Association Between Retinal Nerve Fiber Layer Thickness and Incident Dementia in the European Prospective Investigation into Cancer in Norfolk Cohort.

BACKGROUND: Retinal nerve fiber layer (RNFL) thickness may reflect cerebral status. OBJECTIVE: This study assessed the relationship between RNFL thickness and incident all-cause dementia in the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) Eye Study. METHODS: Glaucoma detection with variable corneal compensation (GDx-VCC) and Heidelberg Retinal Tomograph II (HRT II) derived global mean RNFL thickness from dementia-free participants at baseline within the EPIC-Norfolk Eye Study were analyzed. Incident dementia was identified through linkage to electronic medical records. Cox proportional hazard mixed-effects regression models adjusted for key confounders were used to examine the associations between RNFL thickness and incident dementia in four separate models. RESULTS: 6,239 participants were included with 322 cases of incident dementia and mean age of 67.5-years old, with 49.7% women (median follow-up 13.2-years, interquartile range (11.7 to 14.6 years). Greater RNFL thickness (GDx-VCC) was not significantly associated with a lower risk of incident dementia in the full adjusted model [HR per quartile increase 0.95; 95% CI 0.82-1.10]. Similarly, RNFL thickness assessed with HRT II was also not associated with incident dementia in any model (full adjusted model; HR per quartile increase: 1.06; [95% CI 0.93-1.19]. Gender did not modify any associations under study. CONCLUSION: GDx-VCC and HRT II derived RNFL thickness are unlikely to be useful predictors of incident dementia. Higher resolution optical imaging technologies may clarify whether there are useful relationships between neuro-retinal morphology and brain measures.

Professional Development in Health Sciences: Scoping Review on Equity, Diversity, Inclusion, Indigeneity, and Accessibility Interventions.

INTRODUCTION: Equity, diversity, inclusion, indigeneity, and accessibility (EDIIA) are critical considerations in the formation of professional development (PD) programs for health care workers. Improving EDIIA competency in health care serves to enhance patient health, staff confidence and well-being, delivery of care, and the broader health care system. There is a gap in the literature as to the efficacy of EDIIA-based PD programs and their individual components. The present article will review available quantitative data pertaining to EDIIA-based PD programs for health care workers as well as their effectiveness. METHOD: A scoping review of articles published in the EBSCOhost, MEDLINE, PubMed, EMBASE, and CINAHL databases was performed. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: A total of 14,316 references were identified with 361 reaching full-text review. A final 36 articles were included in the scoping review with 6552 total participants (72.9% women; 26.9% men; 0.2% nonbinary). EDIIA-based PD interventions were developed around the topics of culture (n = 22), gender (n = 11), sexual orientation (n = 9), indigeneity (n = 6), race (n = 6), ableism (n = 1), and ageism (n = 1). DISCUSSION: Despite an increased interest in developing EDIIA-based PD curricula for health care workers, there are glaring disparities in the quality of care received by marginalized and equity-seeking populations. The present scoping review delineated key features which were associated with increased quantitative efficacy of EDIIA-based PD training programs. Future work should focus on large-scale implementation and evaluation of these interventions across health care sectors and levels of training.

Does Immediate Breast Reconstruction Lead to a Delay in Adjuvant Chemotherapy for Breast Cancer? A Meta-Analysis and Systematic Review.

Timely delivery of adjuvant chemotherapy is crucial. With an increasing frequency of immediate breast reconstructions (IBR) following mastectomy (MAS), concerns have arisen regarding its complication rates and effects on time to chemotherapy. The aim was to conduct a systematic review and meta-analysis to determine if there is a prolonged time to chemotherapy (TTC) after IBR and MAS. Electronic databases, reference lists and relevant articles were searched systematically. Eligibility criteria included women receiving adjuvant chemotherapy who underwent either MAS only or MAS and IBR. Random-effects models were used in the analysis. A total of 29 studies were included in qualitative analysis, comprising of 156,000 patients (IBR: 57,159; MAS: 98,841). But 23 studies had sufficient data to be included in the meta-analysis. Sixteen papers concluded there was no difference in TTC compared to MAS. There was a difference of 3.50 days between TTC in IBR versus MAS (95% CI [0.42, 6.57], P value = .0256; IBR = 43.56 days, MAS = 40.38 days). The rate of patients being delayed past 90 days was not significantly higher in IBR (OR = 1.34, 95% CI [0.76, 2.38], P = .310). IBR patients were more likely to have complications compared to the MAS group (OR = 2.04, 95% CI [1.04-4.01], P < .01). We concluded that there is a statistically significant longer time to chemotherapy following IBR of 3.50 days, yet there is no difference in delays past 90 days. Therefore, the longer TTC in IBR is unlikely to be of any clinical significance.

Predictors of Transfusion in Trauma and Their Utility in the Prehospital Environment: A Scoping Review.

Background: Hemorrhage is a leading cause of preventable mortality from trauma, necessitating resuscitation through blood product transfusions. Early and accurate identification of patients requiring transfusions in the prehospital setting may reduce delays in time to transfusion upon arrival to hospital, reducing mortality. The purpose of this study is to characterize existing literature on predictors of transfusion and analyze their utility in the prehospital context.Objectives: The objectives of this study are to characterize the existing quantity and quality of literature regarding predictor scores for transfusion in injured patients, and to analyze the utility of predictor scores for massive transfusions in the prehospital setting and identify prehospital predictor scores for future research.Methods: A search strategy was developed in consultation with information specialists. A literature search of OVID MEDLINE from 1946 to the present was conducted for primary studies evaluating the predictive ability of scoring systems or single variables in predicting transfusion in all trauma settings.Results: Of the 5,824 studies identified, 5,784 studies underwent title and abstract screening, 94 studies underwent full text review, and 72 studies were included in the final review. We identified 16 single variables and 52 scoring systems for predicting transfusion. Among single predictor variables, fluids administered and systolic blood pressure had the highest reported sensitivity (100%) and specificity (89%) for massive transfusion protocol (MTP) activation, respectively. Among scoring systems for transfusion, the Shock Index and Modified Shock Index had the highest reported sensitivity (96%), whereas the Pre-arrival Model had the highest reported specificity (95%) for MTP activation. Overall, 20 scores were identified as applicable to the prehospital setting, 25 scores were identified as potentially applicable, and 7 scores were identified as not applicable.Conclusions: We identified an extensive list of predictive single variables, validated scoring systems, and derived models for massive transfusion, presented their properties, and identified those with potential utility in the prehospital setting. By further validating applicable scoring tools in the prehospital setting, we may begin to administer more timely transfusions in the trauma population.

Ocular surface squamous neoplasia in a patient following oral steroids for contralateral necrotising scleritis.

A male patient in his 70s presented with left eye necrotising scleritis. His ocular history was significant for pterygium excision with mitomycin C 3 months prior in the affected eye, open-angle glaucoma, nuclear sclerosis cataract and previous sixth cranial nerve palsy. Scleral culture was negative and blood work was positive for rheumatoid factor and HLA-B27. The patient was treated for necrotising scleritis with oral doxycycline, vitamin C, ranitidine and prednisone with gradual taper over 45 days. Two months after initiating treatment, his necrotising scleritis achieved complete resolution; however, a new-onset ocular surface squamous neoplasia (OSSN) was identified at the temporal limbus of the contralateral eye. He was treated with topical interferon alpha-2b 1 million IU qid and achieved complete resolution after 4 months. The case highlights both the acute precipitation of OSSN following oral steroids and a sight-threatening complication following pterygium excision.

Effectiveness of pelvic floor muscle training alone or combined with either a novel biofeedback device or conventional biofeedback for improving stress urinary incontinence: A randomized controlled pilot trial.

PURPOSE: To (i) compare the acceptance of a newly developed, novel biofeedback device (PelviSense) with that of conventional biofeedback (CB) using an intravaginal probe for the treatment of stress urinary incontinence (SUI) in women, (ii) examine the feasibility and safety of using the PelviSense device as a pelvic floor muscle (PFM) training (PFMT) adjunct, and (iii) compare the PFMT adherence and effectiveness of CB, the PelviSense device, with PFMT alone for women with SUI. METHODS: An assessor-blinded, three-arm, randomized controlled pilot trial was conducted among 51 women with SUI. Women were randomly allocated to one of three study groups (PelviSense-assisted PFMT, CB-assisted PFMT, or PFMT alone [control]). Outcome measures included the International Consultation on Incontinence Questionnaire-Short Form, the 1-h pad test, and the Modified Oxford Scale. RESULTS: Participants in the PelviSense-assisted PFMT group expressed good device acceptance. PFMT adherence was greater in the PelviSense-assisted PFMT group than in the unassisted or CB-assisted PFMT groups. Between-groups analysis revealed significant effects on improved SUI symptoms, urine loss severity, and PFM strength for the PelviSense-assisted PFMT group compared with the CB-assisted and PFMT alone groups. CONCLUSIONS: The pilot trial results demonstrated moderate to high PFMT adherence in the PelviSense-assisted PFMT group and supported the safety of using the PelviSense device. The preliminary results of the pilot trial showed that PelviSense-assisted PFMT was more effective for reducing SUI symptoms among women than unassisted or CB-assisted PFMT. TRIAL REGISTRATION: This trial was registered in http://ClinicalTrials.gov (reference number: NCT04638348) before the recruitment of the first participant.

HflX is a GTPase that controls hypoxia-induced replication arrest in slow-growing mycobacteria.

GTPase high frequency of lysogenization X (HflX) is highly conserved in prokaryotes and acts as a ribosome-splitting factor as part of the heat shock response in Escherichia coli. Here we report that HflX produced by slow-growing Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a GTPase that plays a critical role in the pathogen's transition to a nonreplicating, drug-tolerant state in response to hypoxia. Indeed, HflX-deficient M. bovis BCG (KO) replicated markedly faster in the microaerophilic phase of a hypoxia model that resulted in premature entry into dormancy. The KO mutant displayed hallmarks of nonreplicating mycobacteria, including phenotypic drug resistance, altered morphology, low intracellular ATP levels, and overexpression of Dormancy (Dos) regulon proteins. Mice nasally infected with HflX KO mutant displayed increased bacterial burden in the lungs, spleen, and lymph nodes during the chronic phase of infection, consistent with the higher replication rate observed in vitro in microaerophilic conditions. Unlike fast growing mycobacteria, M. bovis BCG HlfX was not involved in antibiotic resistance under aerobic growth. Proteomics, pull-down, and ribo-sequencing approaches supported that mycobacterial HflX is a ribosome-binding protein that controls translational activity of the cell. With HflX fully conserved between M. bovis BCG and M. tuberculosis, our work provides further insights into the molecular mechanisms deployed by pathogenic mycobacteria to adapt to their hypoxic microenvironment.

Author Correction: Selective, high-contrast detection of syngeneic glioblastoma in vivo.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Women's age and total motile normal morphology sperm count predict fecundability: a prospective cohort study.

OBJECTIVE: This study investigated the role of women's age, serum anti-Müllerian hormone (AMH) level and semen parameters in predicting fecundability. METHODS: This was a prospective cohort study on couples attending for preconceptional health check. Occurrence of conception at 1 year after ceasing contraception and time to pregnancy were noted by telephone follow-up. The women's age, serum AMH level and total motile normal morphology sperm count (TMNC) were compared between those who conceived and those who did not after 1 year; their independent predictive value on conception at 1 year was analysed by logistic regression. Among those conceiving within 1 year, Spearman's correlations between time to pregnancy and the clinical parameters were studied. RESULTS: Of the 100 couples analysed, we found younger age of the women (p=0.008), higher serum AMH level (p=0.038) and higher TMNC (p=0.015) in those that conceived within 1 year. Multivariate logistic regression found that women's age (OR 0.867, 95% CI 0.761 to 0.988, p=0.032) and TMNC (OR 1.089, 95% 1.001-1.185, p=0.047), but not serum AMH level, significantly predicted conception within 1 year. Among those that conceived within 1 year, none of the parameters analysed were correlated with time to pregnancy within 1 year. CONCLUSIONS: Women's age and TNMC are significant independent predictors of conception within 1 year. No parameter was shown to predict the time to pregnancy within 1 year. This finding can aid preconceptional counselling of couples who are planning for pregnancy.

Selective, high-contrast detection of syngeneic glioblastoma in vivo.

Glioblastoma is a highly malignant, largely therapy-resistant brain tumour. Deep infiltration of brain tissue by neoplastic cells represents the key problem of diffuse glioma. Much current research focuses on the molecular makeup of the visible tumour mass rather than the cellular interactions in the surrounding brain tissue infiltrated by the invasive glioma cells that cause the tumour's ultimately lethal outcome. Diagnostic neuroimaging that enables the direct in vivo observation of the tumour infiltration zone and the local host tissue responses at a preclinical stage are important for the development of more effective glioma treatments. Here, we report an animal model that allows high-contrast imaging of wild-type glioma cells by positron emission tomography (PET) using [18 F]PBR111, a selective radioligand for the mitochondrial 18 kDa Translocator Protein (TSPO), in the Tspo-/- mouse strain (C57BL/6-Tspotm1GuMu(GuwiyangWurra)). The high selectivity of [18 F]PBR111 for the TSPO combined with the exclusive expression of TSPO in glioma cells infiltrating into null-background host tissue free of any TSPO expression, makes it possible, for the first time, to unequivocally and with uniquely high biological contrast identify peri-tumoral glioma cell invasion at preclinical stages in vivo. Comparison of the in vivo imaging signal from wild-type glioma cells in a null background with the signal in a wild-type host tissue, where the tumour induces the expected TSPO expression in the host's glial cells, illustrates the substantial extent of the peritumoral host response to the growing tumour. The syngeneic tumour (TSPO+/+) in null background (TSPO-/-) model is thus well suited to study the interaction of the tumour front with the peri-tumoral tissue, and the experimental evaluation of new therapeutic approaches targeting the invasive behaviour of glioblastoma.

Use of a modified Liverpool care pathway in a tertiary Asian hospital: is there still a role for it?

BACKGROUND: In 2007, the Care of the Dying clinical coordinated Pathway (CDP) was adapted from the United Kingdom Liverpool Care Pathway (LCP) and implemented in a tertiary hospital in Singapore to improve care in oncology and subsequently renal patients. With concerns about its use after the Neuberger review, an audit of patients on the CDP was performed to determine if the use of such a pathway should be continued locally. METHODS: A two-year retrospective audit of CDP use was conducted. Aspects of communication, initiation of CDP, patient monitoring, medications, nutrition, and hydration were assessed. RESULTS: In the 111 patient records reviewed, there were documented extent of care discussions with 94% of caregivers and 29% of patients before CDP initiation. Of the 88% of CDPs initiated within office hours, 90% fulfilled the inclusion criteria. All patients were monitored at least every eight hours. Seventy-three patients (66%) were prescribed opioids or sedatives and subsequently monitored appropriately, albeit 56% had no documented prior discussion with caregivers regarding medication use. Indications for opioid use were documented for all patients and only one patient had documentation of excessive sedation. Oral feeding and parenteral hydration were continued in 85% and 74% of patients, respectively. CONCLUSION: There was no documented compromise in medication safety, clinical monitoring, and provision of nutrition and hydration for patients on the CDP. However, documentation of important end-of-life decisions and conversations remain poor. Development of an alternative care tool encouraging systematic discussion and documentation of individualized end-of-life care plans should be considered.

A randomized clinical trial comparing the short-term side effects of sublingual and buccal routes of misoprostol administration for medical abortions up to 63 days' gestation.

BACKGROUND: Buccal misoprostol 800 mcg and sublingual misoprostol 800 mcg show high efficacy when used with 200 mg mifepristone for early pregnancy termination but have different side effect profiles. This is the first double-blind randomized trial comparing the side effect profiles of these two routes of administration of misoprostol when used with mifepristone for termination of pregnancies up to 63 days' gestation. STUDY DESIGN: Eligible women (n=90) who requested legal termination of pregnancy up to 63 days' gestation were randomized to two groups and given 200 mg of oral mifepristone followed 48 h later by 800 mcg of either sublingual (n=45) or buccal (n=45) misoprostol. RESULTS: Most of the side effects including fever were more common in the sublingual group, but only the incidence of chills was significantly higher in the sublingual group (55.6% vs 91.1%, p=.0001). Complete abortion occurred in 95.4% [95% confidence interval (CI): 84.9-99.5] of women in the buccal group and 97.8% (95% CI: 88.2-99.9) in the sublingual group. CONCLUSIONS: When combined with mifepristone for termination of pregnancy up to 63 days, both the buccal and sublingual routes are effective routes of administration. The sublingual route tended to be associated with more side effects.

Serum anti-müllerian hormone level is not altered in women using hormonal contraceptives.

BACKGROUND: Anti-müllerian hormone (AMH) is secreted from granulosa cells of antral follicles into the circulation of adult women and hence could serve as an ovarian function test. This would be of value to hormonal contraceptive users if its serum level is unaffected by the use of hormonal contraceptives. STUDY DESIGN: We prospectively recruited 95 women using combined oral contraceptive (n=23), combined injectable contraceptive (n=23), progestogen-only pills (n=9), progestogen-only injectable (n=20) and levonorgestrel intrauterine system (n=20), and measured their serum AMH concentration before and 3-4 months after treatment. RESULTS: No significant difference in pre- and post-treatment serum AMH level was evident in all the treatment groups studied. CONCLUSIONS: Being unaffected by hormonal contraceptives, serum AMH measurement is potentially a useful clinical test in hormonal contraceptive users for the differential diagnosis of anovulatory disorders and determination of menopause.

Changes in medical students' attitudes towards end-of-life decisions across different years of medical training.

BACKGROUND: Decisions to forgo life-sustaining medical treatments in terminally ill patients are challenging, but ones that all doctors must face. Few studies have evaluated the impact of medical training on medical students' attitudes towards end-of-life decisions and none have compared them with an age-matched group of non-medical students. OBJECTIVE: To assess the effect of medical education on medical students' attitudes towards end-of-life decisions in acutely ill patients. DESIGN: Cross-sectional study. PARTICIPANTS: Four hundred and two students at The Chinese University of Hong Kong. MEASUREMENTS: Completion of a questionnaire focused on end-of-life decisions. MAIN RESULTS: The number of students who felt that cardiopulmonary resuscitation must always be provided was higher in non-medical students (76/90 (84%)) and medical students with less training (67/84 (80%) in year 1 vs. 18/67 (27%) in year 5) (p < 0.001). Discontinuing life-support therapy was more accepted among senior medical students compared to junior medical and non-medical students (27/66 (41%) in year 5 vs. 18/83 (22%) in year 1 and 20/90 (22%) in non-medical students) (p = 0.003). An unexpectedly large proportion of non-medical students (57/89 (64%)) and year 1 medical students (42/84 (50%)) found it acceptable to administer fatal doses of drugs to patients with limited prognosis. Euthanasia was less accepted with more years of training (p < 0.001). When making decisions regarding limitation of life-support therapy, students chose to involve patients (98%), doctors (92%) and families (73%) but few chose to involve nurses (38%). CONCLUSIONS: Medical students' attitudes towards end-of-life decisions changed during medical training and differed significantly from those of non-medical students.

Nonlinear optical studies of the agricultural antibiotic morantel interacting with silica/water interfaces.

It is now known that the untreated discharge of pharmaceuticals into the environment can impact human health and development and lead to increased drug resistance in biota. Here, we present the first direct interface-specific studies that address the mobility of the widely used agricultural antibiotic morantel, which is commonly present in farm runoff. Surface-bound morantel was spectroscopically identified using second harmonic generation (SHG) via a two-photon resonance of its n-pi* transition and in the C-H stretching region by vibrational sum frequency generation (VSFG). Resonantly enhanced SHG adsorption isotherm measurements carried out at the silica/water interface between 6 x 10(-7) and 5 x 10(-5) M morantel concentration result in a free energy of adsorption of 42(2) kJ/mol at pH 7. Finally, real-time tracking of morantel interaction with the silica/water interface shows that the binding events are fully reversible, consistent with its high mobility in silica-rich soil environments. This work thus indicates that pharmaceuticals discharged into the environment can enter the groundwater supply of municipal water systems, at which point their removal is challenging. In addition, the high mobility of morantel in silica-rich soil environments could lead to developing increased interaction of this antibiotic with target organisms, which could respond by increased drug resistance.

Acceptability and clinical performance of a copper-containing frameless IUCD in Hong Kong.

This is the first study conducted in Hong Kong to evaluate the acceptability and clinical performance of a copper-containing frameless intrauterine contraceptive device (IUCD; GyneFix/Ji Ni). Sixty-two women chose to use the frameless IUCD for contraception. A learning curve was demonstrated in the insertion technique of this new device. Pain associated with insertion was acceptable. No pregnancy was reported during the 1-year trial period. Objectively, the amount of menstrual loss did not change and dysmenorrhea improved, but the duration of menstrual flow was slightly prolonged during the use of this device. However, there was a 10.7% request rate for removal of the device because of its side effects. The expulsion rate during the first year was 5.3%, and the continuation rate at the end of the first year was 76.7%. It was found that 85% of the 40 subjects interviewed upon the completion of the 1-year trial period wished to replace the same device after the product expiration date and that 92.5% would recommend this device to their friends. In summary, the clinical performance of the frameless IUCD was comparable to its framed counterparts. The device was considered acceptable to a majority of the women.

A study of co-treatment of nonsteroidal anti-inflammatory drugs (NSAIDs) with misoprostol for cervical priming before suction termination of first trimester pregnancy.

This double-blind randomized control study was conducted to evaluate whether a nonsteroidal anti-inflammatory drug (NSAID) could act as an effective pain control method during first trimester suction abortion, and whether co-treatment of NSAID with misoprostol will decrease the efficacy of the cervical ripening effect of misoprostol. Subjects were randomized to receive misoprostol alone or misoprostol together with diclofenac sodium. Both groups of subjects suffered from similar incidence of preoperative side effects. Co-treatment of NSAID with misoprostol did not attenuate the cervical ripening efficacy of misoprostol. There was no significant pain reduction in the group treated with NSAID, except that a marginal benefit was found in the subgroup of multiparous women. About two thirds of the subjects in both treatment groups found that this was a satisfactory pain relief method during the procedure.