Genomic and computational analysis of four novel variants of MPL gene in Congenital Amegakaryocytic Thrombocytopenia.

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, genetic, autosomal recessive disorder characterized by severe thrombocytopenia, due to inefficient bone marrow megakaryopoiesis eventually leading to aplasia. Majority of the cases are due to homozygous or compound heterozygous mutations in MPL gene encoding for thrombopoietin (THPO) receptor protein. CAMT can be diagnosed at early phase of life, with major complication of transfusion dependency and hematopoietic transplantation as only curative treatment. We have investigated the sequence variations in MPL gene of 7 bone marrow failure (BMF) subjects, who presented with clinically diverse phenotypes, through next generation sequencing (NGS). Plasma THPO levels were estimated using ELISA. Insilico sequence and structure-based analyses were performed to understand the structural and functional implications of mutations, identified through NGS. We studied 7 CAMT subjects suspected of BMF, who presented with severe thrombocytopenia followed by pancytopenia, bleeding manifestation and physical anomalies. The plasma THPO levels were significantly elevated (p<0.05) in all the cases. Molecular analysis by NGS identified 9 genomic mutations in MPL gene. These included 7 non-synonymous substitution, 1 nonsense substitution and 1 in-del mutations, of which 4 are novel mutations. Insilico analysis predicted damaging effects on THPO-R and its reduced affinity for THPO for all the identified mutations. CAMT is a rare disorder with diverse clinical phenotypes and diagnosis is challenging. The elevated plasma THPO levels should be considered for the primary diagnosis and prognosis of the disease. However, molecular analysis of MPL gene is important for the diagnosis and management of the disease through genetic counselling. Though the cytokines, THPO-R agonist are used for the treatment of CAMT, HSCT is the only curative therapy.

Orange peel-derived Cu2O/RGO nanocomposite: Mesoporous binary system for degradation of doxycycline in water.

In recent times, there is a mammoth challenge for the world and mankind to deal with the frequent use and misuse of antibiotics and its casual discard to the water bodies. The scavenging degradation of antibiotics which are no longer in use from the environment is a growing concern and compulsively needs to be addressed. Herein, we have devised a novel and green protocol for the synthesis of Cu2O decorated on reduced graphene oxide (Cu2O/RGO) nanocomposite (NCs) using agro-waste, i.e., orange pomace extract (OPE) as a reducing and stabilizing agent for the degradation of antibiotic. The biogenically synthesized Cu2O/RGO NCs proved to emerge as an excellent degradation catalyst exhibiting efficiency of 98.68% within 15 min and 86.38% within 30 min for 10 mg/L DC concentration assisted by ultrasound waves and solar light respectively in separate reactions. The complete degradation process followed a pseudo-first-order kinetics with a rate constant of 0.29 min- 1 and 0.0542 min- 1 for sonocatalytic and photocatalytic degradation process, respectively. Surface area analysis showed that with the increase in the GO amount, the doxycycline degradation increases. An in-depth mechanistic account of sonocatalytic and photocatalytic process has been discussed followed by a radical scavenging test which validated the major role of the synthesized NCs in the degradation of DC. The extraordinary catalytic indulgence of biogenically synthesized graphene-based nanocatalyst opens newer avenues for future research in green chemistry and catalytic field. Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-022-02895-2.

Remote versus In-Person Health Education: Feasibility, Satisfaction, and Health Literacy for Diverse Older Adults.

OBJECTIVES: Health education may improve health in geriatric patients. To evaluate differences between remote and in-person education, the DREAMS (Developing a Research Participation Enhancement and Advocacy Training Program for Diverse Seniors) health seminar series compared in-person and remote learning groups to assess feasibility, satisfaction, adherence, health literacy, and cognitive outcomes. RESEARCH DESIGN: Nonrandomized two-arm interventions occurred remotely or in-person. About 130 diverse, older adults (M age: 70.8 ± 9.2 years; in-person n = 95; remote, n = 35) enrolled. Data from 115 completers (In-person n = 80; Remote n = 35) were analyzed for performance outcomes. Feasibility, adherence, and satisfaction benchmarks were evaluated at baseline, immediately post intervention, and 8 weeks post intervention. Adjusting for baseline performances, outcomes on health literacy and cognitive measures were compared between groups after intervention (at posttest and at 8-week follow-up) using adjusted mean differences (ß coefficients). RESULTS: Eighty in-person and all remote participants completed at least six modules. Both programs had high satisfaction, feasibility, and strong adherence. After adjusting for demographic covariates and baseline values, cognitive and motor cognitive measures between groups were domain specific (e.g., global cognition, executive function, spatial memory, mental tracking capacity, and cognitive integration). DISCUSSION AND IMPLICATIONS: This work explores feasible measures of knowledge acquisition and its link to health literacy and cognitive outcomes. Identifying effective delivery methods may increase involvement in clinical research. Future studies may encourage remote learning for increased accessibility.

Psychosocial Effects of Remote Reading with Telephone Support versus In-Person Health Education for Diverse, Older Adults.

This study evaluated initial information about psychosocial differences of 130 diverse, older adults (M age: 70.8 ± 9.2 years) who received a "low-tech" remote (independent reading with telephone support) or in-person education through DREAMS (Developing a Research Participation Enhancement and Advocacy Training Program for Diverse Seniors) health seminar series. Outcomes on measures of depression, quality of life, and spatial extent of lifestyle of 115 completers were analyzed at baseline, immediately post-intervention, and 8-week follow-up. Adjusted at baseline, psychosocial outcomes were compared between groups at post-test and 8-week follow-up using adjusted mean differences. Post-participation, compared to remote participants, in-person participants had significantly lower depression on Beck Depression Inventory-II, Geriatric Depression Scale, and significantly higher mental quality of life on Short Form-12. This study links knowledge acquisition via in-person learning with decreased stress, depression, and increased quality of life among seniors. Identifying effective educational delivery methods may increase clinical research involvement for aging communities.

Variation in timely surgery for severe open tibial fractures by time and place of presentation in England from 2012 to 2019 : a cohort study using data collected nationally by the Trauma Audit and Research Network.

AIMS: Several studies have reported that patients presenting during the evening or weekend have poorer quality healthcare. Our objective was to examine how timely surgery for patients with severe open tibial fracture varies by day and time of presentation and by type of hospital. This cohort study included patients with severe open tibial fractures from the Trauma Audit and Research Network (TARN). METHODS: Provision of prompt surgery (debridement within 12 hours and soft-tissue coverage in 72 hours) was examined, using multivariate logistic regression to derive adjusted risk ratios (RRs). Time was categorized into three eight-hour intervals for each day of the week. The models were adjusted for treatment in a major trauma centre (MTC), sex, age, year of presentation, injury severity score, injury mechanism, and number of operations each patient received. RESULTS: We studied 8,258 patients from 175 hospitals. Patients presenting during the day (08:00 to 15:59; risk ratio (RR) 1.11, 95% confidence interval (CI) 1.02 to 1.20) were more likely to receive debridement within 12 hours, and patients presenting at night (16:00 to 23:59; RR 0.56, 95% CI 0.51 to 0.62) were less likely to achieve the target; triage to a MTC had no effect. Day of presentation was associated with soft-tissue coverage within 72 hours; patients presenting on a Thursday or Friday being less likely to receive this surgery within 72 hours (Thursday RR 0.88, 95% CI 0.81 to 0.97; Friday RR 0.89, 95% CI 0.81 to 0.98), and the standard less likely to be achieved for those treated in 'non-MTC' hospitals (RR 0.76, 95% CI 0.70 to 0.82). CONCLUSION: Variations in care were observed for timely surgery for severe open tibial fractures with debridement surgery affected by time of presentation and soft-tissue coverage affected by day of presentation and type of hospital. The variation is unwarranted and highlights that there are opportunities to substantially improve the delivery and quality of care for patients with severe open tibial fracture.Cite this article: Bone Jt Open 2022;3(12):941-952.

Sociodemographic variables associated with risk for diabetic retinopathy.

BACKGROUND: Several systemic and sociodemographic factors have been associated with the development and progression of diabetic retinopathy (DR). However, there is limited investigation of the potential role sociodemographic factors may play in augmenting systemic risk factors of DR. We hypothesize that age, sex, race, ethnicity, income, and insurance payor have an impact on hemoglobin A1c (HbA1c), body mass index, and systolic blood pressure, and therefore an upstream effect on the development of DR and vision-threatening forms of DR (VTDR). METHODS: Multivariable analysis of longitudinal electronic health record data at a large academic retina clinic was performed. Sociodemographic factors included race, ethnicity, income, and insurance payor. Systemic risk factors for DR included hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and body mass index (BMI). VTDR was identified from encounter diagnostic codes indicating proliferative retinopathy or diabetic macular edema. Patient-reported primary address zip codes were used to approximate income level, stratified into quartiles. RESULTS: From 2016 to 2018, 3,470 patients with diabetes totaled 11,437 visits were identified. Black patients had higher HbA1c and SBP compared to White patients. White patients had higher BMI and SBP compared to patients of unknown/other race and greater odds of VTDR than the latter. Patients of Hispanic ethnicity had significantly higher SBP than non-Hispanic patients. Low-income patients had higher BMI and SBP than high-income patients and greater odds of VTDR than the latter. Medicaid recipients had greater odds of VTDR than those with Blue Care Network (BCN) and Blue Cross Blue Shield (BCBS) insurance. Medicaid and Medicare recipients had higher SBP compared to BCBS recipients. Finally, both higher HbA1c and SBP had greater odds of VTDR. There were no differences in odds of VTDR between White and Black patients or between Hispanic and non-Hispanic patients. CONCLUSION: Significant associations exist between certain sociodemographic factors and well-known risk factors for DR. Income and payor were associated with increased severity of systemic risk factors and presence of VTDR. These results warrant further investigation of how risk factor optimization and disease prevention may be further improved by targeted intervention of these modifiable sociodemographic factors.

The influence of mode of anaesthesia on perioperative outcomes in people with hip fracture: a prospective cohort study from the National Hip Fracture Database for England, Wales and Northern Ireland.

BACKGROUND: Delirium is common after hip fracture surgery, affecting up to 50% of patients. The incidence of delirium may be influenced by mode and conduct of anaesthesia. We examined the effect of spinal anaesthesia (with and without sedation) compared with general anaesthesia on early outcomes following hip fracture surgery, including delirium. METHODS: We used prospective data on 107,028 patients (2018 to 2019) from the National Hip Fracture Database, which records all hip fractures in patients aged 60 years and over in England, Wales and Northern Ireland. Patients were grouped by anaesthesia: general (58,727; 55%), spinal without sedation (31,484; 29%), and spinal with sedation (16,817; 16%). Outcomes (4AT score on post-operative delirium screening; mobilisation day one post-operatively; length of hospital stay; discharge destination; 30-day mortality) were compared between anaesthetic groups using multivariable logistic and linear regression models. RESULTS: Compared with general anaesthesia, spinal anaesthesia without sedation (but not spinal with sedation) was associated with a significantly reduced risk of delirium (odds ratio (OR)=0.95, 95% confidence interval (CI)=0.92-0.98), increased likelihood of day one mobilisation (OR=1.06, CI=1.02-1.10) and return to original residence (OR=1.04, CI=1.00-1.07). Spinal without sedation (p<0.001) and spinal with sedation (p=0.001) were both associated with shorter hospital stays compared with general anaesthesia. No differences in mortality were observed between anaesthetic groups. CONCLUSIONS: Spinal and general anaesthesia achieve similar outcomes for patients with hip fracture. However, this equivalence appears to reflect improved perioperative outcomes (including a reduced risk of delirium, increased likelihood of mobilisation day one post-operatively, shorter length of hospital stay and improved likelihood of returning to previous residence on discharge) among the sub-set of patients who received spinal anaesthesia without sedation. The role and effect of sedation should be studied in future trials of hip fracture patients undergoing spinal anaesthesia.

Incidence and quality of care for open fractures in England between 2008 and 2019 : a cohort study using data collected by the Trauma Audit and Research Network.

AIMS: This study estimated trends in incidence of open fractures and the adherence to clinical standards for open fracture care in England. METHODS: Longitudinal data collected by the Trauma Audit and Research Network were used to identify 38,347 patients with open fractures, and a subgroup of 12,170 with severe open fractures of the tibia, between 2008 and 2019 in England. Incidence rates per 100,000 person-years and 95% confidence intervals were calculated. Clinical care was compared with the British Orthopaedic Association Standards for Trauma and National Major Trauma Centre audit standards. RESULTS: In total, 60% of all open fractures occurred in males; the median age was 48 years (interquartile range (IQR) 29 to 68). Between 2012 and 2019, the overall incidence in England was 6.94 per 100,000 person-years. In males, the highest incidence observed was in those aged 20 to 29 years (11.50 per 100,000 person-years); in females, incidence increased with age, peaking at 32.11/100,000 person-years at 90 years of age and over. Among those with severe open fractures of the tibia, there was a bimodal distribution in males, peaking at 20 to 29 years (3.71/100,000 person-years) and greater than 90 years of age (2.84/100,000 person-years) respectively; among females, incidence increased with age to a peak of 9.91/100,000 person years at 90 years of age and over. There has been variable improvement with time in the clinical care standards for patients with severe open fractures of the tibia. The median time to debridement was 13.0 hours (IQR 6.4 to 20.9); almost two-thirds of patients underwent definitive soft-tissue coverage within 72 hours from 2016 to 2019. CONCLUSION: This is the first time the incidence of all open fractures has been studied using data from a national audit in England. While most open fractures occurred in young males, the incidence increased with age in females to a much greater level than observed in older males. The degree of missing data in the national audit is startling, and limits the certainty of inferences drawn concerning open fracture care. Cite this article: Bone Joint J 2022;104-B(6):736-746.

Novel deletion of exon 3 in TYR gene causing Oculocutaneous albinism 1B in an Indian family along with intellectual disability associated with chromosomal copy number variations.

BACKGROUND: Oculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by hypo-pigmentation of skin, hair, and eyes. The OCA clinical presentation is due to a deficiency of melanin biosynthesis. Intellectual disability (ID) in OCA cases is a rare clinical presentation and appropriate diagnosis of ID is challenging through clinical examination. We report an Indian family with a rare co-inheritance of OCA1B and ID due to a novel TYR gene variant and chromosomal copy number variations. METHODS: We have done a study on three siblings (2 males and 1 female) of a family where all of them presented with hypopigmented skin, hair and eyes. The male children and their father was affected with ID. Targeted exome sequencing and multiplex ligation-dependent probe amplification analysis were carried out to identify the OCA1B and ID associated genomic changes. Further Array-CGH was performed using SurePrint G3 Human CGH + SNP, 8*60 K array. RESULTS: A rare homozygous deletion of exon 3 in TYR gene causing OCA1B was identified in all three children. The parents were found to be heterozygous carriers. The Array-CGH analysis revealed paternally inherited heterozygous deletion(1.9 MB) of 15q11.1-> 15q11.2 region in all three children. Additionally, paternally inherited heterozygous deletion(2.6 MB)of 10q23.2-> 10q23.31 region was identified in the first male child; this may be associated with ID as the father and the child both presented with ID. While the 2nd male child had a denovo duplication of 13q31.1-> 13q31.3 chromosomal region. CONCLUSION: A rare homozygous TYR gene exon 3 deletion in the present study is the cause of OCA1B in all three children, and the additional copy number variations are associated with the ID. The study highlights the importance of combinational genetic approaches for diagnosing two different co-inherited disorders (OCA and ID). Hence, OCA cases with additional clinical presentation need to be studied in-depth forthe appropriate management of the disease.

The Relationship Between Attitudes about Research and Health Literacy among African American and White (Non-Hispanic) Community Dwelling Older Adults.

BACKGROUND: Ethnic minority representation lacks in research. Understanding factors that promote minorities in research helps address this participation gap. Minorities often face representation disparities, including health education, socioeconomic status, and race. Compared to other races in the USA, over 50% of African Americans (AA) over age 65 face obstacles towards achieving basic health literacy skills. This study aims to investigate differences in beliefs regarding research and health literacy between White and AA participants. METHODS: This cross-sectional study compared 46 AA vs. 60 White healthy older adults (n = 106; age = 73.97 ± 10.6 years). Participants were assessed once with the Participant Attitudes and Beliefs towards Research Questionnaire (PABRQ) and two validated health literacy measures, the Rapid Estimate of Adult Literacy in Medicine (REALM) and the Short Test of Functional Health Literacy for Adults (S-TOFHLA). RESULTS: Controlling for age, sex, and education, AA performed significantly worse on REALM. Compared to White participants, AA more likely believed that researchers were motivated to perform studies to increase their general knowledge. Participants with lower health literacy scores more likely believed that scientists were motivated to conduct research to minimize treatment expenses. About 83-85% of participants reported not being familiar with the informed consent process, 90-95% had positive attitudes towards research involvement, and 38-52% believed researchers performed to promote their own careers. CONCLUSION: This work helps link older adults' beliefs towards research, health literacy, and their participation in research. Future research is needed to remove barriers to participation in research for underserved, older adults.

A Dive Into Oliceridine and Its Novel Mechanism of Action.

The current state of the opioid epidemic has revealed the need of utilizing proper pain management, especially in the postoperative setting where there is overuse of potent analgesics. However, the adequate treatment of pain is necessary to reduce mortality and cost of burden while increasing recovery and improving quality of life. Treatment of pain can be difficult to standardize as the guidelines from the American Pain Society discuss the importance of tailoring treatment options based on a patient's sensitivities and risk factors. An effective fast-acting analgesic with adequate potency and few adverse events is the key to alleviating acute pain. Oliceridine (Olinvyk®, Trevena Inc., Chesterbrook, USA) is a novel G protein-biased µ-opioid receptor agonist designed to decrease opioid-related adverse events (ORAEs) compared to conventional opioids. This article discusses oliceridine's novel mechanism of action and current place in therapy. After a literature search on clinicaltrials.gov, three clinical trials were analyzed to understand the safety and efficacy of oliceridine. These trials demonstrated a comparable efficacy to morphine with a decreased risk for serious adverse events. However, further studies need to be conducted to evaluate the true safety impact of oliceridine compared to conventional opioids.

Assessment of Long-Term in vitro Multiplied Human Wharton's Jelly-Derived Mesenchymal Stem Cells prior to Their Use in Clinical Administration.

The quantity of mesenchymal stem/stromal cells (MSCs) required for a particular therapy demands their subsequent expansion through ex vivo culture. During in vitro multiplication, they undergo replicative senescence which may alter their genetic stability. Therefore, this study was aimed to analyze cellular, molecular, and chromosomal alterations in Wharton's jelly-derived MSCs (WJ-MSCs) during their in vitro sequential passages, where WJ-MSCs were sequentially passaged up to P14 and cells were evaluated at an interval of P2, P6, P10, and P14. They were examined for their morphology, tumorigenicity, surface markers, stemness markers, DNA damage, chromosomal aberration, and telomere length. We have processed five full-term delivered human umbilical cord samples to obtain WJ-MSCs. Morphological appearance observed at initial stages was small fine spindle-shaped WJ-MSCs which were transformed to flat, long, and broader cells in later passages. The cell proliferation rate was gradually decreased after the 10th passage. WJ-MSCs have expressed stemness markers OCT-4 and NANOG, while they showed high expression of positive surface markers CD90 and CD105 and lower expression of CD34 and CD45. They were non-tumorigenic with slow cellular aging during subsequent passages. There was no chromosomal abnormality up to the 14th passage, while increase in comet score and decrease in telomere length were observed in later passages. Hence, our study suggests that early and middle passaged (less than P10) WJ-MSCs are good candidates for clinical administration for treatment.

Severe telomere shortening in Fanconi anemia complementation group L.

Fanconi Anemia (FA) is a rare genetic disease with the incidence of 1 in 360,000 and is characterised by bone marrow failure, physical abnormalities, pancytopenia, and high frequency of chromosomal breakage and increased risk of evolving into malignancy. Telomere plays an important role in genomic stability, ageing process and cancers. Telomere shortening has been reported in FA. We studied telomere length in FA subjects and compared with complementation groups. Chromosomal breakage analysis from PHA stimulated, MMC induced peripheral blood culture was carried out in 37 clinically diagnosed FA. Molecular study of FANCA, G, and L was done through Sanger sequencing and next generation sequencing. Telomere length was estimated using real time quantitative polymerase chain reaction (qPCR) method. Student t-test was applied to test the significance. A high frequency of chromosomal breakage was observed in all the patients compared to healthy controls. We found significantly shorter telomere length in all the three complementation groups compare to age matched healthy controls. Among all complementation groups, FANCL showed severe telomere shortening (P value 0.0001). A negative correlation was observed between telomere length and chromosomal breakage frequency (R = -0.3116). Telomere shortening is not uncommon in FA subjects. However the telomere length shortening is different in complementation groups as FANCL showed severe telomere shortening in FA subjects. Though BM transplantation is essential for the management of the FA subjects, the telomere length can be considered as biological marker to understand the prognosis of the disease as FA subjects primarily treated with androgens.

Variation in timely surgery for hip fracture by day and time of presentation: a nationwide prospective cohort study from the National Hip Fracture Database for England, Wales and Northern Ireland.

BACKGROUND AND OBJECTIVE: Several studies report poorer quality healthcare for patients presenting at weekends. Our objective was to examine how timely surgery for patients with hip fracture varies with day and time of their presentation. METHODS: This population-based cohort study used 2017 data from the National Hip Fracture Database, which recorded all patients aged 60 years and over who presented with a hip fracture at a hospital in England, Wales and Northern Ireland. Provision of prompt surgery (surgery within 36 hours of presentation) was examined, using multivariable logistic regression with generalised estimating equations to derive adjusted risk ratios (RRs). Time was categorised into three 8-hour intervals (day: 08:00-15:59, evening: 16:00-23:59 and night: 00:00-07:59) for each day of the week. The model accounted for clustering by hospital and was adjusted by sex, age, fracture type, operation type, American Society of Anesthesiologists grade, preinjury mobility and location. RESULTS: We studied 68 977 patients from 177 hospitals. The average patient presenting during the day on Friday or Saturday was significantly less likely to undergo prompt surgery (Friday during 08:00-15:59, RR=0.93, 95% CI 0.91 to 0.96; Saturday during 08:00-15:59, RR=0.91, 95% CI 0.88 to 0.94) than patients in the comparative category (Thursday, during the day). Patients presenting during the evening (16:00-23:59) were consistently significantly less likely to undergo prompt surgery, and the effect was more marked on Fridays and Saturdays (Friday during 16:00-23:59, RR=0.83, 95% CI 0.80 to 0.85; Saturday during 16:00-23:59, RR=0.81, 95% CI 0.78 to 0.85). Patients presenting overnight (00:00-07:59), except on Saturdays, were significantly more likely to undergo surgery within 36 hours (RR>1.07). CONCLUSION: The provision of prompt hip fracture surgery was complex, with evidence of both an 'evening' and a 'night' effect. Investigation of weekly variation in hip fracture care is required to help implement strategies to reduce the variation in timely surgery throughout the entire week.

Superusers' Engagement in Asthma Online Communities: Asynchronous Web-Based Interview Study.

BACKGROUND: Superusers, defined as the 1% of users who write a large number of posts, play critical roles in online health communities (OHCs), catalyzing engagement and influencing other users' self-care. Their unique online behavior is key to sustaining activity in OHCs and making them flourish. Our previous work showed the presence of 20 to 30 superusers active on a weekly basis among 3345 users in the nationwide Asthma UK OHC and that the community would disintegrate if superusers were removed. Recruiting these highly skilled individuals for research purposes can be challenging, and little is known about superusers. OBJECTIVE: This study aimed to explore superusers' motivation to actively engage in OHCs, the difficulties they may face, and their interactions with health care professionals (HCPs). METHODS: An asynchronous web-based structured interview study was conducted. Superusers of the Asthma UK OHC and Facebook groups were recruited through Asthma UK staff to pilot and subsequently complete the questionnaire. Open-ended questions were analyzed using content analysis. RESULTS: There were 17 superusers recruited for the study (14 patients with asthma and 3 carers); the majority were female (15/17). The age range of participants was 18 to 75 years. They were active in OHCs for 1 to 6 years and spent between 1 and 20 hours per week reading and 1 and 3 hours per week writing posts. Superusers' participation in OHCs was prompted by curiosity about asthma and its medical treatment and by the availability of spare time when they were off work due to asthma exacerbations or retired. Their engagement increased over time as participants furthered their familiarity with the OHCs and their knowledge of asthma and its self-management. Financial or social recognition of the superuser role was not important; their reward came from helping and interacting with others. According to the replies provided, they showed careful judgment to distinguish what can be dealt with through peer advice and what needs input from HCPs. Difficulties were encountered when dealing with misunderstandings about asthma and its treatment, patients not seeking advice from HCPs when needed, and miracle cures or dangerous ideas. Out of 17 participants, only 3 stated that their HCPs were aware of their engagement with OHCs. All superusers thought that HCPs should direct patients to OHCs, provided they are trusted and moderated. In addition, 9 users felt that HCPs themselves should take part in OHCs. CONCLUSIONS: Superusers from a UK-wide online community are highly motivated, altruistic, and mostly female individuals who exhibit judgment about the complexity of coping with asthma and the limits of their advice. Engagement with OHCs satisfies their psychosocial needs. Future research should explore how to address their unmet needs, their interactions with HCPs, and the potential integration of OHCs in traditional healthcare.

Randomized Safety and Feasibility Trial of Ultra-Rapid Cooling Anesthesia for Intravitreal Injections.

PURPOSE: To test the safety and preliminary efficacy of rapid, nonpharmacologic anesthesia via cooling for intravitreal injections. DESIGN: Single-center, randomized phase 1 dose-ranging safety study (ClinicalTrials.gov identifier, NCT02872012). PARTICIPANTS: Adults 18 years of age or older with a diagnosis of exudative macular degeneration or diabetic macular edema requiring bilateral anti-vascular endothelial growth factor therapy were included. METHODS: A handheld device was developed to provide anesthesia via cooling to a focal area on the surface of the eye before intravitreal treatment (IVT). In 22 patients undergoing bilateral IVT, 1 eye was randomized to receive standard of care (SOC) lidocaine-based anesthesia and the other eye received cooling-anesthesia at 1 of 5 different temperatures and cooling times. Subjective pain was assessed via the visual analog scale (VAS; range, 1-10) at 2 time points: (1) immediately after IVT and (2) 4 hours after IVT. Treated eyes were assessed for ocular safety 24 hours after IVT. MAIN OUTCOME MEASURES: We determined the occurrence of adverse events in eyes treated with cooling anesthesia. Mean VAS pain scores immediately after IVT and 4 hours after IVT in eyes receiving cooling anesthesia were compared with eyes receiving SOC. RESULTS: A total of 44 eyes were treated, 22 with cooling anesthesia and 22 with SOC. No dose-related toxicity was found with cooling anesthesia. Mild, transient adverse events were recorded in 32% of patients treated with cooling anesthesia versus 44% of patients receiving SOC. The mean±standard error of the mean (SEM) VAS pain scores immediately after intravitreal injection were 2.3 ± 0.4 for patients receiving SOC and 2.2 ± 0.6 in patients receiving -10° C cooling anesthesia (P = 0.8). Mean±SEM pain scores 4 hours after injection were 1.6 ± 0.4 for SOC and 1.2 ± 0.5 in the combined -10° C arms (P = 0.56). Total mean±SEM procedure time was 124 ± 5 seconds for patients treated with cooling anesthesia versus 395 ± 40 seconds for SOC (P < 0.0001). CONCLUSIONS: Ultra-rapid cooling of the eye for anesthesia was well tolerated, with -10° C treatment resulting in comparable levels of anesthesia to SOC with a reduction in procedure time.

Shedding light on a potential hazard: Dental light-curing units.

BACKGROUND: Dental light-curing units (LCUs) are powerful sources of blue light that can cause soft-tissue burns and ocular damage. Although most ophthalmic research on the hazards of blue light pertains to low levels from personal electronic devices, computer monitors, and light-emitting diode light sources, the amount of blue light emitted from dental LCUs is much greater and may pose a "blue light hazard." METHODS: The authors explain the potential risks of using dental LCUs, identify the agencies that provide guidelines designed to protect all workers from excessive exposure to blue light, discuss the selection of appropriate eye protection, and provide clinical tips to ensure eye safety when using LCUs. RESULTS: While current literature and regulatory standards regarding the safety of blue light is primarily based on animal studies, sufficient evidence exists to suggest that appropriate precautions should be taken when using dental curing lights. The authors found it difficult to find on the U.S. Food and Drug Administration database which curing lights had been cleared for use in the United States or Europe and could find no database that listed which brands of eyewear designed to protect against the blue light has been cleared for use. The authors conclude that more research is needed on the cumulative exposure to blue light in humans. Manufacturers of curing lights, government and regulatory agencies, employers, and dental personnel should collaborate to determine ocular risks from blue light exist in the dental setting, and recommend appropriate eye protection. Guidance on selection and proper use of eye protection should be readily accessible. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The Centers for Disease Control and Prevention Guidelines for Infection Control in the Dental Health-Care Setting-2003 and the Occupational Safety and Health Administration Bloodborne Pathogen Standard do not include safety recommendations or regulations that are directly related to blue light exposure. However, there are additional Occupational Safety and Health Administration regulations that require employers to protect their employees from potentially injurious light radiation. Unfortunately, it is not readily evident that these regulations apply to the excessive exposure to blue light. Consequently employers and dental personnel may be unaware that these Occupational Safety and Health Administration regulations exist.

Blood Pressure Is Associated with Receiving Intravitreal Anti-Vascular Endothelial Growth Factor Treatment in Patients with Diabetes.

PURPOSE: Intravitreal anti-vascular endothelial growth factor (VEGF) injections are used commonly in the treatment of diabetic retinopathy (DR), but the need for treatment and frequency of administration vary considerably among patients. There is no way to predict which patients will require treatment and how frequently injections will be needed. This study aimed to identify factors associated with receiving anti-VEGF injections and the number of treatments received in an 18-month period in patients with diabetes. DESIGN: Retrospective cohort study. PARTICIPANTS: Two thousand nine hundred sixteen patients with diabetes treated at the Kellogg Eye Center Retina Clinic from June 1, 2016, through December 31, 2017. METHODS: Retrospective analysis was performed with institutional review board approval using data collected from diabetic patients treated at the retina clinic at the Kellogg Eye Center. Logistic regression was used to identify demographic and medical factors associated with receiving at least 1 injection. Negative binomial regression was used to model the number of anti-VEGF injections. MAIN OUTCOME MEASURES: Receiving at least 1 anti-VEGF injection and the number of anti-VEGF injections received during the study period. RESULTS: Systolic blood pressure and a diagnosis of DR were associated significantly with receiving an injection. A history of kidney disease was associated positively with the number of injections received. Type 1 diabetes was associated negatively with receiving an injection and the number of injections. Current hemoglobin A1c level was not associated with either receiving an injection or the number of injections. CONCLUSIONS: Elevated blood pressure is associated significantly with the need for treatment with anti-VEGF injections in patients with diabetes, and a diagnosis of type 1 diabetes is associated negatively with both receiving treatment and the number of injections. Of note, current glycemic control is not associated significantly with either outcome measure. To our knowledge, these associations have not been previously reported, and imply that factors that confer risk for DR development may not be the same that confer risk for treatment.

Treatment of first-time traumatic anterior shoulder dislocation: the UK TASH-D cohort study.

BACKGROUND: Shoulder dislocations are the most common joint dislocations seen in emergency departments. Most traumatic cases are anterior and cause recurrent dislocations. Management options include surgical and conservative treatments. There is a lack of evidence about which method is most effective after the first traumatic anterior shoulder dislocation (TASD). OBJECTIVES: To produce UK age- and sex-specific incidence rates for TASD. To assess whether or not surgery within 6 months of a first-time TASD decreases re-dislocation rates compared with no surgery. To identify clinical predictors of recurrent dislocation. DESIGN: A population-based cohort study of first-time TASD patients in the UK. An initial validation study and subsequent propensity-score-matched analysis to compare re-dislocation rates between surgery and no surgery after a first-time TASD. Prediction modelling was used to identify potential predictors of recurrent dislocation. SETTING: UK primary and secondary care data. PARTICIPANTS: Patients with a first-time TASD between 1997 and 2015. INTERVENTIONS: Stabilisation surgery within 6 months of a first-time TASD (compared with no surgery). Stabilisation surgery within 12 months of a first-time TASD was also carried out as a sensitivity analysis. MAIN OUTCOME MEASURE: Re-dislocation rate up to 2 years after the first TASD. METHODS: Eligible patients were identified from the Clinical Practice Research Datalink (CPRD) (1997-2015). Accuracy of shoulder dislocation coding was internally validated using the CPRD General Practitioner questionnaire service. UK age- and sex-specific incidence rates for TASD were externally validated against rates from the USA and Canada. A propensity-score-matched analysis using linked CPRD and Hospital Episode Statistics (HES) data compared re-dislocation rates for patients aged 16-35 years, comparing surgery with no surgery. Multivariable Cox regression models for predicting re-dislocation were developed for the surgical and non-surgical cohorts. RESULTS: Shoulder dislocation was coded correctly for 89% of cases in the CPRD [95% confidence interval (CI) 83% to 95%], with a 'primary' dislocation confirmed for 76% of cases (95% CI 67% to 85%). Far fewer patients than expected received stabilisation surgery within 6 months of a first TASD, leading to an underpowered study. Around 20% of re-dislocation rates were observed for both surgical and non-surgical patients. The sensitivity analysis at 12 months also showed little difference in re-dislocation rates. Missing data on risk factors limited the value of the prediction modelling; however, younger age, epilepsy and sex (male) were identified as statistically significant predictors of re-dislocation. LIMITATIONS: Far fewer than the expected number of patients had surgery after a first-time TASD, resulting in an underpowered study. This and residual confounding from missing risk factors mean that it is not possible to draw valid conclusions. CONCLUSIONS: This study provides, for the first time, UK data on the age- and sex-specific incidence rates for TASD. Most TASD occurs in men, but an unexpected increased incidence was observed in women aged > 50 years. Surgery after a first-time TASD is uncommon in the NHS. Re-dislocation rates for patients receiving surgery after their first TASD are higher than previously expected; however, important residual confounding risk factors were not recorded in NHS primary and secondary care databases, thus preventing useful recommendations. FUTURE WORK: The high incidence of TASD justifies investigation into preventative measures for young men participating in contact sports, as well as investigating the risk factors in women aged > 50 years. A randomised controlled trial would account for key confounders missing from CPRD and HES data. A national TASD registry would allow for a more relevant data capture for this patient group. STUDY REGISTRATION: Independent Scientific Advisory Committee (ISAC) for the Medicines and Healthcare Products Regulatory Agency (ISAC protocol 15_0260). FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Traumatic anterior shoulder dislocation (TASD) happens when the top of the arm bone is forced frontwards out of the shoulder socket. After a TASD, the shoulder joint can become 'unstable' and keep dislocating. The main treatments are surgery or physiotherapy; however, we do not know which treatment is best at stopping more dislocations. Two large NHS computer databases were studied to assess this problem. This has allowed us to produce information on the extent of this problem in the UK. We also looked for any differences in the number of people who suffered more shoulder dislocations when treated with either surgery or no surgery. The results showed that young men aged 16­20 years and women aged > 50 years suffer the most with this problem. In young people, the cause is thought to be due to sports injuries. These findings in women aged > 50 years are new and suggest that further research is needed to discover what puts them at a greater risk of TASD. When patients who had surgery and those who did not were compared, there appeared to be no difference in the number of people suffering a re-dislocation. Although, overall, this might suggest that surgery after only one dislocation does not have any extra benefit in preventing more dislocations, this research discovered that important information used to help decide on whether or not surgical treatment is needed is not reported in the databases. Some patients may be at a greater risk of more dislocations than other patients based on risk factors, such as sport and occupation, and this information is not recorded in the NHS databases. Therefore, the research question cannot be answered by studying these NHS databases and so other methods, such as a research trial or a custom database built especially for shoulder dislocation patients, would be needed.