dosage patterns, and the recognition and management of tolerance. Sociodemographic and professional data were also collected. Results: A total of 220 pain specialists (52% female) completed the survey; 28% had over 20 years of clinical experience. Satisfaction with current pharmacological options was modest, with 52% reporting dissatisfaction or indifference. Prescribing was mainly guided by clinical experience (43%) and guideline recommendations (36%). Gabapentin (45%) and pregabalin (40%) were the most frequent first‐line choices, followed by tricyclic antidepressants (amitriptyline; 9%), duloxetine (5%) and venlafaxine (1%). Tramadol dominated second‐line use (65%), followed by capsaicin (22%) or lidocaine (5%) patches. Half of the participants reported tolerance, typically after 3–12 months, managed mainly by dose escalation or switching drug classes. Dosage practices for gabapentinoids and antidepressants showed marked heterogeneity, with frequent deviations from recommended titration protocols. Conclusions: NP management in Spain shows variability and partial alignment with international guidelines. Gabapentinoids, tricyclic antidepressants and duloxetine remain preferred treatments, but reliance on personal experience and awareness of tolerance hinder evidence‐based practice. Quantifying Spanish pain specialists' views on tolerance supports calls for national consensus, better dosing education and further research to harmonise care and improve outcomes. Significance: This nationwide survey provides the first systematic assessment of neuropathic pain management in Spain, revealing marked variability, only partial adherence to international guidelines, and persistent reliance on clinical experience over evidence. It confirms gabapentinoids, tricyclic antidepressants and duloxetine as preferred treatments, identifies continued tramadol use despite conflicting recommendations, and quantifies for the first time clinicians' perception and management of tolerance. These findings fill a major evidence gap and directly inform future national consensus, educational initiatives and clinical practice improvement
A call to action to address four decades of stagnant tuberculosis case detection in Somalia
Get PDFTuberculosis (TB) remains a leading cause of death of infectious diseases globally, with progress towards elimination slowest in fragile and conflict-affected settings. In Somalia, tuberculosis case detection has stagnated at approximately 40–45% for over 4 decades, representing one of the most persistent case-detection gaps worldwide. TB incidence and mortality remain among the highest in the World Health Organization Eastern Mediterranean Region, despite substantial donor investment and the scale-up of advanced diagnostic technologies. TB care delivery remains highly fragmented, with limited or no integration into primary care services. Rural, remote, displaced, pastoralist and conflict-affected populations face persistent barriers to essential health services, including TB care, hampering sustained community transmission. This editorial examines four decades of TB control in Somalia, shaped by protracted instability, humanitarian substitution, donor-dependency, and vertically organised programming. It argues that achieving meaningful, impactful, equitable and sustainable progress requires repositioning tuberculosis control as a core public health priority. This requires anchoring TB services in integrated primary healthcare, supported by community-based delivery models
Combined dark matter search towards dwarf spheroidal galaxies with Fermi -LAT, HAWC, H.E.S.S., MAGIC, and VERITAS
Get PDFDwarf spheroidal galaxies (dSphs) are excellent targets for indirect dark matter (DM) searches using gamma-ray telescopes because they are thought to have high DM content and a low astrophysical background. The sensitivity of these searches is improved by combining the observations of dSphs made by different gamma-ray telescopes. We present the results of a combined search by the most sensitive currently operating gamma-ray telescopes, namely: the satellite-borne Fermi-LAT telescope; the ground-based imaging atmospheric Cherenkov telescope arrays H.E.S.S., MAGIC, and VERITAS; and the HAWC water Cherenkov detector. Individual datasets were analyzed using a common statistical approach. Results were subsequently combined via a global joint likelihood analysis. We obtain constraints on the velocity-weighted cross section 〈σv〉 for DM self-annihilation as a function of the DM particle mass. This five-instrument combination allows the derivation of up to 2-3 times more constraining upper limits on 〈σv〉 than the individual results over a wide mass range spanning from 5 GeV to 100 TeV. Depending on the DM content modeling, the 95% confidence level observed limits reach 1.5×10-24 cm3s-1 and 3.2×10-25 cm3s-1, respectively, in the τ + τ - annihilation channel for a DM mass of 2 TeV
Bedside measurements of oxygen consumption and end-expiratory lung volume in mechanically ventilated patients
Get PDFCritical care medicine relies heavily on physiological monitoring, however, several fundamental variables remain difficult to measure at the bedside. This thesis focuses on two of these variables: oxygen consumption (V̇O2) and end-expiratory lung volume (EELV). Both are central to understanding metabolic and respiratory function, but their reliable quantification in mechanically ventilated patients has historically been challenging. The overarching aim of this work was to determine whether V̇O2 and EELV can be measured with sufficient accuracy to provide clinically meaningful information in the intensive care setting. Chapters 1 and 2 provide the physiological background to V̇O2 and EELV, outlining their importance and the challenges associated with their measurement in critical care. Chapter 3 introduces Computed Cardiopulmonography (CCP), a technique composed of in-airway highly-precise and time-resolved measurements of respired gas composition and flow (Molecular Flow Sensor; MFS) along with robust cardiopulmonary modelling. The first experimental strand (Chapters 4 and 5) investigated V̇O2 measurement using the MFS. In healthy volunteers, the MFS showed strong agreement with the Douglas bag method, and in mechanically ventilated patients it provided precise V̇O2 assessments over a prolonged measurement window. A novel quality control approach based on nitrogen balance was developed to construct confidence intervals around each individual V̇O2 measurement. V̇O2 trends were captured in tandem with fluctuations in body temperature, muscle activity, and haemodynamic status, supporting the feasibility of its real-time monitoring in critical care. The second experimental strand (Chapters 6 and 7) examined the estimation of EELV using CCP. In healthy volunteers, CCP-derived volumes agreed with body plethysmography. EELV values obtained by CCP under partial and full multi-breath nitrogen washout stimulus were compared and proven to provide equivalent results. In mechanically ventilated patients, CCP delivered reproducible EELV estimates. An application of such estimates was conducted to assess the changes in absolute volume induced by lung recruitment manoeuvres: the total lung volume change was highly variable and did not correlate with existing predictors of lung recruitability. Chapter 8 summarises the main conclusions of the thesis. Together, these studies demonstrate that V̇O2 and EELV can be made measurable at the bedside with sufficient accuracy to inform clinical care and potentially aid in decision-making
Mapping sex differences in brain and cognition in relation to APOE ε4 and amyloid burden: A longitudinal normative modelling study
Get PDFINTRODUCTION: Sex differences in Alzheimer's disease (AD) risk are increasingly recognized, with females exhibiting higher global prevalence rates. Yet, it remains unclear how genetic and biomarker indicators of AD risk, such as apolipoprotein E (APOE) ε4 and amyloid burden, relate to sex differences in brain and cognitive health during the preclinical stage. METHODS: Using established normative models trained on ≈ 58,000 healthy participants, we computed regional Z scores from T1‐weighted magnetic resonance imaging scans in 372 cognitively normal participants from the Insight 46 cohort. Scans were acquired at two timepoints, ≈ 3 years apart, beginning at age 70. Regions with Z scores < –1.96 were classified as brain‐structure outliers and summarized as total outlier count (tOC). We used linear mixed effects models to examine how sex, age, and AD risk (APOE ε4 status and amyloid burden) predict tOC and cognitive outcomes (Preclinical Alzheimer Cognitive Composite [PACC] scores). We examined cross‐sectional associations and longitudinal changes in tOC and PACC scores, and tested whether the effects of APOE ε4 status and amyloid burden on brain and cognitive measures differed by sex. RESULTS: Cross‐sectional analyses showed that males had greater tOC than females at younger ages. At timepoint 1, spatial maps showed more outlier regions in males, though high outlier proportions were limited to occipital areas. By timepoint 2, sex differences became more spatially distinct, with males and females showing deviations in different regions. Longitudinally, older males exhibited steeper increases in tOC over time compared to females. Greater tOC and amyloid burden were both associated with poorer cognitive outcomes, with a trend toward stronger associations in female APOE ε4 carriers. We found no evidence that AD risk influenced age‐related changes in tOC or cognition over time. DISCUSSION: These findings highlight normative modelling's utility in revealing the complex interplay among sex, age, and AD risk in shaping brain structure and cognition in later life. Highlights: Normative models detect sex‐ and Alzheimer's disease risk‐related brain changes in older adults. Sex‐specific brain outlier patterns emerge in distinct regions over time. Younger males show more brain outliers (greater cortical thinning) than females. Older males exhibit faster accumulation of brain‐structure outliers. More outliers and amyloid predict worse cognition, stronger in female apolipoprotein E ε4 carriers
FITrig: a high-performance detection technique for efficient ultra-long-period pulsars
Get PDFUltra-long-period (ULP) pulsars, a newly identified class of celestial transients, offer unique insights into astrophysics, though very few have been detected to date. In radio astronomy, most time-domain detection methods cannot find these pulsars, and current image-based detection approaches still face challenges, including low sensitivity, high false positive rate, and low computational efficiency. In this article, we develop Fast Imaging Trigger (FITrig), a GPU-accelerated, statistics-based method for ULP pulsar detection and localisation. FITrig includes two complementary approaches — an image domain and an image-frequency domain strategy. FITrig offers advantages by increasing sensitivity to faint pulsars, suppressing false positives (from noise, processing artefacts, or steady sources), and improving search efficiency in large-scale wide-field images. Compared to the state-of-the-art source finder SOFIA 2, FITrig increases the detection speed by 4.3 times for large images ( 50 K × 50 K pixels) and reduces false positives by up to 858.8 times (at 6 σ significance) for the image domain branch, while the image-frequency domain branch suppresses false positives even further. FITrig maintains the capability to detect pulsars that are 20 times fainter than surrounding steady features, even under critical Nyquist sampling conditions. In this article, the performance of FITrig is demonstrated using both real-world data (MeerKAT observations of PSR J0901-4046) and simulated datasets based on MeerKAT and SKA Array Assembly (AA) 2 telescope configurations. With its real-time processing capabilities and scalability, FITrig is a promising tool for next-generation telescopes, such as the SKA, with the potential to uncover hidden ULP pulsars
Multilateralism in crisis: a historical perspective - background paper for Nuffield Humanitarian Forum 18 March 2026
Get PDFA primer on large-sample statistical inference for epidemiologists
No full textStatistical theory forms a foundation for how epidemiologists learn about populations in public health and medical studies and is fundamental for the understanding of more advanced epidemiological methods (e.g., in causal inference and machine learning). Textbooks provide indepth coverage of probability and statistical theory, but with such comprehensive coverage that it can be easy to miss the forest for the trees. Here, we provide a summary of fundamental concepts from large-sample statistical theory to allow for more focused understanding tailored to epidemiologists and health science researchers. This primer aims to promote appropriate understanding and application of statistical methods in epidemiologic research. We clarify several often-confused statistical topics and provide a motivation for the application of largesample inferential methods to data from population health and medical studies. Assumptions underlying commonly used statistical methods that must be considered for valid inference are also discussed. These ideas are contextualized with an example from the Women’s Interagency HIV Study
An international consensus on screening and monitoring early‐stage type 1 diabetes: A roadmap to European implementation
Get PDFType 1 diabetes (T1D) is a chronic autoimmune disease that results in loss of insulin‐secreting pancreatic β‐cells in the islets of Langerhans. A diagnosis of T1D is typically associated with children and adolescents, yet half of all diagnoses of T1D are made in adults. In children and adolescents, T1D is often first recognized following hospitalization for diabetic ketoacidosis (DKA), which occurs in approximately 20%–50% of new‐onset T1D for people younger than 18 years of age in Europe. For adults with new‐onset T1D, DKA rates of up to 24% are estimated. Early‐stage T1D, during the asymptomatic period, can be detected through screening for multiple islet autoantibodies in blood samples, including capillary and venous samples, and such programs are made more popular by the availability of disease‐modifying therapies for early‐stage T1D. For individuals who screen positive for early‐stage T1D, participation in monitoring programs can greatly reduce the incidence of DKA once symptomatic hyperglycemia develops, as well as reducing severity of symptoms of T1D at onset. Education and awareness of the clinically relevant features of symptomatic T1D can also support the psychological wellbeing of people with early‐stage T1D and minimize distress at the point when insulin treatment is necessary. All of these consequences come with a predicted reduced burden of healthcare costs for managing T1D at a population level, and general population screening for islet autoantibodies is underway. In this European perspective, we discuss the imperatives and the components of implementation of general population screening for early‐stage T1D
Labial Frenectomy: Current Clinical Practice Among a Sample of Oral Surgeons and Oral and Maxillofacial Surgeons in the United Kingdom
Get PDFIntroduction: The aim of this study was to obtain the views of oral surgeons (OS) and oral and maxillofacial surgeons (OMFS) in the United Kingdom on labial frenectomies regarding their indication, timing and preferred surgical techniques. Materials and Methods: This was a cross‐sectional, questionnaire‐based study. A 20‐item online questionnaire was sent to both OS and OMFS by distribution through the British Association of Oral Surgeons (BAOS) and British Association of Oral and Maxillofacial Surgeons (BAOMS). It included demographics of respondents, diagnostic methods for aberrant labial frenums as well as their preferred timing, surgical techniques, and instruments for labial frenectomies. Descriptive statistics were used to summarise the study sample characteristics and questionnaire responses. Results: One hundred and thirty‐nine OS and 41 OMFS responded to the questionnaire with a response rate of 18.3% and 3.4% respectively. 84.4% of OS and 68.3% of OMFS believed that a low and hypertrophic frenum can be an important aetiological factor in the development of a median diastema. If a labial frenectomy was to be carried out as part of orthodontic treatment, the preferred timing among OS was just before closure of the median diastema (37.0%) while the majority of OMFS felt that timing did not matter (31.7%). More than half (55.7%) of the respondents used the Archer and Kruger classical technique exclusively for frenectomies, and a large majority (94.3%) preferred the use of a scalpel over electrosurgery or lasers. Conclusions: Considerable variation was found in the diagnostic approach to aberrant frenums and preferred timing of frenectomies among OS and OMFS; however, some consensus was noted in their choice of surgical technique and instrument. Further studies are required to provide more insight on the appropriate indication and timing for labial frenectomies as well as the need for adjunctive orthodontic treatment for the closure of median diastemas following frenectomy procedures