bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuromuscular Disorders Associated With COVID-19
Authors: Morgan Larry , Hollist Mary , Au Katherine , Ayari Lena , Betts Colton , Kirmani Batool F
Published: May 2023

The coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on practically every aspect of daily life, and those with neuromuscular disorders have certainly not been spared. The effects of COVID-19 infection are far-reaching, going well beyond respiratory symptoms alone. From simple myalgias to debilitating critical illness neuromyopathies, we continue to learn and catalog the diverse pathologies presented by the severe acute respiratory syndrome coronavirus 2 (SARS -CoV-2) as it relates to the neuromuscular system. Complications have been documented both as a direct result of primary infection but also in those with pre-existing neuromuscular disorders from myasthenia gravis to devastating critical illness neuromyopathies. In this review, we will discuss the relationship between COVID-19 infection and critical illness neuromyopathy, peripheral nerve palsies, myalgias, positional compressive neuropathy, myasthenia gravis, and Guillain-Barré syndrome.
Repair of the Medial Ulnar Collateral Ligament of the Elbow With Internal Brace Augmentation
Authors: Nauert Richard F. , Yu Kristin E. , Camp Christopher L.
Published: May 2023

Background:

The medial ulnar collateral ligament (MUCL) is the primary restraint to valgus force across the elbow during throwing. The incidence of MUCL continues to rise, and injuries are common in overhead throwing athletes often leading to elbow pain and instability. While MUCL reconstruction remains the gold standard for high-level throwing athletes with midsubstance tears, MUCL repair remains an option for select athletes and affords good functional outcomes with quicker return to sport compared with reconstruction.

Indications:

Indications for MUCL repair include acute injuries, proximal or distal avulsions, young and lower demand athletes, non-throwing athletes, or older athletes who may be nearing retirement.

Technique Description:

An incision is made over the medial elbow from the medial epicondyle to the sublime tubercle. Dissection is carried down to fascia which is split in line with its fibers. The flexor pronator muscle group is bluntly divided, and the ligament exposed. Care is taken to identify and dissect the native ligament. The avulsed portion of the ligament is secured with a 0 FiberWire suture in a running locked whipstitch fashion. The footprint of the avulsed ligament is gently debrided and prepared using a scalpel. The 0-FiberWire suture tails are then loaded onto a suture anchor preloaded with suture tape. This is then secured at the footprint of the ligament. The FiberWires are cut, and the suture tape is then pulled back over the native ligament and fixed at the other attachment site for the ligament. 0-Vicryl sutures are then used to suture the internal brace to the underlying ligament so the construct would move as a single unit.

Results:

Biomechanical testing has demonstrated that MUCL repair with internal brace augmentation has similar time-zero failure strength when compared with the original Jobe reconstruction technique while also having greater resistance to gapping. In addition, recent literature has shown that well-selected patients can have excellent functional outcomes and quicker return to sport with MUCL repair as opposed to reconstruction.

Discussion:

Medial ulnar collateral ligament repair with internal brace augmentation can be a successful treatment in the appropriately indicated athlete to allow for good functional results and quicker return to sport.

Patient Consent Disclosure Statement:

The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
The hops (Humulus lupulus) genome contains a mid-sized terpene synthase family that shows wide functional and allelic diversity
Authors: Chen Xiuyin , Wang Mindy Y. , Deng Cecilia H. , Beatson Ron A. , Templeton Kerry R. , Atkinson Ross G. , Nieuwenhuizen Niels J.
Published: May 2023

Background

Hops (Humulus lupulusL.) are a dioecious climbing perennial, with the dried mature “cones” (strobili) of the pistillate/female inflorescences being widely used as both a bittering agent and to enhance the flavour of beer. The glandular trichomes of the bract and bracteole flowering structures of the cones produce an abundance of secondary metabolites, such as terpenoids, bitter acids and prenylated phenolics depending on plant genetics, developmental stage and environment. More knowledge is required on the functional and allelic diversity of terpene synthase (TPS) genes responsible for the biosynthesis of volatile terpenes to assist in flavour-directed hop breeding.

Results

Major volatile terpene compounds were identified using gas chromatography–mass spectrometry (GC–MS) in the ripe cones of twenty-one hop cultivars grown in New Zealand. All cultivars produced the monoterpene β-myrcene and the sesquiterpenes α-humulene and β-caryophyllene, but the quantities varied broadly. Other terpenes were found in large quantities in only a smaller subset of cultivars, e.g. β-farnesene (in seven cultivars) and α-pinene (in four). In four contrasting cultivars (Wakatu™, Wai-iti™, Nelson Sauvin™, and ‘Nugget’), terpene production during cone development was investigated in detail, with concentrations of some of the major terpenes increasing up to 1000-fold during development and reaching maximal levels from 50–60 days after flowering. Utilising the publishedH. lupulusgenome, 87 putative full-length and partial terpene synthase genes were identified. Alleles corresponding to seven TPS genes were amplified from ripe cone cDNA from multiple cultivars and subsequently functionally characterised by transient expressionin planta. Alleles of the previously characterisedHlSTS1produced humulene/caryophyllene as the major terpenes.HlRLSalleles produced (R)-(-)-linalool, whilst alleles of two sesquiterpene synthase genes,HlAFS1andHlAFS2produced α-farnesene. Alleles ofHlMTS1,HlMTS2andHlTPS1were inactive in all the hop cultivars studied.

Conclusions

Alleles of four TPS genes were identified and shown to produce key aroma volatiles in ripe hop cones. Multiple expressed but inactive TPS alleles were also identified, suggesting that extensive loss-of-function has occurred during domestication and breeding of hops. Our results can be used to develop hop cultivars with novel/improved terpene profiles using marker-assisted breeding strategies to select for, or against, specific TPS alleles.
Efficacy and safety of remimazolam tosilate versus propofol in patients undergoing day surgery: a prospective randomized controlled trial
Authors: Luo Wenchen , Sun Minli , Wan Jie , Zhang Zhenyu , Huang Jian , Zhang Jinlin , Xiong Wanxia , Xia Lirong , Xu Peiyao , Miao Changhong , Zhang Xuesong , Liu Mingyue , Zhong Jing
Published: May 2023

Background

Remimazolam tosilate (RT) is a novel short-acting GABA (A) receptor agonist that has a rapid recovery from procedural sedation and can be fully reversed by flumazenil. To date, there have been relatively few articles comparing RT and propofol for general anesthesia. This study aimed to assess the efficacy and safety of RT with or without flumazenil compared with propofol in general anesthesia for day surgery.

Methods

115 patients scheduled for day surgery were randomized into three groups: RT (n = 39), RT + flumazenil (n = 38) and propofol (n = 38). The primary endpoints were anesthesia induction time and time until fully alert. Anesthesia success rate, bispectral index (BIS) values, injection pain, opioid and vasopressor dosages, postoperative recovery profiles and perioperative inflammatory and cognitive changes were assessed. Any adverse events were recorded.

Results

Induction times were similar among the three groups (P = 0.437), but the median time until fully alert in patients treated with RT was longer than that of the propofol or RT + flumazenil groups (17.6 min vs. 12.3 min vs. 12.3 min, P < 0.001). The three groups had comparable postoperative recovery quality and inflammatory and cognitive state changes (P > 0.05). Smaller percentages of patients who received RT (26.3%) and RT + flumazenil (31.6%) developed hypotension during anesthesia maintenance compared with propofol (68.4%), and consequently less ephedrine (P < 0.001) and phenylephrine (P = 0.015) were needed in the RT group. Furthermore, serum triglyceride levels were lower (P < 0.001) and injection pain was much less frequent in the RT with or without flumazenil groups compared with the propofol group (5.3% vs. 0% vs. 18.4%).

Conclusion

RT permits rapid induction and comparable recovery profile compared with propofol in general anesthesia for day surgery, but has a prolonged recovery time without flumazenil. The safety profile of RT was superior to propofol in terms of hypotension and injection pain.

Trial registration

The study was registered at Chinese Clinical Trial Registry http://www.chictr.org.cn/ (Registration date: 19/7/2021; Trial ID: ChiCTR2100048904).
The association between HIV self-test awareness and recent HIV testing uptake in the male population in Gambia: data analysis from 2019–2020 demographic and health survey
Authors: Soe Phyumar , Johnston Lisa G. , Makuza Jean Damascene , Karim Mohammad Ehsanul
Published: May 2023

Background

The Gambian Ministry of Health is supportive of HIV self-testing (HIVST) and HIVST initiatives are being piloted as an additional strategy to increase HIV testing for individuals not currently reached by existing services, particularly men. This study aimed to determine awareness of HIVST among Gambian men, and whether prior awareness of HIVST is associated with recent HIV testing uptake.

Methods

We used men’s cross-sectional data from the 2019–2020 Gambian Demographic and Health Survey. We employed design-adjusted multivariable logistic regression to examine the association between HIVST awareness and recent HIV testing. Propensity-score weighting was conducted as sensitivity analyses.

Results

Of 3,308 Gambian men included in the study, 11% (372) were aware of HIVST and 16% (450) received HIV testing in the last 12 months. In the design-adjusted multivariable analysis, men who were aware of HIVST had 1.76 times (95% confidence interval: 1.26–2.45) the odds of having an HIV test in the last 12 months, compared to those who were not aware of HIVST. Sensitivity analyses revealed similar findings.

Conclusion

Awareness of HIVST may help increase the uptake of HIV testing among men in Gambia. This finding highlights HIVST awareness-raising activities to be an important intervention for nationwide HIVST program planning and implementation in Gambia.
Mothers’ involvement in providing care for their hospitalised sick newborns in Kenya: a focused ethnographic account
Authors: Oluoch Dorothy , Hinton Lisa , English Mike , Irimu Grace , Onyango Truphena , Jones Caroline O. H.
Published: May 2023

Introduction

There is growing evidence that parental participation in the care of small and sick newborns benefits both babies and parents. While studies have investigated the roles that mothers play in newborn units in high income contexts (HIC), there is little exploration of how contextual factors interplay to influence the ways in which mothers participate in the care of their small and sick newborn babies in very resource constrained settings such as those found in many countries in sub-Saharan Africa.

Methods

Ethnographic methods (observations, informal conversations and formal interviews) were used to collect data during 627 h of fieldwork between March 2017 and August 2018 in the neonatal units of one government and one faith-based hospital in Kenya. Data were analysed using a modified grounded theory approach.

Results

There were marked differences between the hospitals in the participation by mothers in the care of their sick newborn babies. The timing and types of caring task that the mothers undertook were shaped by the structural, economic and social context of the hospitals. In the resource constrained government funded hospital, the immediate informal and unplanned delegation of care to mothers was routine. In the faith-based hospital mothers were initially separated from their babies and introduced to bathing and diaper change tasks slowly under the close supervision of nurses. In both hospitals appropriate breast-feeding support was lacking, and the needs of the mothers were largely ignored.

Conclusion

In highly resource constrained hospitals with low nurse to baby ratios, mothers are required to provide primary and some specialised care to their sick newborns with little information or support on how undertake the necessary tasks. In better resourced hospital settings, most caring tasks are initially performed by nurses leaving mothers feeling powerless and worried about their capacity to care for their babies after discharge. Interventions need to focus on how to better equip hospitals and nurses to support mothers in caring for their sick newborns, promoting family centred care.
Work and health during the COVID-19 crisis among Dutch workers and jobseekers with (partial) work disabilities: a mixed methods study
Authors: de Visser Mara , de Graaf-Zijl Marloes , Anema Johannes R. , Huysmans Maaike A.
Published: May 2023

Background

The consequences of restrictive measures during the COVID-19 outbreak have potentially been enormous, especially for those in a vulnerable position in the labour market. This study aims to describe the impact of the COVID-19 crisis on work status, working conditions and health among people with (partial) work disabilities—with and in search of work—during the COVID-19 pandemic in the Netherlands.

Methods

A mixed methods design was used, combining a cross-sectional online survey and ten semi-structured interviews with people with a (partial) work disability. The quantitative data included responses to job-related questions, self-reported health, and demographics. The qualitative data consisted of participants’ perceptions about work, vocational rehabilitation, and health. We used descriptive statistics to summarize the responses, conducted logistic and linear regression and integrated our qualitative findings with the quantitative findings, aiming at complementarity.

Results

Five hundred and eighty-four participants (response rate 30.2%) completed the online survey. The majority of participants experienced no change in work status: 39 percent remained employed, 45 percent remained unemployed, six percent of respondents lost their job, and ten percent became employed during the COVID-19 crisis. In general, the results showed a deterioration in self-rated health during the COVID-19 outbreak, both for participants at work and in search of work. Participants who lost their job during the COVID-19 crisis reported the highest deterioration in self-rated health. Interview findings revealed that loneliness and social isolation were persistent during the COVID-19 crisis, especially among those in search of work. Additionally, employed participants identified a safe work environment and the possibility to work at the office as important factors for overall health.

Conclusions

The vast majority of study participants (84.2%) experienced no change in work status during the COVID-19 crisis. Nonetheless, people at work and in search of work encountered barriers to maintaining or (re)gaining employment. People with a (partial) work disability who lost their job during the crisis appeared to be most affected in terms of health. Employment and health protections could be strengthened for persons with (partial) work disabilities in order to build resilience in times of crisis.
The association of dietary intake of riboflavin and thiamine with kidney stone: a cross-sectional survey of NHANES 2007–2018
Authors: Di Xing-peng , Gao Xiao-shuai , Xiang Li-yuan , Wei Xin
Published: May 2023

Background

Kidney stone disease (KSD) is a common condition that affects 10% population in the United States (US). The relationship between thiamine and riboflavin intake and KSD has not been well-studied. We aimed to investigate the prevalence of KSD and the association between dietary thiamine and riboflavin intake with KSD in the US population.

Methods

This large-scale, cross-sectional study included subjects from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. KSD and dietary intake were collected from questionnaires and 24-hour recall interviews. Logistic regression and sensitivity analyses were performed to investigate the association.

Results

This study included 26,786 adult participants with a mean age of 50.12 ± 17.61 years old. The prevalence of KSD was 9.62%. After adjusting for all potential covariates, we found that higher riboflavin intake was negatively related to KSD compared with dietary intake of riboflavin < 2 mg/day in the fully-adjusted model (OR = 0.541, 95% CI = 0.368 to 0.795, P = 0.002). After stratifying by gender and age, we found that the impact of riboflavin on KSD still existed in all age subgroups (P < 0.05) but only in males (P = 0.001). No such associations were found between dietary intake of thiamine and KSD in any of the subgroups.

Conclusions

Our study suggested that a high intake of riboflavin is independently inversely associated with kidney stones, especially in male population. No association was found between dietary intake of thiamine and KSD. Further studies are needed to confirm our results and explore the causal relationships.
Knowledge, attitude and preventive practices of COVID-19 among deaf persons in the Greater Accra region of Ghana
Authors: Jnr Reginald Arthur-Mensah , Quao Jacob Nartey , Yeboah Louisa , Dassah Zanu , Kyei Abigail Agartha
Published: May 2023

Background

Since the emergence of the COVID-19 pandemic, studies continue to investigate the KAP of COVID-19 among diverse groups. We examined the KAP of COVID-19 among deaf persons living in the Ayawaso North Municipality in Accra.

Methods

A descriptive cross-sectional design was used for this study. Our sample comprised deaf persons registered with the Municipal Directorate. In all, 144 deaf persons were interviewed using an adapted KAP COVID-19 questionnaire.

Results

Regarding knowledge, majority of the deaf persons (> 50%) were not in the know of 8 out of 12 items of the knowledge subscale. For attitude, deaf persons (> 50%) showed optimistic attitude in all 6 items of the attitude subscale. Deaf persons “always” practised 5 items and “sometimes” practised 4 items in the preventive practices to COVID-19. A positive moderate and significant correlation existed between the subscales. Regression analysis showed that, a one-unit increase in knowledge will result in a 1.033-unit increase in preventive practices while a one-unit increase in knowledge will result in a 0.587-unit increase in attitude.

Conclusions

Campaigns about COVID-19 should emphasize the teaching of the science of the virus and the disease and not just the preventive practices, paying special attention to deaf persons.
Accidents, diseases and health complaints among seafarers on German-flagged container ships
Authors: Bilir Nora Annelies , Scheit Lorenz , Dirksen-Fischer Martin , Terschüren Claudia , Herold Robert , Harth Volker , Oldenburg Marcus
Published: May 2023

Background

For seafarers on the high seas health hazards are various and due to the setting also specific. The spectrum of job-related health impairments and accidents is mainly influenced by the maritime characteristics. The aim of this study is to assess the kind of accidents and the frequency of diseases and health complaints among seafarers on German container ships by evaluating medical log books.

Methods

A systematic analysis of 14,628 medical entries from 95 medical log books of 58 container ships under German flag from 1995 to 2015 was performed. This monocentric retrospective and descriptive study used information on accidents, diseases and health complaints among different occupational groups and medical treatment procedures for the analysis and evaluation.

Results

The analysis showed that more than one third of all consultations with the Health Officer on board are related to internal (33.7%) and surgical (31.3%) symptoms. Almost twenty percent of consultations were due to respiratory infections (19.6%) and accidents (17.9%). Accidents represented the most frequent reason for unfitness for sea service (31.2%). Based on occupational categories, most injuries occurred among deck crew (22.5%), followed by ratings working in the engine room (18.9%). In 106 cases, telemedical contact with a physician ashore was necessary. In total, 15 seafarers had to be evacuated from the ship for further medical treatment onshore. Medicine/drug application was the most common therapeutic measure on board, accounting for 77% of all consultations.

Conclusions

The high proportion of health complaints and accidents among seafarers shows that there is a need to optimize medical care at sea and accident prevention, e.g. by standardized treatment algorithms or improving the medical training of Health Officers. The development and introduction of a digital patient file to record medical treatments on the vessels could also improve medical documentation on board.
The neutrophil to lymphocyte ratio (NLR) positively correlates with the presence and severity of metabolic syndrome in obese adults, but not in obese children/adolescents
Authors: Marra Alice , Bondesan Adele , Caroli Diana , Grugni Graziano , Sartorio Alessandro
Published: May 2023

Metabolic syndrome (MetS) associated with obesity is a pathological condition increasing worldwide. Recent studies have demonstrated that the neutrophil to lymphocyte ratio (NLR) can be successfully used to stage MetS in obese adults. The aim of the study was to evaluate NLR values in 552 children/adolescents (M 219, F 333; 14.8 [12.9–16.3] years) and 231 adults (M 88, F 143; 52.3 [36.4–63.3] years) with morbid obesity, subdivided into subgroups according with the presence or absence of MetS. Adult patients with obesity showed a higher prevalence of MetS compared to the pediatric population (71% vs 26%), associated with a greater number of subjects with 3 and 4–5 altered components for MetS. NLR was higher (P-value = 0.041) in adults with MetS compared with those without. NLR values also positively correlated with the severity grade of the syndrome (P-value = 0.032). By contrast, in pediatric subjects with obesity with MetS, NLR values were comparable with those recorded in subjects without MetS (P-value = 0.861), no correlation being found with MetS severity (P-value = 0.441). Our study confirms the importance of NLR as an inflammatory indicator associated with MetS in adult subjects with severe obesity, while it excludes a similar role in children/adolescents.
The Black women first initiative: using implementation science to examine bundled interventions to improve care and treatment coordination for Black women with HIV
Authors: Rajabiun Serena , Heath Corliss , Walter Angela Wangari , Scott Judith C. , Downes Alicia , Jennings Esther , Cabral Howard J. , Flores-Rodriguez Cecilia , Sprague Martinez Linda
Published: May 2023

Background

Black cisgender and transgender women are disproportionately affected by the HIV epidemic compared to women of other racial and ethnic identities. Twelve demonstration sites across the United States are adapting, implementing and evaluating a comprehensive bundle of two or more evidence informed interventions to improve health and outcomes and quality of life for Black women with HIV.

Methods

Guided by Greenhalgh’s Conceptual Model of Diffusion of Innovations in Health Service Organizations and Proctor’s model for use of implementation strategies and evaluating implementation, service and client outcomes, this mixed methods study documents outcomes at the client, organization, and system level. Participant eligibility for the bundled interventions includes: individuals who are 18 years or older, identify as Black or African-American, identify as cisgender or transgender female and have a diagnosis of HIV. Qualitative data are collected systematically through a series of annual site visits and a standardized monthly call form to assess the barriers and facilitators to the implementation process and the key determinants impacting the intervention uptake and implementation strategies. Quantitative data collection for the implementation, service and client outcomes is conducted through a pre-post prospective study to examine the impact on Black women’s health and well-being. Implementation outcomes include: the reach to Black women with HIV, adoption of interventions across the sites and their community; the fidelity to the components of the bundled interventions; the costs of the intervention; and the sustainability of the intervention in the organization and community. Primary service and client outcomes are improved linkage to and retention in HIV care and treatment, increased and sustained viral suppression, improved quality of life and resilience, and stigma reduction.

Discussion

The study protocol presented is specifically designed to advance the evidence for adopting culturally responsive and relevant care into clinic and public health settings to improve the health and well-being for Black women with HIV. In addition the study may advance the implementation science field by furthering what is known about the ways in which bundled interventions can address barriers to care and facilitate the uptake of organizational practices to improve health.
Clinical and economic evaluations of natalizumab, rituximab, and ocrelizumab for the management of relapsing-remitting multiple sclerosis in Saudi Arabia
Authors: Alharbi Mansour A. , Aldosari Fahad , Althobaiti Ahmed Hasan , Abdullah Faris M. , Aljarallah Salman , Alkhawajah Nuha M. , Alanazi Miteb , AlRuthia Yazed
Published: May 2023

Introduction

The advent of new disease-modifying therapies (DMTs), such as monoclonal antibodies (mAbs), resulted in significant changes in the treatment guidelines for Multiple sclerosis (MS) and improvement in the clinical outcomes. However, mAbs, such as rituximab, natalizumab, and ocrelizumab, are expensive with variable effectiveness rates. Thus, the present study aimed to compare the direct medical cost and consequences (e.g., clinical relapse, disability progression, and new MRI lesions) between rituximab and natalizumab in managing relapsing-remitting multiple sclerosis (RRMS) in Saudi Arabia. Also, the study aimed to explore the cost and consequence of ocrelizumab in managing RRMS as a second-choice treatment.

Methods

The electronic medical records (EMRs) of patients with RRMS were retrospectively reviewed to retrieve the patients’ baseline characteristics and disease progression from two tertiary care centers in Riyadh, Saudi Arabia. Biologic–naïve patients treated with rituximab or natalizumab or those switched to ocrelizumab and treated for at least six months were included in the study. The effectiveness rate was defined as no evidence of disease activity (NEDA-3) (i.e., absence of new T2 or T1 gadolinium (Gd) lesions as demonstrated by the Magnetic Resonance Imaging (MRI), disability progression, and clinical relapses), while the direct medical costs were estimated based on the utilization of healthcare resources. In addition, bootstrapping with 10,000 replications and inverse probability weighting based on propensity score were conducted.

Results

Ninety–three patients met the inclusion criteria and were included in the analysis (natalizumab (n = 50), rituximab (n = 26), ocrelizumab (n = 17)). Most of the patients were otherwise healthy (81.72%), under 35 years of age (76.34%), females (61.29%), and on the same mAb for more than one year (83.87%). The mean effectiveness rates for natalizumab, rituximab, and ocrelizumab were 72.00%, 76.92%, and 58.83%, respectively. Natalizumab mean incremental cost compared to rituximab was $35,383 (95% CI: $25,401.09– $49,717.92), and its mean effectiveness rate was 4.92% lower than rituximab (95% CI: -30–27.5) with 59.41% confidence level that rituximab will be dominant.

Conclusions

Rituximab seems to be more effective and is less costly than natalizumab in the management of RRMS. Ocrelizumab does not seem to slow the rates of disease progression among patients previously treated with natalizumab.
Clients’ experiences on North America’s first take-home injectable opioid agonist treatment (iOAT) program: a qualitative study
Authors: Oviedo-Joekes Eugenia , Dobischok Sophia , Carvajal José , MacDonald Scott , McDermid Cheryl , Klakowicz Piotr , Harrison Scott , LaJeunesse Julie , Chow Nancy , Brown Murray , Gill Sam , Schechter Martin
Published: May 2023

Background

To support public health measures during the COVID-19 pandemic, oral opioid agonist treatment (OAT) take-home doses were expanded in Western countries with positive results. Injectable OAT (iOAT) take-home doses were previously not an eligible option, and were made available for the first time in several sites to align with public health measures. Building upon these temporary risk-mitigating guidelines, a clinic in Vancouver, BC continued to offer two of a possible three daily doses of take-home injectable medications to eligible clients. The present study explores the processes through which take-home iOAT doses impacted clients’ quality of life and continuity of care in real-life settings.

Methods

Three rounds of semi-structured qualitative interviews were conducted over a period of seventeen months beginning in July 2021 with eleven participants receiving iOAT take-home doses at a community clinic in Vancouver, British Columbia. Interviews followed a topic guide that evolved iteratively in response to emerging lines of inquiry. Interviews were recorded, transcribed, and then coded using NVivo 1.6 using an interpretive description approach.

Results

Participants reported that take-home doses granted them the freedom away from the clinic to have daily routines, form plans, and enjoy unstructured time. Participants appreciated the greater privacy, accessibility, and ability to engage in paid work. Furthermore, participants enjoyed greater autonomy to manage their medication and level of engagement with the clinic. These factors contributed to greater quality of life and continuity of care. Participants shared that their dose was too essential to divert and that they felt safe transporting and administering their medication off-site. In the future, all participants would like more accessible treatment such as access longer take-home prescriptions (e.g., one week), the ability to pick-up at different and convenient locations (e.g., community pharmacies), and a medication delivery service.

Conclusions

Reducing the number of daily onsite injections from two or three to only one revealed the diversity of rich and nuanced needs that added flexibility and accessibility in iOAT can meet. Actions such as licencing diverse opioid medications/formulations, medication pick-up at community pharmacies, and a community of practice that supports clinical decisions are necessary to increase take-home iOAT accessibility.
Ex vivo RSA and pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017
Authors: Yade Mamadou Samb , Dièye Baba , Coppée Romain , Mbaye Aminata , Diallo Mamadou Alpha , Diongue Khadim , Bailly Justine , Mama Atikatou , Fall Awa , Thiaw Alphonse Birane , Ndiaye Ibrahima Mbaye , Ndiaye Tolla , Gaye Amy , Tine Abdoulaye , Diédhiou Younouss , Mbaye Amadou Mactar , Doderer-Lang Cécile , Garba Mamane Nassirou , Bei Amy Kristine , Ménard Didier , Ndiaye Daouda
Published: May 2023

Background

Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapy (ACT), the current frontline malaria curative treatment. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in sub-Saharan Africa, where most malaria deaths occur.

Methods

Here, ex vivo susceptibility to dihydroartemisinin (DHA) was evaluated from 38 Plasmodium falciparum isolates collected in 2017 in Thiès (Senegal) expressed in the Ring-stage Survival Assay (RSA). Both major and minor variants were explored in the three conserved-encoding domains of the pfkelch13 gene, the main determinant of ART resistance using a targeted-amplicon deep sequencing (TADS) approach.

Results

All samples tested in the ex vivo RSA were found to be susceptible to DHA (parasite survival rate < 1%). The non-synonymous mutations K189T and K248R in pfkelch13 were observed each in one isolate, as major (99%) or minor (5%) variants, respectively.

Conclusion

The results suggest that ART is still fully effective in the Thiès region of Senegal in 2017. Investigations combining ex vivo RSA and TADS are a useful approach for monitoring ART resistance in Africa.
Efficacy of concurrent chemoradiotherapy with retrograde super selective intra-arterial infusion combined with cetuximab for synchronous multifocal oral squamous cell carcinomas
Authors: Chen Xuefei , Kioi Mitomu , Hayashi Yuichiro , Koizumi Toshiyuki , Koike Izumi , Yamanaka Shoji , Hata Masaharu , Mitsudo Kenji
Published: May 2023

Background

The incidence of multicentric oral cancer is increasing. However, treatment encounters difficulty if each tumor needs to be treated simultaneously. The objective of this clinical case report is to highlight the effect of concurrent chemoradiotherapy with retrograde superselective intra-arterial infusion combined with systemic administration of cetuximab on synchronous multifocal oral squamous cell carcinomas.

Case presentation

A 70-year-old man presented to the hospital with multiple tumors and oral pain. Three independent tumors were found in the right dorsal tongue, left edge of the tongue, and left lower lip. Based on the characteristic appearance of the lesions and further evaluation, clinical diagnoses of right tongue cancer “T3”, left tongue cancer “T2” and lower left lip cancer “T1”, N2cM0 were made. Treatment was initiated with systemic administration of cetuximab, followed by intra-arterial chemoradiotherapy. Treatment results were complete response on all three local lesions, and left neck dissection was performed following the initial treatment. The patient showed no evidence of recurrence during the 4 years follow-up period.

Conclusions

This novel combination treatment seems to be a promising strategy for patients with synchronous multifocal oral squamous cell carcinoma.
CPEB2 enhances cell growth and angiogenesis by upregulating ARPC5 mRNA stability in multiple myeloma
Authors: Zeng Piaorong , Wang Fujue , Long Xingxing , Cao Yixiong , Wen Feng , Li Junjun , Luo Zeyu
Published: May 2023

Background

The process of multiple myeloma (MM) is the result of the combined action of multiple genes. This study aims to explore the role and mechanism of cytoplasmic polyadenylation element binding protein2 (CPEB2) in MM progression.

Methods

The mRNA and protein expression levels of CPEB2 and actin-related protein 2/3 complex subunit 5 (ARPC5) were assessed by quantitative real-time PCR and western blot analysis. Cell function was determined by cell counting kit 8 assay, soft-agar colony formation assay, flow cytometry and tube formation assay. Fluorescent in situ hybridization assay was used to analyze the co-localization of CPEB2 and ARPC5 in MM cells. Actinomycin D treatment and cycloheximide chase assay were performed to assess the stability of ARPC5. The interaction between CPEB2 and ARPC5 was confirmed by RNA immunoprecipitation assay.

Results

CPEB2 and ARPC5 mRNA and protein expression levels were upregulated in CD138+ plasma cells from MM patients and cells. CPEB2 downregulation reduced MM cell proliferation, angiogenesis, and increased apoptosis, while its overexpression had an opposite effect. CPEB2 and ARPC5 were co-localized at cell cytoplasm and could positively regulate ARPC5 expression by mediating its mRNA stability. ARPC5 overexpression reversed the suppressive effect of CPEB2 knockdown on MM progression, and it knockdown also abolished CPEB2-promoted MM progression. Besides, CPEB2 silencing also reduced MM tumor growth by decreasing ARPC5 expression.

Conclusion

Our results indicated that CPEB2 increased ARPC5 expression through promoting its mRNA stability, thereby accelerating MM malignant process.
The Metreleptin Effectiveness and Safety Registry (MEASuRE): concept, design and challenges
Authors: Haymond Morey W , Araújo-Vilar David , Balser John , Lewis James H , Louzado Ruth , Musso Carla , von Schnurbein Julia , Wabitsch Martin ,   on behalf of the MEASuRE group
Published: May 2023

Background

Metreleptin, a recombinant analog of human leptin, is an approved therapy, adjunct to diet, to treat the metabolic complications of leptin deficiency in patients with lipodystrophy – a group of rare diseases characterized by a paucity of adipose tissue. MEASuRE (Metreleptin Effectiveness And Safety Registry) is a post-authorization, voluntary registry that gathers long-term safety and effectiveness data on metreleptin. Here, we present the aims and evolution of MEASuRE.

Methods

MEASuRE was established to collect data from patients receiving commercially supplied metreleptin in the United States (US) and European Union (EU). MEASuRE aims to determine the incidence and severity of safety events and describe the clinical characteristics and therapeutic outcomes in the metreleptin-treated population. A key feature of MEASuRE is that it accumulates data from different sources to meet post-authorization objectives. US data are received directly from treating physicians via a contract research organization-mediated electronic data capture system. In the EU, data are received via the European Registry of Lipodystrophies managed by the European Consortium of Lipodystrophies (ECLip), a platform established by researchers and physicians to advance the knowledge of lipodystrophy. MEASuRE complies with applicable regulatory requirements governing privacy, and the storage, management, and access of data.

Results

Leveraging processes, infrastructure, and data from the ECLip registry presented several challenges that were addressed during MEASuRE’s development, including the expansion of the ECLip registry to accommodate MEASuRE-specific data elements, extensive data matching processes to ensure data consistency regardless of source, and rigorous data validation following the amalgamation of global data. Through the support of ECLip, MEASuRE is now a fully operational registry with the capacity for gathering and integrating standardized US- and EU-derived data. As of 31st October 2022, 15 US and four EU sites have participated in the MEASuRE, enrolling 85 patients globally.

Conclusions

Our experiences show that a post-authorization product registry can be successfully integrated into an existing patient registry. We propose that, through collaboration with existing registries and use of their established resources, patient enrolment timelines and data collection for new registries can be expedited. The learnings presented here may be applicable to other registries with similar objectives.

Trial registration

NCT02325674; Registered 25 December 2014 - Retrospectively registered’. https://clinicaltrials.gov/ct2/show/NCT02325674.
LEP promoter methylation in the initiation and progression of clonal cytopenia of undetermined significance and myelodysplastic syndrome
Authors: Kaastrup Katja , Gillberg Linn , Mikkelsen Stine U. , Ørskov Andreas D. , Schöllkopf Claudia , Mortensen Bo K. , Porse Bo , Hansen Jakob W. , Grønbæk Kirsten
Published: May 2023

Background

Idiopathic non-clonal cytopenia (ICUS) and clonal cytopenia (CCUS) are common in the elderly population. While these entities have similar clinical presentations with peripheral blood cytopenia and less than 10% bone marrow dysplasia, their malignant potential is different and the biological relationship between these disorders and myeloid neoplasms such as myelodysplastic syndrome (MDS) is not fully understood. Aberrant DNA methylation has previously been described to play a vital role in MDS and acute myeloid leukemia (AML) pathogenesis. In addition, obesity confers a poorer prognosis in MDS with inferior overall survival and a higher rate of AML transformation. In this study, we measured DNA methylation of the promoter for the obesity-regulated gene LEP, encoding leptin, in hematopoietic cells from ICUS, CCUS and MDS patients and healthy controls. We investigated whether LEP promoter methylation is an early event in the development of myeloid neoplasms and whether it is associated with clinical outcome.

Results

We found that blood cells of patients with ICUS, CCUS and MDS all have a significantly hypermethylated LEP promoter compared to healthy controls and that LEP hypermethylation is associated with anemia, increased bone marrow blast percentage, and lower plasma leptin levels. MDS patients with a high LEP promoter methylation have a higher risk of progression, shorter progression-free survival, and inferior overall survival. Furthermore, LEP promoter methylation was an independent risk factor for the progression of MDS in a multivariate Cox regression analysis.

Conclusion

In conclusion, hypermethylation of the LEP promoter is an early and frequent event in myeloid neoplasms and is associated with a worse prognosis.
Side population cells derived from hUCMSCs and hPMSCs could inhibit the malignant behaviors of Tn+ colorectal cancer cells from modifying their O-glycosylation status
Authors: Hu Wen , Ding Ruisong , Wang Mengyang , Huang Panpan , Wei Xia , Hu Xingyou , Hu Tao
Published: May 2023

Background

Cosmc (C1GalT1C1) mutation could cause aberrant O-glycosylation and result in expression of Tn antigen on the surface of tumor cells (Tn+ cells), which is associated with the metastasis and prognosis of cancer progression. Mesenchymal stem cells (MSCs) could participate in immunoregulation, tissue damage repair, and tumor inhibition and be seen as an ideal candidate for tumor therapy due to their inherent capacity to migrate to tumor sites. However, their therapeutic effectiveness in different tumors is inconsistent and still controversial. Of note, emerging data reveal that side population (SP) cells have a stronger multilineage developmental potential than main population cells and can function as stem/progenitor cells. The effect of SP cells derived from MSCs on the biological behaviors and the O-glycosylation status of tumor cells remains unclear.

Methods

SP cells were isolated from human umbilical cord MSCs (hUCMSCs) and human placenta MSCs (hPMSCs). Tn+ cells (LS174T-Tn+ and HT-29-Tn+ cells) and matching Tn− cells (LS174T-Tn− and HT-29-Tn− cells) were isolated from human colorectal cancer cell (CRC) lines LS174T and HT-29 by immune magnetic beads. The proliferation, migration, apoptosis, Tn antigen expression, and O-glycome in Tn+ and Tn− CRC cells before and after co-cultured with SP-MSCs were detected using real-time cell Analysis (RTCA), flow cytometry (FCM), and cellular O-glycome reporter/amplification (CORA), respectively. Cosmc protein and O-glycosyltransferase (T-synthase and C3GnT) activity in CRC cells were, respectively, assessed using western blotting and fluorescence method.

Results

Both SP cells derived from hUCMSCs and hPMSCs could inhibit proliferation and migration, promote apoptosis of CRC cells, significantly reduce Tn antigen expression on Tn+ CRC cells, generate new core 1-, 2-, and 3-derived O-glycans, increase T-synthase and C3GnT activity, and elevate the levels of Cosmc and T-synthase protein.

Conclusion

SP-hUCMSCs and SP-hPMSCs could inhibit proliferation and migration and promote apoptosis of Tn+ CRC cells via increasing O-glycosyltransferase activity to modify O-glycosylation status, which further adds a new dimension to the treatment of CRC.
The feasibility of negative pressure wound therapy versus standard dressings in paediatric hand and foot burns protocol: a pilot, single-centre, randomised control trial
Authors: Lumsden Emma , Kimble Roy , McMillan Catherine , Storey Kristen , Ware Robert S. , Griffin Bronwyn
Published: May 2023

Introduction

The goal of paediatric hand and foot burn management is hypertrophic scar and/or contracture prevention. The risk of scar formation may be minimised by integrating negative pressure wound therapy (NPWT) as an acute care adjunct as it decreases the time to re-epithelialisation. NPWT has known associated therapeutic burden; however, this burden is hypothesised to be outweighed by an increased likelihood of hypertrophic scar prevention. This study will assess the feasibility, acceptability and safety of NPWT in paediatric hand and foot burns with secondary outcomes of time to re-epithelialisation, pain, itch, cost and scar formation.

Methods and analysis

This is a single-site, pilot randomised control trial. Participants must be aged ≤ 16 years, otherwise well and managed within 24 h of sustaining either a hand or foot burn. Thirty participants will be randomised to either standard care (Mepitel®—a silicone wound interface contact dressing—and ACTICOAT™—a nanocrystalline silver-impregnated dressing) or standard care plus NPWT. Patients will be reviewed until 3 months post-burn wound re-epithelialisation, with measurements taken at dressing changes to assess primary and secondary outcomes. Surveys, randomisation and data storage will be done via online platforms and physical data storage collated at the Centre for Children’s Health Research, Brisbane, Australia. Analysis will be performed using the Stata statistical software.

Ethics and dissemination

Queensland Health and Griffith University Human Research ethics approval including a site-specific assessment was obtained. The findings of this study will be disseminated through clinical meetings, conference presentations and peer reviewed journals.

Trial registration

Registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12622000044729, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381890&isReview=true, registered 17/01/2022).
Anesthetic management for withdrawal from a right ventricular assist device and Fontan procedure in a patient with an implantable left ventricular assist device for fulminant cardiomyopathy
Authors: Kida Naka , Morinaga Masahiro , Tadokoro Naoki , Maeda Takuma , Onishi Yoshihiko
Published: May 2023

Background

We herein report the anesthetic management for extracardiac conduit–total cavopulmonary connection (EC-TCPC) for weaning from an extracorporeal right ventricular assist device (RVAD) in a patient with an implantable left ventricular assist device (LVAD) for fulminant cardiomyopathy.

Case presentation

A 24-year-old man developed fulminant cardiomyopathy and was placed on a biventricular assist device (BiVAD) comprising an implantable LVAD and an extracorporeal RVAD. The Fontan procedure was performed to wean the patient from the RVAD and allow him to be discharged home. Atrial septal defect creation, right ventricular suture, and tricuspid valve closure were then simultaneously performed to ensure sufficient left ventricular preload to drive the LVAD. Furthermore, to keep the central venous pressure lower, the inflow cannula of the LVAD was oriented in the correct direction.

Conclusion

This is the first report of anesthetic management of the Fontan procedure in a patient with a BiVAD.