bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical implications of pachyvessels in polypoidal choroidal vasculopathy
Authors: Ijuin Nobuo , Tsujinaka Hiroki , Hirai Hiromasa , Jimura Hironobu , Nakao Shigeya , Yamashita Mariko , Nishi Tomo , Ueda Tetsuo , Ogata Nahoko
Published: April 2020

Background

Polypoidal choroidal vasculopathy (PCV) is one of the disorders within the pachychoroid spectrum diseases. The presence of pachyvessels is one of the characteristics of pachychoroid disorders. However, the relationship between the presence of pachyvessels and the clinical characteristics of PCV eyes has not been determined. The purpose of this study was to determine the relationship between the presence of choroidal pachyvessels and the clinical characteristics of eyes with PCV.

Methods

The medical records of patients who were diagnosed with PCV and were treatment-naïve were reviewed. Fluorescein and indocyanine green angiography, fundus photography, spectral domain optical coherence tomography (SD-OCT), and enhanced depth imaging OCT (EDI-OCT) were used to obtain images of the choroid. The presence of pathologically dilated outer choroidal vessels, pachyvessels, was determined by ICGA images. These pachyvessels were confirmed to correspond with the large choroidal vessels in the EDI OCT images. The PCV eyes were divided into two groups based on the presence or absence of pachyvessels and clinical features and subfoveal choroidal thickness (SFCT) were evaluated between the two groups.

Results

Eighty-six eyes of 84 patients with PCV were evaluated. Pachyvessels were detected in 48 eyes (55.8%). The mean SFCT was 203.9 ± 83.9 μm in all 86 eyes, and it was significantly thinner in eyes with pachyvessels (+) than without pachyvessels (−) (183.2 ± 58.4 μm vs 230.2 ± 103.1 μm; P = 0.01). The differences in the incidence of subretinal fluid, pigment epithelial detachments, and hemorrhages between the two groups were not significant. However, the PCV eyes in pachyvessels (+) group with hemorrhage had the thinnest choroid (P = 0.047). The choroidal features of the fellow eyes were similar to those of the PCV affected eyes, that is, the fellow eyes in pachyvessels (+) group had pachyvessels and the fellow eyes in pachyvessels (−) group did not have pachyvessels.

Conclusions

Pachyvessels were presented 55.8% in eyes with PCV, and these eyes had the thin SFCT. The presence of pachyvessels and attenuation of the inner choroid were probably due to the pathological changes in the eyes with PCV.
Two cases of diabetic macular edema complicated by an atypical macular hole
Authors: Yoshida Yuich , Sato Takaki , Oosuka Shou , Mimura Masashi , Fukumoto Masanori , Kobayashi Takatoshi , Kida Teruyo , Ikeda Tsunehiko
Published: April 2020

Background

Here we report two patients who developed an atypical macular hole (MH) during the treatment course for diabetic macular edema (DME).

Case presentations

Patient 1 was a 73-year-old male. Optical coherence tomography (OCT) revealed perifoveal retinoschisis (RS) in addition to cystoid macular edema and serous retinal detachment (SRD) in his left eye, and that an MH had developed during the clinical course. A convex surface was formed at the MH margin toward the vitreous cavity, and granular shadows were observed in the fluid cuff. Intraoperative findings revealed a thin epiretinal macular membrane (ERM) around the MH. Patient 2 was a 79-year-old male. Although the patient underwent pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) in both eyes, RS and a thin ERM in addition to SRD was observed in his left eye after surgery, and an MH developed during the clinical course. As in Patient 1, a convex surface was formed at the fluid cuff margin toward the vitreous cavity.

Conclusions

Both patients had persistent DME, SRD, RS, and a thin ERM before the development of the MH. OCT revealed the formation of a convex surface at the MH margin toward the vitreous cavity, suggesting that the fragility of the layered structure of the retina combined with tangential retinal traction may have been involved in the atypical MH form.
The prevalence of hepatitis C virus infection in β-thalassemia patients in Pakistan: a systematic review and meta-analysis
Authors: Akhtar Sohail , Nasir Jamal Abdul , Hinde Andrew
Published: April 2020

Background

Hepatitis C virus infection is the most commonly reported bloodborne infection in Pakistan. Frequent blood transfusions in β-thalassemia patients expose them to a high risk of HCV infection. The purpose of this paper is to summarise the current data on the prevalence of HCV infection in β-thalassemia patients in Pakistan by using a systematic review and meta–analysis.

Methods

PubMed, EMBASE, Web of Sciences, the Cochrane Library, Directory of Open Access Journal and local databases were systematically searched for studies published between January 1st, 1995 and May 31st, 2019. Meta-analysis was performed using the DerSimonian and Laird random-effects models with inverse variance weighting. The presence of publication bias was tested by Egger test, and the methodological quality of each included article was evaluated by the STROBE.

Results

We identified a total of 229 potential studies, of which 27 studies were finally considered in the meta-analysis. The pooled prevalence of HCV in β-thalassemia patients in Pakistan was 36.21% (95% CI: 28.98–43.75%) based on 5789 β-thalassemia patients, but there was considerable heterogeneity. Meta-analysis estimated the HCV prevalence among the β-thalassemia patients at 45.98% (95% CI: 38.15–53.90%) in Punjab, 31.81% (95% CI: 20.27–44.59%) in Sindh, and 28.04% (95% CI: 13.58–45.26%) in Khyber Pakhtunkhwa. Meta–regression analysis showed that geographical location was a key source of heterogeneity.

Conclusions

The pooled prevalence of HCV in β-thalassemia patients in Pakistan was more than one in three, and higher than in neighbouring countries. It varies regionally within the country. With the use of standard prevention procedures during blood transfusion, the risk of HCV transmission in β-thalassemia patients could be controlled and the prevalence of HCV in β-thalassemia patients reduced.
Development and outcomes of a comprehensive multidisciplinary incidental lung nodule and lung cancer screening program
Authors: LeMense Gregory P. , Waller Ernest A. , Campbell Cheryl , Bowen Tyler
Published: April 2020

Background

Appropriate management of lung nodules detected incidentally or through lung cancer screening can increase the rate of early-stage diagnoses and potentially improve treatment outcomes. However, the implementation and management of comprehensive lung nodule programs is challenging.

Methods

This single-center, retrospective report describes the development and outcomes of a comprehensive lung nodule program at a community practice in Tennessee. Computed tomography (CT) scans potentially revealing incidental lung nodules were identified by a computerized search. Incidental or screening-identified lung nodules that were enlarging or not seen in prior scans were entered into a nodule database and guideline-based review determined whether to conduct a diagnostic intervention or radiologic follow-up. Referral rates, diagnosis methods, stage distribution, treatment modalities, and days to treatment are reported.

Results

The number of patients with lung nodules referred to the program increased over 2 years, from 665 patients in Year 1 to 745 patients in Year 2. Most nodules were incidental (62–65%). Nodules identified with symptoms (15.2% in Year 1) or through screening (12.6% in Year 1) were less common. In Year 1, 27% (182/665) of nodules required a diagnostic intervention and 18% (121/665) were malignant. Most diagnostic interventions were image-guided bronchoscopy (88%) or percutaneous biopsy (9%). The proportion of Stage I-II cancer diagnoses increased from 23% prior to program implementation to 36% in Year 1 and 38% in Year 2. In screening cases, 71% of patients completed follow-up scans within 18 months. Only 2% of Year 1 patients under watchful waiting required a diagnostic intervention, of which 1% received a cancer diagnosis.

Conclusions

The current study reports outcomes over the first 2 years of a lung cancer screening and incidental nodule program. The results show that the program was successful, given the appropriate level of data management and oversight. Comprehensive lung nodule programs have the potential to benefit the patient, physician, and hospital system.
Contribution of social factors to readmissions within 30 days after hospitalization for COPD exacerbation
Authors: Goto Tadahiro , Yoshida Kazuki , Faridi Mohammad Kamal , Camargo Carlos A. , Hasegawa Kohei
Published: April 2020

Background

To investigate whether, in patients hospitalized for COPD, the addition of social factors improves the predictive ability for the risk of overall 30-day readmissions, early readmissions (within 7 days after discharge), and late readmissions (8–30 days after discharge).

Methods

Patients (aged ≥40 years) hospitalized for COPD were identified in the Medicare Current Beneficiary Survey from 2006 through 2012. With the use of 1000 bootstrap resampling from the original cohort (training-set), two prediction models were derived: 1) the reference model including age, comorbidities, and mechanical ventilation use, and 2) the optimized model including social factors (e.g., educational level, marital status) in addition to the covariates in the reference model. Prediction performance was examined separately for 30-day, early, and late readmissions.

Results

Following 905 index hospitalizations for COPD, 18.5% were readmitted within 30 days. In the test-set, for overall 30-day readmissions, the discrimination ability between reference and optimized models did not change materially (C-statistic, 0.57 vs. 0.58). By contrast, for early readmissions, the optimized model had significantly improved discrimination (C-statistic, 0.57 vs. 0.63; integrated discrimination improvement [IDI], 0.018 [95%CI, 0.003–0.032]) and reclassification (continuous net reclassification index [NRI], 0.298 [95%CI 0.060–0.537]). Likewise, for late readmissions, the optimized model also had significantly improved discrimination (C-statistic, 0.65 vs. 0.68; IDI, 0.026 [95%CI 0.009–0.042]) and reclassification (continuous NRI, 0.243 [95%CI 0.028–0.459]).

Conclusions

In a nationally-representative sample of Medicare beneficiaries hospitalized for COPD, we found that the addition of social factors improved the predictive ability for readmissions when early and late readmissions were examined separately.
Comparison of explicit values clarification method (VCM), implicit VCM and no VCM decision aids for men considering prostate cancer screening: protocol of a randomized trial
Authors: Baptista S. , Heleno B. , Teixeira A. , Taylor K. L. , Martins C.
Published: April 2020

Background

Screening with prostate-specific antigen (PSA) test for prostate cancer is considered a preference sensitive decision; meaning it does not only depend on what is best from a medical point of view, but also from a patient value standpoint. Decision aids are evidence-based tools which are shown to help people feel clearer about their values; therefore it has been advocated that decision aids should contain a specific values clarification method (VCM). VCMs may be either implicit or explicit, but the evidence concerning the best method is scarce. We aim to compare the perceived clarity of personal values in men considering PSA screening using decision aids with no VCM versus an implicit VCM versus an explicit VCM.

Methods

Male factory employees from an industrial facility in the Northern region of Portugal aged 50 to 69 years old will be randomly assigned to one of three decision aid groups used to support prostate cancer screening decisions: (i) decision aid with information only (control), (ii) decision aid with information plus an implicit VCM, (iii) decision aid with information plus an explicit VCM.

Men will be allowed release time from work to attend a session at their workplace. After a brief oral presentation, those willing to participate in the study will fill the baseline questionnaire, plus a 5 point-Likert scale question about intentions to undergo screening, and will then receive the intervention materials to complete.

We estimated a total sample size of 276 participants; with 92 in each group.

The primary outcome will be the perceived clarity of personal values assessed by the Portuguese validated translation of the three subscales of the Decisional Conflict Scale. Secondary outcomes will be intention to be screened (before and after the intervention), the total score from the Decisional Conflict Scale and the self-report of having or not undergone screening at 6 months.

Discussion

This study will add to the body of evidence on the role of decision aids to support health preference-sensitive choices and provide further insight on the impact of different methods for eliciting people’s values embedded within a decision aid.

Trial registration

NCT03988673 - clinicalTrials.gov (2019/06/17).
Pharmacy professionals’ experiences and perceptions of providing NHS patient medicines helpline services: a qualitative study
Authors: Williams Matt , Jordan Abbie , Scott Jenny , Jones Matthew D.
Published: April 2020

Background

Patient medicines helpline services (PMHS) have been established at some National Health Service (NHS) Trusts in England, with the aim of providing medicines-related support to patients after they have been discharged. Addressing an important knowledge gap, this qualitative study sought to examine pharmacy professionals’ experiences and perceptions of their PMHS, including perceived benefits of the services, and areas for improvement.

Methods

Invitations to participate were sent to all NHS Trusts within England that were known to provide a PMHS (n = 117). Semi-structured interviews were conducted via telephone with 34 pharmacy professionals who provide a PMHS (female = 76%, male = 24%; predominantly from Acute NHS Trusts, 76%). Interviews were audio-recorded and transcribed verbatim. The RE-AIM framework for evaluating interventions (RE-AIM: Reach, Effectiveness, Adoption, Implementation, Maintenance) informed the development of the interview schedule and the analysis of the data using framework analysis.

Results

Two themes were generated from the analysis:Resources,andPerceived benefits. Findings illustrate how providing a PMHS with limited resources (e.g., no specific funding, understaffed) negatively impacts the implementation, maintenance and reach of PMHS, and the ability to evidence their effectiveness. Despite operating with limited resources, PMHS are considered to have many benefits for patients and healthcare organisations (e.g., providing a ‘safety net’ to patients during the transfer of care period, providing reassurance to patients, helping to optimise patients’ medicines, resolving medicines-related errors, reducing the burden upon other services, and providing the potential to improve hospital services based upon the content of enquiries). However, actually establishing the effectiveness and cost-effectiveness of PMHS is challenging due to perceived logistical difficulties of collecting data, and the difficulty measuring hard outcomes (e.g., prevention of readmissions).

Conclusions

PMHS are typically perceived to be under-resourced, although they are considered by pharmacy professionals to have several benefits for service users and NHS Trusts. For those sites that provide a PMHS, we recommend using enquiry data to improve hospital services, and to share ideas for implementing and maintaining a PMHS within a resource-limited context. High-quality research is needed to evidence the effectiveness and cost-effectiveness of PMHS, which may help to secure adequate resources for this service in the future.
Assessment of a novel scanner-supported system for processing of child health and immunization data in Uganda
Authors: Äijö Annika , Schäffner Ina , Waiswa Peter , Kananura Rornald Muhumuza , Tessma Mesfin Kassaye , Hanson Claudia
Published: April 2020

Background

Electronic data capturing has the potential to improve data quality and user-friendliness compared to manually processed, paper-based documentation systems. The MyChild system uses an innovative approach to process immunization data by employing detachable vouchers integrated into a vaccination booklet which are then scanned and converted into individual-level health data. The aim was to evaluate the MyChild data capturing system by assessing the proportion of correctly processed vouchers and to compare the user-friendliness in term of time spent on documentation and health worker experiences with the standard health information system at health facilities in Uganda.

Methods

We used a mixed method approach. Documented data were manually copied and compared to processed health records to calculate the proportion of correctly registered vouchers. To compare time spend on documentation we did a continuous observational time-motion study and analyzed data using a Mann-Whitney U test. Semi-structured interviews were conducted to assess health workers’ experiences and analyzed using conventional content analysis. Data was collected in 14 health facilities in two districts in Uganda using different systems.

Results

The MyChild system processed 97% (224 of 231) of the vouchers correctly. Recording using the MyChild system increased time spend on documentation of vaccination follow-up visits by 24 s compared to the standard system (02:25 vs. 02:01 min/child, Mann-Whitney U = 6293, n1 = 115, n2 = 151, p < 0.001 two-tailed, Z = − 3.861, r = 0.186). However, high variance between health centers using the same health information system suggests that documentation time differences can be attributed to other factors than the way information was processed. Health workers perceived both health management information systems as predominantly functional and easy to use, while the MyChild system achieved a higher level of satisfaction.

Conclusions

The MyChild system electronically processes individual-level immunization data correctly without increasing significantly time spent on recording and is appreciated by health providers making it a potential solution to overcome shortcomings of present paper-based health information systems in health centers.
A systematic review of changing malaria disease burden in sub-Saharan Africa since 2000: comparing model predictions and empirical observations
Authors: Kamau Alice , Mogeni Polycarp , Okiro Emelda A. , Snow Robert W. , Bejon Philip
Published: April 2020

Background

The most widely used measures of declining burden of malaria across sub-Saharan Africa are predictions from geospatial models. These models apply spatiotemporal autocorrelations and covariates to parasite prevalence data and then use a function of parasite prevalence to predict clinical malaria incidence. We attempted to assess whether trends in malaria cases, based on local surveillance, were similar to those captured by Malaria Atlas Project (MAP) incidence surfaces.

Methods

We undertook a systematic review (PROSPERO International Prospective Register of Systematic Reviews; ID = CRD42019116834) to identify empirical data on clinical malaria in Africa since 2000, where reports covered at least 5 continuous years. The trends in empirical data were then compared with the trends of time-space matched clinical malaria incidence from MAP using the Spearman rank correlation. The correlations (rho) between changes in empirically observed and modelled estimates of clinical malaria were displayed by forest plots and examined by meta-regression.

Results

Sixty-seven articles met our inclusion criteria representing 124 sites from 24 African countries. The single most important factor explaining the correlation between empirical observations and modelled predictions was the slope of empirically observed data over time (rho = − 0.989; 95% CI − 0.998, − 0.939; p < 0.001), i.e. steeper declines were associated with a stronger correlation between empirical observations and modelled predictions. Factors such as quality of study, reported measure of malaria and endemicity were only slightly predictive of such correlations.

Conclusions

In many locations, both local surveillance data and modelled estimates showed declines in malaria burden and hence similar trends. However, there was a weak association between individual surveillance datasets and the modelled predictions where stalling in progress or resurgence of malaria burden was empirically observed. Surveillance data were patchy, indicating a need for improved surveillance to strengthen both empiric reporting and modelled predictions.
O-GlcNAcylation and its role in the immune system
Authors: Chang Yi-Hsuan , Weng Chia-Lin , Lin Kuo-I
Published: April 2020

O-linked-N-acetylglucosaminylation (O-GlcNAcylation) is a type of glycosylation that occurs when a monosaccharide, O-GlcNAc, is added onto serine or threonine residues of nuclear or cytoplasmic proteins by O-GlcNAc transferase (OGT) and which can be reversibly removed by O-GlcNAcase (OGA). O-GlcNAcylation couples the processes of nutrient sensing, metabolism, signal transduction and transcription, and plays important roles in development, normal physiology and physiopathology. Cumulative studies have indicated that O-GlcNAcylation affects the functions of protein substrates in a number of ways, including protein cellular localization, protein stability and protein/protein interaction. Particularly, O-GlcNAcylation has been shown to have intricate crosstalk with phosphorylation as they both modify serine or threonine residues. Aberrant O-GlcNAcylation on various protein substrates has been implicated in many diseases, including neurodegenerative diseases, diabetes and cancers. However, the role of protein O-GlcNAcylation in immune cell lineages has been less explored. This review summarizes the current understanding of the fundamental biochemistry of O-GlcNAcylation, and discusses the molecular mechanisms by which O-GlcNAcylation regulates the development, maturation and functions of immune cells. In brief, O-GlcNAcylation promotes the development, proliferation, and activation of T and B cells. O-GlcNAcylation regulates inflammatory and antiviral responses of macrophages. O-GlcNAcylation promotes the function of activated neutrophils, but inhibits the activity of nature killer cells.
Establishment and characterization of stable red, far-red (fR) and near infra-red (NIR) transfected canine prostate cancer cell lines
Authors: Liu Wen , Sender Sina , Kong Weibo , Beck Julia , Sekora Anett , Bornemann-Kolatzki Kirsten , Schuetz Ekkehart , Junghanss Christian , Brenig Bertram , Nolte Ingo , Murua Escobar Hugo
Published: April 2020

Background

Canine prostate cancer represents a unique model for human prostate cancer. In vitro systems offer various possibilities but Xenograft in vivo imaging allows studying complex tasks as tumor progression and drug intervention longitudinal. Herein, we established three canine prostate carcinoma cell lines stably expressing fluorescent proteins allowing deep tissue in vivo imaging.

Methods

Three canine prostate carcinoma (cPC) cell lines were stably transfected with fluorescent proteins in red, far-red and near infra-red spectrum, followed by G418 selection. Fluorescent protein expression was demonstrated by microscopy, flow cytometry and a NightOWL LB 983 in vivo imaging system. Cellular and molecular characteristics of the generated cell lines were compared to the parental cell line CT1258. Cell proliferation, metabolic activity and sphere formation capacity were analyzed. Stem cell marker expression was examined by qPCR and genomic copy number variation by genomic DNA whole genome sequencing.

Results

Three stably fluorescent protein transfected cPC cell lines were established and characterized. Compared to the parental cell line, no significant difference in cell proliferation and metabolic activity were detected. Genomic copy number variation analyses and stem cell marker gene expression revealed in general no significant changes. However, the generated cell line CT1258-mKate2C showed uniquely no distal CFA16 deletion and an elevated metabolic activity. The introduced fluorescencent proteins allowed highly sensitive detection in an in vivo imaging system starting at cell numbers of 0.156 × 106. Furthermore, we demonstrated a similar sphere formation capacity in the fluorescent cell lines. Interestingly, the clone selected CT1258-mKate2C, showed increased sphere formation ability.

Discussion

Starting from a well characterized cPC cell line three novel fluorescent cell lines were established showing high cellular and molecular similarity to the parental cell line. The introduction of the fluorescent proteins did not alter the established cell lines significantly. The red fluorescence allows deep tissue imaging, which conventional GFP labeling is not able to realize.

Conclusion

As no significant differences were detected between the established cell lines and the very well characterized parental CT1258 the new fluorescent cell lines allow deep tissue in vivo imaging for perspective in vivo evaluation of novel therapeutic regimens.
Risk and reward: extending stochastic glycaemic control intervals to reduce workload
Authors: Uyttendaele Vincent , Knopp Jennifer L. , Shaw Geoffrey M. , Desaive Thomas , Chase J. Geoffrey
Published: April 2020

Background

STAR is a model-based, personalised, risk-based dosing approach for glycaemic control (GC) in critically ill patients. STAR provides safe, effective control to nearly all patients, using 1–3 hourly measurement and intervention intervals. However, the average 11–12 measurements per day required can be a clinical burden in many intensive care units. This study aims to significantly reduce workload by extending STAR 1–3 hourly intervals to 1 to 4-, 5-, and 6-hourly intervals, and evaluate the impact of these longer intervals on GC safety and efficacy, using validated in silico virtual patients and trials methods. A Standard STAR approach was used which allowed more hyperglycaemia over extended intervals, and a STAR Upper Limit Controlled approach limited nutrition to mitigate hyperglycaemia over longer intervention intervals.

Results

Extending STAR from 1–3 hourly to 1–6 hourly provided high safety and efficacy for nearly all patients in both approaches. For STAR Standard, virtual trial results showed lower % blood glucose (BG) in the safe 4.4–8.0 mmol/L target band (from 83 to 80%) as treatment intervals increased. Longer intervals resulted in increased risks of hyper- (15% to 18% BG > 8.0 mmol/L) and hypo- (2.1% to 2.8% of patients with min. BG < 2.2 mmol/L) glycaemia. These results were achieved with slightly reduced insulin (3.2 [2.0 5.0] to 2.5 [1.5 3.0] U/h) and nutrition (100 [85 100] to 90 [75 100] % goal feed) rates, but most importantly, with significantly reduced workload (12 to 8 measurements per day). The STAR Upper Limit Controlled approach mitigated hyperglycaemia and had lower insulin and significantly lower nutrition administration rates.

Conclusions

The modest increased risk of hyper- and hypo-glycaemia, and the reduction in nutrition delivery associated with longer treatment intervals represent a significant risk and reward trade-off in GC. However, STAR still provided highly safe, effective control for nearly all patients regardless of treatment intervals and approach, showing this unique risk-based dosing approach, modulating both insulin and nutrition, to be robust in its design. Clinical pilot trials using STAR with different measurement timeframes should be undertaken to confirm these results clinically.
Magnitude and determinants of multimorbidity and health care utilization among patients attending public versus private primary care: a cross-sectional study from Odisha, India
Authors: Pati Sanghamitra , Swain Subhashisa , Knottnerus J. André , Metsemakers Job F. M. , van den Akker Marjan
Published: April 2020

Background

Multimorbidity in primary care is a challenge not only for developing countries but also for low and medium income countries (LMIC). Health services in LMIC countries are being provided by both public and private health care providers. However, a critical knowledge gap exists on understanding the true extent of multimorbidity in both types of primary care settings.

Methods

We undertook a study to identify multimorbidity prevalence and healthcare utilization among both public and private primary care attendees in Odisha state of India. A total of 1649 patients attending 40 primary care facilities were interviewed using a structured multimorbidity assessment questionnaire collecting information on 22 chronic diseases, medication use, number of hospitalization and number of outpatient visits.

Result

The overall prevalence of multimorbidity was 28.3% and nearly one third of patients of public facilities and one fourth from private facilities had multimorbidity. Leading diseases among patients visiting public facilities included acid peptic diseases, arthritis and chronic back pain. No significant difference in reporting of hypertension and diabetes across the facilities was seen. Besides age, predictors of multimorbidity among patients attending public facilities were, females [AOR: 1.6; 95% CI 1.1–1.3] and non-aboriginal groups [AOR: 1.6; 95%CI 1.1–2.3] whereas, in private females [AOR: 1.6; 95%CI 1.1–2.4], better socioeconomic conditions [AOR 1.4; 95% CI 1.0–2.1] and higher educational status [primary school completed [AOR 2.6; 95%CI 1.6–4.2] and secondary schooling and above [AOR 2.0; 95%CI 1.1–3.6] with reference to no education were seen to be the determinants of multimorbidity. Increased number of hospital visits to public facilities were higher among lower educational status patients [IRR: 1.57; 95% CI 1.13–2.18] whereas, among private patients, the mean number of hospital visits was 1.70 times more in higher educational status [IRR: 1.70; 95%CI 1.01–3.69]. The mean number of medicines taken per day was higher among patients attending private hospitals.

Conclusion

Our findings suggest that, multimorbidity is being more reported in public primary care facilities. The pattern and health care utilization in both types of settings are different. A comprehensive care approach must be designed for private care providers.
Impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections and adverse events of special interest in patients with rheumatoid arthritis or spondyloarthritis: a systematic analysis of the literature and meta-analysis
Authors: Vinson D. , Molet-Benhamou L. , Degboé Y. , den Broeder A. , Ibrahim F. , Pontes C. , Westhovens R. , Závada J. , Pham T. , Barnetche T. , Constantin A. , Ruyssen-Witrand A.
Published: April 2020

Objectives

To systematically review the impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections and severe adverse events (SAEs) in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) in remission or low disease activity (LDA) state.

Materials and methods

A meta-analysis based on a systematic review of PubMed, Embase, Cochrane, until August 2019, as well as relevant databases of international conferences, was used to evaluate the risk difference (RD) at 95% confidence interval (95% CI) of incidence density of serious infections, SAEs, malignancies, cardiovascular adverse events (CV AEs), or deaths after tapering (dose reduction or spacing) compared to continuation of targeted therapies.

Results

Of the 1957 studies initially identified, 13 controlled trials (9 RA and 4 SpA trials) were included in the meta-analysis. 1174 patient-years were studied in the tapering group (TG) versus 1086 in the usual care group (UC). There were 1.7/100 patient-year (p-y) serious infections in TG versus 2.6/100 p-y in UC (RD (95% CI) 0.01 (0.00 to 0.02), p = 0.13) and 7.4/100 p-y SAEs in TG versus 6.7/100 p-y in UC (RD 0.00 (− 0.02 to 0.02), p = 0.82). The risk of malignancies, CV AEs, or deaths did not differ between the tapering and the usual care groups. Subgroup analysis (RA and SpA) detected no significant differences between the two groups.

Conclusion

We could not show significant impact of tapering bDMARD or JAKi over continuation concerning the risk of serious infections, SAEs, malignancies, CV AEs, or deaths in RA and SpA patients in remission or LDA state.
Lemon seed allergy: a case presentation
Authors: Kayode O. Stephanie , Prado Nuevalynne , Thursfield David J. , Till Stephen J. , Siew Leonard Q. C.
Published: April 2020

Background

We report a case of IgE-mediated hypersensitivity to lemon seed. We demonstrate for the first time a pattern of cross-sensitisation between seeds of citrus hybrid species from similar ancestral species origins.

Case report

Described is a case of a 26-year-old female with recurrent anaphylaxis on exposure to lemon seed with sensitisation shown on prick to prick testing. Prick to prick testing was also performed to a variety of citrus fruit seeds and edible foods from additional notable families of the Sapindale order.

Conclusion

In cases of unexplained or recurrent anaphylaxis in adult patients, citrus seed allergy should be considered.
On stable entire solutions of sub-elliptic system involving advection terms with negative exponents and weights
Authors: Rahal Belgacem
Published: April 2020

We examine the weighted Grushin system involving advection terms given by $$ \textstyle\begin{cases} \Delta _{G} u - a \cdot \nabla _{G} u =(1+ \Vert \mathbf{z} \Vert ^{2(\alpha +1)})^{ \frac{\gamma }{2(\alpha +1)}} v^{-p} &\text{in $\mathbb {R}^{n}$}, \\ \Delta _{G} v - a \cdot \nabla _{G} v =(1+ \Vert \mathbf{z} \Vert ^{2(\alpha +1)})^{ \frac{\gamma }{2(\alpha +1)}} u^{-q} &\text{in $\mathbb {R}^{n}$}, \end{cases} $${ΔGu−a⋅∇Gu=(1+∥z∥2(α+1))γ2(α+1)v−pin Rn,ΔGv−a⋅∇Gv=(1+∥z∥2(α+1))γ2(α+1)u−qin Rn, where $\Delta _{G} u= \Delta _{x} u+ |x|^{2\alpha } \Delta _{y} u$ΔGu=Δxu+|x|2αΔyu, $\mathbf{z}=(x,y) \in \mathbb {R}^{n}:= \mathbb {R}^{n_{1}} \times \mathbb {R}^{n_{2}}$z=(x,y)∈Rn:=Rn1×Rn2 is the Grushin operator, $\alpha \geq 0$α≥0, $p \geq q >1$p≥q>1, $\|\mathbf{z}\|^{2(\alpha +1)}= |x|^{2(\alpha +1)} + |y|^{2} $∥z∥2(α+1)=|x|2(α+1)+|y|2, $\gamma \geq 0$γ≥0 and a is a smooth divergence-free vector that we will specify later. Inspired by recent progress in the study of the Lane–Emden system, we establish some Liouville-type results for bounded stable positive solutions of the system. In particular, we prove the comparison principle to establish our result. As consequences, we obtain a Liouville-type theorem for the weighted Grushin equation involving advection terms $$ \Delta _{G} u - a \cdot \nabla _{G} u =\bigl(1+ \Vert \mathbf{z} \Vert ^{2(\alpha +1)}\bigr)^{ \frac{\gamma }{2(\alpha +1)}} u^{-p} \quad \mbox{in } \mathbb {R}^{n}. $$ΔGu−a⋅∇Gu=(1+∥z∥2(α+1))γ2(α+1)u−pin Rn. The main tools in the proof of the main result are the comparison principle, nonlinear integral estimates via the stability assumption and the bootstrap argument. Our results generalize and improve the previous work in (Duong et al. in Complex Var. Elliptic Equ. 64(12):2117–2129, 2019).
Affine-periodic solutions by asymptotic and homotopy equivalence
Authors: Xing Jiamin , Yang Xue
Published: April 2020

This paper studies the existence of affine-periodic solutions which have the form of$x(t+T)=Qx(t)$x(t+T)=Qx(t)with some nonsingular matrixQ. Depending on the structure ofQ, they can be periodic, anti-periodic, quasi-periodic or even unbounded. Krasnosel’skii–Perov type existence theorem, asymptotic and homotopy equivalence approaches are given.
Methodological issues on “challenges and opportunities towards the road of universal health coverage (UHC) in Nepal: a systematic review”
Authors: Amir-Behghadami Mehrdad , Janati Ali , Gholizadeh Masoumeh
Published: April 2020

Systematic reviews adhere to the principle that science is cumulative and attempt to identify all empirical evidence in accordance with pre-determined eligibility criteria to answer a specific research question. Therefore, in order to achieve reliable findings, these studies must use an explicit method, as they are increasingly used to guide political decision and the direction of future research. We would like to thank the authors Chhabi Lal Ranabhat et al., for the article “Challenges and opportunities towards the road of universal health coverage (UHC) in Nepal: a systematic review”. Although the authors have stated that they reported th according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, some items have not been well reported. We critically appraised it using the PRISMA guidelines. Results of the study were significantly valuable, but some important points that hamper the utility of the study need to be considered by the audors. The purpose of this letter is to improve the quality of study and present methodological issues about the search strategy, quality assessment of included studies, and data analysis and synthesis.
Methodological issues on ‘challenges and opportunities towards the road of universal health coverage (UHC) in Nepal: a systematic review’
Authors: Ranabhat Chhabi Lal , Acharya Devaraj
Published: April 2020

Challenges and opportunities towards the road of universal health coverage (UHC) in Nepal: a systematic review’ is a policy review paper and we published in BMC – Archives of Public Health. Policy research is the process of conducting research, analysis of, a fundamental social problem in order to provide policymakers with pragmatic, action-oriented recommendations for alleviating the problem. The objective of this paper is to illustrate some methodological issues used in that paper.
Primary breast non-Hodgkin’s lymphoma in a 14-year-old girl: a case report
Authors: Ishizuka Yumiko , Horimoto Yoshiya , Fujimura Junya , Ogata Kozue , Murakami Fumi , Onagi Hiroko , Arakawa Atsushi , Saito Mitsue
Published: April 2020

Background

Primary breast lymphoma is rare. Occurrence rates of malignant breast tumors in children are also quite low. We herein report a B-lymphoblastic lymphoma of the breast arisen in an adolescent girl. To the best of our knowledge, this is the youngest case with primary breast non-Hodgkin’s lymphoma.

Case presentation

A 14-year-old Japanese girl felt a lump in her right breast and came to our hospital. A circumscribed soft mass, 30 mm in diameter, was palpable. Histological examination revealed atypical lymphoid cells diffusely spreading into the breast tissue. Based on results of immunohistochemistry and flow cytometry, her disease was diagnosed as B-lymphoblastic lymphoma (stage I). She was then referred to the pediatric department and received combination chemotherapy, based on a chemotherapy regimen for children with acute lymphoblastic leukemia. Following remission induction therapy, we confirmed no FDG uptake in the right breast on PET-CT scan.

Conclusions

We have described a rare malignant lymphoma arising in the breast of an adolescent female. Histological assessment is necessary for diagnosis of breast lymphoma. However, it can be challenging with several reasons, and clinical information may contribute to the assessment. Moreover, treatments for lymphoma vary according to disease types. Thus, surgeons should collaborate closely with pathologists, pediatricians, and hematologists.
Translating pharmacogenetics from research to routine clinical practice – a survey of the IGNITE Network
Authors: Levy Kenneth D. , Wu R. Ryanne , Goto Daisuke , Ramos Michelle A. , Pratt Victoria M. , Hicks J. Kevin , Madden Ebony B. , Bell Gillian C. , Blake Kathryn V. , Cohen Michelle , Duong Benjamin Q. , Franciosi James P. , Orlando Lori A. , Sanghavi Kunal , Ginsburg Geoffrey S.
Published: April 2020

Background

Translating pharmacogenetic research findings that have shown clinical efficacy into sustainable, routine clinical care at the institutional level requires strong evidence of improved patient outcomes bolstered by equitable reimbursement and a sound financial analysis. Although extensive research on the clinical value of pharmacogenetics has been completed, adoption into clinical practice lags due to a lack of evidence of clinical effectiveness and limited reimbursement.

Methods

The Sustainability Working Group within the NHGRI IGNITE I Network conducted an online survey of funded and non-funded IGNITE members to determine which genes they are researching, which have been translated into clinical practice, and how tests are billed. Data from the online surveys was consolidated and analyzed with results being tabulated for key findings. Due to the limited sample size, statistical analysis was forgone and results should be considered directional in nature.

Results

Fifteen out of twenty (75%) online survey responses were received and analyzed from IGNITE member sites delivering clinical care. Forty different genes were identified as being used for either research or clinical care. Thirty-two different genes were reported as being used clinically, an average of 6.9 genes were reported per site. Twenty-two and twenty-one genes were reported as being billed to third party payers or patients respectively. Although the survey did not ask whether sites submitting for reimbursement received payment, Medicare and Medicaid only reimburse for 6 of the 40 (15%) genes being tested. Of the 40 genes, 18 are rated by CPIC as having A/B level of evidence with the remainder being rated as C/D or having no rating. Approximately 32% more A/B rated genes were being reported clinically than non-A/B.

Conclusion

Adoption of pharmacogenetic testing continues to lag even at sites where leading experts conduct research and have the capability to report tests clinically. Clinical research that supports CPIC A level of evidence is important for provider and payer support. Adoption of pharmacogentic testing must also be justified financially, reimbursement is one key factor, and more health economic studies are needed in order to capture the value created by preventing drug-gene adverse events, emergency room visits, and hospitalizations.
Machine learning applications for electroencephalograph signals in epilepsy: a quick review
Authors: Si Yang
Published: April 2020

Machine learning (ML) is a fundamental concept in the field of state-of-the-art artificial intelligence (AI). Over the past two decades, it has evolved rapidly and been employed wildly in many fields. In medicine the widespread usage of ML has been observed in recent years. The present review examines various ML approaches for electroencephalograph (EEG) signal procession in epilepsy research, highlighting applications in the aspect of automated seizure detection, prediction and orientation. The present review also presents advantage, challenge and future direction of ML techniques in the analysis of EEG signals in epilepsy.
Reflections on community mental healthcare around the world
Authors: Skuse David
Published: April 2020

This editorial introduces three papers inBJPsych Internationalon community mental healthcare in the diverse cultures of Greece, Cambodia and Malawi.
A CRISPR/Cas9 genome editing pipeline in the EndoC-βH1 cell line to study genes implicated in beta cell function
Authors: Grotz Antje K. , Abaitua Fernando , Navarro-Guerrero Elena , Hastoy Benoit , Ebner Daniel , Gloyn Anna L.
Published: April 2020

Type 2 diabetes (T2D) is a global pandemic with a strong genetic component, but most causal genes influencing the disease risk remain unknown. It is clear, however, that the pancreatic beta cell is central to T2D pathogenesis. In vitro gene-knockout (KO) models to study T2D risk genes have so far focused on rodent beta cells. However, there are important structural and functional differences between rodent and human beta cell lines. With that in mind, we have developed a robust pipeline to create a stable CRISPR/Cas9 KO in an authentic human beta cell line (EndoC-βH1). The KO pipeline consists of a dual lentiviral sgRNA strategy and we targeted three genes (INS, IDE, PAM) as a proof of concept. We achieved a significant reduction in mRNA levels and complete protein depletion of all target genes. Using this dual sgRNA strategy, up to 94 kb DNA were cut out of the target genes and the editing efficiency of each sgRNA exceeded >87.5%. Sequencing of off-targets showed no unspecific editing. Most importantly, the pipeline did not affect the glucose-responsive insulin secretion of the cells. Interestingly, comparison of KO cell lines for NEUROD1 and SLC30A8 with siRNA-mediated knockdown (KD) approaches demonstrate phenotypic differences. NEUROD1-KO cells were not viable and displayed elevated markers for ER stress and apoptosis. NEUROD1-KD, however, only had a modest elevation, by 34%, in the pro-apoptotic transcription factor CHOP and a gene expression profile indicative of chronic ER stress without evidence of elevated cell death. On the other hand, SLC30A8-KO cells demonstrated no reduction in KATP channel gene expression in contrast to siRNA silencing. Overall, this strategy to efficiently create stable KO in the human beta cell line EndoC-βH1 will allow for a better understanding of genes involved in beta cell dysfunction, their underlying functional mechanisms and T2D pathogenesis.
Primary Incidence of Autoimmune Tyroiditis in the Republic of Belarus and Radiation Factor
Authors: Rozhko V. , Veyalkin I. , Sharshakova T.
Published: April 2020

Actuality: In the Belarus, the primary incidence of thyroid pathology is in the 2d rank among endocrine diseases after diabetes. Studying the trends in the primary incidence of autoimmune thyroiditis (AIT) in the Belarus is important for improving organizational decisions and further improving the quality of medical care for the population.

Purpose: Is to conduct a comparative analysis of the incidence of AIT in the population and in the affected population based on an epidemiological study in the Belarus, taking into account the radiation and organizational components in the formation of pathology.

Material and methods: The data of the republican statistical reports and the data of the Chernobyl Register from 1997 to 2017 were analyzed. Standard methods of descriptive epidemiology were used in the work.

Results: According to Chernobyl Registry, during the observation period (1997–2017), the primary incidence of AIT decreased by 1.4 times (1997 – 135.1 ± 15.77 0/0000; 2017 – 98.4 ± 7.55 0/0000). The incidence was statistically significantly higher in women than men (ratios ranged from 2.39: 1 in 2004 to 4.0: 1 in 2000). Moreover, the incidence according to Chernobyl Registry was higher than in the adult population, but in children where was no difference with population data. This indicates a high-quality clinical examination of the children’s population. Two organizational and medical approaches have been formed in the republic. The first approach (Grodno, Brest, Minsk regions and Minsk) is characterized by periods of moderate growth, decline, and growth again. In the second approach (Vitebsk, Mogilev and Gomel regions), there are two periods when the increase in incidence sharply changes to decrease before the end of the study period. An analysis of the odds ratio allowed us to conclude that insignificant effect of radioactive iodine on the incidence of AIT in children at the time of the accident and its absence in the adult population.

Conclusion: The study confirms the importance of the organizational component in the early diagnosis of AIT.