bluuebunny/crossref_metadata_2025 huggingface dataset:
The transition from diet to blood: Exploring homeostasis in the insect haemolymph nutrient pool
Authors: Holdbrook Robert , Andongma Awawing A. , Randall Joanna L. , Reavey Catherine E. , Tummala Yamini , Wright Geraldine A. , Simpson Stephen J. , Smith Judith A. , Wilson Kenneth , Cotter Sheena C.
Published: April 2024

Nutrition is vital to health, but while the link between diet and body nutritional composition is well explored in humans and other vertebrates, this information is not well understood in insects, despite the vital roles they play in ecosystems, and their increasing use as experimental models. Here we used Nutritional Geometry to explore the rapid physiological response to ingested nutrients in the haemolymph nutritional profile of Spodoptera littoralis caterpillars. We ask whether blood nutrients are maintained homeostatically in the face of variable nutritional intake, or if regulation is more flexible for some nutrients than others (allostasis), which allows animals to adapt to stress by responding in a way that prioritises efficiency of responses in the face of trade‐offs. Caterpillars were placed on 1 of 20 diets, systematically varying in their nutrient ratios (protein: carbohydrate) and density (calorie content), and their consumption was measured. After 48 h, caterpillars were bled, and the macronutrient (protein, carbohydrates and lipids) and nutrient metabolite (amino acids and simple sugars) content of the haemolymph was measured. Proteins comprised 93% of the haemolymph macronutrient pool on average and their concentration increased with protein eaten. The amino acid (AA) pool was dominated by five AAs, and the total pool increased with total nutrient intake. However, the ratio of essential to non‐essential AAs increased as the proportion of protein consumed increased. Carbohydrates were tightly controlled, increasing only on the most extreme carbohydrate intakes. Simple sugars were dominated by glucose and trehalose, and overall, the simple sugar pool showed high levels of homeostasis. Rather than strict homeostasis of blood nutritional properties, an allostatic model seemed to be a better fit for blood nutrient regulation in this generalist herbivore. This flexibility in response to the nutritional composition of the diet may, in part, explain how this species has evolved to extreme dietary generalism and may play a role in its worldwide pest status. Given the range of fitness‐related processes affected by the haemolymph, future studies should examine the physiological impacts of blood nutrient variation on reproduction, growth and response to infection and the trade‐offs between them.
A survey of the use of ultrasound by small animal veterinary clinicians
Authors: Zelachowski Kendra A. , Rishniw Mark , DeFrancesco Teresa C.
Published: April 2024

This study aimed to determine the current use of ultrasound amongst small animal veterinarians. A total of 1216 small animal veterinary practitioners responded to an electronic survey that was administered through the Veterinary Information Network to all its members. Descriptive statistics were generated; limited inferential statistics were performed to examine specific relationships. Eighty‐four percent of respondents had access to an ultrasound unit, and 86% of respondents reported using their unit multiple times per week. The most common uses were assistance with cystocentesis (93%) and abdominocentesis (71%), pregnancy diagnosis (69%), limited abdominal evaluation (63%), to aid in thoracocentesis (59%), and limited thoracic evaluation (52%). Eighty‐nine percent of respondents received some formal training in ultrasound, most commonly from continuing education courses. Most respondents (52%) reported receiving ≤25 h of training. Additionally, 88% of respondents believed it was either extremely or very important for there to be ultrasound training for veterinary students prior to graduation. Based on this survey, most small animal practitioners commonly use ultrasound for limited examinations, being most confident in the sonographic evaluation and centesis of the bladder and for the detection and centesis of effusion in a body cavity. With most respondents having ≤25 h of training in ultrasound, typically obtained in postgraduate courses, an expansion in standardized basic ultrasound training within the veterinary curriculum may be warranted.
La comunidad municipalizada en el estado de Tlaxcala: reflexiones sobre el alcance del comunalismo en la democracia local
Authors: Chávez Reyes Miriam Zarahí , Pérez Sergio Alejandro
Published: April 2024

El objetivo de este artículo es analizar la forma en que se relaciona actualmente el orden social comunitario microlocal del estado de Tlaxcala con su orden político municipal y de reconocimiento de derechos indígenas. Existe un complejo comunitario en este estado de la República mexicana que no está visibilizado debido a la ausencia de un movimiento indígena que lo haya reivindicado, el cual está parcialmente cristalizado en las figuras políticas submunicipales denominadas presidencias de comunidad, cuyas facultades se encuentran definidas en la ley orgánica municipal estatal, entre las que destaca actuar con voz y voto en las sesiones de cabildo. De esta manera, la estructura del ayuntamiento tlaxcalteca de nuestros días incluye regidores de mayoría relativa, de representación proporcional y de pueblo o comunidad. El trabajo reconoce las posibilidades y debilidades de las presidencias de comunidad, que se pueden caracterizar como la vía tlaxcalteca para el reconocimiento de las estructuras comunitarias que existen en dicho estado. La metodología empleada fue de corte cualitativo, y consistió en la revisión crítica y en el análisis de fuentes teóricas, institucionales, histórico-contextuales y de experiencias locales.
Implant Strength Contributes to the Osseointegration Strength of Porous Metallic Materials
Authors: Mathey Elizabeth , Pelletier Matthew H. , Walsh William R. , Gall Ken , Carpenter Dana
Published: April 2024

Creating the optimal environment for effective and long term osseointegration is a heavily researched and sought-after design criteria for orthopedic implants. A validated multimaterial finite element (FE) model was developed to replicate and understand the results of an experimental in vivo push-out osseointegration model. The FE model results closely predicted global force (at 0.5 mm) and stiffness for the 50–90% porous implants with an r2 of 0.97 and 0.98, respectively. In addition, the FE global force at 0.5 mm showed a correlation to the maximum experimental forces with an r2 of 0.90. The highest porosity implants (80–90%) showed lower stiffnesses and more equitable load sharing but also failed at lower a global force level than the low porosity implants (50–70%). The lower strength of the high porosity implants caused premature plastic deformation of the implant itself during loading as well as significant deformations in the ingrown and surrounding bone, resulting in lower overall osseointegration strength, consistent with experimental measurements. The lower porosity implants showed a balance of sufficient bony ingrowth to support osseointegration strength coupled with implant mechanical properties to circumvent significant implant plasticity and collapse under the loading conditions. Together, the experimental and finite element modeling results support an optimal porosity in the range of 60–70% for maximizing osseointegration with current structure and loading.
Exploring the Influence of Facet Orientation and Tropism on Neutral Zone Properties
Authors: Trevorrow Rory M. , Zehr Jackie D. , Barrett Jeff M. , Callaghan Jack P. , Fewster Kayla M.
Published: April 2024

Lumbar spine pathologies have been linked independently to both neutral zone (NZ) properties and facet joint anatomical characteristics; however, the effect of facet joint orientation (FO) and tropism (FT) on NZ properties remains unclear. The aim of the present study was to investigate how axial plane FO and FT relate to NZ range and stiffness in the human lumbar spine and porcine cervical spine. Seven human lumbar functional spine units (FSUs) and 94 porcine cervical FSUs were examined. FO and FT were measured, and in vitro mechanical testing was used to determine anterior-posterior (AP) and flexion–extension (FE) NZ range and stiffness. FO and FT were found to have no significant relationship with AP and FE NZ range. Increases in FT were associated with greater FE and AP NZ stiffness in human FSUs, with no FT-NZ stiffness relationship observed in porcine specimens. A significant relationship (p < 0.001) between FO and FE NZ stiffness was observed for both porcine and human FSUs, with a more sagittal orientation of the facet joints being associated with decreased FE NZ stiffness. Given the link between NZ stiffness and pathological states of the lumbar spine, further research is warranted to determine the practical significance of the observed facet joint anatomical characteristic-NZ property relationship.
Dual and opposing roles for the kinesin-2 motor, KIF17, in Hedgehog-dependent cerebellar development
Authors: Waas Bridget , Carpenter Brandon S. , Franks Nicole E. , Merchant Olivia Q. , Verhey Kristen J. , Allen Benjamin L.
Published: April 2024

While the kinesin-2 motors KIF3A and KIF3B have essential roles in ciliogenesis and Hedgehog (HH) signal transduction, potential role(s) for another kinesin-2 motor, KIF17, in HH signaling have yet to be explored. Here, we investigated the contribution of KIF17 to HH-dependent cerebellar development, where
Kif17
is expressed in both HH-producing Purkinje cells and HH-responding cerebellar granule neuron progenitors (CGNPs). Germline
Kif17
deletion in mice results in cerebellar hypoplasia due to reduced CGNP proliferation, a consequence of decreased HH pathway activity mediated through decreased Sonic HH (SHH) protein. Notably, Purkinje cell–specific
Kif17
deletion partially phenocopies
Kif17
germline mutants. Unexpectedly, CGNP-specific
Kif17
deletion results in the opposite phenotype—increased CGNP proliferation and HH target gene expression due to altered GLI transcription factor processing. Together, these data identify KIF17 as a key regulator of HH-dependent cerebellar development, with dual and opposing roles in HH-producing Purkinje cells and HH-responding CGNPs.
Vagus nerve stimulation modulates distinct acetylcholine receptors on B cells and limits the germinal center response
Authors: Kurata-Sato Izumi , Mughrabi Ibrahim T. , Rana Minakshi , Gerber Michael , Al-Abed Yousef , Sherry Barbara , Zanos Stavros , Diamond Betty
Published: April 2024

Acetylcholine is produced in the spleen in response to vagus nerve activation; however, the effects on antibody production have been largely unexplored. Here, we use a chronic vagus nerve stimulation (VNS) mouse model to study the effect of VNS on T-dependent B cell responses. We observed lower titers of high-affinity IgG and fewer antigen-specific germinal center (GC) B cells. GC B cells from chronic VNS mice exhibited altered mRNA and protein expression suggesting increased apoptosis and impaired plasma cell differentiation. Follicular dendritic cell (FDC) cluster dispersal and altered gene expression suggested poor function. The absence of acetylcholine-producing CD4
+
T cells diminished these alterations. In vitro studies revealed that α7 and α9 nicotinic acetylcholine receptors (nAChRs) directly regulated B cell production of TNF, a cytokine crucial to FDC clustering. α4 nAChR inhibited coligation of CD19 to the B cell receptor, presumably decreasing B cell survival. Thus, VNS-induced GC impairment can be attributed to distinct effects of nAChRs on B cells.
New avenues for potentially seeking microbial responses to climate change beneath Antarctic ice shelves
Authors: Llorenç-Vicedo Aitana , Lluesma Gomez Monica , Zeising Ole , Kleiner Thomas , Freitag Johannes , Martinez-Hernandez Francisco , Wilhelms Frank , Martinez-Garcia Manuel
Published: April 2024

The signs of climate change are undeniable, and the impact of these changes on ecosystem function heavily depends on the response of microbes that underpin the food web. Antarctic ice shelf is a massive mass of floating ice that extends from the continent into the ocean, exerting a profound influence on global carbon cycles. Beneath Antarctic ice shelves, marine ice stores valuable genetic information, where marine microbial communities before the industrial revolution are archived. Here, in this proof-of-concept, by employing a combination of single-cell technologiesand metagenomics, we have been able to sequence frozen microbial DNA (≈300 years old) stored in the marine ice core B15 collected from the Filchnner-Ronne Ice Shelf. Metagenomic data indicated that
Proteobacteria
and
Thaumarchaeota
(e.g.,
Nitrosopumilus
spp.), followed by
Actinobacteria
(e.g., Actinomarinales), were abundant. Remarkably, our data allow us to “travel to the past” and calibrate genomic and genetic evolutionary changes for ecologically relevant microbes and functions, such as
Nitrosopumilus
spp., preserved in the marine ice (≈300 years old) with those collected recently in seawater under an ice shelf (year 2017). The evolutionary divergence for the ammonia monooxygenase gene
amoA
involved in chemolithoautotrophy was about 0.88 amino acid and 2.8 nucleotide substitution rate per 100 sites in a century, while the accumulated rate of genomic SNPs was 2,467 per 1 Mb of genome and 100 years. Whether these evolutionary changes remained constant over the last 300 years or accelerated during post-industrial periods remains an open question that will be further elucidated.

IMPORTANCE

Several efforts have been undertaken to predict the response of microbes under climate change, mainly based on short-term microcosm experiments under forced conditions. A common concern is that manipulative experiments cannot properly simulate the response of microbes to climate change, which is a long-term evolutionary process. In this proof-of-concept study with a limited sample size, we demonstrate a novel approach yet to be fully explored in science for accessing genetic information from putative past marine microbes preserved under Antarctic ice shelves before the industrial revolution. This potentially allows us estimating evolutionary changes as exemplified in our study. We advocate for gathering a more comprehensive Antarctic marine ice core data sets across various periods and sites. Such a data set would enable the establishment of a robust baseline, facilitating a better assessment of the potential effects of climate change on key genetic signatures of microbes.
The impact of hypertension on clinical manifestations of Omicron variant BA.1 infection in adult patients
Authors: Wang Jingyu , Dong Henan , Zhao Jie , Zhou Chunlei , Wang Meng , Cui Yuechuan , Gao Guangfeng , Ji Xiaodong , Mu Hong , Peng Lin
Published: April 2024

COVID-19 caused by Omicron BA.1 has resulted in a global humanitarian crisis. In this COVID-19 pandemic era, hypertension has been receiving increased attention. Omicron BA.1 infection combined with hypertension created a serious public health problem and complicated the treatment and prognosis of COVID-19. The aim of our study was to assess the implications of hypertension for the clinical manifestations of adult patients (APs) infected with Omicron BA.1. This single-center retrospective cohort study enrolled consecutive COVID-19 APs, who were admitted to Tianjin First Central Hospital from 01 August 2022 to 30 November 2022. All included APs were divided into two groups: hypertension and non-hypertension group. The APs’ baseline demographic, laboratory, clinical, and radiological characteristics were collected and analyzed. Of 512 APs admitted with PCR proven COVID-19, 161 (31.45%) APs had comorbid hypertension. Hypertension APs have older age, higher body mass index, lower Ct-values of the viral target genes at admission, and longer hospital stay than non-hypertension APs. Furthermore, hypertension aggravates the clinical classification, impairs liver, kidney, and myocardium function, and abnormalizes the coagulation system in Omicron BA.1- infected APs. Moreover, hypertension elevates inflammation levels and lung lesion involvement while weakened virus-specific IgM level in APs with Omicron BA.1 infection. Hypertension APs tend to have worse clinical conditions at baseline than those non-hypertension APs. This study indicates that hypertension is a contributor to the poor clinical manifestations of Omicron BA.1-infected APs and supports that steps to control blood pressure should be a vital consideration for reducing the burden of Omicron BA.1 infection in hypertension individuals.

IMPORTANCE

This study provided inclusive insight regarding the relationship between hypertension and Omicron BA.1 infection and supported that hypertension was an adverse factor for COVID-19 APs. In conclusion, this study showed that hypertension was considered to be associated with severe conditions, and a contributor to poor clinical manifestations. Proper medical management of hypertension patients is an imperative step in mitigating the severity of Omicron BA.1 variant infection.
Regional Sources and CH4 Seasonal Cycle in Central Siberia and the Arctic: Observations and Numerical Calculations
Authors: Moiseenko K. B. , Shtabkin Yu. A. , Vasileva A. V. , Skorokhod A. I. , Fedorova E. I.
Published: April 2024

Contributions of anthropogenic and wetland methane emissions in Northern Eurasia (>40° N) and Russia into the near-surface CH4 abundance are quantified using GEOS-chem global chemical transport model at ZOTTO, Teriberka, and Tiksi measurement sites. Numerical results agree well with the proposed semianalytical solution, in which the total contribution (atmospheric response) in the CH4 level at a given site is decomposed into direct (synoptic) and global terms. On an advection timescale corresponding to a synoptic time interval, the annual average direct contribution of Russian anthropogenic emissions into the CH4 mixing ratio measured at ZOTTO (38.6 ppbv) is more than twice as large as that for Western Europe sources (17.7 ppbv). For the Arctic sites, the anthropogenic inputs from Russian and European sources are roughly similar (19.5 and 12.4 ppbv, respectively). The input from continental sources into near-surface methane abundance and its annual variations at the Arctic sites are generally lower compared to those at the ZOTTO site due to larger transport times from upstream CH4 source regions. Model-based atmospheric responses in methane levels at the Teriberka and Tiksi sites to continental CH4 sources are found to be very close owing to the relatively homogeneous (circumpolar) spatial distributions of the anthropogenic and biogenic signals at high latitudes.
Radiographical bony lesions after discontinuation of immunosuppressant therapy: bone involvement in sarcoidosis
Authors: Pullins Christopher , Varghese Cyril , Koneru Sethu Sandeep , Bracamonte Jesse D
Published: April 2024

We describe a patient who had failed renal transplant after 13 years, eventually requiring a graft nephrectomy and discontinuation of immunosuppressive therapy, including antithymocyte globulin, tacrolimus and mycophenolate while on steroid avoidance protocol. Within a few months of complete discontinuation of the immunosuppressive medications, she developed lower back pain associated with numbness in her right anterolateral thigh. The radiological imaging demonstrated multiple bony lesions throughout her axial and appendicular skeleton with normal pulmonary findings. A computerised tomography-guided bone biopsy from the left iliac crest revealed fragments of bone with granulomatous inflammation, thus making the diagnosis of extrapulmonary sarcoidosis. Initiating treatment with prednisone resulted in near-complete resolution of symptoms. Long-term immunosuppressive therapy is administered to all renal transplant recipients to help prevent acute rejection and loss of renal allograft. This case highlights that immunosuppressants can conceal the presence of underlying conditions in transplant patients.
Delayed targeted atelectasis in a case of bronchoscopic lung volume reduction with endobronchial valves
Authors: Chandra Nikitha C , Fernandez-Bussy Isabel , Walsh Katherine L , Abia-Trujillo David
Published: April 2024

A woman in her late 60s with severe chronic obstructive pulmonary disease (COPD) and emphysema underwent bronchoscopic lung volume reduction (BLVR) with endobronchial valves (EBV) to address hyperinflation. The initial EBV placement has led to partial lobar atelectasis of the left lower lobe and resulted in significant improvement in the patient’s symptoms and lung function. However, valve migration occurred later due to pneumothorax unrelated to valves, leading to suboptimal clinical improvement. The patient achieved delayed full lobar atelectasis 21 months after EBV placement, which led to a significant clinical improvement. The patient decided to be delisted from the lung transplant list due to the improvement. This case highlights the importance of considering delayed atelectasis as a possible outcome of EBV placement and suggests the need for further exploration of the long-term implications and associations of this procedure.
Clinical, electrophysiologic and serologic evidence of cancer associated retinopathy preceding a diagnosis of breast cancer
Authors: Ball Jordan E , Smith Brian M , Zocchi Kent , Doyle Jennifer
Published: April 2024

We report the case of a woman in her 50s who presented headaches, blurred vision, diplopia and loss of peripheral vision. She was treated for normal tension glaucoma based on optic nerve cupping prior to the development of diplopia. Records demonstrated visual field constriction over 4 months despite well-controlled intraocular pressures. Examination revealed decreased visual acuity and visual field constriction. The multifocal electroretinogram was abnormal. After a thorough review of her medical and family history, a concern for cancer-associated retinopathy developed. Blood samples were positive for antiretinal antibodies against 23 kDA and 46 kDA proteins. Cancer screening was recommended as the aetiology for retinopathy was unknown and revealed a left breast lump. Following lumpectomy with adjuvant chemoradiation, her visual acuity normalised and visual field defects completely resolved. This case serves to provide an example that distant systemic symptoms may be a manifestation of the underlying malignancy and the importance of clinical suspicion with prompt evaluation.
Randomised multicentre effectiveness trial of rapid syndromic testing by panel assay in children presenting to European emergency departments with acute respiratory infections—trial protocol for the ADEQUATE Paediatric trial
Authors:   ADEQUATE Paediatric Trial Group
Published: April 2024

Introduction

Syndromic panel assays, that is, using one test to simultaneously target multiple pathogens with overlapping signs and symptoms, have been integrated into routine paediatric care over the past decade, mainly for more severely ill and hospitalised patients. Their wider availability and short turnaround times open the possibility to apply them to non-hospitalised patients as well. In this context, it is important to trial how clinicians make use of pathogen detection data and if their early availability influences management decisions, particularly antibiotic use and hospitalisation.

Methods and analysis

Advanced Diagnostics for Enhanced QUality of Antibiotic prescription in respiratory Tract infections in Emergency rooms is an individually randomised, controlled, open-label effectiveness trial comparing the impact of a respiratory pathogen panel assay (BIOFIRE Respiratory Panel 2.1plus) used as a rapid syndromic test on nasopharyngeal swabs in addition to the standard of care versus standard of care alone. The trial will 1:1 randomise 520 participants under the age of 18 at 7 paediatric emergency departments in 5 European countries. Inclusion criteria for the trial consist of two sets, with the first describing respiratory tract infections in paediatric patients and the second describing the situation of potential management uncertainty in which test results may immediately affect management decisions. Enrolment started in July 2021 and is expected to be completed in early 2024. We will perform a two-sample t-test assuming a pooled variance estimate to compare the log-transformed mean time on antibiotic treatment (in hours) and number of days alive out of the hospital within 14 days after study enrolment between the control and intervention arms.

Ethics and dissemination

The trial protocol and materials were approved by research ethics committees in all participating countries. The respiratory pathogen panel assay is CE marked (assessed to meet European regulations) and FDA (United States Food and Drug Administration) cleared for diagnostic use. Participants and caregivers provide informed consent prior to study procedures commencing. The trial results will be published in peer-reviewed journals and at national and international conferences. Key messages will also be disseminated via press and social media where appropriate.

Trial registration number

NCT04781530.
HIV pre-exposure prophylaxis uptake, retention and adherence among female sex workers in sub-Saharan Africa: a systematic review
Authors: Mpirirwe Ruth , Segawa Ivan , Ojiambo Kevin Ouma , Kamacooko Onesmus , Nangendo Joanita , Semitala Fred C , Kyambadde Peter , Kalyango Joan N , Kiragga Agnes , Karamagi Charles , Katahoire Anne , Kamya Moses , Mujugira Andrew
Published: April 2024

Objective

To evaluate oral pre-exposure prophylaxis (PrEP) uptake, retention and adherence among female sex workers (FSWs) receiving care through community and facility delivery models in sub-Saharan Africa (SSA).

Design

Systematic review and meta-analysis.

Data sources

We searched online databases (PubMed, MEDLINE, SCOPUS, EMBASE, Google Scholar, Cochrane Database of Systematic Reviews and Web of Science) between January 2012 and 3 April 2022.

Eligibility criteria for studies

Randomised controlled trials, cohort studies, cross-sectional studies and quasi-experimental studies with PrEP uptake, adherence and retention outcomes among FSWs in SSA.

Data extraction and synthesis

Seven coders extracted data. The framework of the Cochrane Consumers and Communication Review Group guided data synthesis. The Risk of Bias In Non-Randomized Studies of Interventions tool was used to evaluate the risk of bias. Meta-analysis was conducted using a random-effects model. A narrative synthesis was performed to analyse the primary outcomes of PrEP uptake, adherence and retention.

Results

Of 8538 records evaluated, 23 studies with 40 669 FSWs were included in this analysis. The pooled proportion of FSWs initiating PrEP was 70% (95% CI: 56% to 85%) in studies that reported on facility-based models and 49% (95% CI: 10% to 87%) in community-based models. At 6 months, the pooled proportion of FSWs retained was 66% (95% CI: 15% to 100%) for facility-based models and 83% (95% CI: 75% to 91%) for community-based models. Factors associated with increased PrEP uptake were visiting a sex worker programme (adjusted OR (aOR) 2.92; 95% CI: 1.91 to 4.46), having ≥10 clients per day (aOR 1.71; 95% CI: 1.06 to 2.76) and lack of access to free healthcare in government-run health clinics (relative risk: 1.16; 95% CI: 1.06 to 1.26).

Conclusions

A hybrid approach incorporating both facility-based strategies for increasing uptake and community-based strategies for improving retention and adherence may effectively improve PrEP coverage among FSWs.

PROSPERO registration number

CRD42020219363.
Access to innovative anticancer medicines in China: a national survey on availability, price and affordability
Authors: Li Wei , Lu Wei , Chen Hongdou , Zhang Chi , Wang Menglei , Zheng Fangfang , Wu Huan-Huan , Wan Guang-Wen , Yang Qingqing , Ye Lu
Published: April 2024

Objectives

This study aimed to investigate the availability, price, and affordability of nationally negotiated innovative anticancer medicines in China.

Design

Retrospective observational study based on data from a nationwide medical database.

Data sources/setting

Quarterly data about the use of innovative anticancer medicines from 2020 to 2022 were collected from the Chinese Medicine Economic Information Network. This study covered 895 public general hospitals in 30 provincial administrative regions in China. Of the total hospitals, 299 (33.41%) were secondary and 596 (66.59%) were tertiary.

Main outcome measures

The adjusted WHO and Health Action International methodology was used to calculate the availability and affordability of 33 nationally negotiated innovative anticancer medicines in the investigated hospitals. Price is expressed as the defined daily dose cost.

Results

On average, the total availability of 33 innovative anticancer medicines increased annually from 2020 to 2022. The median availability of all investigated medicines in tertiary hospitals from 2020 to 2022 was 24.04%, 33.60% and 37.61%, respectively, while the indicators in secondary hospitals were 4.90%, 12.54% and 16.48%, respectively. The adjusted prices of the medicines newly put in Medicare (in March 2021) decreased noticeably, with the decline rate ranging from 39.98% to 82.45% in 2021 compared with those in 2020. Most generic brands were priced much lower than the originator brands. The affordability of anticancer medicines has improved year by year from 2020 to 2022. In comparison, rural residents had lower affordability than urban residents.

Conclusions

The overall accessibility of 33 nationally negotiated innovative anticancer medicines improved from 2020 to 2022. However, the overall availability of most anticancer medicines in China remained at a low level (less than 50%). Further efforts should be made to sufficiently and equally benefit patients with cancer.
Child acute illness presentation and referrals at primary health clinics in Malawi: a secondary analysis of ASPIRE
Authors: Iroh Tam Pui-Ying , Twabi Hussein H , Gondwe Mtisunge , O'Byrne Thomasena , Lufesi Norman , Desmond Nicola
Published: April 2024

Objectives

We aimed to assess the prevalence, presentation and referral patterns of children with acute illness attending primary health centres (PHCs) in a low-resource setting.

Design, setting and participants

We conducted a secondary analysis of ASPIRE. Children presenting at eight PHCs in urban Blantyre district in southern Malawi with both recorded clinician and mHealth (non-clinician) triage data were included, and patient records from different data collection points along the patient healthcare seeking pathway were consolidated and analysed.

Results

Between April 2017 and September 2018, a total of 204 924 children were triaged, of whom 155 931 had both recorded clinician and mHealth triage data. The most common presenting symptoms at PHCs were fever (0.3%), cough (0.2%) and difficulty breathing (0.2%). The most common signs associated with referral for under-5 children were trauma (26.7%) and temperature (7.4%). The proportion of emergency and priority clinician triage were highest among young infants <2 months (0.2% and 81.4%, respectively). Of the 3004 referrals (1.9%), 1644 successfully reached the referral facility (54.7%). Additionally, 372 children were sent home from PHC who subsequently self-referred to the referral facility (18.7%).

Conclusions

Fever and respiratory symptoms were the most common presenting symptoms, and trauma was the most common reason for referral. Rates of referral were low, and of successful referral were moderate. Self-referrals constituted a substantial proportion of attendance at the referral facility. Reducing gaps in care and addressing dropouts as well as self-referrals along the referral pathway could improve child health outcomes.
Evaluating low and high vitamin D levels in Ecuadorian cities from 2018 to 2022: interrupted time series and a cross-sectional study
Authors: Zurita-Salinas Camilo , Tello Betzabé , Dueñas-Espín Iván , Zurita Jeannete , Acosta William , León Cristina Aguilera , Andrade-Muñoz Andrés , Pareja-Maldonado José
Published: April 2024

Objectives

To identify differences in the mean vitamin D concentrations in samples obtained from a private laboratory in Quito and to explore their relationship with the pre-pandemic and pandemic periods spanning from 2018 to 2022.

Design

A combination of an interrupted time series design and a retrospective cross-sectional approach.

Setting and participants

The study involved 9285 participants who had their 25-hydroxyvitamin D (25(OH)D) levels tested at a well-known private laboratory in Quito, Ecuador, from 2018 to 2022.

Primary and secondary outcome measures

The 25(OH)D levels were analysed and assessed for correlations with age, and the year the measurements were taken.

Results

The mean 25(OH)D level was 27.53 ng/mL (± 14.11). Approximately 68.8% of participants had serum 25(OH)D levels of less than 30 ng/mL, and 0.6% showed potential harm from excess 25(OH)D, with levels over 100 ng/mL. The analysis indicated a significant monthly increase of 0.133 units in 25(OH)D levels (p=0.006). However, the period after March 2020, compared with before, saw a non-significant decrease of 1.605 units in mean 25(OH)D levels (p=0.477).

Conclusions

The study’s findings indicate a significant prevalence of 25(OH)D deficiency, underscoring the necessity for preventative measures. However, the increasing trend in high 25(OH)D levels is concerning, emphasising the importance of prudent vitamin D supplement prescriptions and public education against self-medication. For efficient resource allocation and targeting of those with higher risks, it may be advantageous to concentrate vitamin D testing on specific population groups.
Screening for those at risk for anxiety and depression warranting further clinical evaluation among patients presenting to breast services: a single-centre, cross-sectional study
Authors: Husain Sakina , Rao Shilpa , Suresh Sridhar , Jesudoss Kevin Victor Albert , Krishna Balamurali , Raj Jeffrey Pradeep
Published: April 2024

Objectives

Studies show that anxiety and depression are widespread across patients presenting to outpatient services for medical illnesses. We expect similar or even higher prevalence in patients with breast complaints owing to the relevance of breasts in terms of sexuality, identity and confidence. Thus, this study was proposed to estimate the prevalence and identify risk factors for being at risk for anxiety and depression in patients seeking breast services.

Design

Descriptive, cross-sectional study.

Setting

Tertiary care teaching hospital in Mumbai, Western India.

Participants

Patients seeking breast services for either benign or malignant conditions.

Outcome measures

Proportion of those at risk for clinical depression (defined as a score of ≥10 on Patient Health Questionnaire-9) and proportion of those at risk for clinical anxiety warranting further clinical evaluation (defined as a score of ≥10 on Generalized Anxiety Disorder-7) and their predictors.

Results

A total of 208 patients were screened, and 192 consenting patients were enrolled. The prevalence of those at risk for anxiety requiring further clinical evaluation was 46.4% (95% CI 39.2% to 53.7%) and for those at risk for major depression that warrants further clinical evaluation by a mental health provider was 29.7% (95% CI 23.3% to 36.7%). The predictors of anxiety were age (adjusted odds ratio (aOR) 1.053; 95% CI 1.024 to 1.083; p<0.001) and postmenopausal status (aOR 2.475; 95% CI 1.200 to 5.103; p=0.014). The predictors of depression were age (aOR 0.954; 95% CI 1.927 to 0.981; p=0.001) and rural place of residence (aOR 2.362; 95% CI 1.023 to 5.433; p=0.044).

Conclusions

There is a high prevalence of being at risk for anxiety and depression among patients who seek breast services warranting further clinical evaluation. The predictors of being at risk for anxiety were higher age and postmenopausal status, and for those at risk for depression were young age and residing in rural areas.
Perception and needs: a qualitative study on sense of job security among nurses in central and western China
Authors: Xiong Wanhong , Liao Changju , Zhang Cuicui , Liang Yufen , Xiong Wanfen , Zhu Aiqun
Published: April 2024

Aims

To explore nurses’ perceptions of sense of job security and their needs to improve it.

Design

A descriptive qualitative study employed an in-depth, in-person interview from February to April in 2021. The data analysis software NVivo V.11.0 was used to assist with the data organisation, and content analysis methods were conducted to explore key concepts.

Setting

Three tertiary hospitals in central and western China were selected by convenience sampling method.

Participants

A total of 20 nurses participated in this study.

Results

Four categories and 13 subcategories were extracted. The four main categories included: (1) enrich connotation of sense of job security; 2) challenges to sense of job security; (3) consequences of a sense of insecurity; and (4) the need to improve nurses’ sense of job security.

Conclusions

Nurses expressed a multidimensional perception of a sense of security about the nursing profession, and they highlighted the importance of communication skills training and supervisors’ humanistic care and support. It is necessary to improve the training system for nurses' ability improvement, a harmonious work environment, policies and psychological health support to enhance their sense of job security.
Effect of acyclovir therapy on the outcome of mechanically ventilated patients with lower respiratory tract infection and detection of herpes simplex virus in bronchoalveolar lavage: protocol for a multicentre, randomised controlled trial (HerpMV)
Authors: Hagel Stefan , Brillinger Nicole , Decker Sebastian , Deja Maria , Ertmer Christian , Fiedler Sandra , Franken Philipp , Heim Markus , Weigand Markus A , Zarbock Alexander , Pletz Mathias W
Published: April 2024

Introduction

Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients and is associated with a worse outcome. The aim of this study is to determine whether antiviral therapy in HSV-positive patients improves outcome.

Methods and analysis

Prospective, multicentre, open-label, randomised, controlled trial in parallel-group design. Adult, mechanically ventilated patients with pneumonia and HSV type 1 detected in bronchoalveolar lavage (≥105copies/mL) are eligible for participation and will be randomly allocated (1:1) to receive acyclovir (10 mg/kg body weight every 8 hours) for 10 days (or until discharge from the intensive care unit if earlier) or no intervention (control group). The primary outcome is mortality measured at day 30 after randomisation (primary endpoint) and will be analysed with Cox mixed-effects model. Secondary endpoints include ventilator-free and vasopressor-free days up to day 30. A total of 710 patients will be included in the trial.

Ethics and dissemination

The trial was approved by the responsible ethics committee and by Germany’s Federal Institute for Drugs and Medical Devices. The clinical trial application wassubmittedunder the newClinical TrialsRegulation throughCTIS(The Clinical Trials Information System). In this process, only one ethics committee, whose name is unknown to the applicant, and Germany’s Federal Institute for Drugs and Medical Devices are involved throughout the entire approval process. Results will be published in a journal indexed in MEDLINE and CTIS. With publication, de-identified, individual participant data will be made available to researchers.

Trial registration number

NCT06134492.
The impact of social media interventions on eating behaviours and diet in adolescents and young adults: a mixed methods systematic review protocol
Authors: Tang Hao , Spreckley Marie , van Sluijs Esther , Ahern Amy L , Smith Andrea D
Published: April 2024

Introduction

Adolescents and young adults are susceptible population when it comes to healthy eating and dietary behaviours. The increasing use of social media by this age group presents a unique opportunity to promote healthy eating habits. Social media has become a popular platform for promoting health interventions, particularly among young people. However, there is a lack of consensus on the effectiveness of social media interventions in this population. This mixed-method systematic review aims to synthesise the available evidence on the impact of social media interventions on healthy eating behaviours among young people, their qualitative views and user experiences, and the intervention characteristics, behaviour change theories and techniques used to promote healthy eating.

Methods and analysis

We will conduct a comprehensive search of seven electronic databases, including ASSIA, Cochrane Library, Embase, MEDLINE, PsycINFO, Scopus and Web of Science. The search strategy will use a combination of Medical Subject Headings terms and keywords covering three domains: social media, eating behaviours and young people. The search will be limited to peer-reviewed published papers in any language, published from 2000. Three independent reviewers will screen studies based on predetermined eligibility criteria. Data will be extracted and analysed using a convergent segregated mixed-method approach. We will use random-effect meta-analysis or Synthesis Without Meta-analysis for quantitative data and thematic synthesis for qualitative data. Finally, narrative synthesis using concurrent triangulation will be used to bring together the results of the mixed-method data analysis to provide a comprehensive and integrated understanding of the impact and other features of social media interventions. This systematic review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Ethics and dissemination

Ethical approval is not required since this systematic review will not collect original data. The outcomes of this review will be shared through peer-reviewed publications and conference presentations and will contribute to the PhD thesis of the primary author.

PROSPERO registration number

CRD42023414476.
Outcome, predictors and longitudinal trajectories of subjects with critical illness polyneuropathy and myopathy (CINAMOPS): study protocol of an observational cohort study in a clinical and post-clinical setting
Authors: Bergmann Jeannine , Egger Marion , Müller Friedemann , Jahn Klaus
Published: April 2024

Introduction

Critical illness polyneuropathy and myopathy (CIP/CIM) are frequent complications in the intensive care unit (ICU) with major consequences for the progress and outcome of subjects. CIP/CIM delays the weaning process, prolongs the hospital stay and increases the mortality rate. Additionally, it may have long-term consequences beyond the hospitalisation phase with prolonged disability. Even though there is growing interest in CIP/CIM, research about the clinical and post-clinical course as well as the middle-term and long-term outcomes of subjects with CIP/CIM is scarce. A large prospective study of critically ill subjects is needed with accurate diagnosis during the acute stage and comprehensive assessment during long-term follow-up.

Methods and analysis

This prospective observational cohort study aims to compare the clinical and post-clinical course of chronically critically ill subjects with and without the diagnosis of CIP/CIM and to determine predictors for the middle-term and long-term outcomes of subjects with CIP/CIM. In addition, the influence of the preclinical health status and the preclinical frailty on the long-term outcome of subjects with CIP/CIM will be investigated.

This single-centre study will include 250 critically ill patients who were invasively ventilated for at least 5 days at the ICU and show reduced motor strength. At five study visits at admission and discharge to neurological rehabilitation, and 12, 18 and 24 months after disease onset, a comprehensive test battery will be applied including assessments of functioning and impairment, independence, health-related quality of life, activity and participation, cognition, gait and balance, fatigue, mental health and frailty.

Secondary objectives are the documentation of therapy goals, therapy content and achieved milestones during the rehabilitation, to evaluate the clinimetric properties of the Mini-BESTest in critically ill patients, and to evaluate the time course and outcome of subjects with CIP/CIM after SARS-CoV-2 infection.

Ethics and dissemination

The study was approved by the ethical committee of the Ludwig-Maximilians University Munich. Participants will be included in the study after having signed informed consent.

Results will be published in scientific, peer-reviewed journals and at national and international conferences.

Trial registration number

German Clinical Trial Register (DRKS00021753).
Climate change for gastroenterologists: understanding the basics
Authors: Eling Judith Chantal , Barker Jennifer , Barna Stefi
Published: April 2024

The healthcare sector is a significant producer of greenhouse gas emissions. Gases that contribute to climate change include carbon dioxide, methane, nitrous oxide and chlorofluorocarbons. Climate change will impact the types and prevalence of diseases seen in clinical practice. Practising preventive medicine in gastroenterology can protect population health and reduce the need for health services, thus reducing the carbon footprint of the health sector. Increasing patient empowerment, making care pathways leaner and minimising the environmental impact of treatments and interventions could also make healthcare more sustainable.
Does stereotactic thrombolysis with alteplase for intracerebral haemorrhage alter intraventricular haematoma volume? A secondary analysis of the MISTIE-III trial
Authors: Sun Philip , Badihian Shervin , Avadhani Radhika , Walborn Nathan , Yarava Anusha , Alimoradi Donya , Awad Issam , Hanley Daniel , Murthy Santosh , Ziai Wendy
Published: April 2024

Background

Stereotactic thrombolysis reduces intracerebral haemorrhage (ICH) volume in patients with spontaneous ICH. Whether intrahaematomal alteplase administration is associated with a change in intraventricular haemorrhage volume (deltaIVH) and functional outcomes is unknown.

Methods

Post hoc secondary analysis of the Minimally Invasive Surgery plus Alteplase for Intracerebral Hemorrhage Evacuation Phase III (MISTIE-III) trial in patients with IVH on the stability CT scan. Exposure was minimally invasive surgery plus alteplase (MIS+alteplase). Primary outcome was deltaIVH defined as IVH volume on end-of-treatment CT minus IVH volume on stability CT scan. Secondary outcomes were favourable functional outcome (modified Rankin Scale 0–3) and mortality at 365 days. We assessed the relationship between MIS+alteplase and deltaIVH in the primary analysis using multivariable linear regression, and between deltaIVH and functional outcomes in secondary analyses using multiple logistic regression.

Results

Of 499 patients in MISTIE-III, 310 (62.1%) had IVH on stability scans; mean age (SD) was 61.2±12.3 years. A total of 146 (47.1%) received the MISTIE procedure and 164 (52.9%) standard medical care (SMC) only. The MIS+alteplase group had a greater mean reduction in IVH volume compared with the SMC group (deltaIVH: −2.35 (5.30) mL vs −1.15 (2.96) mL, p=0.02). While IVH volume decreased significantly in both treatment groups, in the primary analysis, MIS+alteplase was associated with greater deltaIVH in multivariable linear regression analysis adjusted for potential confounders (β −0.80; 95% CI −1.37 to −0.22, p=0.007). Secondary analysis demonstrated no associations between IVH reduction and functional outcomes (adjusted OR (aOR) for poor outcome 1.02; 95% CI 0.96 to 1.08, p=0.61; aOR for mortality 0.99; 95% CI 0.92 to 1.06, p=0.77).

Conclusions

Alteplase delivered into the ICH in MISTIE-III subjects with IVH was associated with a small reduction in IVH volume. This reduction did not translate into a significant benefit in mortality or functional outcomes at 365 days.

Trial registration number

NCT01827046.