The Lancet and colonialism: past, present, and future.

The historical and contemporary alignment of medical and health journals with colonial practices needs elucidation. Colonialism, which sought to exploit colonised people and places, was justified by the prejudice that colonised people's ways of knowing and being are inferior to those of the colonisers. Institutions for knowledge production and dissemination, including academic journals, were therefore central to sustaining colonialism and its legacies today. This invited Viewpoint focuses on The Lancet, following its 200th anniversary, and is especially important given the extent of The Lancet's global influence. We illuminate links between The Lancet and colonialism, with examples from the past and present, showing how the journal legitimised and continues to promote specific types of knowers, knowledge, perspectives, and interpretations in health and medicine. The Lancet's role in colonialism is not unique; other institutions and publications across the British empire cooperated with empire-building through colonisation. We therefore propose investigations and raise questions to encourage broader contestation on the practices, audience, positionality, and ownership of journals claiming leadership in global knowledge production.

Livestock associated Staphylococcus aureus in cystic fibrosis patients in Spain: Detection of MRSA and MSSA CC398.

PURPOSE: Staphylococcus aureus is one of the most prevalent pathogens in cystic fibrosis (CF), being of special relevance those methicillin-resistant (MRSA). The livestock-associated (LA)-MRSA lineage CC398 is an emerging problem, specially related to pig-farming (PF) environments. The objective was to characterize the S. aureus isolates recovered from CF-patients in a Spanish hospital located in a region with high-PF activity. METHODS: Forty-two isolates were obtained (January-October/2022) and characterised (one/patient). The antimicrobial resistance phenotype/genotype was evaluated by Microscan/PCR. The presence of virulence and Immune Evasion Cluster (IEC) genes as well as the agr type was determined by PCR. MLST and spa-typing were studied by PCR-sequencing. RESULTS: Nine of the 42 isolates were MRSA (21.4 %), and 8 of them multidrug resistant (MDR). Among MRSA, 6 spa-types were detected, assigned to CC1, CC5, CC8, CC30, and CC398. Four MRSA isolates belonged to the lineage CC398-t011-IEC negative (animal adapted-clade, LA-MRSA). The remaining 33 isolates were methicillin-susceptible (MSSA), of 26 spa-types and associated with 11 CCs (predominant: CC5, CC30, and CC398). Seven MSSA isolates were of the lineage CC398 (spa-types t034, t108, t571, t20352); four of them were IEC-positive and erm(T)-positive (t571, and t20352, human-adapted CC398 clade), being IEC-negative the remaining three. The tst and eta/etb genes were identified in 12 and 2 isolates, respectively (none CC398). Small-colony-variants were demonstrated in 9 isolates (two CC398, both MDR). CONCLUSION: The lineage CC398 was very frequent among CF-patients (26.2 %), both among MSSA and MRSA. The emergence of LA-MRSA-CC398 in CF-patients requires monitorization, especially in hospitals of high-PF-regions.

STUB1 Mutations as Possible Genetic Modifiers in Spinocerebellar Ataxia Type 8.

BACKGROUND: Spinocerebellar ataxia type 8 (SCA8) is a dominantly inherited expansion disorder with highly variable penetrance. ATXN8OS/ATXN8 expanded alleles have been identified in association with other types of hereditary ataxias, pointing to a possible genetic synergism. OBJECTIVES: We aimed to further investigate the molecular background of patients with SCA8 diagnosis. METHODS: Patients were selected from our cohort of 346 families. A total of 14 probands with SCA8 underwent additional investigation through exome sequencing. RESULTS: Pathogenic heterozygous STUB1 variants were found in 21.4% of SCA8 patients (3 of 14) compared to only 0.5% in the non-SCA8 group (1 of 222), indicating a statistically significant association (P < 0.05). CONCLUSIONS: The findings reported in this study might suggest a genetic synergism between STUB1 and ATXN8OS/ATXN8 expanded alleles. Further studies are needed to validate this observation and better define the clinical impact of this genetic interaction.

Secondary pseudohypoaldosteronism: a 15-year experience and a literature review.

BACKGROUND: Secondary pseudohypoaldosteronism (S-PHA) is a rare condition resulting from renal tubular resistance to aldosterone in children with urinary tract infection (UTI) and/or nephrourological malformations. It is characterized by nonspecific symptoms but with the potential for life-threatening complications. We aim to evaluate the clinical manifestations, diagnostic approach, and therapeutic interventions in children with S-PHA, along with a review of recent publications. METHODS: A retrospective observational descriptive study was conducted on S-PHA cases diagnosed over the last 15 years at a tertiary pediatric nephrology unit. The literature for the last 10 years was reviewed. RESULTS: Twelve patients (10 males, 6 days to 6 months) were identified. Weight loss was the main reason for consultation (50%). Ninety-two percent of patients had an underlying nephrourological pathology and 62% concomitant confirmed UTI. Seven out of 12 children were admitted to the PICU. A subsequent extrapontine myelinolysis was observed in one patient as neurological sequelae. Twenty-one articles related to S-PHA have been identified on PubMed and Embase. CONCLUSIONS: S-PHA should be considered in infants under 6 months of age with UTI and/or CAKUT. Obstructive anomalies and vesicoureteral reflux can be found, affecting both unilateral and bilateral systems. Early medical and surgical interventions are crucial and require close monitoring to avoid iatrogenic complications.

Minimally invasive left colectomy with total intracorporeal anastomosis versus extracorporeal anastomosis. A single center cohort study. Stage 2b IDEAL framework for evaluating surgical innovation.

PURPOSE: Performing intracorporeal anastomoses in minimally invasive colon surgery appears to provide better short-term outcomes for patients with colon cancer. The aim of the study is to compare surgical aspects and short-term outcomes between intracorporeal and extracorporeal techniques in left colectomies with both laparoscopic and robotic approaches and evaluate advantages and disadvantages of intracorporeal anastomosis according to IDEAL framework (Exploration, stage 2b). METHODS: This is a single center, ambispective cohort study comparing total intracorporeal anastomosis (TIA) and standard surgery with extracorporeal anastomosis (EA). Patients with colon cancer treated by left colectomy, sigmoidectomy and high anterior resection by total intracorporeal anastomosis between May 2020 and January 2023 without exclusion criteria were prospectively included in a standardized database. Short-term outcomes in the group undergoing TIA were compared with a historical EA cohort. The main assessment outcomes were intraoperative complications, postoperative morbidity according to the Clavien-Dindo scale and the comparison of pathological. We conducted a preliminary comparative study within the TIA group between approaches, a primary analysis between the two anastomotic techniques, and a propensity score matched analysis including only the laparoscopic approach, between both anastomotic techniques. RESULTS: Two hundred and forty-six patients were included: 103 who underwent TIA, 35 of them with laparoscopic approach and 68 with robotic approach, and a comparison group comprising another 103 eligible consecutive patients who underwent laparoscopic EA. There were no statistically significant differences between the two groups in terms of demographic variables. No statistically significant differences were observed in anastomotic dehiscence. Intraoperative complications are fewer in the TIA group, with a higher C-Reactive Protein levels. Relevant anastomotic bleeding and the number of retrieved lymph nodes were higher in EA group. Nevertheless, no differences were observed in terms of overall morbidity. CONCLUSION: Minimally invasive left colectomy with intracorporeal resection and anastomosis is technically feasible and safe suing either a laparoscopic or a robotic approach. Clinical data from this cohort demonstrate outcomes comparable to those achieved through the conventional EA procedure in relation to postoperative morbidity and oncological efficacy, with indications suggesting that the utilization of robotic-assisted techniques may play a contributing role in enhancing overall treatment outcomes.

Pan American climate resilient health systems: a training course for health professionals.

Objectives: To describe the development, implementation, and results of a training course designed to equip health professionals from the Pan American Health Organization region with the knowledge and tools needed to adapt health systems to current climate realities. Methods: The Pan American climate resilient health systems course was a 9-week live-virtual course in March-April 2023, which was delivered through Zoom and offered in English, Spanish, and French. All lectures were delivered by local and regional climate and health experts. The curricular foundation of this initiative was the Global Consortium on Climate and Health Education core competencies for health professionals. Participants completed pre- and post-course surveys. Results: A total of 1212 participants attended at least one of the nine sessions and 489 (from 66 countries) attended at least six sessions. Of these, 291 participants completed both the pre- and post-course surveys which were used in the analysis. Longitudinal survey results suggested an improvement in participants' climate and health communication, an increased frequency of incorporating climate knowledge in professional practice, and improved confidence in engaging in climate initiatives. At the same time, many participants expressed a need for additional training. Conclusions: The results indicate that live-virtual courses have the potential to empower health professionals to contribute to climate resilience efforts by: increasing their communication skills; changing their professional practice; increasing their ability to lead climate and health activities; and preparing them to assess vulnerability and adaptation in health systems, measure and monitor environmental sustainability, and apply a health equity lens.

Treatment of chronic and complex meniscal tears with arthroscopic meniscus repair augmented with collagen matrix wrapping: failure rate and functional outcomes.

PURPOSE: Meniscal wrapping is a fully arthroscopic technique that involves enhanced meniscal repair with a tissue-engineered collagen matrix wrapping. This study aims to investigate the feasibility of using the meniscal wrapping technique for the treatment of chronic or complex meniscal tears. The primary objective is to assess its failure rate. The secondary objectives are to analyse complication rate, functional outcomes and overall patient satisfaction. METHODS: This retrospective case series study included patients who sustained chronic and complex tears undergoing meniscal wrapping with autologous liquid bone marrow injection. Failure rate was considered if the patient underwent partial or complete meniscectomy or knee replacement during the follow-up, while other unexpected knee reoperations were considered as complications. Clinical outcomes were evaluated through the IKDC score, Tegner Activity Score and Short Assessment of Patient Satisfaction. RESULTS: Twenty-one patients were included (15 non-acute bucket-handle tears, three non-acute horizontal tears and three non-acute complex injuries). The failure rate was 9.5% at 33 months. The rate of other unplanned reoperations was 14.3%, but none of these complications were apparently directly related to the wrapping technique. The average postoperative IKDC was 73.3/100. No statistically significant difference was encountered between preinjury and postoperative Tegner Activity Score. The mean overall patient satisfaction was 88.3/100. CONCLUSIONS: Meniscal wrapping can be safely used as an adjunctive technique to meniscal repair in such difficult-to-treat cases to preserve the meniscus. The technique achieves a low failure rate and promising results of knee function, and patient satisfaction.

Response to Fingolimod in Multiple Sclerosis Patients Is Associated with a Differential Transcriptomic Regulation.

Fingolimod is an immunomodulatory sphingosine-1-phosphate (S1P) analogue approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The identification of biomarkers of clinical responses to fingolimod is a major necessity in MS to identify optimal responders and avoid the risk of disease progression in non-responders. With this aim, we used RNA sequencing to study the transcriptomic changes induced by fingolimod in peripheral blood mononuclear cells of MS-treated patients and their association with clinical response. Samples were obtained from 10 RRMS patients (five responders and five non-responders) at baseline and at 12 months of fingolimod therapy. Fingolimod exerted a vast impact at the transcriptional level, identifying 7155 differentially expressed genes (DEGs) compared to baseline that affected the regulation of numerous signaling pathways. These DEGs were predominantly immune related, including genes associated with S1P metabolism, cytokines, lymphocyte trafficking, master transcription factors of lymphocyte functions and the NF-kB pathway. Responder and non-responder patients exhibited a differential transcriptomic regulation during treatment, with responders presenting a higher number of DEGs (6405) compared to non-responders (2653). The S1P, NF-kB and TCR signaling pathways were differentially modulated in responder and non-responder patients. These transcriptomic differences offer the potential of being exploited as biomarkers of a clinical response to fingolimod.

Multiligament knee injuries. Ten years' experience at a public university, level I Trauma Center.

PURPOSE: To describe our institutional experience and results in the surgical management of multiligament knee injuries (MLKI). MATERIALS AND METHODS: Retrospective series of MLKI consecutively operated on at a single, level I Trauma Center. Data on patients' baseline characteristics, injuries, treatments, and outcomes were recorded up to one-year follow-up. Recorded outcomes included the Tegner-Lysholm Knee Scoring Scale (TLKSS), return to work, and patient satisfaction. RESULTS: MLKI incidence was 0.03% among 9897 orthopedic trauma admissions. Twenty-four patients of mean age 43.6 years were included in analysis. The mean Injury Severity Score was 12.6. Five patients presented with knee dislocations and six had fracture-dislocations, two of them open fractures. There was one popliteal artery injury requiring a bypass and four common peroneal nerve palsies. Staged ligamental reconstruction was performed in all cases. There were seven postoperative complications. The median TLKSS was 80 and, though patient satisfaction was high, and dissatisfaction was largely restricted to recreational activities (only 58.3% satisfied). Seventeen patients returned to their previous employment. CONCLUSIONS: We found a high aggregation of fracture-dislocations secondary to road traffic accidents. One in four patients experienced complications, particularly stiffness. Complications were more common in cases involving knee dislocation. Most patients had good functional results, but 25% were unable to return to their previous work, which demonstrates the long-lasting sequelae of this injury.

Post-transplant diabetes mellitus and renal cell cancer after renal transplantation.

BACKGROUND: Diabetes is a risk factor for cancer in the general population. However, few data are available on the association between post-transplant diabetes mellitus (PTDM) and cancer after transplantation. METHODS: We analyzed this issue in a Spanish cohort of patients without diabetes before transplantation. PTDM was diagnosed with consensus criteria at 12 months after transplantation and 12 months before the diagnosis of cancer. The association between PTDM and cancer (overall and specific types) was evaluated with regression analysis. RESULTS: During a follow-up of 12 years (interquartile range 8-14), 85 cases of 603 developed cancer (829/100 000/year) and 164 (27%) PTDM. The most frequent cancers were renal cell cancer (RCC) n = 15, 146/cases/100 000/year), lung (n = 12, 117/cases/100 000/year), colon (n = 9, 88/cases/100 000/year) and prostate (n = 9, 88/cases/100 000/year). In logistic regression, PTDM was not associated with cancer. Eight of the 164 patients with PTDM (4.9%) vs 7 of the 439 without PTDM developed RCC (1.6%) (P = .027). In multivariate analysis, PTDM was independently associated with RCC [odds ratio (OR) 2.92, confidence interval (CI) 1.03-8.27], adjusting for smoking (OR 4.020, 95% CI 1.34-12.02) and other covariates. PTDM was not associated with other types of cancer. CONCLUSIONS: Patients with PTDM must be considered a population at risk for RCC and accordingly, the subject of active surveillance.

Gait Function after High-Intensity Focused Ultrasound Thalamotomy for Essential Tremor: Searching for Technique Optimization.

INTRODUCTION: Essential tremor (ET) is one of the most prevalent movement disorders in adults and may be highly disabling for some. Magnetic resonance image-guided high-intensity focused ultrasound (MRIgFUS) has been shown to control tremor efficaciously and with acceptable risk. To date, paresthesia and ataxia are the most common adverse effects (AE). Nevertheless, the impact of MRIgFUS thalamotomy on balance is not well established. METHODS: Thirty-two patients underwent MRIgFUS for ET and completed 6 months of follow-up. Tremor severity and functional disability were assessed using the Essential Tremor Rating Scale and the Quality of Life in Essential Tremor Questionnaire. The Berg Balance Scale (BBS) was applied to objectively measure balance status. RESULTS: All treatments were successful. The sonication target was 1-2 mm above the depth of the intercommissural line. Procedures lasted less the 2 h, with an average of 8 sonications per patient. Twenty-four patients were included in the tremor analysis. The hand tremor score was improved by 76% after 6 months of follow-up and 87% of patients self-reported marked improvement (≥75%). Disability scores showed marked improvement (78%), leading to a significant improvement in quality of life. At the final follow-up, 48% of the patients reported no side effects. When present, AE were generally transient and were considered mild in 96% of affected patients. Paresthesia and subjective feeling of unsteadiness were the most common persistent complaints (23% and 20%, respectively). Regarding objective ataxia, BBS scores remained stable throughout follow-up for most patients. Only 2 patients suffered a mild worsening of balance although no patients experienced moderate or severe ataxia. CONCLUSIONS: Subjective feeling of unsteadiness is one of the most frequent AE after MRIgFUS, although objective ataxia is infrequent and mild. Selecting the most appropriate lesion location and procedural parameters should increase treatment benefits while reducing side effects.

Allografts and lateral extra-articular tenodesis for revision anterior cruciate ligament reconstruction: enhanced rotational stability and improved functional outcomes.

PURPOSE: Multiple studies have shown higher failure rate and patient-reported outcomes to be significantly worse following revision anterior cruciate ligament reconstructive (ACLR) surgery, especially using allografts. One of the reasons being rotational instability. Because of this, augmentation with lateral extra-articular tenodesis (LET) is often considered. Good short-term results in regards to functional and perceived scores and low complication rate can be expected in revision ACLR using allografts in combination with LET. METHODS: Between 2014 and 2021, 46 patients were registered for revision ACLR using allografts and extra-articular augmentation (modified Lemaire) and included in this prospective study. Patients' demographic and clinical data were collected preoperatively, postoperatively, and during the follow-up period of 12 months. RESULTS: Patient-reported functional outcomes were statistically significant for IKDC, Lysholm, and SF-12 physical scale (p < 0.05). Tegner score showed a decreased number of patients who were able to return to sport at their previous level (p = 0.001). Stability examination tests (Lachman and pivot-shift) showed significant improvements. Concomitant lesions were present in 76.1% of patients. Ten patients (21.7%) presented major complications, including six cases of anteroposterior instability, three cases of knee pain and one graft re-rupture. CONCLUSION: Revision procedures are inherently challenging with a high number of associated chondral and meniscus lesions. However, good short-term functional outcomes and enhanced rotational stability with an acceptable complication rate can be expected in most cases where revision ACLR using allografts is augmented with LET. STUDY DESIGN: Prospective; Case series; Level of evidence IV.

Good rates of return-to-sport in athletes after revision anterior cruciate ligament reconstruction using autologous patellar tendon and lateral extra-articular tenodesis: a 2-year follow-up prospective study.

BACKGROUND: Most athletes who undergo revision of the anterior cruciate ligament reconstruction (ACLR) aim to return to their preinjury sport at a similar level of performance while minimizing the risk for reinjury. Additional lateral extra-articular tenodesis (LET) has recently been correlated with improved outcomes and low complication rate. Yet, there are few series evaluating return-to-sport (RTS) and clinical outcomes after revision ACLR using bone-patellar tendon-bone (BPTB) and LET in athletes. METHODS: The study cohort consisted of 19 eligible athletes who had undergone their first revision ACLR using BPTB and LET (modified Lemaire) between January 2019 and 2020. Patients were prospectively followed and interviewed in a sports activity survey during a 2-year follow-up. RESULTS: Despite all patients returning to sports after revision ACLR surgery, 52.6% resumed playing at their preinjury level. Furthermore, patient-reported functional outcomes improved significantly following revision surgery, as evidenced by improvements in IKDC [64.4 (± 12) to 87.8 (± 6)], Lysholm [71.27 (± 12) to 84.2 (± 9.7)], and SF-12 scales [Physical: 53.3 (± 3) 57 (± 1.2); Mental: 50.2 (± 3.3) to 52.7 (± 2.4)]. One case (5.3%) experienced persistent pain and underwent reoperation for a partial meniscectomy. CONCLUSION: After revision ACLR using autologous BPTB and LET, all active individuals are expected to RTS, similar to primary ACLR. The difference comes down to returning to the preinjury level, where the levels are lower depending on the sport and initial level of play. Good mid-term functional outcomes with a low complication rate can be expected in most cases. STUDY DESIGN: Case series; Level of evidence IV. ETHICAL COMMITTEE APPROVAL NUMBER: PR(ATR)79/2021 and HCB/2023/0173.

The Validity of the Energy Expenditure Criteria Based on Open Source Code through two Inertial Sensors.

Through this study, we developed and validated a system for energy expenditure calculation, which only requires low-cost inertial sensors and open source R software. Five healthy subjects ran at ten different speeds while their kinematic variables were recorded on the thigh and wrist. Two ActiGraph wireless inertial sensors and a low-cost Bluetooth-based inertial sensor (Lis2DH12), assembled by SensorID, were used. Ten energy expenditure equations were automatically calculated in a developed open source R software (our own creation). A correlation analysis was used to compare the results of the energy expenditure equations. A high interclass correlation coefficient of estimated energy expenditure on the thigh and wrist was observed with an Actigraph and Sensor ID accelerometer; the corrected Freedson equation showed the highest values, and the Santos-Lozano vector magnitude equation and Sasaki equation demonstrated the lowest one. Energy expenditure was compared between the wrist and thigh and showed low correlation values. Despite the positive results obtained, it was necessary to design specific equations for the estimation of energy expenditure measured with inertial sensors on the thigh. The use of the same formula equation in two different placements did not report a positive interclass correlation coefficient.

The tale of microencapsulated rifampicin: is it useful for the treatment of periprosthetic joint infection?

PURPOSE: Microencapsulation techniques have allowed the addition of rifampicin to bone cement, but its in vivo efficacy has not been proven. The aim of our study is to determine the superiority of cement containing gentamicin and rifampicin microcapsules in the treatment of PJI versus cement exclusively containing gentamicin. METHODS: An S. aureus PJI was induced in 15 NZW rabbits. A week after inoculation, the first stage of replacement was carried out, and the animals were divided into two groups: group R received a spacer containing gentamicin and rifampicin microcapsules, and group C received a spacer containing gentamicin. Intra-articular release curve of rifampicin and infection and toxicity markers were monitored for four weeks post-operatively, when microbiological analysis was performed. RESULTS: The microbiological cultures showed a significantly lower growth of S. aureus in soft tissue (2.3·104 vs 0; p = 0.01) and bone (5.7·102 vs 0; p = 0.03) in the group with rifampicin microcapsules. No differences were found in systemic toxicity markers. Rifampicin release from the cement spacer showed higher concentrations than the staphylococcal MIC throughout the analysis. CONCLUSION: The in vivo analyses demonstrated the superiority of cement containing gentamicin and rifampicin microcapsules versus the isolated use of gentamicin in the treatment of PJI in the rabbit model without serious side effects due to the systemic absorption of rifampicin. Given the increasing incidence of staphylococci-related PJI, the development of new strategies for intra-articular administration of rifampicin for its treatment has a high clinical impact.

Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias.

Our clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype.

Risk and outcomes of COVID-19 in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Limited information is available on incidence and outcomes of COVID-19 in patients with multiple sclerosis (MS). This study investigated the risks of SARS-CoV-2 infection and COVID-19-related outcomes in patients with MS, and compared these with the general population. METHODS: A regional registry was created to collect data on incidence, hospitalization rates, intensive care unit admission, and death in patients with MS and COVID-19. National government outcomes and seroprevalence data were used for comparison. The study was conducted at 14 specialist MS treatment centers in Madrid, Spain, between February and May 2020. RESULTS: Two-hundred nineteen patients were included in the registry, 51 of whom were hospitalized with COVID-19. The mean age ± standard deviation was 45.3 ± 12.4 years, and the mean duration of MS was 11.9 ± 8.9 years. The infection incidence rate was lower in patients with MS than the general population (adjusted incidence rate ratio = 0.78, 95% confidence interval [CI] = 0.70-0.80), but hospitalization rates were higher (relative risk = 5.03, 95% CI = 3.76-6.62). Disease severity was generally low, with only one admission to an intensive care unit and five deaths. Males with MS had higher incidence rates and risk of hospitalization than females. No association was found between the use of any disease-modifying treatment and hospitalization risk. CONCLUSIONS: Patients with MS do not appear to have greater risks of SARS-CoV-2 infection or severe COVID-19 outcomes compared with the general population. The decision to start or continue disease-modifying treatment should be based on a careful risk-benefit assessment.

Mutational spectrum of GNAL, THAP1 and TOR1A genes in isolated dystonia: study in a population from Spain and systematic literature review.

OBJECTIVE: We aimed to investigate the prevalence of TOR1A, GNAL and THAP1 variants as the cause of dystonia in a cohort of Spanish patients with isolated dystonia and in the literature. METHODS: A population of 2028 subjects (including 1053 patients with different subtypes of isolated dystonia and 975 healthy controls) from southern and central Spain was included. The genes TOR1A, THAP1 and GNAL were screened using a combination of high-resolution melting analysis and direct DNA resequencing. In addition, an extensive literature search to identify original articles (published before 10 August 2020) reporting mutations in TOR1A, THAP1 or GNAL associated to dystonia was performed. RESULTS: Pathogenic or likely pathogenic variants in TOR1A, THAP1 and GNAL were identified in 0.48%, 0.57% and 0.29% of our patients, respectively. Five patients carried the variation p.Glu303del in TOR1A. A very rare variant in GNAL (p.Ser238Asn) was found as a putative risk factor for dystonia. In the literature, variations in TOR1A, THAP1 and GNAL accounted for about 6%, 1.8% and 1.1% of published dystonia patients, respectively. CONCLUSIONS: There is a different genetic contribution to dystonia of these three genes in our patients (about 1.3% of patients) and in the literature (about 3.6% of patients), probably due the high proportion of adult-onset cases in our cohort. As regards age at onset, site of dystonia onset, and final distribution, in our population there is a clear differentiation between DYT-TOR1A and DYT-GNAL, with DYT-THAP1 likely to be an intermediate phenotype.

Use of Data to Understand the Social Determinants of Depression in Two Middle-Income Countries: the 3-D Commission.

Depression accounts for a large share of the global disease burden, with an estimated 264 million people globally suffering from depression. Despite being one of the most common kinds of mental health (MH) disorders, much about depression remains unknown. There are limited data about depression, in terms of its occurrence, distribution, and wider social determinants. This work examined the use of novel data sources for assessing the scope and social determinants of depression, with a view to informing the reduction of the global burden of depression.This study focused on new and traditional sources of data on depression and its social determinants in two middle-income countries (LMICs), namely, Brazil and India. We identified data sources using a combination of a targeted PubMed search, Google search, expert consultations, and snowball sampling of the relevant literature published between October 2010 and September 2020. Our search focused on data sources on the following HEALTHY subset of determinants: healthcare (H), education (E), access to healthy choices (A), labor/employment (L), transportation (T), housing (H), and income (Y).Despite the emergence of a variety of data sources, their use in the study of depression and its HEALTHY determinants in India and Brazil are still limited. Survey-based data are still the most widely used source. In instances where new data sources are used, the most commonly used data sources include social media (twitter data in particular), geographic information systems/global positioning systems (GIS/GPS), mobile phone, and satellite imagery. Often, the new data sources are used in conjunction with traditional sources of data. In Brazil, the limited use of new data sources to study depression and its HEALTHY determinants may be linked to (a) the government's outsized role in coordinating healthcare delivery and controlling the data system, thus limiting innovation that may be expected from the private sector; (b) the government routinely collecting data on depression and other MH disorders (and therefore, does not see the need for other data sources); and (c) insufficient prioritization of MH as a whole. In India, the limited use of new data sources to study depression and its HEALTHY determinants could be a function of (a) the lack of appropriate regulation and incentives to encourage data sharing by and within the private sector, (b) absence of purposeful data collection at subnational levels, and (c) inadequate prioritization of MH. There is a continuing gap in the collection and analysis of data on depression, possibly reflecting the limited priority accorded to mental health as a whole. The relatively limited use of data to inform our understanding of the HEALTHY determinants of depression suggests a substantial need for support of independent research using new data sources. Finally, there is a need to revisit the universal health coverage (UHC) frameworks, as these frameworks currently do not include depression and other mental health-related indicators so as to enable tracking of progress (or lack thereof) on such indicators.

Data Sources for Understanding the Social Determinants of Health: Examples from Two Middle-Income Countries: the 3-D Commission.

The expansion in the scope, scale, and sources of data on the wider social determinants of health (SDH) in the last decades could bridge gaps in information available for decision-making. However, challenges remain in making data widely available, accessible, and useful towards improving population health. While traditional, government-supported data sources and comparable data are most often used to characterize social determinants, there are still capacity and management constraints on data availability and use. Conversely, privately held data may not be shared. This study reviews and discusses the nature, sources, and uses of data on SDH, with illustrations from two middle-income countries: Kenya and the Philippines. The review highlights opportunities presented by new data sources, including the use of big data technologies, to capture data on social determinants that can be useful to inform population health. We conducted a search between October 2010 and September 2020 for grey and scientific publications on social determinants using a search strategy in PubMed and a manual snowball search. We assessed data sources and the data environment in both Kenya and the Philippines. We found limited evidence of the use of new sources of data to study the wider SDH, as most of the studies available used traditional sources. There was also no evidence of qualitative big data being used. Kenya has more publications using new data sources, except on the labor determinant, than the Philippines. The Philippines has a more consistent distribution of the use of new data sources across the HEALTHY determinants than Kenya, where there is greater variation of the number of publications across determinants. The results suggest that both countries use limited SDH data from new data sources. This limited use could be due to a number of factors including the absence of standardized indicators of SDH, inadequate trust and acceptability of data collection methods, and limited infrastructure to pool, analyze, and translate data.