Global Health Needs Modernized Containment Strategies to Prepare for the Next Pandemic

COVID-19 continues to be a public health crisis, while severely impacting global financial markets causing significant economic and social hardship. As with any emerging disease, pharmaceutical interventions required time, emphasizing the initial and continuing need for non-pharmaceutical interventions. We highlight the role of anthropological and historical perspectives to inform approaches to non-pharmaceutical interventions for future preparedness. The National Academy of Medicine, a not-for-profit, non-governmental US-based medical watchdog organization, published a key document early in the COVID-19 pandemic which points to inadequate quarantine and containment infrastructure as a significant obstacle to an effective pandemic response. In considering how to implement effective quarantine policies and infrastructure, we argue that it is essential to take a longitudinal approach to assess interventions that have been effective in past pandemics while simultaneously addressing and eliminating the negative socio-historical legacies of ineffective quarantine practices. Our overview reinforces the need for social equity and compassion when implementing containment

Comorbidity burden in axial spondyloarthritis: a cluster analysis

Objectives To examine how comorbidities cluster in axial spondyloarthritis (axSpA) and whether these clusters are associated with quality of life, global health and other outcome measures. Methods We conducted a cross-sectional study of consecutive patients meeting ASAS criteria for axSpA in Liverpool, UK. Outcome measures included quality of life (EQ5D), global health and disease activity (BASDAI). We used hierarchical cluster analysis to group patients according to 38 pre-specified comorbidities. In multivariable linear models, the associations between distinct comorbidity clusters and each outcome measure were compared, using axSpA patients with no comorbidities as the reference group. Analyses were adjusted for age, gender, symptom duration, BMI, deprivation, NSAID-use and smoking. Results We studied 419 patients (69% male, mean age 46 years). 255 patients (61%) had at least one comorbidity, among whom the median number was 1 (range 1–6). Common comorbidities were hypertension (19%) and depression (16%). Of 15 clusters identified, the most prevalent clusters were hypertension-coronary heart disease and depression-anxiety. Compared with patients with no comorbidities, the fibromyalgia-irritable bowel syndrome cluster was associated with adverse patient-reported outcome measures; these patients reported 1.5-unit poorer global health (95%CI 0.01, 2.9), reduced quality of life (0.25-unit lower EQ5D; 95%CI −0.37, −0.12) and 1.8-unit higher BASDAI (95% CI 0.4, 3.3). Similar effect estimates were found for patients in the depression-anxiety cluster. Conclusion Comorbidity is common among axSpA patients. The two most common comorbidities were hypertension and depression. Patients in the depression-anxiety and fibromyalgia-IBS clusters reported poorer health and increased axSpA severity

Impact of Smoking in Response to Tumor Necrosis Factor Inhibitors in Axial Spondyloarthritis : Methodologic Considerations for Longitudinal Observational Studies

We are grateful to Professor Gary Macfarlane (Chief Investigator of BSRBR-AS), the staff of the BSRBR-AS (Claudia Zabke, Elizabeth Ferguson-Jones, Maureen Heddle, Nafeesa Nazlee, and Barry Morris), and the recruiting staff at the clinical centers.Peer reviewedPostprin

Integrating genetic and oral histories of Southwest Indian populations

India is home to thousands of ethno-linguistically distinct groups, many maintaining strong self-identities that derive from oral traditions and histories. However, these traditions and histories are only partially documented and are in danger of being lost over time. More recently, genetic studies have established the existence of ancestry gradients derived from both western and eastern Eurasia as well as evidence of practices such as endogamy and consanguinity, revealing complexity in the regional population structure with consequences for the health landscape of local populations. Despite the increase in genome-wide data from India, there is still sparse sampling across finer-scale geographic regions leading to gaps in our understanding of how and when present-day genetic structure came into existence. To address the gaps in genetic and oral histories, we analyzed whole-genome sequences of 70 individuals from Southwest India identifying as Bunt, Kodava, and Nair—populations that share unique oral histories and origin narratives—and 78 recent immigrants to the United States with Kodava ancestry as part of a community-led initiative. We additionally generated genome-wide data from 10 individuals self-identifying as Kapla, a population from the same region that is socio-culturally different to the other three study populations. We supplemented existing but limited anthropological records on these populations with oral history accounts narrated by community members and non-member contacts during sampling and subsequent community engagement. Overall, we find that components of genetic ancestry are relatively homogeneous among the Bunt, Kodava, and Nair populations and comparable to neighboring populations in India, which motivates further investigation of non-local origin narratives referenced in their oral histories. A notable exception is the Kapla population, with a higher proportion of ancestry represented in the Onge from the Andaman Islands, similar to several South Indian tribal populations. Utilizing haplotype-based methods, we find latent genetic structure across South India, including the sampled populations available under aCC-BY-NC-ND 4.0 International license.was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made bioRxiv preprint doi: https://doi.org/10.1101/2022.07.06.498959; this version posted July 7, 2022. The copyright holder for this preprint (which 2 from Southwest India, suggesting more recent population structure between geographically proximal populations in the region. This study represents an attempt for community-engaged anthropological and genetic investigations in India and presents results from both sources, underscoring the need to recognize that oral and genetic histories should not be expected to overlap. Ultimately, oral traditions and unique self-identities, such as those held close by some of the study populations, warrant more community-driven anthropological investigations to better understand how they originate and their relationship to genetic histories

Lakeside Cemeteries in the Sahara: 5000 Years of Holocene Population and Environmental Change

Background: Approximately two hundred human burials were discovered on the edge of a paleolake in Niger that providea uniquely preserved record of human occupation in the Sahara during the Holocene (,8000 B.C.E. to the present). CalledGobero, this suite of closely spaced sites chronicles the rapid pace of biosocial change in the southern Sahara in response tosevere climatic fluctuation.Methodology/Principal Findings: Two main occupational phases are identified that correspond with humid intervals in theearly and mid-Holocene, based on 78 direct AMS radiocarbon dates on human remains, fauna and artifacts, as well as 9 OSLdates on paleodune sand. The older occupants have craniofacial dimensions that demonstrate similarities with mid-Holocene occupants of the southern Sahara and Late Pleistocene to early Holocene inhabitants of the Maghreb. Theirhyperflexed burials compose the earliest cemetery in the Sahara dating to ,7500 B.C.E. These early occupants abandon thearea under arid conditions and, when humid conditions return ,4600 B.C.E., are replaced by a more gracile people withelaborated grave goods including animal bone and ivory ornaments.Conclusions/Significance: The principal significance of Gobero lies in its extraordinary human, faunal, and archaeologicalrecord, from which we conclude the following:(1) The early Holocene occupants at Gobero (7700–6200 B.C.E.) were largely sedentary hunter-fisher-gatherers withlakeside funerary sites that include the earliest recorded cemetery in the Sahara.(2) Principal components analysis of craniometric variables closely allies the early Holocene occupants at Gobero with askeletally robust, trans-Saharan assemblage of Late Pleistocene to mid-Holocene human populations from the Maghreband southern Sahara.(3) Gobero was abandoned during a period of severe aridification possibly as long as one millennium (6200–5200 B.C.E).(4) More gracile humans arrived in the mid-Holocene (5200–2500 B.C.E.) employing a diversified subsistence economybased on clams, fish, and savanna vertebrates as well as some cattle husbandry.(5) Population replacement after a harsh arid hiatus is the most likely explanation for the occupational sequence at Gobero.(6) We are just beginnin

Research Recommendations Following the Discovery of Pain Sensitizing IgG Autoantibodies in Fibromyalgia Syndrome

BACKGROUND: Fibromyalgia syndrome (FMS) is the most common chronic widespread pain condition in rheumatology. Until recently, no clear pathophysiological mechanism for fibromyalgia had been established, resulting in management challenges. Recent research has indicated that serum IgGs may play a role in FMS. We undertook a research prioritisation exercise to identify the most pertinent research approaches that may lead to clinically implementable outputs. METHODS: Research priority setting was conducted in five phases: situation analysis; design; expert group consultation; interim recommendations; consultation and revision. A dialogue model was used, and an international multi-stakeholder expert group was invited. Clinical, patient, industry, funder, and scientific expertise was represented throughout. Recommendation-consensus was determined via a voluntary closed eSurvey. Reporting guideline for priority setting of health research were employed to support implementation and maximise impact. RESULTS: Arising from the expert group consultation (n = 29 participants), 39 interim recommendations were defined. A response rate of 81.5% was achieved in the consensus survey. Six recommendations were identified as high priority- and 15 as medium level priority. The recommendations range from aspects of fibromyalgia features that should be considered in future autoantibody research, to specific immunological investigations, suggestions for trial design in FMS, and therapeutic interventions that should be assessed in trials. CONCLUSIONS: By applying the principles of strategic priority setting we directed research towards that which is implementable, thereby expediating the benefit to the FMS patient population. These recommendations are intended for patients, international professionals and grant-giving bodies concerned with research into causes and management of patients with fibromyalgia syndrome

Smoking status and cause-specific discontinuation of tumour necrosis factor inhibitors in axial spondyloarthritis

Availability of data and materials BSRBR-AS data are held at the University of Aberdeen. Funding The BSRBR-AS is funded by the British Society for Rheumatology (BSR) who have received funding for this from Pfizer, AbbVie and UCB. These companies receive advance copies of manuscripts for comments. They have no input in determining the topics for analysis or work involved in undertaking it. SZ was supported by awards from the Royal College of Physicians (John Glyn bursary) and Royal Society of Medicine (Kovacs fellowship). KY received financial support for his doctoral study from the Pharmacoepidemiology Program at the Harvard T.H. Chan School of Public Health (partially supported by training grants from Pfizer, Takeda, Bayer and ASISA) and Honjo International Scholarship Foundation. DHS was supported by grants from the National Institute of Health (NIH-P30-AR072577 (VERITY) and NIH-K24AR055989) and has received funding from Abbvie and Amgen unrelated to this work. Acknowledgements We are grateful to Professor Gary Macfarlane (Chief Investigator of BSRBR-AS) and the staff of the BSRBR-AS register who are currently Claudia Zabke, Elizabeth Ferguson-Jones, Maureen Heddle, Nafeesa Nazlee and Barry Morris, and to the recruiting staff at the clinical centres, details of which are available at: https://www.abdn.ac.uk/iahs/research/epidemiology/spondyloarthritisPeer reviewedPublisher PD

Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine

DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14–41%); the intent-to-treat response rate was 21% (CI 95%: 12–34%). Median time to neurologic progression was 49 days (range 1–515(+)); median survival was 88 days (range 1–515(+)), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians. © 2001 Cancer Research Campaign http://www.bjcancer.co

B Cell Synovitis and Clinical Phenotypes in Rheumatoid Arthritis: Relationship to Disease Stages and Drug Exposure.

OBJECTIVE: To define the relationship of synovial B cells to clinical phenotypes at different stages of disease evolution and drug exposure in rheumatoid arthritis (RA). METHODS: Synovial biopsy specimens and demographic and clinical data were collected from 2 RA cohorts (n = 329), one of patients with untreated early RA (n = 165) and one of patients with established RA with an inadequate response to tumor necrosis factor inhibitors (TNFi-IR; n = 164). Synovial tissue was subjected to hematoxylin and eosin and immunohistochemical staining and semiquantitative assessment for the degree of synovitis (on a scale of 0-9) and of CD20+ B cell infiltrate (on a scale of 0-4). B cell scores were validated by digital image analysis and B cell lineage-specific transcript analysis (RNA-Seq) in the early RA (n = 91) and TNFi-IR (n = 127) cohorts. Semiquantitative CD20 scores were used to classify patients as B cell rich (≥2) or B cell poor (<2). RESULTS: Semiquantitative B cell scores correlated with digital image analysis quantitative measurements and B cell lineage-specific transcripts. B cell-rich synovitis was present in 35% of patients in the early RA cohort and 47.7% of patients in the TNFi-IR cohort (P = 0.025). B cell-rich patients showed higher levels of disease activity and seropositivity for rheumatoid factor and anti-citrullinated protein antibody in early RA but not in established RA, while significantly higher histologic synovitis scores in B cell-rich patients were demonstrated in both cohorts. CONCLUSION: We describe a robust semiquantitative histologic B cell score that closely replicates the quantification of B cells by digital or molecular analyses. Our findings indicate an ongoing B cell-rich synovitis, which does not seem to be captured by standard clinimetric assessment, in a larger proportion of patients with established RA than early RA