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F1000 Research Ltd

Preprints posted in the last 7 days, ranked by how well they match F1000Research's content profile, based on 88 papers previously published here. The average preprint has a 0.12% match score for this journal, so anything above that is already an above-average fit.

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Glaucoma and Diabetes Mellitus: A Comparative Evaluation of Comorbid Effect on Tear Quantity among Patients in Owerri, Imo State, Nigeria.

Chukwuoha, C. M.; Ovenseri-Ogbomo, G.; Azuamah, Y. C.; Odimegwu, N. E.; Obioma-Elemba, J. E.; Ugwoke, G.; Nkeremuzor, E. C.; Eronini, Y.; Ikoro, N. C.; Esenwah, E. C.

2026-09-02 ophthalmology 10.64898/2026.08.30.26361782 medRxiv
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Abstract Objective: Glaucoma is a chronic disorder that impairs ocular health and may exacerbate ocular surface disease leading to tear film instability, dry eye symptoms and decreased quality of life. This study compared changes in tear quantity among glaucoma subjects living with and without diabetes mellitus, attending an eye clinic in Nigeria. Methods: A comparative cross sectional research design was used. 157 subjects which comprised 74 glaucoma subjects living with diabetes mellitus and 83 glaucoma subjects living without diabetes mellitus participated in the study. Tear quantity assessment included the Schirmer I test and tear meniscus height (TMH) measurement. Descriptive statistics, independent samples t-test and Chi-square test were used to examine the data at 0.05 level of significance. Results: Glaucoma subjects living with diabetes mellitus showed substantially decreased tear production (11.4 +/- 6.8 mm) compared with glaucoma subjects living without diabetes mellitus (19.6 +/- 9.6 mm; p < 0.001). Tear meniscus height in glaucoma subjects living with diabetes mellitus (0.8 +/- 0.3 mm) was significantly greater than in subjects living without diabetes mellitus (0.7 +/- 0.3 mm; p = 0.034). Conclusion: Diabetes mellitus dramatically deteriorates the ocular surface function in glaucoma subjects by decreasing tear production, altering the tear meniscus height and increasing the severity of ocular surface symptoms. Routine glaucoma care, especially in patients with diabetes mellitus, should include a full ocular surface evaluation including Schirmer I test, TBUT, TMH, and OSDI assessment to allow early detection and management of ocular surface disease, better treatment adherence, and improved visual outcomes. Keywords: Glaucoma, Diabetes Mellitus, Tear production, Tear Meniscus Height, Ocular Surface Disease.

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Patient factors influencing participation in aerobic exercise during inpatient and outpatient rehabilitation post stroke: a prospective cohort study

Barzideh, A.; Devasahayam, A. J.; Marzolini, S.; Munce, S.; Sibley, K. M.; Inness, E. L.; Mansfield, A.

2026-08-31 rehabilitation medicine and physical therapy 10.64898/2026.08.26.26361451 medRxiv
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Background: Aerobic exercise is recommended during stroke rehabilitation to improve cardiorespiratory fitness and support recovery; however, participation rates remain low. While institutional and system-level barriers have been widely examined, less is known about how individual patient factors influence engagement in aerobic exercise during rehabilitation. Objectives: We aimed to determine whether depressive symptoms, apathy, self-efficacy and outcome expectations for exercise, perceived barriers, or past exercise history were associated with aerobic exercise participation in stroke rehabilitation. Methods: In this prospective cohort sub-study, adults admitted to in- or out-patient stroke rehabilitation at three urban hospitals completed validated questionnaires assessing depressive symptoms, apathy, exercise self-efficacy, outcome expectations for exercise, perceived barriers to being active, and premorbid exercise history. Participants were separated into two groups for analysis: those who completed aerobic exercise during rehabilitation and those who did not. Equivalence testing and between-group comparisons were performed. Results: Sixty-two participants were enrolled; 16 participated in aerobic exercise and 46 did not. Groups were not equivalent on any individual-level factors. Compared to non-participants, those who performed aerobic exercise had significantly higher depressive symptom scores (p=0.0025) and lower self-efficacy for exercise (p=0.0087). Non-participants demonstrated significantly higher apathy (p=0.0007). No significant differences were found for outcome expectations, perceived barriers, or exercise history. Conclusion: Depressive symptoms and lower self-efficacy did not impede aerobic exercise participation during rehabilitation. Increased apathy, however, was associated with non-participation. Findings highlight the need for individually tailored aerobic exercise prescriptions that consider motivational and affective factors to optimize engagement during stroke rehabilitation.

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Optimizing Aqueous Humor Liquid Biopsy: Safety and Performance of a Short, Low-Dead-Space Ophthalmic Needle for Anterior Chamber Paracentesis

Singh, A. M.; Yeh, T.-C.; DeBoer, C.; Al-Moujahed, A.; Lin, J. B.; Smith, S. J.; Sanislo, S.; Janjua, K. A.; Lin, T.-C.; Almeida, D. R. P.; Mruthyunjaya, P.; Mahajan, V. B.

2026-09-02 ophthalmology 10.64898/2026.08.26.26361364 medRxiv
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Purpose: To evaluate the safety, procedural performance, sample recovery, and surgeon preference of an ophthalmic needle designed specifically for anterior chamber (AC) paracentesis. Methods: In this multicenter study, AC paracentesis was performed in clinic and operating-room settings using a 32-gauge x 4-mm needle with low dead space. The procedure was evaluated using a standardized physician survey. Prespecified outcomes included procedure-related adverse events (primary outcome), needle entry and handling, aspiration and sample recovery, comparative performance versus a 30-gauge needle, and physician preference for future use. Results: A total of 110 needle uses by eight surgeons were included. No ocular complications occurred, including lens or iris injury, hyphema, AC collapse, wound leak, hypotony, infection, or retinal complication, and no procedure required needle exchange or conversion to another device. Two technical events without ocular sequelae were noted, in which needle entry was partial thickness and did not reach the AC (1.8%; exact 95% CI, 0.2%-6.4%). Physicians rated needle entry, handling and sample recovery as good or excellent. Compared with a 30-gauge needle, the study needle was rated as at least comparable across all assessed domains. All surgeons rated it better or much better for intra-procedural safety and preferred it for future AC taps. Conclusions and Relevance: This short, 32-gauge low-dead-space ophthalmic needle demonstrated a favorable safety profile and was preferred over a 30-gauge needle by all surgeons. As aqueous humor liquid biopsy expands in clinical diagnostics and trials, an ophthalmic-specific needle design may help improve the consistency and safety of aqueous humor collection for molecular analysis and broader clinical use. Keywords: Anterior chamber paracentesis; Aqueous humor; Liquid biopsy; Low dead space; Ophthalmic needle

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Predictors of Time to Start of Trophic Feeding in Preterm Neonates Admitted to Neonatal Intensive Care Unit of Adama Hospital Medical College, Ethiopia: A Retrospective Cohort Study

Misha, B.; Dassie, G. A.; Mohammad, I.

2026-08-31 epidemiology 10.64898/2026.08.26.26361481 medRxiv
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Background: Early trophic feeding promotes gut maturation, feeding tolerance, and growth in preterm neonates. However, delays remain common despite recommendations for initiation within 24 hours of birth, especially in resource-limited settings. Evidence on feeding initiation timing and predictors among Ethiopian preterm neonates is limited. Objective: To determine time to trophic feeding initiation and identify predictors among preterm neonates admitted to Adama Hospital Medical College, Ethiopia. Methods: A hospital-based retrospective cohort study was performed on 436 randomly chosen preterm neonates admitted to NICU. Data extraction was performed using a structured checklist. Time to trophic feeding initiation was analyzed using Kaplan-Meier estimates, log-rank tests, and bivariable and multivariable Cox regression models . Adjusted hazard ratios with 95% CIs were reported. Results:The sample comprised 416 preterm neonates, of whom 311 (74.8%) started trophic feeding during follow-up, and 105 (25.2%) were censored. The rate of initiation of trophic feeding was 1.92 per 100 person-hours (95% CI 1.72 to 2.15). Median time to initiation was 42 hours (interquartile range 24 to 50). Independent predictors of feeding initiation were determined by multivariable analysis and included gestational age, birth weight, maternal anaemia, respiratory distress syndrome and necrotising enterocolitis. Neonates born at 34-36 weeks had earlier initiation than those born at <34 weeks (AHR 1.39; 95 % CI 1.09 to 1.78). Similarly, neonates with a birth weight of [&ge;]1500 g had an earlier initiation than those with a birth weight of <1500 g (AHR 1.41; 95% CI 1.04 to 1.91). Delayed initiation was associated with maternal anaemia (AHR 0.70; 95% CI 0.51-0.95), respiratory distress syndrome (AHR 0.67; 95% CI 0.51-0.88) and necrotising enterocolitis (AHR 0.48; 95% CI 0.33-0.69). Conclusions: Delayed trophic feeding remains common among preterm neonates. Standardized feeding protocols, strengthened maternal care, and individualized nutrition strategies are needed to improve neonatal outcomes in study area.

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Bayesian Borrowing of External Information in Clinical Trials: A Comparison of MAP, RMAP, and SAM Priors

Choi, L.; McNeer, E.; Beck, C. A.; Neul, J. L.

2026-08-31 pharmacology and therapeutics 10.64898/2026.08.26.26360843 medRxiv
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Bayesian borrowing of external information can improve trial efficiency, particularly in pediatric and rare disease settings where patient populations are limited, but may introduce bias and inflate the Type~I error rate when the trial differs from external studies. Recent U.S. Food and Drug Administration (FDA) draft Bayesian guidance emphasizes careful evaluation of external information, prior specification, and assessment of operating characteristics. This paper compares three meta-analytic-predictive (MAP)-based methods for Bayesian borrowing: the MAP prior, robust MAP (RMAP) prior, and self-adapting mixture (SAM) prior. An adaptive platform trial design in Rett syndrome is used as a case study. Simulation studies evaluate frequentist operating characteristics under varying prior--data conflict, between-study heterogeneity, treatment effects, and clinically significant differences (CSDs) for the SAM prior. The MAP prior achieved the greatest efficiency when external and current data were compatible but exhibited the largest bias under substantial prior--data conflict. The RMAP priors improved robustness through fixed robust-component weights, whereas the SAM prior adaptively adjusted borrowing and was less sensitive to prior--data conflict while retaining efficiency gains when the data were compatible. Although the CSD influenced the degree of adaptive borrowing, as reflected by effective sample size, it had only a modest impact on frequentist operating characteristics. Sensitivity analyses using a skeptical robust component yielded similar qualitative conclusions, while accentuating the differences between the MAP and RMAP priors. These findings provide guidance for evaluating and selecting MAP-based borrowing strategies before trial implementation, particularly in rare disease settings, consistent with current FDA recommendations.

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Medial Plantar Nerve Shear Wave Elastography and Viscosity Imaging for Differentiating Mild from Moderate Diabetic Peripheral Neuropathy

Gao, X.; Li, Y.

2026-09-02 radiology and imaging 10.64898/2026.08.28.26361645 medRxiv
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Objective: To examine how medial plantar nerve shear wave speed (Cs) and viscosity coefficient (Vi) are associated with the severity of diabetic peripheral neuropathy (DPN), and to assess their ability to differentiate adjacent severity categories. Materials and Methods: Based on TCSS, the 113 patients with type 2 diabetes mellitus were assigned to the non-DPN (n = 33), mild DPN (n = 46), and moderate DPN (n = 34) groups. Medial plantar nerve Cs and Vi were measured using shear wave elastography and viscosity imaging. Receiver operating characteristic analysis evaluated Cs, Vi, and their logistic regression-based combination; areas under the curves (AUCs) were compared using DeLong tests. Results: Cs and Vi increased progressively across the three groups (both P < 0.001). For non-DPN versus mild DPN, the AUCs of Cs, Vi, and the combined model were 0.688 (95% CI, 0.604-0.772), 0.741 (0.660-0.822), and 0.745 (0.665-0.826), respectively, without significant pairwise differences. For mild versus moderate DPN, the corresponding AUCs were 0.707 (0.625-0.789), 0.794 (0.724-0.865), and 0.799 (0.731-0.867). The combined model outperformed Cs (P = 0.045), whereas Cs versus Vi and Vi versus the combined model did not differ significantly (P = 0.162 and 1.000, respectively). Conclusion: Medial plantar nerve Cs and Vi increased with DPN severity. Their combination improved discrimination between mild and moderate DPN compared with Cs alone but not with Vi alone. Quantitative medial plantar nerve viscoelastic assessment may complement clinical severity grading.

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Integrated MB-PhD training is a long-term investment in the clinician-scientist workforce

Jafree, D. J.; Sun, M.; Stewart, G. W.; Gishen, F.; Swanton, C.; Motallebzadeh, R.; UCL MB-PhD Outcomes Study Group,

2026-08-31 health policy 10.64898/2026.08.26.26361003 medRxiv
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Background: Clinician-scientists translate clinical observation into discovery, trials, and policy, yet this workforce is shrinking across health systems worldwide. Integrated MB-PhD training, pausing medical training to complete a PhD before clinical exposure or specialisation, is one route into this career. We aimed to evaluate the long-term value of MB-PhD training and the barriers to clinical-academic careers these face after graduation. Methods: We evaluated all 131 graduates (29.8% female) who entered the University College London (UCL) MB-PhD programme over a 25-year period (1994-2018). Bibliometric outputs were collated via an inter-linked information system. Concurrently, all 131 graduates were invited to respond to open-ended questions on career benefits and structural barriers; 99 (75.6%) responded, and responses were independently coded into themes, which were then reviewed and confirmed by a Study Group of 107 individuals, including the 91 respondents who agreed to participate further. Results: Graduates produced 5,877 publications (1,141 first-author, 819 corresponding-author), attracting 350,754 citations, with a mean relative citation ratio of 3.30 {+/-} 0.47, approximately three times the field average and sustained across three decades of programme entry. Graduates secured an estimated $157.55 million across 99 grants, released 465 public datasets, and were named investigators on 31 clinical trials across five continents. Among the 99 survey respondents, 49.5% held consultant-grade posts, 72.7% remained research-active, and 25.3% had reached senior academic grade. Open-ended responses were coded into five recurring structural barriers, subsequently confirmed by the Study Group: insufficient protected research time (72.2% of responses), unsupportive training structures and limited career opportunities (36.7%, 24.4% of responses), funding and pay barriers (22.2% of responses), and lack of mentorship or geographical/family constraints (14.4%, 13.3% of responses). Conclusions: Integrated MB-PhD training generates sustained academic productivity and leadership, but structural barriers threaten retention of graduates within clinical-academic careers. Protecting research time, stabilising funding and pay, and reducing geographic instability are needed to retain the clinician-scientists that health systems have already invested in training.

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Stakeholder perspectives on the potential introduction of a novel tuberculosis vaccine for adolescents and adults in Pakistan: A qualitative study

Hassan, Z.; Zurez, Z.; Saad, M.; Ahsan, N.; Clark, R. A.; White, R. G.; Kazi, A. M.; Nelson, K.

2026-08-31 public and global health 10.64898/2026.08.26.26360963 medRxiv
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Background: Tuberculosis (TB) remains a major public health challenge globally, with Pakistan ranking among the highest TB burden countries worldwide. Although several novel TB vaccine candidates for adolescents and adults are advancing through late-stage clinical trials, little is known about how these vaccines may be introduced in high-burden settings such as Pakistan. Understanding stakeholder perspectives is crucial for informing early implementation planning and policy development. Methods: We conducted an exploratory qualitative study using semi-structured in-depth interviews with key stakeholders involved in TB control, immunization, clinical care, and health policy in Pakistan. Participants were purposively selected from national and provincial TB programs, Expanded Programme on Immunization (EPI), clinical settings, and academia. Interviews were conducted in English or Urdu, audio-recorded, transcribed verbatim, and analyzed using reflexive thematic analysis following the Braun and Clarke framework. A hybrid deductive-inductive coding approach was used. Results: Ten stakeholders participated including one whose interview also served as a pilot test of the interview guide. Participants expressed strong support for the introduction of a new TB vaccine, driven largely by Pakistan's high TB burden and the limitations of current prevention strategies. However, support was based on the availability of strong evidence regarding vaccine safety, effectiveness, and feasibility. Key barriers to vaccine acceptability included low perceived risk of TB, misinformation, stigma, sociocultural influences, and limited public awareness. Stakeholders emphasized community engagement, trusted healthcare providers, and effective communication as critical enablers. Health system challenges included workforce shortages, cold chain limitations, and financing constraints. Household contacts of TB patients were consistently identified as the priority group followed by adolescents and people living with HIV. A phased implementation strategy was broadly preferred followed by gradual integration into existing health services. Conclusion: Stakeholders in Pakistan broadly support new TB vaccines for adolescents and adults. Successful implementation will require addressing sociocultural barriers, strengthening health system capacity, and developing context-specific delivery and prioritization strategies. Early stakeholder engagement and implementation planning are essential for meaningful public health impact in Pakistan.

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Usability, acceptability and feasibility of continuous glucose monitoring among children and adolescents with type 1 diabetes in Kenya

Amolo, P.; Mungai, L.; Karume, A. K.; Kibugi, J.; Mwende, W.; Botella, N.; Haldane, C.; Kamau, Y.; Marban-Castro, E.

2026-09-01 endocrinology 10.64898/2026.08.27.26361447 medRxiv
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Introduction Continuous Glucose Monitoring (CGM) is considered standard care in high-income countries. There is, however, limited published evidence on CGM use in low- and middle-income countries. The purpose of this study was to assess the usability, acceptability, and feasibility of CGM use among people living with type 1 diabetes (T1D) and caregivers in a low-resource setting. Research Design and Methods This prospective study conducted at the Kenyatta National Hospital purposively enrolled persons aged 4-25 years who had been on management for T1D for at least six months, and caregivers of those under 18 years. Fourty youth living with T1D used CGM for three months in place of self monitoring of blood glucose (SMBG). The System Usability Scale (SUS), a Theoretical Framework of Acceptability-based questionnaire, the Diabetes Distress Scale (DDS), the Glucose Monitoring Satisfaction Survey (GMSS), and a feasibility survey were administered. Outcomes were summarized descriptively, including means, medians, and frequencies using R statistical software. Results The median SUS score was 98.8 (IQR 92.5-100.0). Acceptability was high, and the median total GMSS score improved from 3.73 to 4.73. Among adolescents and adults, the median overall DDS score reduced from 1.54 to 1.36, with reductions in scores in all domains, except for hypoglycemia distress which increased, and physician distress which remained low. Among caregivers, the median overall DDS score declined from 2.05 (moderate distress) to 1.90 (low distress), with modest reductions in teen management and parent-teen relationship distress and a slight increase in personal distress. Median CGM active wear time was 89%. Conclusion This study comprehensively evaluated CGM across usability, acceptability, and feasibility outcomes, with the findings supporting the integration of CGM into routine diabetes management in low-resource settings. The short follow-up period, however, may not capture changing perceptions or long-term adherence.

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PyiTOL: reproducible Python workflows for iTOL annotation and taxonomic monophyly assessment

Zeng, Z.; Wang, Y.

2026-08-29 bioinformatics 10.64898/2026.08.27.747471 medRxiv
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Motivation: The Interactive Tree of Life (iTOL) is widely used to display and annotate phylogenetic trees, but managing its format-sensitive annotation files impede reproducible high-throughput analyses. Among the maintained Python packages and versions evaluated, none combined template generation, taxonomic monophyly assessment and iTOL batch operations. Results: PyiTOL validates inputs, generates 31 iTOL template schemas (22 accepted by the live batch uploader), performs LCA-based monophyly classification with nested-monophyly detection, sampling-completeness states and polyphyletic subgroup decomposition, plus API upload and session replay. On a topology-constructed benchmark, all calls matched prespecified labels for 4,389 groups; on a 700-genome tree, binary mono/non-mono calls agreed with ETE4 for 409 genera; 17,294 GTDB R232 genera were processed in about 17 s. Availability and Implementation: PyiTOL 1.0.3 (Python [&ge;]3.10; Linux, macOS and Windows) is MIT-licensed at https://github.com/ZengZichao/PyiTOL and archived with test data at Zenodo (https://doi.org/10.5281/zenodo.22106806).

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Postoperative analgesia and recovery after minimally invasive cardiac surgery

Note, H.; Kajiura, T.; Muramatsu, A.; Inagaki, Y.; Takahashi, T.; Sato, K.; Nakamura, K.; Sadatoshi, T.; Sakurai, Y.; Tochii, M.; Watanuki, H.; Matsuyama, K.; Okamoto, S.

2026-08-31 intensive care and critical care medicine 10.64898/2026.08.27.26361580 medRxiv
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Introduction Postoperative analgesic management after minimally invasive cardiac surgery (MICS) should facilitate early recovery while providing adequate pain control. However, direct evidence comparing postoperative remifentanil- and fentanyl-based analgesic strategies after MICS remains limited. We compared these strategies and explored their associations with postoperative recovery, postoperative nausea and vomiting (PONV), and pain management. Methods This retrospective single-center observational cohort study included patients who underwent MICS via a right mini-thoracotomy between January 2023 and June 2026. Patients were categorized according to postoperative remifentanil- or fentanyl-based analgesia in the intensive care unit. Outcomes included time to extubation, PONV, postoperative pain assessed using the numerical rating scale (NRS), additional analgesic use, and intensive care unit length of stay. Multivariable logistic regression examined the association between postoperative opioid strategy and PONV, adjusting for age, sex, and smoking history. Results PONV occurred less frequently in the remifentanil group than in the fentanyl group (20.6% vs 45.0%, P = 0.004), and this association remained significant after adjustment (adjusted odds ratio, 0.23; 95% confidence interval, 0.10-0.56; P = 0.001). Time to extubation was shorter with remifentanil (median, 179 [interquartile range, 134-240.5] vs 247 [190.2-276.5] min; P < 0.001). In contrast, NRS pain scores on postoperative day 0 were higher with remifentanil (3 [1-6] vs 1 [0-2]; P < 0.001), and additional analgesics were used more frequently (80.6% vs 33.3%; P < 0.001). Pain scores on postoperative day 1 did not differ significantly between groups. Conclusion Postoperative remifentanil-based analgesia after MICS was associated with less PONV and earlier extubation but also with greater early postoperative pain and more frequent additional analgesic use than fentanyl-based analgesia. Appropriate transition to longer-acting analgesics with multimodal analgesia may help preserve the potential benefits of remifentanil while maintaining adequate postoperative pain control.

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Preferences for receiving study results among pregnant women participating in a phase III clinical trial in Papua New Guinea.

Mengi, A.; Bagita-Vangana, M.; Tesine, P.; Laman, M.; Bolnga, J. W.; Ome-Kaius, M.; Kulimbao, J.; Mase, J.; Mal, L. S.; Mnjala, H.; Lee, G.; Cassidy-Seyoum, S. A.; Thriemer, K.; Unger, H. W.

2026-08-31 medical ethics 10.64898/2026.08.27.26361571 medRxiv
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Disseminating study results to participants is an ethical responsibility for researchers but remains uncommon in low- and middle-income countries, and participants preferences for receiving study results are poorly understood. This study examined study result dissemination preferences among pregnant women in a phase III malaria prevention trial in Papua New Guinea (PNG). Participants completed an interviewer-administered questionnaire (survey) assessing their interest in and motivation for receiving trial results and preferences for dissemination methods and content. Associations between participants characteristics and dissemination preferences were explored using multivariable logistic regression analysis. Of 1172 trial participants, 96.0% (1125/1172) completed the survey, and of these 99.6% (1121/1125) wanted to learn about the trial results. The main motivation factors driving participants interest were an acknowledgment of their contribution to research (51.7%; n=579) and a better understanding of the study (45.0%; n=505). Most participants (78.9%; n=884) wanted to learn about the trial findings through written summary and a group meeting with other participants at the nearest clinic (31.1%, n=349). Multivariable regression analysis indicated that participants from rural/peri-urban clinics were more likely to choose non-electronic media dissemination approaches such as a group meeting as compared to urban-dwelling participants. Frequently selected items (>50% of participants) for content included information regarding good results of the study, purpose of the study, medical treatment advances, results specific to me, and how study was conducted. There was heterogenicity in the preference for dissemination content: compared to urban clinics rural clinics are less likely to want to learn about how and why study was conducted and medical and scientific advances. Overall, the majority wanted to learn about trial results, highlighting the importance of integrating dissemination into research activities in PNG. Variation in preferences for mode and content of dissemination between study clinics suggests that dissemination activities could be tailored to local context and preferences.

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A target trial emulation study to estimate the causal effect of intravenous iron use during pregnancy and its effect on haematological and birth outcomes in Pakistan

Yazdani, N. S.; Oakley, E.; Khan, A.; Qazi, M. F.; Khakwani, S.; Sheikh, A.; Mazhar, A.; Iqbal, U. M.; Marquis, J.; Liaqat, B.; Kumari, K.; Caniglia, E. C.; Hotwani, A.; Nisar, I.; Jehan, F.; Smith, E. R.; Hoodbhoy, Z.

2026-09-03 epidemiology 10.64898/2026.08.29.26361700 medRxiv
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Background: Despite several trials on the hematological outcomes of intravenous (IV) iron in pregnancy, only few have examined its effect on birth outcomes. We estimated the causal effect of IV-iron on moderate or severe anaemia and birth outcomes. Methods: Women presenting to routine antenatal care in Pakistan with haemoglobin <10 g/dL were eligible for treatment. We used target trial emulation (TTE) methodology to estimate the effect of IV-iron treatment within 14 days of anaemia identification, compared to no treatment, on anaemia status at follow-up. A modified TTE analysis examined birth outcomes at delivery for singleton pregnancies, including birthweight, size-for-gestational-age, and mortality. We conducted a separate TTE for each of five gestational-age periods and pooled the results of each TTE. Results: We screened 3115 pregnancies of which 1715 were eligible for IV-iron; 1043 participants were treated during pregnancy. Those who received IV-iron had half the risk of moderate or severe anaemia in pregnancy compared with no treatment (pooled relative risk (RR) 0.40; 95% confidence interval (CI): 0.27, 0.59). The pooled effect of IV-iron on stillbirth suggested an 83% risk reduction (95% CI 55-94%), and trends were similar for perinatal and neonatal mortality. Conclusion: IV-iron treatment improved haematological status in pregnant women and was associated with a large reduction in stillbirth. Given limited data from randomised trials regarding fetal death and treatment earlier in pregnancy, this study contributes important information to the potential benefit of IV-iron in contexts where anaemia and its sequelae are a major public health problem.

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Best Practice Manufacturing and Quality Standards for Bacteriophage Therapy Products: Australian Consensus Statements

Watts, K.; Lin, R. C.; Lynch, S.; Warning, J.; Barr, J. J.; Ben Zakour, N.; Campbell, A.; Chan, J.; Collie, L.; Hedges, M.; Hudson, B.; Irwin, A.; Khatami, A.; Kicic, A.; Laucirica, D.; Lauter, C.; Ling, K.-m.; Ng, R.; Pavuk, N.; Rahmatullah, R.; Sinclair, H.; Tucker, E.; Vreugde, S.; Warner, M.; Velickovic, Z.; iredell, j.

2026-08-31 public and global health 10.64898/2026.08.26.26361487 medRxiv
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Objective As antimicrobial resistance (AMR) continues to threaten global public health, bacteriophage therapy products (BTPs) offer a promising alternative to conventional antimicrobials. However, translation into routine clinical practice requires best practice standards for manufacturing and quality control to ensure the consistent safety, quality, and reliability of personalised BTPs produced for individual patients or small cohorts. Design A modified Delphi methodology was used to develop consensus statements, engaging experts from Australia's National Bacteriophage Therapy Regulatory Working Group across the fields of clinical microbiology, phage biology, good manufacturing practice (GMP), regulatory science, and government. The process comprised three iterative phases: (1) structured statement development, (2) an anonymous REDCap survey, and (3) a hybrid consensus meeting. The strength of evidence and recommendations was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. Results Consensus was reached on 35 statements to provide best practice manufacture and quality control guidance for BTPs. These statements address requirements for phage identification and characterisation; define the point at which GMP-aligned processes commence for ubiquitous phages; outline quality control expectations for phage active pharmaceutical ingredient (pAPI) production and maintenance of BTP and host cell repositories. Additional guidance covers quality management systems, including documentation, traceability, and governance. Conclusion These consensus statements provide comprehensive best practice recommendations for the manufacture and quality control of BTPs in Australia. By promoting consistent, safe, and quality-assured approaches to personalised BTPs, they aim to facilitate clinical implementation while remaining aligned with existing international pharmacopoeial standards and regulatory frameworks.

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Acceptability, feasibility, quality of life and diabetes distress score outcomes: A pragmatic randomised clinical trial on continuous glucose monitoring for people with type 1 diabetes

Marban-Castro, E.; Muhwava, L.; Girdwood, S.; Kemp, T.; Freitas, J.; Kamau, Y.; Otieno, M.; Akach, D.; Morato, A.; Sanz, S.; Fiechter, V.; Erkosar, B.; Watson, M.; Vetter, B.; Haldane, C.; Shilton, S.; Rheeder, P.; Dave, J. A.; Carrihill, M.; Karsas, M.

2026-08-31 endocrinology 10.64898/2026.08.26.26361479 medRxiv
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Introduction: Continuous glucose monitoring (CGM) offers an advancement over traditional self-monitoring of blood glucose (SMBG) for people living with type 1 diabetes (T1D). However, evidence on the acceptability and feasibility of different CGM use cases in African populations remains limited. Methods: This was a pragmatic three-arm, randomised controlled trial on CGM conducted among people living with T1D in three public healthcare clinics in South Africa. Participants were assigned to Arm 1 (continuous CGM), Arm 2 (periodic CGM), or Arm 3 (SMBG). Diabetes education was provided at all study visits. Feasibility was assessed by adherence to CGM use and through the Glucose Monitoring Satisfaction Survey (GMSS). Diabetes distress was measured by the Diabetes Distress Scale (DDS), health-related quality of life (HRQoL) by the EQ-5D scales, and acceptability using the Theoretical Framework of Acceptability (TFA). Surveys were collected on paper and transferred to OpenClinica. Analyses were performed in R. The trial was registered in the Clinical Trials Registry (NCT05944718) on July 13, 2023. Results: A total of 83 participants were included in Arm 1, 85 in Arm 2, and 80 in Arm 3. CGM mean active time was 55% in Arm 1 versus 69% in Arm 2. The proportion of participants meeting the [&ge;]70% active time threshold was higher in Arm 2 (52%) than in Arm 1 (34%). Diabetes' distress declined across arms during the intervention period, with no significant difference between arms; distress increased slightly six months post-intervention but remained below baseline. At 6 months, glucose monitoring satisfaction was significantly higher in both CGM arms than in the SMBG arm, and satisfaction increased over time in CGM arms. Health-related quality of life remained stable across arms during the intervention period with no significant difference between arms. High acceptability was observed in both CGM arms, with higher ratings in the periodic arm. Conclusions: CGM was acceptable to people living with type 1 diabetes and feasible to use in public-sector clinics in South Africa, with high acceptability under continuous and periodic use. Health-related quality of life remained stable across arms, and diabetes-related distress declined, during the intervention period, across arms. Glucose monitoring satisfaction rose significantly in both CGM arms compared to SMBG. Periodic CGM might be a promising and potentially more scalable option than continuous use for public-sector care.

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Post-Discharge Experiences of Survivors Following the 2022 Ebola Virus Disease Outbreak in Uganda: An Exploratory Qualitative Study

Natukunda, J.; Muwanguzi, P.; Ngabirano, T. D.; Atuhaire, B.; Nalubega, S. J.; Auma, C.; Nabunya, R.

2026-09-03 public and global health 10.64898/2026.08.29.26361698 medRxiv
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Background: Ebola virus disease is a life-threatening illness caused by the Ebolavirus, with symptoms manifesting two to twenty-one days after infection. Although Uganda has faced multiple Ebola outbreaks, many patients survive only to encounter persistent challenges. Therefore, this study explored the post-discharge experiences of survivors following the 2022 Ebola Virus Disease outbreak in Uganda. Methods: An exploratory qualitative study comprising of in-depth participant interviews was conducted at Mubende Regional Referral Hospital in central Uganda. Interviews were face-to-face and data were analyzed manually by inductive content analysis. Ten male and female participants were Ebola Virus Disease survivors in Mubende district who had lived in the community for at least six months post-discharge from the Ebola Treatment Unit. Results: Four themes emerged: (i) Psychosocial Burdens and Social Exclusion, (ii) Economic Hardship and Loss of Financial Stability, (iii) Chronic Physical and Health Burdens Post-Recovery and (iv) Rebuilding Lives: Psychological, Social, and Medical Pathways to Recovery. Survivors faced significant emotional burdens such as survivor guilt, grief, trauma from loss, and anxiety about transmission risks. They experienced social isolation, stigma, and discrimination, which often led to their exclusion from community activities. Financially, they struggled with debt and the loss of livelihoods, compounded by ongoing health issues. Additionally, survivors endured chronic physical complications, including pain and fatigue, which hindered their recovery. Despite these challenges, survivors sought psychological, social, and medical pathways to recovery, including confirmation of their recovery, support from family and organizations, and health maintenance practices. Supportive medical care and community assistance were crucial in their physical and emotional rehabilitation. Conclusion: Ebola Virus Disease survivors in Uganda face significant psychosocial, health, social, and economic challenges post-discharge. The findings highlight the critical need for comprehensive medical and community-based support systems to aid survivors' recovery and well-being. Further research on long-term neurological effects and community reintegration programmes is needed to inform targeted interventions that support Ebola survivors and reduce stigma and discrimination.

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Sleep Quality and Its Association with Life Satisfaction Among Employees in the United Arab Emirates: A Cross-Sectional Study

Ali, S. I.; Varatharajan, V.; Chacko, S. T.; Hazari, A.; Varghese, S. M.

2026-08-31 public and global health 10.64898/2026.08.28.26361603 medRxiv
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Objectives This study aimed to assess sleep patterns and life satisfaction among employees of a private company in Dubai, United Arab Emirates, and to examine the relationships among sleep quality, life satisfaction, and selected demographic variables. A quantitative descriptive cross-sectional survey design was adopted. Methods A convenience sample of 110 male employees participated in the study. Data were collected using the Sleep Disorder Assessment Scale (16 items; Cronbachs = 0.89) and the Life Satisfaction Scale (5 items). Statistical analysis was performed using SPSS version 29, including descriptive statistics, chi-square tests, and Pearson correlation analysis. Results Most participants (66.4%) were aged 20-30 years, and 82.7% experienced moderate sleep-related problems. Mobile phone use before bedtime was common, with 60.9% reporting occasional use and 35.5% reporting regular use. Overall, 41.8% reported neutral life satisfaction, while 25.5% and 24.6% were slightly and extremely satisfied, respectively. A significant negative correlation was found between poor sleep patterns and life satisfaction (r = -0.389, p < 0.001). Mobile phone use before bedtime and shift work were significantly associated with sleep patterns (p = 0.048). Conclusion Poor sleep quality, particularly among shift workers and frequent bedtime mobile phone users, is associated with lower life satisfaction. Workplace interventions promoting sleep hygiene may enhance employee well-being.

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Immortal time bias reproduces the reported survival benefit of conversion surgery in stage IV gastric cancer: a simulation study

Sah, B. K.; Li, C.; Li, J.; Zhu, Z.

2026-09-03 gastroenterology 10.64898/2026.09.01.26361986 medRxiv
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Background Conversion surgery for stage IV gastric cancer is supported by a pooled overall survival hazard ratio of 0.36 (95% confidence interval 0.32-0.40) and, in the largest international cohort, median survival of 36.7 versus 12.5-13.8 months on chemotherapy. Survival is measured from diagnosis; the median diagnosis-to-gastrectomy interval is 124 days, which patients must survive to be counted surgical. Methods We simulated cohorts of 3,177 stage IV gastric cancer patients from published parameters: background median survival 14.5 months; median diagnosis-to-surgery interval 124 days (category-specific 92-174 days). Surgery had no effect (true hazard ratio 1.00 by construction). Data were analysed as the literature analyses them (exposure fixed at baseline, follow-up from diagnosis), and by time-varying Cox and landmark analysis. Confounding by indication was added in a second scenario. Results Under immortal time bias alone the naive analysis returned a hazard ratio of 0.794 (95% simulation interval 0.743-0.851), median survival 16.8 versus 12.8 months. Time-varying Cox recovered 1.000 and landmark analysis 1.000-1.004. Bias scaled with the interval: 0.849 at 92 days, 0.715 at 174 days. Adding confounding, the naive estimate fell to 0.601 (0.560-0.644) at strength 0.5 and 0.356 (0.323-0.385) at strength 1.5, overlapping the published estimate; median survival 21.9 versus 8.7 months. Correcting immortal time alone left residual bias (hazard ratio 0.439). Conclusions The reported survival advantage of conversion surgery is reproducible where the operation does nothing; published estimates cannot distinguish benefit from bias. Resolving this requires individual patient data analysed with methods that assign person-time correctly, or completion of JCOG2301.

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What Matters Most: A Multi-Stakeholder Study of Outcome Domains in Lower-Limb Prosthesis Use

Ahmed, M. E.; Karlsson-Brown, S.; Koufaki, P.; Ahmadi, M.; Mico-Amigo, E. M.

2026-09-03 rehabilitation medicine and physical therapy 10.64898/2026.08.31.26361544 medRxiv
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Purpose: Lower-limb prosthesis use involves interacting physical, psychosocial, and device-related outcomes that may not be fully captured by conventional clinical assessment. This study aimed to develop and evaluate a stakeholder-informed framework of outcome domains relevant to meaningful everyday prosthesis use. Materials and Methods: A mixed-methods participatory design comprised a structured synthesis of selected clinically relevant content from five established patient-reported outcome measures; semi-structured interviews and importance and actionability ratings with 18 contributors (12 prosthesis users, four clinicians, and two industrial partners); and integration of the synthesis, qualitative, and rating findings. Interview records were analysed using reflexive thematic analysis, and ratings were analysed descriptively. Results: The resulting framework comprised four interrelated domains: Mobility, Physical Function, Psychosocial Wellbeing, and Prosthesis Experience. Mobility showed the clearest convergence across stakeholder perspectives. Prosthesis users showed the largest importance actionability gap for Prosthesis Experience (4.5 vs 3.0), whereas clinicians showed the largest gap for Psychosocial Wellbeing (5.0 vs 3.0). Interviews highlighted day-to-day variability in prosthesis use and the influence of confidence, fatigue, comfort, environmental conditions, social context, and device usability. Conclusions: Meaningful outcome assessment in prosthetic rehabilitation should extend beyond mobility alone to consider physical function, psychosocial wellbeing, and prosthesis experience within everyday contexts. The proposed framework provides a stakeholder-informed foundation for multidimensional outcome assessment in prosthetic rehabilitation.

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Dynamic Clinical States and Transitions During the First 72 Hours of Intensive Care After Acute Stroke

LEI, P.; XU, Y.; ZHANG, Y.

2026-09-01 intensive care and critical care medicine 10.64898/2026.08.30.26361738 medRxiv
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Background: The condition of a patient with acute stroke often changes within hours of ICU admission. Prognostic work here targets fixed endpoints predicted from admission data, and trajectory phenotyping assigns one label per patient. We used longitudinal ICU data to identify interpretable dynamic clinical states, characterize transitions between them, and relate the current state to later events. Methods: Retrospective cohort study of 6368 adults with acute stroke in MIMIC IV v3.1. The first 72 h were divided into twelve 6-hour windows, and a hidden Markov model was fitted to 21 neurological, physiological and organ support variables. State number was chosen against criteria fixed before fitting: statistical fit, restart stability, state occupancy and clinical interpretability. Generalized estimating equations related the current state to new mechanical ventilation and vasopressor use within 12 h, and to ICU death within 72 h. Eleven sensitivity analyses assessed the robustness of the state solution. Results: Four states were selected: neurologically preserved-low support, neurological impairment low support, impairment renal dysfunction and impairment-respiratory support (63.3%, 7.8%, 11.8% and 17.1% of windows). Within 72 h, 40.3% of patients changed state at least once, and transitions ran in both directions rather than along a single severity gradient. States were identified without outcome data, yet ICU mortality by last state ranged from 2.9% to 43.9%. Adjusted for age, sex, subtype and Charlson index, the current state remained associated with organ-support escalation and death. State prevalence differed by at most 1.1 percentage points between training and test sets, and 10 of 11 sensitivity analyses gave a stable four-state solution (ARI 0.754 0.955). Conclusions: The early ICU course of acute stroke can be represented as movement among a small number of clinically interpretable states. The representation was reproducible in a held out set and across admission eras, but requires validation in an independent database before any clinical use.