bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Parenting Style on Body Mass Index, Physical Activity, and Sedentary Time
Authors: Selland Corey A. , Huber-Johnson Emily C. , Bowne Mary , Meendering Jessica R.
Published: September 2021

The purpose of the current study was to determine the influence of parenting style on body mass index (BMI) percentile, physical activity (PA), and sedentary time (ST) in children. Accelerometers were used to assess PA and ST in 152 fifth-grade children. Parenting style was assessed by the child participants’ responses to modified questions from the Parenting Style Inventory II and dichotomized as authoritative or non-authoritative. Multiple linear regression analyses were utilized to identify significant predictors of outcomes of interest. Parenting style did not predict ST or any intensity of PA; however, BMI percentile and gender were significant predictors of moderate-intensity PA, vigorous-intensity PA, and moderate-to-vigorous intensity PA ( P < .01). BMI percentile was predicted to be lower in females with authoritative mothers ( P < .01). While authoritative and non-authoritative parenting style did not predict objectively measured PA or ST in early adolescents, authoritative parenting style did predict BMI percentile in female participants.
Pembrolizumab for B-cell lymphomas relapsing after or refractory to CD19-directed CAR T-cell therapy
Authors: Chong Elise A. , Alanio Cécile , Svoboda Jakub , Nasta Sunita D. , Landsburg Daniel J. , Lacey Simon F. , Ruella Marco , Bhattacharyya Siddharth , Wherry E. John , Schuster Stephen J.
Published: September 2021

CD19-directed chimeric antigen receptor–modified (CAR T) T cells achieve durable remissions in about 30% to 40% of relapsed/refractory large B-cell lymphomas. T-cell exhaustion and/or an immunosuppressive tumor microenvironment may contribute to CAR T-cell failure. Pembrolizumab, an anti-PD1 immune checkpoint inhibitor, may reverse T-cell exhaustion after CAR T-cell therapy. We treated 12 patients with B-cell lymphomas who were either refractory to (n = 9) or relapsed after (n = 3) CD19-directed CAR T-cell (4-1BB–costimulated) therapy with pembrolizumab 200 mg IV every 3 weeks. Median time from CAR T-cell infusion to first pembrolizumab dose was 3.3 months (range, 0.4-42.8 months). Pembrolizumab was well tolerated, and the only grade ≥3 adverse events related to pembrolizumab were neutropenia (n = 3; 25%). Best overall response rate after pembrolizumab was 25% (3 of 12 patients; 1 complete response; 2 partial responses). One (8%) patient had stable disease; thus, 4 of 12 (33%) patients had clinical benefit. After pembrolizumab, 4 patients with clinical benefit had an increase in percentage of CAR T cells by mass cytometry by time of flight (CyTOF); 3 of 4 of these patients also had increases in CAR19 transgene levels by quantitative polymerase chain reaction. Deep immune profiling using CyTOF revealed increased CAR T-cell activation and proliferation and less T-cell exhaustion in clinical responders. Together, PD1 blockade with pembrolizumab after CD19-directed CAR T-cell therapy appears safe and may achieve clinical responses in some patients with B-cell lymphomas refractory to or relapsed after CAR T-cell therapy. This trial was registered at www.clinicaltrials.gove as #NCT02650999.
Population pharmacokinetic modeling of factor concentrates in hemophilia: an overview and evaluation of best practice
Authors: Goedhart Tine M. H. J. , Bukkems Laura H. , Zwaan C. Michel , Mathôt Ron A. A. , Cnossen Marjon H. ,   for the OPTI-CLOT study group and SYMPHONY consortium
Published: September 2021

The accuracy of pharmacokinetic (PK)-guided dosing depends on the clinical and laboratory data used to construct a population PK model, as well as the patient’s individual PK profile. This review provides a detailed overview of data used for published population PK models for factor VIII (FVIII) and factor IX (FIX) concentrates, to support physicians in their choices of which model best suits each patient. Furthermore, to enhance detailed data collection and documentation, we do suggestions for best practice. A literature search was performed; publications describing prophylactic population PK models for FVIII and FIX concentrates based on original patient data and constructed using nonlinear mixed-effect modeling were included. The following data were collected: detailed demographics, type of product, assessed and included covariates, laboratory specifications, and validation of models. Included models were scored according to our recommendations for best practice, specifically scoring the quality of data documentation as reported. Respectively, 20 models for FVIII and 7 for FIX concentrates were retrieved. Although most models (22/27) included pediatric patients, only 4 reported detailed demographics. The wide range of body weights suggested that overweight and obese adults were represented. Twenty-six models reported the assay applied to measure factor levels, whereas only 16 models named reagents used. Eight models were internally validated using a data subset. This overview presents detailed information on clinical and laboratory data used for published population PK models. We provide recommendations on data collection and documentation to increase the reliability of PK-guided prophylactic dosing of factor concentrates in hemophilia A and B.
Tumor-associated antigen–specific T cells with nivolumab are safe and persist in vivo in relapsed/refractory Hodgkin lymphoma
Authors: Dave Hema , Terpilowski Madeline , Mai Mimi , Toner Keri , Grant Melanie , Stanojevic Maja , Lazarski Christopher , Shibli Abeer , Bien Stephanie A. , Maglo Philip , Hoq Fahmida , Schore Reuven , Glenn Martha , Hu Boyu , Hanley Patrick J. , Ambinder Richard , Bollard Catherine M.
Published: September 2021

Hodgkin lymphoma (HL) Reed Sternberg cells express tumor-associated antigens (TAA) that are potential targets for cellular therapies. We recently demonstrated that TAA-specific T cells (TAA-Ts) targeting WT1, PRAME, and Survivin were safe and associated with prolonged time to progression in solid tumors. Hence, we evaluated whether TAA-Ts when given alone or with nivolumab were safe and could elicit antitumor effects in vivo in patients with relapsed/refractory (r/r) HL. Ten patients were infused with TAA-Ts (8 autologous and 2 allogeneic) for active HL (n = 8) or as adjuvant therapy after hematopoietic stem cell transplant (n = 2). Six patients received nivolumab priming before TAA-Ts and continued until disease progression or unacceptable toxicity. All 10 products recognized 1 or more TAAs and were polyfunctional. Patients were monitored for safety for 6 weeks after the TAA-Ts and for response until disease progression. The infusions were safe with no clear dose-limiting toxicities. Patients receiving TAA-Ts as adjuvant therapy remain in continued remission at 3+ years. Of the 8 patients with active disease, 1 patient had a complete response and 7 had stable disease at 3 months, 3 of whom remain with stable disease at 1 year. Antigen spreading and long-term persistence of TAA-Ts in vivo were observed in responding patients. Nivolumab priming impacted TAA-T recognition and persistence. In conclusion, treatment of patients with r/r HL with TAA-Ts alone or in combination with nivolumab was safe and produced promising results. This trial was registered at www.clinicaltrials.gov as #NCT022039303 and #NCT03843294.
An mRNA assay system demonstrates proteasomal-specific degradation contributes to cardiomyopathic phospholamban null mutation
Authors: Rohner Eduarde , Witman Nevin , Sohlmer Jesper , De Genst Erwin , Louch William E. , Sahara Makoto , Chien Kenneth R.
Published: September 2021

Background

The human L39X phospholamban (PLN) cardiomyopathic mutant has previously been reported as a null mutation but the detailed molecular pathways that lead to the complete lack of detectable protein remain to be clarified. Previous studies have shown the implication between an impaired cellular degradation homeostasis and cardiomyopathy development. Therefore, uncovering the underlying mechanism responsible for the lack of PLN protein has important implications in understanding the patient pathology, chronic human calcium dysregulation and aid the development of potential therapeutics.

Methods

A panel of mutant and wild-type reporter tagged PLN modified mRNA (modRNA) constructs were transfected in human embryonic stem cell-derived cardiomyocytes. Lysosomal and proteasomal chemical inhibitors were used together with cell imaging and protein analysis tools in order to dissect degradation pathways associated with expressed PLN constructs. Transcriptional profiling of the cardiomyocytes transfected by wild-type or L39X mutant PLN modRNA was analysed with bulk RNA sequencing.

Results

Our modRNA assay system revealed that transfected L39X mRNA was stable and actively translated in vitro but with only trace amount of protein detectable. Proteasomal inhibition of cardiomyocytes transfected with L39X mutant PLN modRNA showed a fourfold increase in protein expression levels. Additionally, RNA sequencing analysis of protein degradational pathways showed a significant distinct transcriptomic signature between wild-type and L39X mutant PLN modRNA transfected cardiomyocytes.

Conclusion

Our results demonstrate that the cardiomyopathic PLN null mutant L39X is rapidly, actively and specifically degraded by proteasomal pathways. Herein, and to the best of our knowledge, we report for the first time the usage of modified mRNAs to screen for and illuminate alternative molecular pathways found in genes associated with inherited cardiomyopathies.
Patency period of a metallic ureteral stent and its determinants in patients with malignant ureteral obstruction: a prospective review
Authors: Kobayashi Yasuyuki , Arai Hiroki , Honda Masahito
Published: September 2021

Background

Malignant ureteral obstruction caused by extrinsic compression of a primary malignant tumour or by metastatic disease is an indicator of poor prognosis with a median life expectancy of about one year. We examined clinical outcomes following Resonance Metallic Ureteral Stent (Cook Medical, Bloomington, IN) placement in patients with malignant ureteral obstruction.

Methods

This was a prospective study of patients with malignant ureteral obstruction who underwent Resonance Metallic Ureteral Stent placement from April 2016 to March 2021. We registered 21 patients (27 collecting systems) with malignant ureteral obstruction and observed them prospectively. The patients first underwent polymer ureteral stent placement followed by replacement with a metallic ureteral stent one month later. Primary outcome was the metallic ureteral stent patency period based on both serum creatinine and the level of hydronephrosis; secondary outcomes were factors affecting patency period and stent-related complications such as symptoms of obstruction (flank pain), bladder irritation, haematuria, and urinary tract infection (presence or absence of fever).

Results

The study comprised 21 patients (six men, 15 women) with a mean age of 72 years. The median stent patency period in days was not available (NA) (95% CI 210–NA) due to the inability to extract this value from the Kaplan–Meier curve because the event rate did not reach 50%, and the one-year patency rate was 59.2% (95% CI 23.2–82.9). A normal serum creatinine (0.65 to 1.07 mg/dL for men and 0.46 to 0.79 mg/dL for women) one week after polymer ureteral stent placement was a significant factor affecting the long-term metallic ureteral stent patency period. There were no major complications.

Conclusion

The Resonance Metallic Ureteral Stent was effective and safe for patients with malignant ureteral obstruction. A normal serum creatinine level one week after placement of a polymer ureteral stent may predict a longer patency period of metallic ureteral stents in patients with malignant ureteral obstruction.
A simulation study of a honeybee breeding scheme accounting for polyandry, direct and maternal effects on colony performance
Authors: Kistler Tristan , Basso Benjamin , Phocas Florence
Published: September 2021

Background

Efficient breeding programs are difficult to implement in honeybees due to their biological specificities (polyandry and haplo-diploidy) and complexity of the traits of interest, with performances being measured at the colony scale and resulting from the joint effects of tens of thousands of workers (called direct effects) and of the queen (called maternal effects). We implemented a Monte Carlo simulation program of a breeding plan designed specifically for Apis mellifera’s populations to assess the impact of polyandry versus monoandry on colony performance, inbreeding level and genetic gain depending on the individual selection strategy considered, i.e. complete mass selection or within-family (maternal lines) selection. We simulated several scenarios with different parameter setups by varying initial genetic variances and correlations between direct and maternal effects, the selection strategy and the polyandry level. Selection was performed on colony phenotypes.

Results

All scenarios showed strong increases in direct breeding values of queens after 20 years of selection. Monoandry led to significantly higher direct than maternal genetic gains, especially when a negative correlation between direct and maternal effects was simulated. However, the relative increase in these genetic gains depended also on their initial genetic variability and on the selection strategy. When polyandry was simulated, the results were very similar with either 8 or 16 drones mated to each queen. Across scenarios, polyandrous mating resulted in equivalent or higher gains in performance than monoandrous mating, but with considerably lower inbreeding rates. Mass selection conferred a ~ 20% increase in performance compared to within-family selection, but was also accompanied by a strong increase in inbreeding levels (25 to 50% higher).

Conclusions

Our study is the first to compare the long-term effects of polyandrous versus monoandrous mating in honeybee breeding. The latter is an emergent strategy to improve specific traits, such as resistance to varroa, which can be difficult or expensive to phenotype. However, if used during several generations in a closed population, monoandrous mating increases the inbreeding level of queens much more than polyandrous mating, which is a strong limitation of this strategy.
A novel automated image analysis pipeline for quantifying morphological changes to the endoplasmic reticulum in cultured human cells
Authors: Garcia-Pardo M. Elena , Simpson Jeremy C. , O’Sullivan Niamh C.
Published: September 2021

Background

In mammalian cells the endoplasmic reticulum (ER) comprises a highly complex reticular morphology that is spread throughout the cytoplasm. This organelle is of particular interest to biologists, as its dysfunction is associated with numerous diseases, which often manifest themselves as changes to the structure and organisation of the reticular network. Due to its complex morphology, image analysis methods to quantitatively describe this organelle, and importantly any changes to it, are lacking.

Results

In this work we detail a methodological approach that utilises automated high-content screening microscopy to capture images of cells fluorescently-labelled for various ER markers, followed by their quantitative analysis. We propose that two key metrics, namely the area of dense ER and the area of polygonal regions in between the reticular elements, together provide a basis for measuring the quantities of rough and smooth ER, respectively. We demonstrate that a number of different pharmacological perturbations to the ER can be quantitatively measured and compared in our automated image analysis pipeline. Furthermore, we show that this method can be implemented in both commercial and open-access image analysis software with comparable results.

Conclusions

We propose that this method has the potential to be applied in the context of large-scale genetic and chemical perturbations to assess the organisation of the ER in adherent cell cultures.
Identification of reference genes for gene expression studies among different developmental stages of murine hearts
Authors: Ren Jie , Zhang Ningning , Li Xiangjie , Sun Xiaogang , Song Jiangping
Published: September 2021

Background

Real-time quantitative polymerase chain reaction (RT-qPCR) is a widely-used standard assay for assessing gene expression. RT-qPCR data requires reference genes for normalization to make the results comparable. Therefore, the selected reference gene should be highly stable in its expression throughout the experimental datasets. So far, reports about the optimal set of reference genes in murine left ventricle (LV) across embryonic and postnatal stages are few. The objective of our research was to identify the appropriate reference genes in murine LV among different developmental stages.

Methods

We investigated the gene expression profiles of 21 widely used housekeeping genes in murine LV from 7 different developmental stages (almost throughout the whole period of the mouse lifespan). The stabilities of the potential reference genes were evaluated by five methods: GeNorm, NormFinder, BestKeeper, Delta-Ct and RefFinder.

Results

We proposed a set of reliable reference genes for normalization of RT-qPCR experimental data in different conditions. Furthermore, our results showed that 6 genes (18S, Hmbs, Ubc, Psmb4, Tfrc and Actb) are not recommended to be used as reference genes in murine LV development studies. The data also suggested that the Rplp0 gene might serve as an optimal reference gene in gene expression analysis.

Conclusions

Our study investigated the expression stability of the commonly used reference genes in process of LV development and maturation. We proposed a set of optimal reference genes that are suitable for accurate normalization of RT-qPCR data in specific conditions. Our findings may be helpful in future studies for investigating the gene expression patterns and mechanism of mammalian heart development.
Transcriptome analysis reveals the molecular mechanisms of heterosis on thermal resistance in hybrid abalone
Authors: Xiao Qizhen , Huang Zekun , Shen Yawei , Gan Yang , Wang Yi , Gong Shihai , Lu Yisha , Luo Xuan , You Weiwei , Ke Caihuan
Published: September 2021

Background

Heterosis has been exploited for decades in different animals and crops due to it resulting in dramatic increases in yield and adaptability. Hybridization is a classical breeding method that can effectively improve the genetic characteristics of organisms through heterosis. Abalone has become an increasingly economically important aquaculture resource with high commercial value. However, due to changing climate, abalone is now facing serious threats of high temperature in summer. Interspecific hybrid abalone (Haliotis gigantea ♀ × H. discus hannai ♂, SD) has been cultured at large scale in southern China and has been shown high survival rates under heat stress in summer. Therefore, SD has become a good model material for heterosis research, but the molecular basis of heterosis remains elusive.

Results

Heterosis in thermal tolerance of SD was verified through Arrhenius break temperatures (ABT) of cardiac performance in this study. Then RNA-Sequencing was conducted to obtain gene expression patterns and alternative splicing events at control temperature (20 °C) and heat stress temperature (30 °C). A total of 356 (317 genes), 476 (435genes), and 876 (726 genes) significantly diverged alternative splicing events were identified in H. discus hannai (DD), H. gigantea (SS), and SD in response to heat stress, respectively. In the heat stress groups, 93.37% (20,512 of 21,969) of the expressed genes showed non-additive expression patterns, and over-dominance expression patterns of genes account for the highest proportion (40.15%). KEGG pathway enrichment analysis showed that the overlapping genes among common DEGs and NAGs were significantly enriched in protein processing in the endoplasmic reticulum, mitophagy, and NF-κB signaling pathway. In addition, we found that among these overlap genes, 39 genes had undergone alternative splicing events in SD. These pathways and genes may play an important role in the thermal resistance of hybrid abalone.

Conclusion

More alternative splicing events and non-additive expressed genes were detected in hybrid under heat stress and this may contribute to its thermal heterosis. These results might provide clues as to how hybrid abalone has a better physiological regulation ability than its parents under heat stress, to increase our understanding of heterosis in abalone.
Regulation of wound ethylene biosynthesis by NAC transcription factors in kiwifruit
Authors: Nieuwenhuizen Niels J. , Chen Xiuyin , Pellan Mickaël , Zhang Lei , Guo Lindy , Laing William A. , Schaffer Robert J. , Atkinson Ross G. , Allan Andrew C.
Published: September 2021

Background

The phytohormone ethylene controls many processes in plant development and acts as a key signaling molecule in response to biotic and abiotic stresses: it is rapidly induced by flooding, wounding, drought, and pathogen attack as well as during abscission and fruit ripening. In kiwifruit (Actinidiaspp.), fruit ripening is characterized by two distinct phases: an early phase of system-1 ethylene biosynthesis characterized by absence of autocatalytic ethylene, followed by a late burst of autocatalytic (system-2) ethylene accompanied by aroma production and further ripening. Progress has been made in understanding the transcriptional regulation of kiwifruit fruit ripening but the regulation of system-1 ethylene biosynthesis remains largely unknown. The aim of this work is to better understand the transcriptional regulation of both systems of ethylene biosynthesis in contrasting kiwifruit organs: fruit and leaves.

Results

A detailed molecular study in kiwifruit (A. chinensis) revealed that ethylene biosynthesis was regulated differently between leaf and fruit after mechanical wounding. In fruit, wound ethylene biosynthesis was accompanied by transcriptional increases in 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS), ACC oxidase (ACO) and members of the NAC class of transcription factors (TFs). However, in kiwifruit leaves, wound-specific transcriptional increases were largely absent, despite a more rapid induction of ethylene production compared to fruit, suggesting that post-transcriptional control mechanisms in kiwifruit leaves are more important. One ACS member,AcACS1, appears to fulfil a dominant double role; controlling both fruit wound (system-1) and autocatalytic ripening (system-2) ethylene biosynthesis. In kiwifruit, transcriptional regulation of both system-1 and -2 ethylene in fruit appears to be controlled by temporal up-regulation of four NAC (NAM, ATAF1/2, CUC2) TFs (AcNAC1–4) that induceAcACS1expression by directly binding to theAcACS1promoter as shown using gel-shift (EMSA) and by activation of theAcACS1promoterin plantaas shown by gene activation assays combined with promoter deletion analysis.

Conclusions

Our results indicate that in kiwifruit the NAC TFs AcNAC2–4 regulate both system-1 and -2 ethylene biosynthesis in fruit during wounding and ripening through control ofAcACS1expression levels but not in leaves where post-transcriptional/translational regulatory mechanisms may prevail.
Monochromic light reduces emergence delirium in children undergoing adenotonsillectomy; a double-blind randomized observational study
Authors: Adler Adam C. , Nathanson Brian H. , Chandrakantan Arvind
Published: September 2021

Background

Emergence delirium (ED) is common in pediatric anesthesia. This dissociative state in which the patient is confused from their surroundings and flailing can be self-injurious and traumatic for parents. Treatment is by administration of sedatives which can prolong recovery. The aim of this study was to determine if exposure to monochromatic blue light (MBL) in the immediate phase of recovery could reduce the overall incidence of emergence delirium in children following general inhalational anesthesia.

Methods

This double blinded randomized controlled study included patients ages 2–6 undergoing adenotonsillectomy. Postoperatively, 104 patients were randomization (52 in each group) for exposure to sham blue or MBL during the first phase (initial 30 min) of recovery. The primary outcome was the incidence of emergence delirium during the first phase. We also examined Pediatric Anesthesia Emergence Delirium (PAED) scores throughout the first phase.

Results

Emergence Delirium was reported in 5.9% of MBL patients versus 33.3% in the sham group, p = 0.001. Using logistic regression adjusting for age, weight, gender, ASA classification and PAED scores provided an adjusted relative risk ratio of 0.18; 95% CI (0.06, 0.54); p = 0.001 for patients in the MBL group. 23.5% of MBL patients versus 52.9% of sham patients had either ED or PAED scores of 12 or more throughout the first phase of recovery, p = 0.002. This produced an adjusted relative risk of 0.46, 95% CI (0.29, 0.75), p = 0.001.

Conclusions

Monochromatic blue light represents a non-pharmacologic method to reduce the incidence of emergence delirium and PAED scores in children.

Trial Registration

#NCT03285243 registered on 15/09/2017
Effects of the addition of dexamethasone on postoperative analgesia after anterior cruciate ligament reconstruction surgery under quadruple nerve blocks
Authors: Aoyama Yuki , Sakura Shinichi , Abe Shoko , Uchimura Erika , Saito Yoji
Published: September 2021

Background

Anterior cruciate ligament (ACL) reconstruction is an invasive surgical procedure for the knee. Quadruple nerve blocks including continuous femoral nerve block and single-injection sciatic, obturator, and lateral femoral cutaneous nerve blocks can provide effective intraoperative anesthesia and analgesia in the early postoperative period. However, severe pain often appears after the effect of single-injection nerve blocks resolves and that is why we conducted two studies. The first study was to determine whether dexamethasone administered along with local anesthetic for sciatic nerve block could prolong the duration of analgesia in patients given quadruple nerve blocks, including continuous femoral nerve block, for ACL reconstruction using a hamstring tendon autograft. The second study was designed to evaluate any difference in effects from dexamethasone administered perineurally versus intravenously.

Methods

Patients undergoing unilateral arthroscopic ACL reconstruction using a hamstring tendon autograft were enrolled into two studies. The first study was prospectively conducted to see if dexamethasone 4 mg could prolong the duration of analgesia when administered perineurally to the subgluteal sciatic nerve with 0.5% ropivacaine. In the second study, we retrospectively evaluated the effects of intravenous dexamethasone 4 mg as compared with those of perineural dexamethasone to the sciatic nerve block and effects with no dexamethasone.

Results

In the first study, perineural dexamethasone prolonged the duration of analgesia by 9.5 h (median duration: 22.5 and 13.0 h with and without perineural dexamethasone, respectively, P = 0.011). In the second study, the duration of analgesia was similarly prolonged for intravenous and perineural dexamethasone compared with no dexamethasone.

Conclusion

Perineural dexamethasone administered along with local anesthetic for single sciatic nerve block prolonged the duration of analgesia of quadruple nerve blocks for ACL reconstruction, however the effects were not different from those of intravenous dexamethasone.

Trial registration

The protocols of both studies were approved by the Institutional Review Board of Shimane University Hospital, Japan (study number 2821 and 3390 for study 1 and study 2, respectively). Study 1 was registered in University Hospital Medical Information Network Clinical Trials Registry (UMIN000028930). Study 2, which was a retrospective study, was not registered.
A mobile swabbing booth to address Singapore GPs’ concerns about swabber protection: human-centred design during the COVID-19 pandemic
Authors: Teo Boon See , Li Esther , Khoo Yi-Lin , Evaristo Michelle , Fang Yang , Smith Helen E.
Published: September 2021

Background

During the COVID-19 pandemic, the Ministry of Health asked Singapore’s private general practitioners (GPs) to perform swab testing in their clinics, but some GPs had concerns about swabber protection. Our aim was to develop a swabbing booth to address these concerns.

Methods

We developed a prototype with potential GP users using a human-centred design approach and piloted it with 10 GP clinics. The pilot was then extended to 170 GP clinics around Singapore. These GPs were then surveyed on user satisfaction.

Results

Ninety-three GPs (54%) responded. The majority (75%) practiced in public residential estates in small practices (mean 1.95 doctors). 86% requested the booth to enhance swabber protection. 74% “would recommend” or “would strongly recommend” the booth to colleagues. 79% continue to use the booth to conduct swab tests. 92% liked that it offered swabber protection. 71% liked that the booth created a separate space for swabbing and 64% liked its ease of disinfection. 47% started swabbing only after receiving the booth and 58% said the booth was “important” or “very important” to their decision to participate in swab testing. However, 34% disliked that it took up too much space and the most frequently critiqued area was the gloves.

Conclusion

The human-centred design approach generated a product that had high user satisfaction, addressed GPs’ concerns of swabber protection and increased GPs’ participation in swab testing. The booth may be useful where GPs are concerned about swabber protection and space is limited.
Impact of the Covid-19 epidemic and related social distancing regulations on social contact and SARS-CoV-2 transmission potential in rural South Africa: analysis of repeated cross-sectional surveys
Authors: McCreesh Nicky , Dlamini Vuyiswa , Edwards Anita , Olivier Stephen , Dayi Njabulo , Dikgale Keabetswe , Nxumalo Siyabonga , Dreyer Jaco , Baisley Kathy , Siedner Mark J. , White Richard G. , Herbst Kobus , Grant Alison D. , Harling Guy
Published: September 2021

Background

South Africa implemented rapid and strict physical distancing regulations to minimize SARS-CoV-2 epidemic spread. Evidence on the impact of such measures on interpersonal contact in rural and lower-income settings is limited.

Methods

We compared population-representative social contact surveys conducted in the same rural KwaZulu-Natal location once in 2019 and twice in mid-2020. Respondents reported characteristics of physical and conversational (‘close interaction’) contacts over 24 hours. We built age-mixing matrices and estimated the proportional change in the SARS-CoV-2 reproduction number (R0). Respondents also reported counts of others present at locations visited and transport used, from which we evaluated change in potential exposure to airborne infection due to shared indoor space (‘shared air’).

Results

Respondents in March–December 2019 (n = 1704) reported a mean of 7.4 close interaction contacts and 196 shared air person-hours beyond their homes. Respondents in June-July 2020 (n = 216), as the epidemic peaked locally, reported 4.1 close interaction contacts and 21 shared air person-hours outside their home, with significant declines in others’ homes and public spaces. Adults aged over 50 had fewer close contacts with others over 50, but little change in contact with 15–29 year olds, reflecting ongoing contact within multigenerational households. We estimate potential R0fell by 42% (95% plausible range 14–59%) between 2019 and June-July 2020.

Conclusions

Extra-household social contact fell substantially following imposition of Covid-19 distancing regulations in rural South Africa. Ongoing contact within intergenerational households highlighted a potential limitation of social distancing measures in protecting older adults.
Understanding issues around use of oral pre exposure prophylaxis among female sex workers in India
Authors: Sahay Seema , Verma Archana , Shewale Suhas , Bangar Sampada , Bijeshkumar Athokpam , Angolkar Mubashir , Subramanian Thilakavathi , Chandhiok Nomita
Published: September 2021

Background

Empowering female sex workers (FSWs) through women controlled HIV prevention option has been in focus globally. FSWs are important target for oral pre exposure prophylaxis (PrEP). A multi-centric qualitative study was conducted to explore the FSWs’ willingness to use oral PrEP in India.

Methods

Seventy three interviews and 02 focus group discussions were conducted at 3 high HIV prevalent states in India during 2013–14. Study explored issues around willingness to use oral PrEP. The study was approved by the respective institutional ethics committee of the study sites. Thematic analysis using grounded theory approach was used to analyze the data in N-VIVO version 8.0.

Results

Thematic analysis showed events of forced condom-less sex. FSWs believed that oral PrEP could provide independence, financial gains, and privacy and therefore hoped to use it as an alternative to male condom. However, any impact on physical/ aesthetic attributes and reproductive system were not acceptable and could become a barrier. Provider initiated oral PrEP was not preferred. Providers voiced safety monitoring concerns. Adherence emerged as a challenge because of: (1) alcohol use; (2) taking PrEP tablet each day being boring; (3) Stigma because Oral PrEP is ARV based. Alcohol use and dread of repetitive dose brings forth the need for long acting oral PrEP.

Conclusion

Oral PrEP is acceptable among FSWs; it should be rolled out alongside strong messages on STI protection and PrEP as compliment to condoms. PrEP roll out requires educating communities about HIV treatment versus prevention. Long-acting oral PrEP could address both ‘boredom’ and alcoholism and sustain adherence.
Identifying women with gestational diabetes based on maternal characteristics: an analysis of four Norwegian prospective studies
Authors: Rai Anam Shakil , Sletner Line , Jenum Anne Karen , Øverby Nina Cecilie , Stafne Signe Nilssen , Lekva Tove , Pripp Are Hugo , Sagedal Linda Reme
Published: September 2021

Background

There is still no worldwide agreement on the best diagnostic thresholds to define gestational diabetes (GDM) or the optimal approach for identifying women with GDM. Should all pregnant women perform an oral glucose tolerance test (OGTT) or can easily available maternal characteristics, such as age, BMI and ethnicity, indicate which women to test? The aim of this study was to assess the prevalence of GDM by three diagnostic criteria and the predictive accuracy of commonly used risk factors.

Methods

We merged data from four Norwegian cohorts (2002–2013), encompassing 2981 women with complete results from a universally offered OGTT. Prevalences were estimated based on the following diagnostic criteria: 1999WHO (fasting plasma glucose (FPG) ≥7.0 or 2-h glucose ≥7.8 mmol/L), 2013WHO (FPG ≥5.1 or 2-h glucose ≥8.5 mmol/L), and 2017Norwegian (FPG ≥5.3 or 2-h glucose ≥9 mmol/L). Multiple logistic regression models examined associations between GDM and maternal factors. We applied the 2013WHO and 2017Norwegian criteria to evaluate the performance of different thresholds of age and BMI.

Results

The prevalence of GDM was 10.7, 16.9 and 10.3%, applying the 1999WHO, 2013WHO, and the 2017Norwegian criteria, respectively, but was higher for women with non-European background when compared to European women (14.5 vs 10.2%, 37.7 vs 13.8% and 27.0 vs 7.8%). While advancing age and elevated BMI increased the risk of GDM, no risk factors, isolated or in combination, could identify more than 80% of women with GDM by the latter two diagnostic criteria, unless at least 70–80% of women were offered an OGTT. Using the 2017Norwegian criteria, the combination “age≥25 years or BMI≥25 kg/m2” achieved the highest sensitivity (96.5%) with an OGTT required for 93% of European women. The predictive accuracy of risk factors for identifying GDM was even lower for non-European women.

Conclusions

The prevalence of GDM was similar using the 1999WHO and 2017Norwegian criteria, but substantially higher with the 2013WHO criteria, in particular for ethnic non-European women. Using clinical risk factors such as age and BMI is a poor pre-diagnostic screening method, as this approach failed to identify a substantial proportion of women with GDM unless at least 70–80% were tested.
Prevalence, socioeconomic factors and obstetric outcomes associated with adolescent motherhood in Ceará, Brazil: a population-based study
Authors: Bruno Shirley Kelly Bedê , Rocha Hermano Alexandre Lima , Rocha Sabrina Gabriele Maia Oliveira , Araújo David Augusto Batista Sá , Campos Jocileide Sales , Silva Anamaria Cavalcante e , Correia Luciano Lima
Published: September 2021

Background

Adolescent motherhood (AM) remains a public health problem, especially in low and middle income countries, where approximately 95% of these births occur. Evidence from studies with population representativeness about events associated with AM is limited. We assessed the prevalence of AM, as well as its association with Socioeconomic Factors and Obstetric Outcomes.

Methods

A population-based cross-sectional study on maternal and child health of women aged 10 to 49 years, living in the state of Ceará, in northeastern Brazil was carried out to assess the prevalence of AM, as well as its association with Socioeconomic Factors and Obstetric Outcomes. The definition of adolescence used in the study was the one utilized by the WHO. In addition to the interview, data were double-checked according to the information in the government’s pregnancy health booklet. Sample-adjusted logistic models to determine the association of socioeconomic factors and AM, as well as the association of AM with obstetric outcomes, with a causal approach to multivariate analyses, were used.

Results

The prevalence of adolescent motherhood was 18.6%. Poverty and household crowding were associated with greater chances of AM (p values of 0.038 and <  0.001, respectively), as well as not being in a stable relationship (OR 2.26 (95%CI: 1.67, 3.07), p <  0.001). AM showed a greater chance of not using community health services (p <  0.001), had fewer prenatal consultations (β − 0.432 (95%CI: − 0.75, − 0.10)) and started prenatal care at a later date (β 0.38 (95%CI: 0.21, 0.55), p <  0.001)). AM are also less likely to be tested for HIV and more likely to have urinary tract infections.

Conclusions

Interventions aimed at socially-vulnerable adolescents are suggested. However, if pregnant, adolescents should receive proactive and differentiated prenatal care.
Newborn pulse oximetry screening for critical congenital heart defects
Authors: Jullien Sophie
Published: September 2021

We looked at existing recommendations and supporting evidence addressing the effectiveness of pulse oximetry effective for detecting critical congenital heart defects (CCHDs) in newborns. We also looked at the impact of timing of oximetry and the site of testing in the accuracy of screening, and at the potential harms and limitations of pulse oximetry screening,

We conducted a literature search up to the 13th of August 2019 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported.

Current evidence supports consistent accuracy for detection of CCHDs in newborns by pulse oximetry screening in addition to antenatal ultrasonography and clinical examination. Overall, early diagnosis of CCHD with pulse oximetry is judged to be beneficial and cost-effective, and potential harms associated with false-positive tests are not serious, while missing CCHDs and other serious diseases detected by hypoxaemia in absence of pulse oximetry screening can lead to serious consequences. The site of testing (post-ductal versus pre- and post-ductal) had no significant effect on sensitivity nor specificity for detection of CCHDs.
Vitamin D prophylaxis in infancy
Authors: Jullien Sophie
Published: September 2021

We looked at existing recommendations and supporting evidence on the effectiveness of vitamin D supplementation in infancy for reducing vitamin D deficiency and for preventing rickets and infections. We also looked at optimal dose of vitamin D and the age until which vitamin D supplementation is beneficial.

We conducted a literature search up to the 17th of July 2019 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported.

A daily dose of 400 international units of vitamin D in infants has shown to be effective for improving bone health and preventing rickets. Evidence is more robust in groups of infants and children at risk. Vitamin D supplementation is well tolerated, and not associated with toxicity. Higher doses have not shown to add benefit while it could potentially cause toxic blood levels and hypercalcemia. Adequate levels of vitamin D might not be achieved with lower daily doses. Universal vitamin D supplementation starting shortly after birth, regardless of the mode of feeding and until 12 months of age, is strongly recommended. Beyond 12 months of age vitamin D supplementation is recommended only in groups of children at risk.
Leflunomide therapy for IgA vasculitis with nephritis in children
Authors: Hou Ling , Zhang Zhou , Du Yue
Published: September 2021

Background

Henoch-Schönlein purpura (HSP), also called IgA vasculitis, is a systemic vasculitis characterized by deposits of immunoglobulin A in blood vessels. Renal impairment of these patients is the main determinant of prognosis. The optimal treatment of HSP nephritis (HSPN) in children remains controversial, but many clinicians administer an immunosuppressive agent with a corticosteroid. A previous study reported that leflunomide (LEF) with a corticosteroid was effective for adult patients with HSPN and nephrotic proteinuria. However, data on this treatment in pediatric patients is limited.

Methods

We described our experience at a single center on the use of LEF in 5 pediatric patients who had IgA vasculitis with proteinuria that was nearly 50 mg/kg (nephrotic range) and remained high despite administration of intravenous steroid, and biopsy-proven nephritis. All patients had class II to IIIb lesions based on the International Study of Kidney Disease in Children (ISKDC).

Results

We successfully treated all 5 children who had IgA vasculitis with nephritis using LEF with a corticosteroid. Four patients achieved a complete remission of proteinuria, and 1 patient had significantly reduced proteinuria. The children received LEF for 6 months to 12 months, and none of them had severe adverse events.

Conclusions

To our knowledge, this is the first case series to report successful treatment of pediatric HSPN with LEF in combination with a corticosteroid.
Risk and protective factors of depression in the general population during the COVID-19 epidemic in Korea
Authors: Kim Sung-Wan , Park In-Hoo , Kim Mina , Park A-La , Jhon Min , Kim Ju-Wan , Kang Hee-Ju , Ryu Seunghyong , Lee Ju-Yeon , Kim Jae-Min
Published: September 2021

Background

The risk of depression has risen in the general population during the COVID-19 epidemic. This study was conducted to explore risk and protective factors associated with depression among the general population uninfected by COVID-19.

Methods

A cross-sectional study was conducted with 1,500 representative South Korean citizens aged 19–65 years through an anonymous online survey. Depression was defined as a Patient Health Questionnaire-9 score of 10 or higher. Other questionnaires included one measuring psycho-behavioural and social changes, and stress, due to COVID-19, a six-item version of the Gratitude Questionnaire (GQ-6), and a three-item version of the UCLA loneliness scale.

Results

Of the 1492 participants not infected by COVID-19, 312 (20.9%) exhibited depression. Multiple logistic regression analysis revealed that depression was positively associated with COVID-19-related stress and psycho-behavioural variables such as disturbances in eating and sleeping, younger age, smoking, underlying mental illness, and loneliness scale scores. In contrast, exercise three or more times per week and GQ-6 scale scores were inversely associated with depression.

Conclusion

During the COVID-19 pandemic, maintaining daily routines including eating, sleeping, and regular exercise and focusing on gratitude may be important for the prevention of depression. In addition, more attention should be paid to vulnerable populations, including young people, those with mental illnesses, and smokers, who might be more susceptible to depression.
Hyperoxaemia and hypoxaemia are associated with harm in patients with ARDS
Authors: Boyle Andrew J. , Holmes David N. , Hackett Jonathan , Gilliland Susanna , McCloskey Michael , O’Kane Cecilia M. , Young Paul , Di Gangi Stefania , McAuley Daniel F.
Published: September 2021

Background

Oxygen therapy is routinely administered to mechanically ventilated patients. However, there remains uncertainty about the optimal oxygen titration target in patients with the acute respiratory distress syndrome (ARDS).

Methods

Prospectively identified adult patients meeting the Berlin definition of ARDS between 1st January 2014 and 13th December 2016 were analyzed. Oxygen exposure variables were collected at 6-hourly intervals. The primary exposure was the average time-weighted partial pressure of arterial oxygen (PaO2) calculated over a maximum of 7 days from meeting ARDS criteria. The primary outcome was ICU mortality. Univariable and multivariable logistic regression analyses were performed to assess the impact of exposure variables on clinical outcomes. Results are presented as odds ratio [95% confidence interval].

Results

202 patients were included in the final analysis. Overall ICU mortality was 31%. The average time-weighted PaO2 during the first 7 days of ARDS was similar between non-survivors and survivors (11.3 kPa [10.2, 12.5] (84.8 mmHg [76.5, 93.8]) vs. 11.9 kPa [10.9, 12.6] (89.3 mmHg [81.8, 94.5]); p = 0.08). In univariable and multivariable analysis, average time-weighted PaO2 demonstrated a U-shaped relationship with ICU mortality. There was a similar relationship identified with hospital mortality.

Conclusions

In patients with ARDS, the predicted probability of both ICU and hospital mortality was lowest when the average time-weighted PaO2 was between 12.5 and 14 kPa (93.8–105.0 mmHg), suggesting this is a reasonable oxygenation target for clinicians to aim for.