Search

James F Donohue,1 Vamsi K Bollu,2 Donald E Stull,3 Lauren M Nelson,4 Valerie SL Williams,4 Michael D Stensland,5 Nicola A Hanania6 1Department of Pulmonary Diseases and Critical Care Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 2Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, 3Data Analytics and Design Strategy, 4Psychometrics, RTI Health Solutions, Research Triangle Park, NC, 5Agile Outcomes Research, Inc., Rochester, MN, 6Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA Background: Symptom severity is the largest factor in determining subjective health in COPD. Symptoms (eg, chronic cough, dyspnea) are associated with decreased health-related quality of life (HRQoL). We evaluated the impact of arformoterol on HRQoL in COPD patients, measured by St George’s Respiratory Questionnaire (SGRQ). Post hoc growth mixture model (GMM) analysis examined symptom response profiles. Methods: We examined data from a randomized, double-blind, parallel-group, 12-month safety trial of twice-daily nebulized arformoterol 15 µg (n=420) versus placebo (n=421). COPD severity was assessed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) status. GMM analysis identified previously unknown patient subgroups and examined the heterogeneity in response to SGRQ Symptoms scores. Results: SGRQ Total score improved by 4.24 points with arformoterol and 2.02 points with placebo (P=0.006). Significantly greater improvements occurred for arformoterol versus placebo in SGRQ Symptoms (6.34 vs 4.25, P=0.031) and Impacts (3.91 vs 0.97, P=0.001) scores, but not in Activity score (3.57 vs 1.75, P=0.057). GMM identified responders and nonresponders based on the SGRQ Symptoms score. End-of-study mean difference in SGRQ Symptoms scores between these latent classes was 20.7 points (P

Lauren M Nelson,1 Valerie SL Williams,1 Sheri E Fehnel,1 Robyn T Carson,2 James MacDougall,3 Mollie J Baird,3 Stavros Tourkodimitris,2 Caroline B Kurtz,3 Jeffrey M Johnston31RTI Health Solutions, Durham, NC, USA; 2Forest Research Institute, Jersey City, NJ, USA; 3Ironwood Pharmaceuticals, Cambridge, MA, USABackground: Measures assessing treatment outcomes in previous CC clinical trials have not met the requirements described in the US Food and Drug Administration's guidance on patient-reported outcomes.Aim: Psychometric analyses using data from one Phase IIb study and two Phase III trials of linaclotide for the treatment of chronic constipation (CC) were conducted to document the measurement properties of patient-reported CC Symptom Severity Measures.Study methods: Each study had a multicenter, randomized, double-blind, placebo-controlled, parallel-group design, comparing placebo to four doses of oral linaclotide taken once daily for 4 weeks in the Phase IIb dose-ranging study (n=307) and to two doses of linaclotide taken once daily for 12 weeks in the Phase III trials (n=1,272). The CC Symptom Severity Measures addressing bowel function (Bowel Movement Frequency, Stool Consistency, Straining) and abdominal symptoms (Bloating, Abdominal Discomfort, Abdominal Pain) were administered daily using interactive voice-response system technology. Intraclass correlations, Pearson correlations, factor analyses, F-tests, and effect sizes were computed.Results: The CC Symptom Severity Measures demonstrated satisfactory test–retest reliability and construct validity. Factor analyses indicated one factor for abdominal symptoms and another for bowel symptoms. Known-groups F-tests substantiated the discriminating ability of the CC Symptom Severity Measures. Responsiveness statistics were moderate to strong, indicating that these measures are capable of detecting change.Conclusion: In large studies of CC patients, linaclotide significantly improved abdominal and bowel symptoms. These psychometric analyses support the reliability, validity, discriminating ability, and responsiveness of the CC Symptom Severity Measures for evaluating treatment outcomes in the linaclotide clinical studies.Keywords: psychometric evaluation, patient-reported outcomes, linaclotide

Menstrual regularity in adolescent girls provides valuable clues about current and future bone integrity. This article explains the importance of using this often overlooked health factor to help your patients achieve and maintain optimum lifelong skeletal health. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to report the outcome of a collaborative project between the Fragile X Research and Treatment Center at the Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute at the University of California at Davis, the National Fragile X Foundation (NFXF), and the Centers for Disease Control and Prevention (CDC). The objective of this collaboration was to develop and disseminate protocols for genetic counseling and cascade testing for the multiple disorders associated with the fragile X mental retardation 1 (FMR1) mutation. Over the last several years, there has been increasing insight into the phenotypic range associated with both the premutation and the full mutation of the FMR1 gene. To help develop recommendations related to screening for fragile X-associated disorders, four, two day advisory focus group meetings were conducted, each with a different theme. The four themes were: (1) fragile X-associated tremor/ataxia syndrome (FXTAS); (2) premature ovarian failure (POF) and reproductive endocrinology; (3) psychiatric, behavioral and psychological issues; and (4) population screening and related ethical issues. [ABSTRACT FROM AUTHOR]

Learning that she has what used to be called premature menopause can devastate a woman in her 20s or 30s. Diagnose this mysterious condition without delay, deliver the bad news in person, and provide sensitive answers to four basic questions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether polymorphisms in the FOXP3 gene are associated with preeclampsia. STUDY DESIGN: Case-control study in which 120 women with preeclampsia were compared with 120 healthy normotensive controls. Genetic variants (single nucleotide polymorphisms and microsatellites) in the FOXP3 gene were analyzed. Polymorphisms were chosen based on studies of the FOXP3 gene in other autoimmune disorders. Correction of P values for multiple comparisons was performed by using the Benjamini-Hochberg procedure. RESULTS: There were no differences in the genotypes or allele frequencies in the single nucleotide polymorphisms between cases and controls. The FOXP3 GT microsatellite allele at 266 bp was less common in cases than controls (1.0% vs 5.2%, P = .0264). However, this did not remain significant after correction for multiple comparisons. CONCLUSION: Preeclampsia is not associated with FOXP3 gene polymorphisms that have been associated with other autoimmune disorders. [ABSTRACT FROM AUTHOR]

What you need to know about preventing and detecting the deadliest of skin cancers. [ABSTRACT FROM AUTHOR]

Purpose: Determine the risk of subsequent cancer following squamous cell skin cancer.Methods: Using computerized surgical pathology records and membership data from a health maintenance organization, we retrospectively identified 822 individuals with primary squamous cell skin cancer (SCSC) and 3662 comparison subjects matched for age, sex, race, residence area, and length of membership. Patients were included in the study if they had no prior history of cancer, and received at least one multiphasic health checkup and questionnaire (MHC). Patients were followed for subsequent invasive cancer up to 24 years, with a mean follow-up time of 7.8 years.Results: SCSC patients had a significantly greater risk [adjusted for body mass index (BMI) and education] for subsequent cancer overall (excluding non-melanoma skin cancer) [risk ratio (RR) = 1.4, 95% confidence interval (CI) = 1.2-1.6], and for basal cell skin cancer (RR = 13.8, 95% CI = 8.8-21.9), digestive (RR = 1.6, 95% CI = 1.1-2.4), and genitourinary cancers (RR = 1.5, 95% CI = 1.0-2.0). An increased, but not statistically significant, adjusted risk (RR > or = 1.4) was also observed for lip, oral cavity, and pharynx cancer (RR = 3.9, 95% CI = 0.6-25.0); non-cutaneous squamous cell cancer (RR = 1.9, 95% CI = 0.9-4.4); and respiratory and intrathoracic cancer (RR = 1.4, 95% CI = 0.8-2.6). The addition of alcohol consumption, combined occupational exposure, marital status, and smoking history to the multivariate model did not materially change any significant positive associations with SCSC.Conclusions: Our results suggest that patients diagnosed with SCSC may be at an increased risk of subsequent cancer at many sites, although several estimated risk estimates were within the limits of chance given no true association. [ABSTRACT FROM AUTHOR]

Background: Estimated GFR (eGFR) has shown poor agreement with measured GFR (mGFR) in several populations. We investigated the impact of age and body composition on the accuracy and precision of eGFR in heart transplant (HTx) recipients., Methods: In a longitudinal, observational, retrospective study design, patients receiving first-time HTx with at least one registered mGFR value within 15 months after HTx and a corresponding plasma creatinine were included. GFR was measured by 51Cr-EDTA and eGFR calculated by creatinine-based CKD-EPI formula., Results: A total of 150 patients with a total of 723 mGFR measurements were included. During the first year after HTx, mean weight increased by 4.2 kg (CI: 3.2 to 5.1) followed by an annual decrease of 0.35 kg/year (Cl: -0.05 to 0.74). mGFR increased by 7.5 mL/min (Cl: 3.2 to 11.8) the first year but was stable hereafter (0.0 mL/min/year; CI: -1.0 to 1.0). The initial weigh gain and increase in mGFR were most pronounced in patients <45 years. Neither eGFR adjusted nor unadjusted for BSA detected the initial increase in mGFR. At 1 year after HTx, limits of agreement on the Bland-Altman plot were -37.2 to 33.1 mL/min with a bias of -2.1 mL/min (Cl: -5.0 to 0.9). In patients <45 years, eGFR significantly overestimated mGFR by 7.1 mL/min (Cl: 1.0 to 13.2) and showed a significant lower precision than patients >45 years. There was no effect of BMI class, weight, BSA, or change in BMI class on the difference between eGFR and mGFR., Conclusion: eGFR is, on average, accurate but imprecise in HTx patients. The agreement is affected by age but not body composition., (© 2024 S. Karger AG, Basel.)

Cyanobacterial harmful algal blooms (CyanoHABs) are a major concern for water quality, public health and viability of aquatic ecosystems. Increased inputs of nutrients, i.e., nitrogen (N) and phosphorus (P), are known to amplify the occurrence, severity, and duration of CyanoHABs. There is growing concern that CyanoHABs are proliferating along the freshwater to marine continuum, including throughout estuaries. We assessed the influence of nutrient enrichment on the abundance and composition of CyanoHABs and accompanying phytoplankton communities in the San Francisco Bay Delta (SFBD) estuarine ecosystem, a vital resource for California's water supply, fisheries, and recreation. In situ nutrient addition bioassays were conducted in June and September 2022, at the end of a record three-year drought period, and May and August 2023, an extremely high rainfall and discharge year. Water was collected from two locations in the SFBD recognized for having CyanoHAB issues, Discovery Bay (DB) and the Stockton Channel (STK). Both sites showed the highest proportion of cyanobacteria in the total phytoplankton community biomass during summer months, and this was particularly noticeable at STK. In June 2022, additions of N and N+P were both shown to increase overall phytoplankton biomass in DB and N+P specifically stimulated cyanobacteria. P alone was not stimulatory. In September 2022, NH 4 promoted the growth of cyanobacteria faster than NO 3 , particularly in DB communities. A similar set of responses to N occurred in 2023 in DB, despite major differences in freshwater input between years. In 2022, nutrient additions had no significant stimulatory effects on STK phytoplankton communities, suggesting nutrients were replete throughout the bloom season. However, in 2023 N limitation became more evident in STK, likely due to a dilution effect from the very high freshwater discharge from a record snowpack and reservoir releases, ultimately changing the availability of inorganic N during the CyanoHAB growth period. The combined effect of high flow and nutrient dilution in 2023 was responsible for the reduced CyanoHAB potential. By examining these key differences between seasons in these hydrologically contrasting years, it appears that internal supplies of "legacy P" ensure P availability throughout the summer bloom season regardless of hydrologic variability, while N enrichment plays a key role in stimulating algal production and CyanoHABs under hydrologically variable conditions. Once N was added, P further stimulated biomass production in some cases, indicating potential N+P co-limitation. We conclude that under varying hydrologic conditions, long-term dual N and P input reductions are needed to control eutrophication and CyanoHAB outbreaks throughout the SFBD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hans Paerl reports financial support was provided by National Science Foundation, National Institutes of Health (NIEH). None if there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mechanisms involved in the supercooling of plant tissues as a means of low temperature survival are still not fully understood. We investigated properties that may promote supercooling in overwintering sweet cherry (Prunus avium) flower buds. We conducted experiments on sweet cherry flower buds using differential thermal analysis (DTA) and observed locations of ice formation in the bud structure. We also used anatomical development and water-soluble dye uptake throughout the overwintering period to identify changes that correlate with gain and loss of supercooling capacity. Our results revealed barriers to ice propagation are likely unique to each primordium, as inferred from exotherms produced from buds subjected to DTA, although multiple primordia may freeze simultaneously. Ice is accommodated between the bud scales and within the bud axis; however, full expression of supercooling was not dependent on the presence of scales. Anatomical and DTA studies revealed a correlation between vascular differentiation in primordia and loss of supercooling in the spring; these observations were at a higher temporal resolution than previously described for Prunus. Furthermore, disturbing tissues subtending the primordia interfered with typical patterns of supercooling, indicated more erratic and numerous exotherms produced during DTA. In summary, sweet cherry flower buds undergo extra-organ freezing. In winter, a barrier to ice propagation in the region directly subtending primordia protects the flower from freezing damage, but in the spring xylem differentiation in primordia provides a conduit for ice propagation that compromises supercooling., (© 2024 His Majesty the King in Right of Canada and The Author(s). Plant Biology published by John Wiley & Sons Ltd on behalf of German Society for Plant Sciences, Royal Botanical Society of the Netherlands. Reproduced with the permission of the Minister of Agriculture and Agri‐Food Canada.)

A comprehensive definition of health includes the assessment of patient experiences of a disease and its treatment. These patient experiences are best captured by standardized patient-reported outcome (PRO) instruments. A PRO is reported directly by the patient (or caregiver) and provides the patient's perspective into how a disease and its treatment impact their lives. PRO instruments are typically standardized, validated questionnaires with items that are scaled and can be combined to represent an underlying health-related construct such as physical, social, and role functioning, psychological well-being, symptoms, pain, and quality of life. Over the past few decades, PROs have become increasingly used in clinical trials as endpoints to better understand treatment benefits from the patient's perspective and in clinical practice to identify unmet needs of patients, health risk surveillance, and monitor outcomes of care. In this paper, we describe the process for developing standardized PRO instruments, from conceptual model development through instrument validation., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Background: Colorectal cancer (CRC) is the second most lethal cancer in the United States (U.S.) with the highest incidence and mortality rates among African Americans (AAs) compared to other racial groups. Despite these disparities, AAs are the least likely to undergo CRC screening, have precancerous colorectal polyps removed, and have CRC detected at stages early enough for curative excision. In addition, compelling evidence links inflammatory dietary patterns to increased CRC and cardiovascular disease risk. Studies show that AA churches can successfully engage in health promotion activities including those related to cancer control. The current study seeks to leverage church-placed Community Health Workers (CHWs) to increase CRC screening and reduce CRC risk., Design and Methods: We aim to (1) increase guideline concordant CRC screening uptake using church-placed CHWs trained in screening with a validated instrument, Brief Intervention using Motivational Interviewing, and Referral to Treatment (SBIRT); and (2) reduce dietary risk factors (inflammatory dietary patterns) linked to CRC. The latter will be addressed by culturally adapting an existing, web-based lifestyle program called Alive!. Using a Hybrid Type 1 Implementation-Effectiveness cluster randomized design, we will randomize 22 AA churches into either the dual intervention arm (CHW-led SBIRT intervention plus Alive!) or a usual care arm comprised of CRC prevention educational pamphlets and a list of CRC screening sites. We will recruit 440 subjects and evaluate the effects of both arms on screening uptake (colonoscopy, fecal DNA) (primary outcome) and dietary inflammation score (secondary outcome) at 6-month follow-up, and Life Simple7 (LS7)-a cardiovascular disease (CVD) risk score-at 6 months and 1 year (secondary outcome). Finally, guided by a racism-conscious adaptation of the Consolidated Framework for Implementation Research (CFIR), we will conduct a mixed-methods process evaluation with key stakeholders to understand multi-level influences on CRC screening and CVD risk behaviors., Discussion: Church-placed CHWs are trusted influential connectors between communities and health systems. Studies have shown that these CHWs can successfully implement health prevention protocols in churches, including those related to cancer control, making them potentially important community mediators of CRC screening uptake and CRC/CVD risk reduction., Trial Registration: NCT05174286; clinicaltrials.gov; August 31 st , 2023., (© 2024. The Author(s).)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Powered ankle-foot prosthetic devices can generate net positive mechanical work during gait, which mimics the physiological ankle. However, gait deviations can persist in individuals with transfemoral limb loss because of habit or lack of rehabilitation. Prosthetic research efforts favor the design or evaluation of prosthetic componentry and rarely incorporate any type of rehabilitation, despite evidence suggesting that it is critical for minimizing gait imbalances. Given the accelerated rate of innovation in prosthetics, there is a fundamental knowledge gap concerning how individuals with transfemoral limb loss should learn to correctly use powered ankle-foot devices for maximum functional benefit. Because of the recent advances in prosthetic technology, there is also a critical unmet need to develop guidelines for the prescription of advanced prosthetic devices that incorporate both physical and psychological components to identify appropriate candidates for advanced technology., Objective: The primary goal of this investigation is to examine the roles of advanced prosthetic technology and a device-specific rehabilitative intervention on gait biomechanics, functional efficacy, and pain in individuals with transfemoral limb loss. The secondary goal is to develop preliminary rehabilitation guidelines for advanced lower limb prosthetic devices to minimize gait imbalances and maximize function and to establish preliminary guidelines for powered ankle-foot prosthetic prescription., Methods: This prospective, multisite study will enroll 30 individuals with unilateral transfemoral limb loss. At baseline, participants will undergo a full gait analysis and assessment of function, neurocognition, cognitive load, subjective preferences, and pain using their current passive prosthesis. The participants will then be fitted with a powered ankle-foot device and randomized into 2 equal groups: a powered device with a device-specific rehabilitation intervention (group A) or a powered device with the current standard of practice (group B). Group A will undergo 4 weeks of device-specific rehabilitation. Group B will receive the current standard of practice, which includes basic device education but no further device-specific rehabilitation. Data collection procedures will then be repeated after 4 weeks and 8 weeks of powered ankle use., Results: This study was funded in September 2017. Enrollment began in September 2018. Data collection will conclude by March 2024. The initial dissemination of results is expected in August 2024., Conclusions: The projected trends indicate that the number of individuals with limb loss will dramatically increase in the United States. The absence of effective, evidence-based interventions may make individuals with transfemoral limb loss more susceptible to increased secondary physical conditions and degenerative changes. With this expected growth, considerable resources will be required for prosthetic and rehabilitation services. Identifying potential mechanisms for correcting gait asymmetries, either through advanced prosthetic technology or rehabilitative interventions, can provide a benchmark for understanding the optimal treatment strategies for individuals with transfemoral limb loss., Trial Registration: ClinicalTrials.gov NCT03625921; https://clinicaltrials.gov/study/NCT03625921., International Registered Report Identifier (irrid): DERR1-10.2196/53412., (©Jason T Maikos, Alison L Pruziner, Brad D Hendershot, David V Herlihy, John M Chomack, Michael J Hyre, Samuel L Phillips, Alexis N Sidiropoulos, Christopher L Dearth, Leif M Nelson. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 26.01.2024.)

Background and Objectives: Neuromyelitis optica spectrum disorder (NMOSD) is a chronic CNS demyelinating autoimmune disorder targeting the astrocyte antigen aquaporin-4 (AQP4), typically presenting with optic neuritis, transverse myelitis, and brain syndromes. Cognitive dysfunction (CD) in NMOSD is under-recognized and poorly understood. The purpose of this study was to evaluate the prevalence and clinical variables associated with CD in NMOSD., Methods: This observational retrospective study with longitudinal follow-up describes a clinical cohort seen in the Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD. Serial Montreal Cognitive Assessments (MoCAs) were performed upon enrollment and at 6-month intervals to evaluate longitudinal cognitive function relative to demographic and disease-related factors. We used 2-tailed t test, analysis of variance, the χ 2 test, linear regression for univariable and adjusted analyses and simultaneous linear regression and mixed-effects model for multivariable analyses., Results: Thirty-four percent (75/219) of patients met criteria for CD (MoCA <26); 29% (64/219) showed mild dysfunction (MoCA 20-26/30), and 5% (11/219) showed moderate (MoCA <20/30) dysfunction. Patients with less neurologic disability and lower pain scores had higher MoCA scores (95% CI 0.24-0.65 and 95% CI 0.09-0.42, respectively). Patients with at least high school education scored higher on the MoCA (95% CI 2.2-5). When comparing patients dichotomized for CD, patients never on rituximab scored higher than patients only treated with rituximab ( p < 0.029). There was no significant association between annualized relapse rate, age, sex, disease duration, AQP4 serostatus or brain lesions, and CD. CD was more pronounced among Black than White patients (95% CI -2.7 to -0.7). Multivariable analysis of serial MoCA did not indicate change ( p = 0.715). Descriptive analysis of serial MoCA showed 30% (45/150) of patients with worsening MoCA performance had impaired language and verbal recall., Discussion: To our knowledge, this is the largest study of diverse cohort to investigate CD in patients with NMOSD. Our findings demonstrate 34% of patients with NMOSD experience mild-to-moderate CD, while 30% of patients demonstrated decline on serial testing. The substantial prevalence of CD in this pilot report highlights the need for improved and validated screening tools and comprehensive measures to investigate CD in NMOSD.

Crown gall disease of grapevines caused by Allorhizobium vitis causes significant damage to vineyards in cold-climate viticulture areas such as Canada and the northern United States. Introduction of the disease into vineyards occurs mainly through planting of infected but asymptomatic nursery material. Because A. vitis is not a regulated pest for import into Canada, no information on the health status of nursery material destined for import into Canada has previously been collected. This study evaluated the health status of ready-to-plant nursery material from domestic and international nurseries in regard to crown gall by determining the abundance of A. vitis in different plant sections via Droplet Digital PCR technology. In addition, different rootstocks from one nursery were compared. Results showed that A. vitis was present in planting material from all nurseries tested. The bacteria were nonuniformly distributed in dormant nursery material, and there was no difference in abundance between the rootstocks tested. In addition, the first A. vitis strain OP-G1 isolated from galls in British Columbia is described. Results showed that a minimum of 5,000 bacterial OP-G1 cells were needed for symptom expression, suggesting that the initiation of symptom development is not based on presence of bacteria in nursery material alone; a minimum threshold is needed, and environmental conditions need to be met., Competing Interests: The author(s) declare no conflict of interest.

Hybrid designs with both randomized arms and an external control cohort preserve key features of randomization and utilize external information to augment clinical trials. In this study, we propose to leverage high-quality, patient-level concurrent registries to enhance clinical trials and illustrate the impact on trial design for amyotrophic lateral sclerosis. The proposed methodology was evaluated in a randomized, placebo-controlled clinical trial. We used patient-level information from a well-defined, population-based registry, that was running parallel to the randomized clinical trial, to identify concurrently nonparticipating, eligible patients who could be matched with trial participants, and integrate them into the statistical analysis. We assessed the impact of the addition of the external controls on the treatment effect estimate, precision, and time to reach a conclusion. During the runtime of the trial, a total of 1,141 registry patients were alive; 473 (41.5%) of them fulfilled the eligibility criteria and 133 (11.7%) were enrolled in the study. A matched control population could be identified among the nonparticipating patients. Augmenting the randomized controls with matched external controls could have avoided unnecessary randomization of 17 patients (-12.8%) as well as reducing the study duration from 30.1 months to 22.6 months (-25.0%). Matching eligible external controls from a different calendar period led to bias in the treatment effect estimate. Hybrid trial designs utilizing a concurrent registry with rigorous matching can minimize bias due to a mismatch in calendar time and differences in standard of care, and may accelerate the development of new treatments., (© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Bacterial strain G20-18 T was previously isolated from the rhizosphere of an Arctic grass on Ellesmere Island, Canada and was characterized and described as Pseudomonas fluorescens . However, new polyphasic analyses coupled with phenotypic, phylogenetic and genomic analyses reported here demonstrate that the affiliation to the species P. fluorescens was incorrect. The strain is Gram-stain-negative, rod-shaped, aerobic and displays growth at 5-25 °C (optimum, 20-25 °C), at pH 5-9 (optimum, pH 6-7) and with 0-4 % NaCl (optimum, 2 % NaCl). The major fatty acids are C 16 : 0 (35.6 %), C 17 : 0 cyclo ω 7 c (26.3 %) and summed feature C 18 : 1 /C 18 : 1  ω7 c (13.6 %). The respiratory quinones were determined to be Q9 (93.5 %) and Q8 (6.5 %) and the major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Strain G20-18 T was shown to synthesize cytokinin and auxin plant hormones and to produce 1-aminocyclopropane-1-carboxylate deaminase. The DNA G+C content was determined to be 59.1 mol%. Phylogenetic analysis based on the 16S rRNA gene and multilocus sequence analysis (concatenated 16S rRNA, gyrB , rpoB and rpoD sequences) showed that G20-18 T was affiliated with the Pseudomonas mandelii subgroup within the genus Pseudomonas . Comparisons of the G20-18 T genome sequence and related Pseudomonas type strain sequences showed an average nucleotide identity value of ≤93.6 % and a digital DNA-DNA hybridization value of less than 54.4 % relatedness. The phenotypic, phylogenetic and genomic data support the hypothesis that strain G20-18 T represents a novel species of the genus Pseudomonas . As strain G20-18 T produces or modifies hormones, the name Pseudomonas hormoni sp. nov. is proposed. The type strain is G20-18 T (=LMG 33086 T =NCIMB 15469 T ).

There is a need to close the gap between knowledge and action in health care. Effective care requires a convenient and reliable distribution process. As global internet and mobile communication increase capacity, innovative approaches to digital health education platforms and care delivery are feasible. We report the case of a young African woman who developed acute secondary amenorrhea at age 18. Subsequently, she experienced a 10-year delay in the diagnosis of the underlying cause. A global digital medical hub focused on women's health and secondary amenorrhea could reduce the chance of such mismanagement. Such a hub would establish more efficient information integration and exchange processes to better serve patients, family caregivers, health care providers, and investigators. Here, we show proof of concept for a global digital medical hub for women's health. First, we describe the physiological control systems that govern the normal menstrual cycle, and review the pathophysiology and management of secondary amenorrhea. The symptom may lead to broad and profound health implications for the patient and extended family members. In specific situations, there may be significant morbidity related to estradiol deficiency: (1) reduced bone mineral density, 2) cardiovascular disease, and 3) cognitive decline. Using primary ovarian insufficiency (POI) as the paradigm condition, the Mary Elizabeth Conover Foundation has been able to address the specific global educational needs of these women. The Foundation did this by creating a professionally managed Facebook group specifically for these women. POI most commonly presents with secondary amenorrhea. Here we demonstrate the feasibility of conducting a natural history study on secondary amenorrhea with international reach to be coordinated by a global digital medical hub. Such an approach takes full advantage of internet and mobile device communication systems. We refer to this global digital women's health initiative as My 28 Days ® ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nelson, Spencer, Hijane, Thinuan, Nelson, Vincent, Gordon, Plant and Fazeli.)

Introduction: There is a growing population of women with limb loss, yet limited research is available to provide evidentiary support for clinical decision-making in this demographic. As such, there is a critical gap in knowledge of evidence-based healthcare practices aimed to maximise the physical and psychosocial needs of women with limb loss. The objective of this study is to develop a comprehensive, survey-based needs assessment to determine the unique impact of limb loss on women, including physical and psychosocial needs., Methods and Analysis: A bank of existing limb loss-specific and non-limb loss-specific surveys were arranged around domains of general health, quality of life, prosthetic use and needs, psychosocial health and behaviours and body image. These surveys were supplemented with written items to ensure coverage of relevant domains. Written items were iteratively refined with a multidisciplinary expert panel. The interpretability of items and relevance to limb loss were then internally tested on a small group of rehabilitation, engineering and research professionals. A diverse sample of 12 individuals with various levels of limb loss piloted the instrument and participated in cognitive interviews. Items from existing surveys were evaluated for relevance and inclusion in the survey, but not solicited for content feedback. Pilot testing resulted in the removal of 13 items from an existing survey due to redundancy. Additionally, 13 written items were deleted, 42 written items were revised and 17 written items were added. The survey-based needs assessment has been crafted to comprehensively assess the wide spectrum of issues facing women with limb loss. The final version of the survey-based needs assessment included 15 subsections., Ethics and Dissemination: This study was approved by the Veterans Affairs Central Institutional Review Board. The results will be disseminated through national and international conferences, as well as through manuscripts in leading peer-reviewed journals., Trial Registration Number: No healthcare intervention on human participants was conducted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)