Atrial fibrillation as a novel risk factor for retinal stroke: A protocol for a population-based retrospective cohort study

by Jay B. Lusk, Lauren Wilson, Vinit Nalwade, Ailin Song, Matthew Schrag, Valerie Biousse, Fan Li, Sven Poli, Jonathan Piccini, Ying Xian, Emily O’Brien, Brian Mac Grory

Central retinal artery occlusion (CRAO; retinal stroke or eye stroke) is an under-recognized, disabling form of acute ischemic stroke which causes severe visual loss in one eye. The classical risk factor for CRAO is ipsilateral carotid stenosis; however, nearly half of patients with CRAO do not have high-grade carotid stenosis, suggesting that other cardiovascular risk factors may exist for CRAO. Specifically, prior studies have suggested that cardioembolism, driven by underlying atrial fibrillation, may predispose patients to CRAO. We describe the design of an observational, population-based study in this protocol. We evaluate two specific objectives: 1) To determine if atrial fibrillation is an independent risk factor for CRAO after adjusting for medical and cardiovascular risk; 2) To determine if use of oral anticoagulation can modify the risk of CRAO for patients with atrial fibrillation. This protocol lays out our strategy for cohort definition, case and control definition, comorbidity ascertainment, and statistical methods.

Portosystemic shunting prevents hepatocellular carcinoma in non-alcoholic fatty liver disease mouse models

by Andrea Peloso, Stéphanie Lacotte, Quentin Gex, Florence Slits, Beat Moeckli, Graziano Oldani, Matthieu Tihy, Aurélie Hautefort, Brenda Kwak, Laura Rubbia-Brandt, Christian Toso

Background and aims

Non-alcoholic fatty liver disease (NAFLD) is one of the leading cause of hepatocellular carcinoma (HCC). This association is supported by the translocation of bacteria products into the portal system, which acts on the liver through the gut-liver axis. We hypothesize that portosystemic shunting can disrupt this relationship, and prevent NAFLD-associated HCC.

Methods

HCC carcinogenesis was tested in C57BL/6 mice fed a high-fat high-sucrose diet (HFD) and injected with diethylnitrosamine (DEN) at two weeks of age, and in double transgenic LAP-tTA and TRE-MYC (LAP-Myc) mice fed a methionine-choline-deficient diet. Portosystemic shunts were established by transposing the spleen to the sub-cutaneous tissue at eight weeks of age.

Results

Spleen transposition led to a consistent deviation of part of the portal flow and a significant decrease in portal pressure. It was associated with a decrease in the number of HCC in both models. This effect was supported by the presence of less severe liver steatosis after 40 weeks, and lower expression levels of liver fatty acid synthase. Also, shunted mice exhibited lower liver oxygen levels, a key factor in preventing HCC as confirmed by the development of less HCCs in mice with hepatic artery ligation.

Conclusions

The present data show that portosystemic shunting prevents NAFLD-associated HCC, utilizing two independent mouse models. This effect is supported by the development of less steatosis, and a restored liver oxygen level. Portal pressure modulation and shunting deserve further exploration as potential prevention/treatment options for NAFLD and HCC.

Anakinra or tocilizumab in patients admitted to hospital with severe covid-19 at high risk of deterioration (IMMCoVA): A randomized, controlled, open-label trial

by Jonas Sundén-Cullberg, Puran Chen, Henrike Häbel, Paul Skorup, Helena Janols, Johan Rasmuson, Katarina Niward, Åse Östholm Balkhed, Katerina Chatzidionysiou, Hilmir Asgeirsson, Ola Blennow, Åsa Parke, Anna-Karin Svensson, Jagadeeswara Rao Muvva, Hans-Gustav Ljunggren, Karolinska KI/K COVID-19 Treatment Working Group , Anna-Carin Horne, Ulrika Ådén, Jan-Inge Henter, Anders Sönnerborg, Jan Vesterbacka, Piotr Nowak, Jon Lampa

Background

Anakinra and tocilizumab are used for severe Covid-19, but only one previous randomized controlled trial (RCT) has studied both. We performed a multi-center RCT comparing anakinra or tocilizumab versus usual care (UC) for adults at high risk of deterioration.

Methods

The study was conducted June 2020 to March 2021. Eligibility required ≥ 5 liters/minute of Oxygen to maintain peripheral oxygen saturation at ≥ 93%, CRP > 70 mg/L, ferritin > 500 μg/L and at least two points where one point was awarded for lymphocytes 9/L; D-dimer ≥ 0.5 mg/L and; lactate dehydrogenase ≥ 8 microkatal/L. Patients were randomly assigned 1:1:1 to receive either a single dose of tocilizumab (8 mg/kg) or anakinra 100 mg IV QID for seven days or UC alone. The primary outcome was time to recovery.

Results

Recruitment was ended prematurely when tocilizumab became part of usual care. Out of a planned 195 patients, 77 had been randomized, 27 to UC, 28 to anakinra and 22 to tocilizumab. Median time to recovery was 15, 15 and 11 days. Rate ratio for recovery for UC vs anakinra was 0.91, 0.47 to 1.78, 95% [CI], p = 0.8 and for UC vs tocilizumab 1.13, 0.55 to 2.30; p = 0.7. There were non-significant trends favoring tocilizumab (and to limited degree anakinra) vs UC for some secondary outcomes. Safety profiles did not differ significantly.

Conclusion

Premature closure of trial precludes firm conclusions. Anakinra or tocilizumab did not significantly shorten time to clinical recovery compared to usual care. (IMMCoVA, NCT04412291, EudraCT: 2020–00174824).

Factors influencing the acceptability of alcohol drinking for a patient with colorectal cancer

by Camille Auriol, Nicole Cantisano, Patrick Raynal

Introduction

Colorectal cancer is the second deadliest cancer worldwide. One of the risk factors for the development of this type of cancer is alcohol consumption. Patients with colorectal cancer may be stigmatized regarding their cancer and regarding drinking behaviors they may exhibit. This study aimed to analyze community persons’ and health professionals’ acceptability judgments regarding alcohol drinkers having colorectal cancer.

Method

This study relies on an experimental method enabling the identification of variables involved in one’s judgment, based on the exhaustive combination of factors yielding several scenarios rated by participants. Scenarios implemented factors possibly influencing participants’ perception of a woman character having colorectal cancer. Factors included her drinking habits, post-diagnosis drinking behavior and type of diagnosis/prognosis. The participants were community persons (N’ = 132) or health professionals (N" = 126). Data were analyzed using a within-subject factorial ANOVA.

Results

In both samples, the "Post-diagnosis behavior" factor had large effect sizes, with drinking cessation being more acceptable than other drinking behaviors. Another factor, "Drinking habits", had significant influences on participants judgments, as higher drinking was considered less acceptable. A third factor, "Diagnosis" (polyps, early- or late-stage cancer), was taken into account by participants when it interacted with "Drinking habits" and "Post-diagnosis behavior". Indeed, participants considered most acceptable to continue drinking in the case of late-stage cancer, especially in the health professional sample where the acceptability of continuing drinking was almost doubled when the character had advanced- rather than early-cancer.

Conclusion

The lesser the drinking behavior, the better the acceptability. However, advanced cancer stage attenuated the poor acceptability of drinking in both samples, as participants’ attitudes were more permissive when the patient had advanced cancer.

Risk of sexually transmitted infections among U.S. military service members in the setting of HIV pre-exposure prophylaxis use

by Jason M. Blaylock, Evan C. Ewers, Elizabeth J. Bianchi, David B. King, Rosemary O. Casimier, Hector Erazo, Stephen Grieco, Jenny Lay, Sheila A. Peel, Kayvon Modjarrad, Charmagne G. Beckett, Jason F. Okulicz, Paul T. Scott, Shilpa Hakre

Background

The evidence for an increased incidence of sexually transmitted infections (STIs) among patients utilizing HIV pre-exposure prophylaxis (PrEP) has been inconsistent. We assessed the risk of incident STI while on PrEP compared to periods off PrEP among military service members starting PrEP.

Methods

Incidence rates of chlamydia, gonorrhea, syphilis, hepatitis C virus, and HIV were determined among military service members without HIV prescribed daily oral tenofovir disoproxil fumarate and emtricitabine for HIV PrEP from February 1, 2014 through June 10, 2016. Hazard ratios for incident STIs were calculated using an Anderson-Gill recurrent event proportional hazard regression model.

Results

Among 755 male service members, 477 (63%) were diagnosed with incident STIs (overall incidence 21.4 per 100 person-years). Male service members had a significantly lower risk of any STIs (adjusted hazard ratio (aHR) 0.21, 95% CI 0.11–0.40) while using PrEP compared to periods off PrEP after adjustment for socio-demographic characteristics, reasons for initiating PrEP, surveillance period prior to PrEP initiation, and the effect of PrEP on site and type of infection in multivariate analysis. However, when stratifying for anatomical site and type of infection, the risk of extragenital gonorrhea infection (pharyngeal NG: aHR 1.84, 95% CI 0.82–4.13, p = 0.30; rectal NG: aHR 1.23, 95% CI 0.60–2.51, p = 1.00) and extragenital CT infection (pharyngeal CT: aHR 2.30, 95% CI 0.46–11.46, p = 0.81; rectal CT: aHR 1.36, 95% CI 0.81–2.31, p = 0.66) was greater on PrEP compared to off PrEP although these values did not reach statistical significance.

Conclusions

The data suggest entry into PrEP care reduced the overall risk of STIs following adjustment for anatomical site of STI and treatment. Service members engaged in PrEP services also receive more STI prevention counseling, which might contribute to decreases in STI risk while on PrEP.

Multiocular defect in the Old English Sheepdog: A canine form of Stickler syndrome type II associated with a missense variant in the collagen-type gene <i>COL11A1</i>

by Katherine Stanbury, Renata Stavinohova, Louise Pettitt, Chris Dixon, Ellen C. Schofield, Bryan Mclaughlin, Inka Pettinen, Hannes Lohi, Sally L. Ricketts, James A. Oliver, Cathryn S. Mellersh

Multiocular defect has been described in different canine breeds, including the Old English Sheepdog. Affected dogs typically present with multiple and various ocular abnormalities. We carried out whole genome sequencing on an Old English Sheepdog that had been diagnosed with hereditary cataracts at the age of five and then referred to a board-certified veterinary ophthalmologist due to owner-reported visual deterioration. An ophthalmic assessment revealed that there was bilateral vitreal degeneration, macrophthalmos, and spherophakia in addition to cataracts. Follow-up consultations revealed cataract progression, retinal detachment, uveitis and secondary glaucoma. Whole genome sequence filtered variants private to the case, shared with another Old English Sheepdog genome and predicted to be deleterious were genotyped in an initial cohort of six Old English Sheepdogs (three affected by multiocular defect and three control dogs without evidence of inherited eye disease). Only one of the twenty-two variants segregated correctly with multiocular defect. The variant is a single nucleotide substitution, located in the collagen-type gene COL11A1, c.1775T>C, that causes an amino acid change, p.Phe1592Ser. Genotyping of an additional 14 Old English Sheepdogs affected by multiocular defect revealed a dominant mode of inheritance with four cases heterozygous for the variant. Further genotyping of hereditary cataract-affected Old English Sheepdogs revealed segregation of the variant in eight out of nine dogs. In humans, variants in the COL11A1 gene are associated with Stickler syndrome type II, also dominantly inherited.

Organisation and delivery of a dedicated multidisciplinary prone ventilation team in the intensive care unit: Strategies and lessons from COVID-19

by Luke Bracegirdle, Matthew Stubbs, Rezaur Rahman, Alexander I. R. Jackson, Helmi C. Burton-Papp, Robert Chambers, Sanjay Gupta, Michael P. W. Grocott, Ahilanandan Dushianthan

Background

COVID-19 placed immense strain on healthcare systems, necessitating innovative responses to the surge of critically ill patients, particularly those requiring mechanical ventilation. In this report, we detail the establishment of a dedicated critical care prone positioning team at University Hospital Southampton in response to escalating demand for prone positioning during the initial wave of the pandemic.

Methods

The formation of a prone positioning team involved meticulous planning and collaboration across disciplines to ensure safe and efficient manoeuvrers. A comprehensive training strategy, aligned with national guidelines, was implemented for approximately 550 staff members from a diverse background. We surveyed team members to gain insight to the lived experience.

Results

A total of 78 full-time team members were recruited and successfully executed over 1200 manoeuvres over an eight-week period. Our survey suggests the majority felt valued and expressed pride and willingness to participate again should the need arise.

Conclusion

The rapid establishment and deployment of a dedicated prone positioning team may have contributed to both patient care and staff well-being. We provide insight and lessons that may be of value for future respiratory pandemics. Future work should explore objective clinical outcomes and long-term sustainability of such services.

“High blood pressure comes from thinking too much”: Understandings of illness among couples living with cardiometabolic disorders and HIV in Malawi

by Jane Jere, Allison Ruark, Julie T. Bidwell, Rita M. Butterfield, Torsten B. Neilands, Sheri D. Weiser, Nancy Mulauzi, James Mkandawire, Amy A. Conroy

Cardiometabolic disorders (CMD) such as hypertension and diabetes are increasingly prevalent in sub-Saharan Africa, placing people living with HIV at risk for cardiovascular disease and threatening the success of HIV care. Spouses are often the primary caregivers for people living with CMD, and understanding patients’ and partners’ conceptions of CMD could inform care. We conducted semi-structured interviews with 25 couples having a partner living with HIV and either hypertension or diabetes. Couples were recruited from HIV clinics in Malawi and were interviewed on beliefs around symptoms, causation, prevention, and treatment for CMD. Data were analyzed at the individual and dyadic levels using framework analysis and Kleinman’s theory of explanatory models as a lens. On average, participants were 51 years old and married for 21 years. Approximately 57%, 14%, and 80% had hypertension, diabetes, and HIV. Couples endorsed a combination of biomedical explanatory models (beliefs around physical and mental health) and traditional explanatory models (beliefs around religion and natural remedies), although tended to emphasize the biomedical model. Half of couples believed stress was the main cause of hypertension. For diabetes, diet was believed to be a common cause. In terms of prevention, dietary changes and physical activity were most frequently mentioned. For disease management, medication adherence and diet modifications were emphasized, with some couples also supporting herbal remedies, stress reduction, and faith in God as strategies. Participants were generally more concerned about CMD than HIV due to poor access to CMD medications and beliefs that CMD could lead to sudden death. Within couples, partners often held many of the same beliefs but diverged around which etiological or preventive factors were most important (e.g., stress versus diet) and the best diet for CMD. Health education programs should involve primary partners to build knowledge of CMD and address overlap with HIV, and reinforce accurate information on lifestyle factors for the prevention and treatment of CMD.

Dietary eating patterns, dairy consumption, and anxiety: A systematic literature review

by Naimisha Movva, Heidi Reichert, Naushin Hooda, Lauren C. Bylsma, Meghan Mitchell, Sarah S. Cohen

Background

Nutrition affects both physical and mental health but evidence is mixed regarding potential associations between anxiety and diet, particularly dairy consumption. We conducted a systematic literature review (SLR) of dairy consumption and/or various dietary patterns and risk of anxiety.

Methods

Literature searches were conducted in PubMed and Embase. All study designs except case reports, small case series, and SLRs were considered for inclusion. Reference lists of previously published SLRs were reviewed for any relevant additional studies. Studies of populations without dairy sensitivities exploring the association between dietary patterns and/or dairy consumption and anxiety published through May 2022 were identified using predefined eligibility criteria. Study quality was determined using the Academy of Nutrition and Dietetics Quality Criteria Checklist.

Results

For this SLR, 132 studies were included; 80 were cross-sectional. Studies examined different dietary patterns (e.g., Mediterranean, gluten-free) and anxiety using various anxiety scales, with 19 studies specifically reporting on whole dairy consumption and anxiety. Dairy consumption was significantly associated with a lower risk of anxiety in 7 studies, while the remaining 12 studies showed no significant associations. Evidence was mixed for the association between various dietary patterns and anxiety, but more studies observed a lower risk of anxiety with greater adherence to “healthy” diets (e.g., Mediterranean, diet quality score, vegetarian/vegan) than a higher risk. Notable heterogeneity in study populations, time periods, geographical locations, dietary assessment methods, and anxiety scales was observed.

Conclusions

The results of this SLR suggest a potential link between diet including diary consumption and anxiety, but future studies, especially with longitudinal designs that measure diet and anxiety at several timepoints and comprehensively adjust for confounders, are needed to fully understand the relationship between diet and anxiety.

Impact of an intervention program on drug adherence in patients with ulcerative colitis: Randomized clinical trial

by Mila Pacheco, Pedro Sá, Gláucia Santos, Ney Boa-Sorte, Kilma Domingues, Larissa Assis, Marina Silva, Ana Oliveira, Daniel Santos, Jamile Ferreira, Rosemeire Fernandes, Flora Fortes, Raquel Rocha, Genoile Santana

Aims

Evaluate the impact of an intervention program in non-adherent patients with ulcerative colitis.

Methods

Parallel controlled randomized clinical trial (1:1), approved by the ethics committee (No. 3.068.511/2018) and registered at The Brazilian Clinical Trials Registry (No. RBR-79dn4k). Non-adherent ulcerative colitis patients according to the Morisky-Green-Levine-test were included. Recruitment began in August 2019 until August 2020, with 6-month follow-up. All participants received standard usual care, and additionally the intervention group received educational (video, educational leaflet, verbal guidance) and behavioral interventions (therapeutic scheme, motivational and reminder type short message services). Researchers were blinded for allocation prior to data collection at Visits 1 and 2 (0 and 6 months). Primary outcome: 180-day adherence rate, with relative risk 95%CI. Secondary outcome: 180-day quality of life according to SF-36 domains, using Student’s t test. Variables with p Results

Forty-six and 49 participants were allocated in control and intervention groups, respectively. Two were excluded due to intervention refusal, and 4 and 6 were lost to follow-up in control and intervention groups. There was no post-intervention adherence rate difference, even after adjustment for type of non-adherence (unintentional/both/intentional) as confounder, or if considered as adherent the intervention group participants lost in follow-up. Interventions promoted better quality of life scores even after multivariate analysis for “Pain”, when adjusted for ulcerative colitis severity, sex, and marital status (β = 18.352, p = 0.004), “Vitality”, when adjusted for ulcerative colitis severity (β = 10.568, p = 0.015) and “Emotional Aspects”, when adjusted for disease severity, income, and education (β = 24.907, p = 0.041).

Conclusions

The intervention program was not able to produce a significant medication adherence rate difference between comparative groups, however, there was a significant improvement in quality of life. Study limitations may include: sample size calculated to identify differences of 30%, leading to a possible insufficient power; non blinded participants, exposing the results to the risk of performance bias; outcomes based on self-reported data.

Implementation of the advanced HIV disease care package with point-of-care CD4 testing during tuberculosis case finding: A mixed-methods evaluation

by Tinne Gils, Mashaete Kamele, Thandanani Madonsela, Shannon Bosman, Thulani Ngubane, Philip Joseph, Klaus Reither, Moniek Bresser, Erika Vlieghe, Tom Decroo, Irene Ayakaka, Lutgarde Lynen, Alastair Van Heerden

During TB-case finding, we assessed the feasibility of implementing the advanced HIV disease (AHD) care package, including VISITECT CD4 Advanced Disease (VISITECT), a semiquantitative test to identify a CD4≤200cells/μl. Adult participants with tuberculosis symptoms, recruited near-facility in Lesotho and South-Africa between 2021–2022, were offered HIV testing (capillary blood), Xpert MTB/RIF and Ultra, and MGIT culture (sputum). People living with HIV (PLHIV) were offered VISITECT (venous blood) and Alere tuberculosis-lipoarabinomannan (AlereLAM, urine) testing. AHD was defined as a CD4≤200cells/μl on VISITECT or a positive tuberculosis test. A CD4≤200cells/μl on VISITECT triggered Immy cryptococcal antigen (Immy CrAg, plasma) testing. Participants were referred with test results. To evaluate feasibility, we assessed i) acceptability and ii) intervention delivery of point-of-care diagnostics among study staff using questionnaires and group discussions, iii) process compliance, and iv) early effectiveness (12-week survival and treatment status) in PLHIV. Predictors for 12-week survival were assessed with logistic regression. Thematic content analysis and triangulation were performed. Among PLHIV (N = 676, 48.6% of 1392 participants), 7.8% were newly diagnosed, 81.8% on ART, and 10.4% knew their HIV status but were not on ART. Among 676 PLHIV, 41.7% had AHD, 29.9% a CD4≤200cells/μl and 20.6% a tuberculosis diagnosis. Among 200 PLHIV tested with Immy CrAg, 4.0% were positive. The procedures were acceptable for study staff, despite intervention delivery challenges related to supply and the long procedural duration (median: 73 minutes). At 12 weeks, among 276 PLHIV with AHD and 328 without, 3.3% and 0.9% had died, 84.8% and 92.1% were alive and 12.0% and 7.0% had an unknown status, respectively. Neither AHD nor tuberculosis status were associated with survival. Implementing AHD care package diagnostics was feasible during tuberculosis-case finding. AHD was prevalent, and not associated with survival, which is likely explained by the low specificity of VISITECT. Challenges with CD4 testing and preventive treatment uptake require addressing.

A high-fat and fructose diet in dogs mirrors insulin resistance and β-cell dysfunction characteristic of impaired glucose tolerance in humans

by Justin M. Gregory, Guillaume Kraft, Chiara Dalla Man, James C. Slaughter, Melanie F. Scott, Jon R. Hastings, Dale S. Edgerton, Mary C. Moore, Alan D. Cherrington

This study examined the impact of a hypercaloric high-fat high-fructose diet (HFFD) in dogs as a potential model for human impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). The HFFD not only led to weight gain but also triggered metabolic alterations akin to the precursors of human T2DM, notably insulin resistance and β-cell dysfunction. Following the HFFD intervention, the dogs exhibited a 50% decrease in insulin sensitivity within the first four weeks, paralleling observations in the progression from normal to IGT in humans. Calculations of the insulinogenic index using both insulin and C-peptide measurements during oral glucose tolerance tests revealed a significant and sustained decrease in early-phase insulin release, with partial compensation in the later phase, predominantly stemming from reduced hepatic insulin clearance. In addition, the Disposition Index, representing the β-cell’s capacity to compensate for diminished insulin sensitivity, fell dramatically. These results confirm that a HFFD can instigate metabolic changes in dogs akin to the early stages of progression to T2DM in humans. The study underscores the potential of using dogs subjected to a HFFD as a model organism for studying human IGT and T2DM.

Predictors of triage pain assessment and subsequent pain management among pediatric patients presenting to the emergency department

by Rahim Valani, Fazila Kassam, Shauna Jose, Mario Hanna, Tanmay Sharma, Jhanahan Sriranjan, Yazad Bhathena, Umairah Boodoo, Aashna Agarwal, Suneel Upadhye

Background

Pediatric patients with pain of various causes present to the emergency department. Appropriate assessment and management of pain are important aspects of emergency department treatment. However, only a few studies have identified the predictors of both outcomes. This study aimed to evaluate the rate of pain assessment at triage and subsequent management and to identify the predictors of each outcome.

Methods

This was a multi-center retrospective study based at five community emergency departments. Pediatric patients ( Results

There were 4,128 patients with an average age of 9.6 years, and 49.1% of them were female. Only 74.2% of the patients underwent assessment for pain at triage, and 18.3% received analgesia. The median time to analgesia was 95 (IQR: 49–154) min. Most patients presented with head/neck (36.1%), upper limb (21.6%), and lower limb (19.9%) pain. The oral route was the most common analgesia delivery method (67.4%), and ibuprofen and acetaminophen were the primary agents used. Younger age, higher acuity, and presenting with head or neck pain were independent predictors of pain assessment at triage, while children 3–5 years and those with lower extremity pain were more likely to receive analgesia.

Conclusion

Although pain assessment at triage has improved in pediatric patients, there is still a major deficiency in adequate pain management. Our study highlights predictors of pain assessment and management that can be considered for improved pediatric care.

Monitoring mobility in older adults using a Global Positioning System (GPS) smartwatch and accelerometer: A validation study

by Marla Beauchamp, Renata Kirkwood, Cody Cooper, Matthew Brown, K. Bruce Newbold, Darren Scott, on behalf of the MacM3 team

There is growing interest in identifying valid and reliable methods for detecting early mobility limitations in aging populations. A multi-sensor approach that combines accelerometry with Global Positioning System (GPS) devices could provide valuable insights into late-life mobility decline; however, this innovative approach requires more investigation. We conducted a series of two experiments with 25 older participants (66.2±8.5 years) to determine the validity of a GPS enabled smartwatch (TicWatch S2 and Pro 3 Ultra GPS) and separate accelerometer (ActiGraph wGT3X-BT) to collect movement, navigation and body posture data relevant to mobility. In experiment 1, participants wore the TicWatchS2 and ActiGraph simultaneously on the wrist for 3 days. In experiment 2, participants wore the TicWatch Pro 2 Ultra GPS on the wrist and ActiGraph on the thigh for 3 days. In both experiments participants also carried a Qstarz data logger for trips outside the home. The TicWatch Pro 3 Ultra GPS performed better than the S2 model and was similar to the Qstarz in all tested trip-related measures, and it was able to estimate both passive and active trip modes. Both models showed similar results to the gold standard Qstarz in life-space-related measures. The TicWatch S2 demonstrated good to excellent overall agreement with the ActiGraph algorithms for the time spent in sedentary and non-sedentary activities, with 84% and 87% agreement rates, respectively. Under controlled conditions, the TicWatch Pro 3 Ultra GPS consistently measured step count in line with the participants’ self-reported data, with a bias of 0.4 steps. The thigh-worn ActiGraph algorithm accurately classified sitting and lying postures (97%) and standing postures (90%). Our multi-sensor approach to monitoring mobility has the potential to capture both accelerometer-derived movement data and trip/life-space data only available through GPS. In this study, we found that the TicWatch models were valid devices for capturing GPS and raw accelerometer data, making them useful tools for assessing real-life mobility in older adults.

Targeted solutions to increase dolutegravir coverage, viral load testing coverage, and viral suppression among children living with HIV in Togo: An analysis of routine facility data

by Caterina Casalini, Yema D’Almeida, Moussa Ariziki Nassam, Essopha Kokoloko, Souley Wade, Jean Paul Tchupo, Messan Damarly, Justin Mandala, Michele Lanham, Natasha Mack, Chris Akolo, Vincent Polakinam Pitche, Hugues Guidigbi, Claver Anoumou Dagnra

Background

According to UNAIDS, Togo halved AIDS-related deaths among children ages 0–14 from 2010 to 2020. However, available data show low dolutegravir (DTG)-containing antiretroviral therapy (ART) coverage and low viral load suppression (VLS) among children living with HIV (CLHIV). We analyzed routine facility data before and after implementation of root-cause-based solutions for improving DTG coverage, viral load (VL) testing coverage, and VLS among CLHIV.

Description

We analyzed routine data for CLHIV ≤14 years from October 2019 through September 2022. We assessed proportion of CLHIV on ART receiving DTG, VL testing coverage (CLHIV on ART with documented VL test result), and VLS (CLHIV with documented VL test result of Results

From baseline (October 2019–September 2020) to endline (October 2021–September 2022), increases were observed for DTG coverage (52% to 71%), VL testing coverage (48% to 90%), and VLS (64% to 82%). Age-disaggregated data showed positive trends.

Conclusions

Root-cause-based solutions and granular data use increased DTG coverage, resulting in increased VL testing and VLS among CLHIV. These interventions should be scaled and become the national standard of care.

Barriers and enablers to and strategies for promoting domestic plasma donation throughout the world: Overarching protocol for three systematic reviews

by Cole Etherington, Amelia Palumbo, Kelly Holloway, Samantha Meyer, Maximillian Labrecque, Kyle Rubini, Risa Shorr, Vivian Welch, Emily Gibson, Terrie Foster, Jennie Haw, Elisabeth Vesnaver, Manavi T. Maharshi, Sheila F. O’Brien, Paul MacPherson, Joyce Dogba, Tony Steed, Mindy Goldman, Justin Presseau

Introduction

The growing demand for plasma protein products has caused concern in many countries who largely rely on importing plasma products produced from plasma collected in the United States and Europe. Optimizing recruitment and retention of a diversity of plasma donors is therefore important for supporting national donation systems that can reliably meet the most critical needs of health services. This series of three systematic reviews aims to synthesize the known barriers and enablers to source plasma donation from the qualitative and survey-based literature and identify which strategies that have shown to be effective in promoting increased intention to, and actual donation of, source plasma.

Methods and analysis

Primary studies involving source or convalescent plasma donation via plasmapheresis will be included. The search strategy will capture all potentially relevant studies to each of the three reviews, creating a database of plasma donation literature. Study designs will be subsequently identified in the screening process to facilitate analysis according to the unique inclusion criteria of each review (i.e., qualitative, survey, and experimental designs). The search will be conducted in the electronic databases SCOPUS, MEDLINE, EMBASE, PsycINFO, and CINAHL without date or language restrictions. Studies will be screened, and data will be extracted, in duplicate by two independent reviewers with disagreements resolved through consensus. Reviews 1 and 2 will draw on the Theoretical Domains Framework and Intersectionality, while Review 3 will be informed by Behaviour Change Intervention Ontologies. Directed content analysis and framework analysis (Review 1), and descriptive and inferential syntheses (Reviews 2 and 3), will be used, including meta-analyses if appropriate.

Discussion

This series of related reviews will serve to provide a foundation of what is known from the published literature about barriers and enablers to, and strategies for promoting, plasma donation worldwide.

Crawling toward obsolescence: The extended lifespan of amylase for pancreatitis

by Naga Sasidhar Kanaparthy, Andrew J. Loza, Ronald George Hauser

The correlation between hyperamylasemia and acute pancreatitis was discovered in 1929, yet another test, lipase, was shown to provide better diagnostic performance in the late 1980s and early 1990s. Subsequent studies demonstrated co-ordering amylase with lipase did not provide additional benefit, only added cost. We sought to investigate the impact of studies advocating for the obsolescence of amylase on its clinical demand. We reviewed 1.3 million reportable results for amylase over 14 years (2009–2022). The trend in utilization of amylase over this period declined by 66% along a linear trajectory (R2 = 0.97). Despite demand for amylase decreasing by an average of 17,003 tests per year, the last year of the study (2022) recorded over 100,000 results for amylase. By interpolating the decline of amylase until the utilization reached zero, we calculated amylase orders will continue for 6 more years until 2028. Tests for creatinine and lipase changed

Bacteriophage-encoded 24B_1 molecule resembles herpesviral microRNAs and plays a crucial role in the development of both the virus and its host

by Sylwia Bloch, Natalia Lewandowska, Joanna Zwolenkiewicz, Paulina Mach, Aleksandra Łukasiak, Mikołaj Olejniczak, Logan W. Donaldson, Grzegorz Węgrzyn, Bożena Nejman-Faleńczyk

The 24B_1 small non-coding RNA molecule has been identified in Escherichia coli after induction of Shiga toxin-converting bacteriophage Φ24_B. In this work, we focused on its direct role during phage and bacterial host development. We observed that in many aspects, this phage sRNA resembles herpesviral microRNAs. Similar to microRNAs, the mature 24B_1 is a short molecule, consisting of just 20 nucleotides. It is generated by cleaving the 80-nt long precursor transcript, and likely it undergoes a multi-step maturation process in which the Hfq protein plays an important role, as confirmed by demonstration of its binding to the 24B_1 precursor, but not to the 24B_1 mature form. Moreover, 24B_1 plays a significant role in maintaining the prophage state and reprogramming the host’s energy metabolism. We proved that overproduction of this molecule causes the opposite physiological effects to the mutant devoid of the 24B_1 gene, and thus, favors the lysogenic pathway. Furthermore, the 24B_1 overrepresentation significantly increases the efficiency of expression of phage genes coding for proteins CI, CII, and CIII which are engaged in the maintenance of the prophage. It seems that through binding to mRNA of the sdhB gene, coding for the succinate dehydrogenase subunit, the 24B_1 alters the central carbon metabolism and causes a drop in the ATP intracellular level. Interestingly, a similar effect, called the Warburg switch, is caused by herpesviral microRNAs and it is observed in cancer cells. The advantage of the Warburg effect is still unclear, however, it was proposed that the metabolism of cancer cells, and all rapidly dividing cells, is adopted to convert nutrients such as glucose and glutamine faster and more efficiently into biomass. The availability of essential building blocks, such as nucleotides, amino acids, and lipids, is crucial for effective cell proliferation which in turn is essential for the prophage and its host to stay in the lysogenic state.

Latent class analyses of multimorbidity and all-cause mortality: A prospective study in Chilean adults

by Gabriela Nazar, Felipe Díaz-Toro, Yeny Concha-Cisternas, Ana María Leiva-Ordoñez, Claudia Troncoso-Pantoja, Carlos Celis-Morales, Fanny Petermann-Rocha

Multimorbidity patterns can lead to differential risks for all-cause mortality. Within the Chilean context, research on morbidity and mortality predominantly emphasizes individual diseases or combinations thereof, rather than specific disease clusters. This study aimed to identify multimorbidity patterns, along with their associations with mortality, within a representative sample of the Chilean population. 3,701 participants aged ≥18 from the Chilean National Health Survey 2009–2010 were included in this prospective study. Multimorbidity patterns were identified from 16 chronic conditions and then classified using latent class analyses. All-cause mortality data were extracted from the Chilean Civil Registry. The association of classes with all-cause mortality was carried out using Cox proportional regression models, adjusting by sociodemographic and lifestyle variables. Three classes were identified: a) Class 1, the healthiest (72.1%); b) Class 2, the depression/cardiovascular disease/cancer class (17.5%); and c) Class 3, hypertension/chronic kidney disease class (10.4%). Classes 2 and 3 showed higher mortality risk than the healthiest class. After adjusting, Class 2 showed 45% higher mortality risk, and Class 3 98% higher mortality risk, compared with the healthiest class. Hypertension appeared to be a critical underlying factor of all-cause morbidity. Particular combinations of chronic diseases have a higher excess risk of mortality than others.

Effect of isokinetic eccentric training on the human shoulder strength, flexibility, and muscle architecture in physically active men: A preliminary study

by Sebastian Vetter, Pierre Hepp, Axel Schleichardt, Stefan Schleifenbaum, Maren Witt, Christian Roth, Hans-Peter Köhler

Strengthening the rotator cuff muscles is important for injury prevention and rehabilitation. Since muscle fascicle length improves motor performance and is suggested to reduce the risk of injury for the hamstring, it may be an important variable to promote multidirectional changes in the function and macroscopic structure for the shoulder. Recent literature reviews overwhelmingly suggest that eccentric exercises improve fascicle length and functional measures for the lower limb. However, there is a research gap for the shoulder. Since ultrasound imaging is the most commonly used imaging technique to quantify muscle structure, but has yielded heterogeneous results in different studies, there is another issue and a research gap for the imaging method. Based on the research gaps, the purpose of this study was to evaluate the effects of standardized eccentric strength training on the function and structure of the external rotator cuff muscles using an isokinetic dynamometer and MRI. Therefore, a preliminary pre-post intervention study was conducted and 16 physically active men were recruited in October 2021. For the right shoulder, an eccentric isokinetic training was performed twice a week for almost six weeks. The primary outcome measures (external rotators) were active and passive range of motion, eccentric and concentric torque at 30, 60, and 180°/s isokinetic speed, and fascicle length and fascicle volume for the supraspinatus and infraspinatus muscles. The findings show a training effect for the absolute mean values of eccentric strength (+24%, p = .008). The torque-angle relationship increased, especially in the final phase of range of motion, although a 4% (p = .002) decrease in passive range of motion was found in the stretch test. Positive changes in muscle structure were shown for the supraspinatus muscle fascicle length (+16%, p = .003) and fascicle volume (+19%, p = .002). Based on the study results, we can conclude that eccentric isokinetic training has a significant positive effect on the shoulder. To our knowledge, this is the first eccentric training study using both isokinetic dynamometer and muscle diffusion tensor imaging to access functional and structural changes in the human shoulder rotator cuff muscles. The methods were shown to be applicable for interventional studies. Based on these results, populations such as high-performance handball players with highly trained shoulders should be included in future studies.