bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphological, physio-biochemical and nutritional status as potential markers for grafting compatibility in Kalamata olive cultivar
Authors: Rashedy Ahmed AbdelHady , Hamed Hamed Hosni
Published: June 2023

Background

Choosing the most compatible and desirable rootstock for Kalamata olive cultivar is an important decision due to the longevity of the orchard and the difficulty rooting of Kalamata cuttings. Therefore, the goal of this study was to examine the morphological, physio-biochemical, and nutritional status as ppotential markers for grafting compatibility between Kalamata olive cultivar and three olive rootstocks (Coratina, Picual, Manzanillo) during two seasons (2020–2021) as well as follow up physio-bichemical and nutritional status of one-year-old Kalamata plants (2022).

Results

The results indicated that, Picual rootstock recorded the highest significant grafting success which was associated with increasing number of leaves, leaf area and SPAD value in Kalamata scions by 22.15%, 36.86% and 14.64% compared to Manzanillo rootstock as mean of both seasons, respectively. While, Manzanillo rootstock recorded the highest significant activity for peroxidase and catalase by 51.41% and 60.1% at grafting union compared to Picual rootstock. Moreover, Picual rootstock for Kalamata scions had the highest acid invertase and sucrose synthase activities by 67.23% and 57.94% compared to Manzanillo rootstock. Furthermore, Picual rootstock recorded the highest significant Gibberellic acid by 52.8% and 18.6% compared to Coratina and Manzanillo rootstocks. Meanwhile, Picual rootstock recorded the lowest significant Abscisic acid by 68.17% and 63.15% as well as the lowest total phenols by 14.36% and 23.47% compared to Coratina and Manzanillo rootstocks.

Conclusions

This study sheds light for the importance of choosing the suitable rootstock for Kalamata cultivar. Also, sucrose synthase and acid invertase may have a novel role in determining grafting compatibility in olives. Increasing growth promoters (Gibberellic, Nitrogen) and decreasing both growth inhibitors (Abscisic, phenols) and oxidative enzyme (catalase, peroxidase) required for better graft compatibility.
Epipericardial fat necrosis in chest CT and MRI: a case report of an unusual cause of chest pain associated with the initial diagnosis of undifferentiated connective tissue disease
Authors: Barreto Inês , Oliveira Francisca Godinho , Barreira Sofia Carvalho , Inácio João Rodrigues
Published: June 2023

Background

Epipericardial fat necrosis (EFN) is a benign and self-limited condition of unknown cause with a good prognosis, usually affecting otherwise healthy patients. Clinically, it presents with severe acute left pleuritic chest pain, often leading the patient to the Emergency Room (ER).

Case presentation

A 23-year-old male, smoker (5 pack-years), was evaluated in the ER due to left pleuritic chest pain, worsening with deep breathing and Valsalva maneuver. It was not associated with trauma and did not present other symptoms.

The physical examination was unremarkable. The arterial blood gases while breathing room air and the laboratory tests, including D-dimers and high-sensitivity cardiac Troponin T, were normal. The chest radiograph, electrocardiogram, and transthoracic echocardiogram showed no abnormalities.

A computed tomography (CT) pulmonary angiogram showed no signs of pulmonary embolism but depicted at the left cardiophrenic angle a focal 3 cm ovoid-shaped fat lesion with stranding and thin soft tissue margins, consistent with necrosis of the epicardial fat, which was confirmed by magnetic resonance (MRI) of the chest.

The patient was medicated with ibuprofen and pantoprazole, with clinical improvement in four weeks. At a two-month follow-up, he was asymptomatic and presented radiologic resolution of the inflammatory changes of the epicardial fat of the left cardiophrenic angle on chest CT. Laboratory tests revealed positive antinuclear antibodies, positive anti-RNP antibody, and positive lupus anticoagulant. The patient complained of biphasic Raynaud’s phenomenon initiated five years ago, and a diagnosis of undifferentiated connective tissue disease (UCTD) was made.

Conclusions

This case report highlights the diagnosis of EFN as a rare and frequently unknown clinical condition, which should be considered in the differential diagnosis of acute chest pain. It can mimic emergent conditions such as pulmonary embolism, acute coronary syndrome, or acute pericarditis. The diagnosis is confirmed by CT of the thorax or MRI. The treatment is supportive and usually includes non-steroidal anti-inflammatory drugs. The association of EFN with UCTD has not been previously described in the medical literature.
Surveillance of diphtheria in the Netherlands between 2000–2021: cutaneous diphtheria supersedes the respiratory form
Authors: Elsinga Jelte , van Meijeren Dimphey , Reubsaet Frans
Published: June 2023

Background

Diphtheria is a severe respiratory or cutaneous infectious disease, caused by exotoxin producing Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis. Diphtheria is once again prevalent due to breakdown of immunisation programmes, social disruption and unrest.

Aim

This study describes the notified diphtheria cases in the Netherlands between 2000–2021 and isolates that were sent to the National Institute for Public Health and the Environment (RIVM).

Methods

File investigation was performed including all notified cases and isolates of C. diphtheriae, C. ulcerans and C. pseudotuberculosis that were tested for toxin production using a toxin-PCR and Elek test. An exploratory review was performed to understand transmission in populations with a high vaccination uptake.

Results

Eighteen diphtheria notifications were made with confirmed toxigenic C. diphtheriae (n = 9) or ulcerans (n = 9) between 2000 and 2021. Seventeen (94.4%) presented with a cutaneous infection. All cases with a suspected source abroad (n = 8) concerned infection with C. diphtheriae. In contrast, 9/10 cases infected in the Netherlands were caused by C. ulcerans, a zoonosis. Secondary transmission was not reported. Isolates of C. ulcerans sent to the RIVM produced more often the diphtheria exotoxin (11/31; 35%) than C. diphtheriae (7/89; 7.9%).

Conclusion

Both human-to-human transmission of C. diphtheriae and animal-to-human transmission of C. ulcerans rarely occurs in the Netherlands. Cases mainly present with a cutaneous infection. Travel-related cases remain a risk for transmission to populations with low vaccination coverage, highlighting the importance of immunization and diphtheria control measures.
Characterization and evaluation of gene fusions as a measure of genetic instability and disease prognosis in prostate cancer
Authors: Schimmelpfennig Carolin , Rade Michael , Füssel Susanne , Löffler Dennis , Blumert Conny , Bertram Catharina , Borkowetz Angelika , Otto Dominik J. , Puppel Sven-Holger , Hönscheid Pia , Sommer Ulrich , Baretton Gustavo B. , Köhl Ulrike , Wirth Manfred , Thomas Christian , Horn Friedemann , Kreuz Markus , Reiche Kristin
Published: June 2023

Background

Prostate cancer (PCa) is one of the most prevalent cancers worldwide. The clinical manifestations and molecular characteristics of PCa are highly variable. Aggressive types require radical treatment, whereas indolent ones may be suitable for active surveillance or organ-preserving focal therapies. Patient stratification by clinical or pathological risk categories still lacks sufficient precision. Incorporating molecular biomarkers, such as transcriptome-wide expression signatures, improves patient stratification but so far excludes chromosomal rearrangements. In this study, we investigated gene fusions in PCa, characterized potential novel candidates, and explored their role as prognostic markers for PCa progression.

Methods

We analyzed 630 patients in four cohorts with varying traits regarding sequencing protocols, sample conservation, and PCa risk group. The datasets included transcriptome-wide expression and matched clinical follow-up data to detect and characterize gene fusions in PCa. With the fusion calling software Arriba, we computationally predicted gene fusions. Following detection, we annotated the gene fusions using published databases for gene fusions in cancer. To relate the occurrence of gene fusions to Gleason Grading Groups and disease prognosis, we performed survival analyses using the Kaplan–Meier estimator, log-rank test, and Cox regression.

Results

Our analyses identified two potential novel gene fusions, MBTTPS2,L0XNC01::SMS and AMACR::AMACR. These fusions were detected in all four studied cohorts, providing compelling evidence for the validity of these fusions and their relevance in PCa. We also found that the number of gene fusions detected in a patient sample was significantly associated with the time to biochemical recurrence in two of the four cohorts (log-rank test, p-value < 0.05 for both cohorts). This was also confirmed after adjusting the prognostic model for Gleason Grading Groups (Cox regression, p-values < 0.05).

Conclusions

Our gene fusion characterization workflow revealed two potential novel fusions specific for PCa. We found evidence that the number of gene fusions was associated with the prognosis of PCa. However, as the quantitative correlations were only moderately strong, further validation and assessment of clinical value is required before potential application.
Prognostic models for upper urinary tract urothelial carcinoma patients after radical nephroureterectomy based on a novel systemic immune-inflammation score with machine learning
Authors: Liu Jianyong , Wu Pengjie , Lai Shicong , Wang Jianye , Hou Huimin , Zhang Yaoguang
Published: June 2023

Purpose

This study aimed to evaluate the clinical significance of a novel systemic immune-inflammation score (SIIS) to predict oncological outcomes in upper urinary tract urothelial carcinoma(UTUC) after radical nephroureterectomy(RNU).

Method

The clinical data of 483 patients with nonmetastatic UTUC underwent surgery in our center were analyzed. Five inflammation-related biomarkers were screened in the Lasso-Cox model and then aggregated to generate the SIIS based on the regression coefficients. Overall survival (OS) was assessed using Kaplan-Meier analyses. The Cox proportional hazards regression and random survival forest model were adopted to build the prognostic model. Then we established an effective nomogram for UTUC after RNU based on SIIS. The discrimination and calibration of the nomogram were evaluated using the concordance index (C-index), area under the time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration curves. Decision curve analysis (DCA) was used to assess the net benefits of the nomogram at different threshold probabilities.

Result

According to the median value SIIS computed by the lasso Cox model, the high-risk group had worse OS (p<0.0001) than low risk-group. Variables with a minimum depth greater than the depth threshold or negative variable importance were excluded, and the remaining six variables were included in the model. The area under the ROC curve (AUROC) of the Cox and random survival forest models were 0.801 and 0.872 for OS at five years, respectively. Multivariate Cox analysis showed that elevated SIIS was significantly associated with poorer OS (p<0.001). In terms of predicting overall survival, a nomogram that considered the SIIS and clinical prognostic factors performed better than the AJCC staging.

Conclusion

The pretreatment levels of SIIS were an independent predictor of prognosis in upper urinary tract urothelial carcinoma after RNU. Therefore, incorporating SIIS into currently available clinical parameters helps predict the long-term survival of UTUC.
Impact of an immersive, interactive medical education initiative on guideline-based retinal disease management knowledge/competence and effectual practice change
Authors: Singh Rishi P. , Welch Lauren , Longo Nicole L. , Frese Matt
Published: June 2023

Background

Retinal diseases, including wet or dry age-related macular degeneration, diabetic macular edema, and diabetic retinopathy (DR), are underdiagnosed and undertreated in the United States. Clinical trials support the effectiveness of anti-vascular endothelial growth factor (anti-VEGF) therapies for several retinal conditions, but real-world data suggest underuse by clinicians, resulting in patients experiencing poorer visual outcomes over time. Continuing education (CE) has demonstrated effectiveness at changing practice behaviors, but more research is needed to understand whether CE can help address diagnostic and treatment gaps.

Methods

This test and control matched pair analysis examined pre-/post-test knowledge of retinal diseases and guideline-based screening and intervention among 10,786 healthcare practitioners (i.e., retina specialists, ophthalmologists, optometrists, primary care providers, diabetes educators, pharmacists/managed care specialists, and other healthcare providers, such as registered nurses, nurse practitioners, and physician assistants) who participated in a modular, interactive CE initiative. An additional medical claims analysis provided data on practice change, evaluating use of VEGF-A inhibitors among retina specialist and ophthalmologist learners (n = 7,827) pre-/post-education, compared to a matched control group of non-learners. Outcomes were pre-/post-test change in knowledge/competence and clinical change in application of anti-VEGF therapy, as identified by the medical claims analysis.

Results

Learners significantly improved knowledge/competence scores on early identification and treatment, identifying patients who could benefit from anti-VEGF agents, using guideline-recommended care, recognizing the importance of screening and referral, and recognizing the importance of early detection and care for DR (all P-values = 0.003 to 0.004). Compared with matched controls, learners’ incremental total injections for anti-VEGF agents for retinal conditions increased more after the CE intervention (P < 0.001); specifically, there were 18,513 more (new) anti-VEGF injections prescribed versus non-learners (P < 0.001).

Conclusions

This modular, interactive, immersive CE initiative resulted in significant knowledge/competence gains among retinal disease care providers and changes in practice-related treatment behaviors (i.e., appropriate consideration and greater incorporation of guideline-recommended anti-VEGF therapies) among participating ophthalmologists and retina specialists compared to matched controls. Future studies will utilize medical claims data to show longitudinal impact of this CE initiative on treatment behavior among specialists and impact on diagnosis and referral rates among optometrists and primary care providers who participate in future programming.
Can protection motivation theory predict protective behavior against ticks?
Authors: Hansen Mette Frimodt , Sørensen Pelle Korsbaek , Sørensen Anja Elaine , Krogfelt Karen Angeliki
Published: June 2023

Background

Cases of reported tick-borne diseases in humans have increased over the past decades. Strategies informing the public about ticks, their associated diseases, and preventive measures are often highlighted as important in limiting pathogen transfer and disease. However, knowledge about the motivation for people to apply preventative measures is sparse.

Methods

The aim was to examine if Protection Motivation Theory, a model of disease prevention and health promotion, can predict the use of protective measures against ticks. Ordinal logistic regression and Chi-square tests were used on data from a cross-sectional survey with respondents from Denmark, Norway, and Sweden (n = 2658). We examined the effect of (1) the perceived seriousness of tick bites, Lyme borreliosis (LB), and tick-borne encephalitis (TBE), and (2) the perceived probability of getting a tick bite, Lyme borreliosis, and tick-borne encephalitis on protection against ticks. Finally, we examined if there was an association between the use of a protective measure and the perceived efficacy of that measure.

Results

The perceived seriousness of a tick bite and LB significantly predict who is more likely to apply protective measures for all three countries combined. The perceived seriousness of TBE did not significantly predict the level of adoption of protective measures applied by respondents. The perceived likelihood of getting a tick bite within the next 12 months and the perceived likelihood of getting LB if bitten by a tick significantly predicted the application of protective measures. However, the increases in the likelihood of protection were very small. The application of a certain type of protection was always correlated with the perceived efficacy of the same protective measure.

Conclusion

Some variables of PMT may be used to predict the level of adoption of protection applied against ticks and tick-borne diseases. We found that the perceived seriousness of a tick bite and LB significantly predict the level of adoption protection. The perceived likelihood of getting a tick bite or LB also significantly predicted the level of adoption of protection, although the change was very small. The results regarding TBE were less clear. Lastly, there was an association between applying a protective measure and the perceived efficacy of the same measure.
A 20-gene mutation signature predicts the efficacy of immune checkpoint inhibitor therapy in advanced non-small cell lung cancer patients
Authors: Hu Xilin , Guo Jing , Shi Jianguang , Li Da , Li Xinjian , Zhao Weijun
Published: June 2023

Background

There is an unmet need to identify novel predictive biomarkers that enable more accurate identification of individuals who can benefit from immune checkpoint inhibitor (ICI) therapy. The US FDA recently approved tumor mutational burden (TMB) score of ≥ 10 mut/Mb as a threshold for pembrolizumab treatment of solid tumors. Our study aimed to test the hypothesis that specific gene mutation signature may predict the efficacy of ICI therapy more precisely than high TMB (≥ 10).

Methods

We selected 20 candidate genes that may predict for the efficacy of ICI therapy by the analysis of data from a published cohort of 350 advanced non-small cell lung cancer (NSCLC) patients. Then, we compared the influences of various gene mutation signatures on the efficacy of ICI treatment. They were also compared with PD-L1 and TMB. The Kaplan-Meier method was utilized to evaluate the prognosis univariates, while selected univariates were adopted to develop a systematic nomogram.

Results

A high mutation signature, where three or more of the 20 selected genes were mutated, was associated with the significant benefits of ICI therapy. Specifically, patients with high mutation signature were confirmed to have better prognosis for ICI treatment, compared with those with wild type (the median PFS: 7.17 vs. 2.90 months, p = 0.0004, HR = 0.47 (95% [CI]:0.32–0.68); the median OS: unreached vs. 9 months, p = 1.8E-8, HR = 0.17 (95% [CI]:0.11–0.25)). Moreover, those patients with the high mutation signature achieved significant ICI treatment benefits, while there was no difference of OS and PFS between patients without the signature but TMB-H (≥ 10) and those without the signature and low TMB(< 10). Finally, we constructed a novel nomogram to evaluate the efficacy of ICI therapy.

Conclusion

A high mutational signature with 3 or more of the 20-gene panel could provide more accurate predictions for the outcomes of ICI therapy than TMB ≥ 10 in NSCLC patients.
Effects of different designs of orthodontic clear aligners on the maxillary central incisors in the tooth extraction cases: a biomechanical study
Authors: Meng Xuehuan , Wang Chunjuan , Xu Wenjie , Wang Rui , Zheng Leilei , Wang Chao , Aversa Raffaella , Fan Yubo
Published: June 2023

Background

Controlling the 3D movement of central incisors during tooth extraction cases with clear aligners is important but challenging in invisible orthodontic treatment. This study aimed to explore the biomechanical effects of central incisors in tooth extraction cases with clear aligners under different power ridge design schemes and propose appropriate advice for orthodontic clinic.

Methods

A series of Finite Element models was constructed to simulate anterior teeth retraction or no retraction with different power ridge designs. These models all consisted of maxillary dentition with extracted first premolars, alveolar bone, periodontal ligaments and clear aligner. And the biomechanical effects were analysed and compared in each model.

Results

For the model of anterior teeth retraction without power ridge and for the model of anterior teeth no retraction with a single power ridge, the central incisors exhibited crown lingual inclination and relative extrusion. For the model of anterior teeth no retraction with double power ridges, the central incisors tended to have crown labial inclination and relative intrusion. For the model of anterior tooth retraction with double power ridges, the central incisors exhibited a similar trend to the first kind of model, but as the depth of the power ridge increased, there was a gradual decrease in crown retraction value and an increase in crown extrusion value. The simulated results showed that von-Mises stress concentration was observed in the cervical and apical regions of the periodontal ligaments of the central incisors. The clear aligner connection areas of adjacent teeth and power ridge areas also exhibited von-Mises stress concentration and the addition of power ridge caused the clear aligner to spread out on the labial and lingual sides.

Conclusions

The central incisors are prone to losing torque and extruding in tooth extraction cases. Double power ridges have a certain root torque effect when there are no auxiliary designs, but they still cannot rescue tooth inclination during tooth retraction period. For tooth translation, it may be a better clinical procedure to change the one-step aligner design to two-step process: tilting retraction and root control.
Using three-dimensional printed models for trainee orbital fracture education
Authors: Rama Martina , Schlegel Lauren , Wisner Douglas , Pugliese Robert , Ramesh Sathyadeepak , Penne Robert , Watson Alison
Published: June 2023

Background

Three-dimensional printing is an underutilized technology in ophthalmology training; its use must be explored in complex educational scenarios. This study described a novel approach to trainee education of orbital fracture repair utilizing three-dimensional (3D) printed models as a teaching tool.

Methods

Ophthalmology residents and oculoplastic fellows from multiple training institutions underwent an educational session on orbital fractures, learning through four different models. Participants analyzed orbital fractures through computerized tomography (CT) imaging alone and then utilizing CT imaging with the aid of a 3D printed model. Participants completed a questionnaire assessing their understanding of the fracture pattern and surgical approach. After the training, participants were surveyed on the impact of the educational session. Components of the training were rated by participants on a 5-point Likert scale.

Results

A statistically significant difference (p < .05) was found in participant confidence conceptualizing the anatomic boundaries of the fracture and planning the orbital fracture approach for repair of three out of four models on pre-test post-test analysis. On exit questionnaire, 84.3% of participants thought the models were a useful tool for surgical planning, 94.8% of participants thought the models were a useful tool for conceptualizing the anatomic boundaries of the fracture, 94.8% of participants thought the models were a useful tool for orbital fracture training, and 89.5% of participants thought the exercise was helpful.

Conclusion

This study supports the value of 3D printed models of orbital fractures as an effective tool for ophthalmology trainee education to improve understanding and visualization of complex anatomical space and pathology. Given the limited opportunities trainees may have for hands-on orbital fracture practice, 3D printed models provide an accessible way to enhance training.
Application of the hybrid BOPPPS teaching model in clinical internships in gynecology
Authors: Xu Zhengfen , Che Xuan , Yang Xiaodi , Wang Xiaoxia
Published: June 2023

Background

The traditional gynecological teaching model is not conducive to the cultivation of trainee doctors’ clinical skills, thinking patterns and doctor‒patient communication ability. This study aims to explore the effect of the application of the hybrid BOPPPS (bridge-in, objective, preassessment, participant learning, postassessment, summary) teaching model in clinical internships in gynecology.

Methods

This observational study was conducted among final-year undergraduate medical trainee doctors at Jiaxing Maternity and Child Health Care Hospital from September 2020 to June 2022. Members of the control group were introduced to the traditional teaching model, while members of the experimental group were introduced to the hybrid BOPPPS teaching model. Trainee doctors’ final examination scores and teaching satisfaction were compared.

Results

The control group consisted of 114 students who entered the university to pursue undergraduate degrees in 2017, and the experimental group consisted of 121 students who entered the university to pursue undergraduate degrees in 2018. The final examination scores attained by trainee doctors in the experimental group were higher than those attained by trainee doctors in the control group (P < 0.05). The final theoretical exam scores attained by members of the control group were significantly higher than their preassessment scores (P < 0.01). The scores differed significantly between female and male subjects before the internship (p<0.05) but not after the internship (p>0.05). In total, 93.4% of trainee doctors in the experimental group thought that the hybrid BOPPPS teaching model helped them improve their case analysis ability, and the difference in this measure between the experimental and control groups was statistically significant (P < 0.05). A total of 89.3% of trainee doctors in the experimental group supported the promotion and application of the hybrid BOPPPS model in practice in other disciplines.

Conclusion

The hybrid BOPPPS teaching model helps improve trainee doctors’ learning environment, stimulate their interest and initiative in learning, enhance their clinical practice ability and increase their satisfaction; therefore, this model is worth promoting and applying in practice in other disciplines.
Joining telehealth in rheumatology: a survey on the role played by personalized experience from patients’ perspective
Authors: Listorti Elisabetta , Ferrara Lucia , Adinolfi Antonella , Gerardi Maria Chiara , Ughi Nicola , Tozzi Valeria D. , Epis Oscar M.
Published: June 2023

Background

The beginning of the Covid-19 pandemic has forced many hospital departments worldwide to implement telehealth strategies for the first time. Telehealth represents the opportunity to increase value for all stakeholders, including patients and healthcare staff, but its success constitutes a challenge for all of them and particularly patients play a crucial role for their needed adherence. This study focuses on the experience of the Rheumatology Unit of Niguarda Hospital in Milan (Italy), where telehealth projects have been implemented for more than a decade with structured design and organized processes. The case study is paradigmatic because patients have experimented personalized mixes of telehealth channels, including e-mails and phone calls, Patient Reported Outcomes questionnaires, and home delivery of drugs. Given all these peculiarities, we decided to deepen patients’ perspective through three main aspects related to the adoption of telehealth: (i) the benefits perceived, (ii) the willingness to enrol in future projects, (iii) the preference on the service-mix between remote contacts and in-person visits. Most importantly, we investigated differences in the three areas among all patients based on the mix of telehealth channels experienced.

Methods

We conducted a survey from November 2021 to January 2022, enrolling consecutively patients attending the Rheumatology Unit of Niguarda Hospital in Milan (Italy). Our survey comprised an introductory set of questions related to personal, social, clinical and ICT skills information, followed by the central part on telehealth. All the answers were analysed with descriptive statistics and regression models.

Results

A complete response was given by 400 patients: 283 (71%) were female, 237 (59%) were 40–64 years old, 213 (53%) of them declared to work, and the disease most represented was Rheumatoid Arthritis (144 patients, 36%). Descriptive statistics and regression results revealed that (i) non-users imagined wide-ranging benefits compared to users; (ii) other things being equal, having had a more intense experience of telehealth increased the odds of accepting to participate to future projects by 3.1 times (95% C.I. 1.04–9.25), compared to non-users; (iii) the more telehealth was experienced, the higher the willingness to substitute in-person with online contacts.

Conclusions

Our study contributes to enlighten the crucial role played by the telehealth experience in determining patients’ preferences.
Factors influencing institutionalization of health technology assessment in Kenya
Authors: Mbau Rahab , Vassall Anna , Gilson Lucy , Barasa Edwine
Published: June 2023

Background

There is a global interest in institutionalizing health technology assessment (HTA) as an approach for explicit healthcare priority-setting. Institutionalization of HTA refers to the process of conducting and utilizing HTA as a normative practice for guiding resource allocation decisions within the health system. In this study, we aimed to examine the factors that were influencing institutionalization of HTA in Kenya.

Methods

We conducted a qualitative case study using document reviews and in-depth interviews with 30 participants involved in the HTA institutionalization process in Kenya. We used a thematic approach to analyze the data.

Results

We found that institutionalization of HTA in Kenya was being supported by factors such as establishment of organizational structures for HTA; availability of legal frameworks and policies on HTA; increasing availability of awareness creation and capacity-building initiatives for HTA; policymakers’ interests in universal health coverage and optimal allocation of resources; technocrats’ interests in evidence-based processes; presence of international collaboration for HTA; and lastly, involvement of bilateral agencies. On the other hand, institutionalization of HTA was being undermined by limited availability of skilled human resources, financial resources, and information resources for HTA; lack of HTA guidelines and decision-making frameworks; limited HTA awareness among subnational stakeholders; and industries’ interests in safeguarding their revenue.

Conclusions

Kenya’s Ministry of Health can facilitate institutionalization of HTA by adopting a systemic approach that involves: - (a) introducing long-term capacity-building initiatives to strengthen human and technical capacity for HTA; (b) earmarking national health budgets to ensure adequate financial resources for HTA; (c) introducing a cost database and promoting timely data collection to ensure availability of data for HTA; (d) developing context specific HTA guidelines and decision-making frameworks to facilitate HTA processes; (e) conducting deeper advocacy to strengthen HTA awareness among subnational stakeholders; and (f) managing stakeholders’ interests to minimize opposition to institutionalization of HTA.
Educational differences in healthcare use among survivors after breast, prostate, lung, and colon cancer – a SEQUEL cohort study
Authors: Levinsen Anne Katrine Graudal , Kjaer Trille Kristina , Maltesen Thomas , Jakobsen Erik , Gögenur Ismail , Borre Michael , Christiansen Peer , Zachariae Robert , Laurberg Søren , Christensen Peter , Kroman Niels , Larsen Signe Benzon , Degett Thea Helene , Hölmich Lisbet Rosenkrantz , Brown Peter de Nully , Johansen Christoffer , Kjær Susanne K. , Thygesen Lau Caspar , Dalton Susanne Oksbjerg
Published: June 2023

Background

Many cancer survivors experience late effects after cancer. Comorbidity, health literacy, late effects, and help-seeking behavior may affect healthcare use and may differ among socioeconomic groups. We examined healthcare use among cancer survivors, compared with cancer-free individuals, and investigated educational differences in healthcare use among cancer survivors.

Methods

A Danish cohort of 127,472 breast, prostate, lung, and colon cancer survivors from the national cancer databases, and 637,258 age- and sex-matched cancer-free individuals was established. Date of entry was 12 months after diagnosis/index date (for cancer-free individuals). Follow-up ended at death, emigration, new primary cancer, December 31st, 2018, or up to 10 years. Information about education and healthcare use, defined as the number of consultations with general practitioner (GP), private practicing specialists (PPS), hospital, and acute healthcare contacts 1–9 years after diagnosis/index date, was extracted from national registers. We used Poisson regression models to compare healthcare use between cancer survivors and cancer-free individuals, and to investigate the association between education and healthcare use among cancer survivors.

Results

Cancer survivors had more GP, hospital, and acute healthcare contacts than cancer-free individuals, while the use of PPS were alike. One-to-four-year survivors with short compared to long education had more GP consultations (breast, rate ratios (RR) = 1.28, 95% CI = 1.25–1.30; prostate, RR = 1.14, 95% CI = 1.10–1.18; lung, RR = 1.18, 95% CI = 1.13–1.23; and colon cancer, RR = 1.17, 95% CI = 1.13–1.22) and acute contacts (breast, RR = 1.35, 95% CI = 1.26–1.45; prostate, RR = 1.26, 95% CI = 1.15–1.38; lung, RR = 1.24, 95% CI = 1.16–1.33; and colon cancer, RR = 1.35, 95% CI = 1.14–1.60), even after adjusting for comorbidity. One-to-four-year survivors with short compared to long education had less consultations with PPS, while no association was observed for hospital contacts.

Conclusion

Cancer survivors used more healthcare than cancer-free individuals. Cancer survivors with short education had more GP and acute healthcare contacts than survivors with long education. To optimize healthcare use after cancer, we need to better understand survivors’ healthcare-seeking behaviors and their specific needs, especially among survivors with short education.
Differential expression of coagulation pathway-related proteins in diabetic urine exosomes
Authors: Liu Tianci , Liu Na , Wang Yizhao , Li Tao , Zhang Man
Published: June 2023

Background

Coagulation function monitoring is important for the occurrence and development of diabetes. A total of 16 related proteins are involved in coagulation, but how these proteins change in diabetic urine exosomes is unclear. To explore the expression changes of coagulation-related proteins in urine exosomes and their possible roles in the pathogenesis of diabetes, we performed proteomic analysis and finally applied them to the noninvasive monitoring of diabetes.

Methods

Subject urine samples were collected. LC-MS/MS was used to collect the information on coagulation-related proteins in urine exosomes. ELISA, mass spectrometry and western blotting were used to further verify the differential protein expression in urine exosomes. Correlations with clinical indicators were explored, and receiver operating characteristic (ROC) curves were drawn to evaluate the value of differential proteins in diabetes monitoring.

Results

Analyzing urine exosome proteomics data, eight coagulation-related proteins were found in this study. Among them, F2 was elevated in urine exosomes of diabetic patients compared with healthy controls. The results of ELISA, mass spectrometry and western blotting further verified the changes in F2. Correlation analysis showed that the expression of urine exosome F2 was correlated with clinical lipid metabolism indexes, and the concentration of F2 was strongly positively correlated with blood TG levels (P < 0.05). ROC curve analysis showed that F2 protein in urine exosomes had a good monitoring value for diabetes.

Conclusion

Coagulation-related proteins were expressed in urine exosomes. Among them, F2 was increased in diabetic urine exosomes and may be a potential biomarker for monitoring diabetic changes.
Phenotypic Bacterial Isolates, Antimicrobial Susceptibility pattern and Associated factors among Septicemia Suspected Patients at a hospital, in Northwest Ethiopia: Prospective cross-sectional study
Authors: Belew Habtamu , Tamir Workineh , Dilnessa Tebelay , Mengist Abeba
Published: June 2023

Background

Septicemia is potentially fatal infection caused by pathogenic bacteria infiltrating the bloodstream, resulting in morbidity and mortality among Ethiopian hospital patients. Multidrug resistance is a therapeutic challenge in this patient population. There is an insufficiency data among hospitals in Ethiopia. Hence, this study aimed to assess the phenotypic bacterial isolates, antimicrobial susceptibility pattern, and associated factors among septicemia suspected patients.

Methods

Prospective cross-sectional study was conducted among 214 septicemia suspected patients from February to June 2021 at Debre Markos Comprehensive Specialized hospital in northwest, Ethiopia. Blood samples were collected aseptically and processed to identify bacterial isolates by using different standard microbiological procedures. Antimicrobial susceptibility pattern was performed using the modified Kirby Bauer disc diffusion on Mueller Hinton agar. Epi-data V4.2 was used to enter data and SPSS V25 for analysis. The variables were assessed using a bivariate logistic regression model with a 95% confidence interval, and declared statistically significant; P-value was < 0.05.

Results

The overall bacterial isolates was found 45/214 (21%) in this study. Gram-negative and positive bacteria were 25/45(55.6%), 20/45(44.4%) respectively. The most common bacterial isolates were Staphylococcus aureus12/45 (26.7%), Klebsiella pneumoniae 8/45(17.8%), Escherichia coli 6/45 (13.3%). Gram-negative bacteria showed susceptibility to amikacin (88%), meropenem, imipenem (76%) but, (92%) resistance to ampicillin, (85.7%) amoxicillin-clavulanic acid. S.aureus (91.7%) was resistance to Penicillin, (58.3%) cefoxitin and (75%) susceptible to ciprofloxacillin. S.pyogenes and S.agalactia were (100%) susceptible to Vancomacin. Multidrug resistance was found in 27/45(60%) of the bacterial isolates. The main predictors related to patients suspected of septicemia were prolonged hospitalization (AOR = 2.29, 95% CI: 1.18, 7.22), fever (AOR = 0.39, 95%CI: 0.18, 0.85) and length of hospital stay (AOR = 0.13, 95%CI: 0.02, 0.82).

Conclusions

Incidence of bacterial isolates among septicemia suspected patients were high. The majority of the bacterial isolates were multidrug-resistant. To prevent antimicrobial resistance, specific antibiotic utilization strategy should be applied.
Usefulness of daptomycin lock therapy in children with catheter-related bacteremia after failed vancomycin lock therapy
Authors: Permuy Celia , Ruiz-Azcárate Jone , Sampedro Mercedes , Jiménez Cristina , Baquero-Artigao Fernando , Calvo Cristina , Méndez-Echevarría Ana
Published: June 2023

Purpose

Catheter-related bacteremia (CRB) is a significant cause of morbidity, resource expenditure and prolonged hospital stays in patients with long-term catheters, whose numbers have increased considerably in recent years. Antibiotic lock therapy reaches high concentrations in the catheter, allowing good penetration into the biofilm, being vancomycin the most commonly used one in gram-positive infections. Several authors have recently reported the superior in vitro efficacy of daptomycin compared with vancomycin, especially for eradicating biofilms. Although there is some data on the use of daptomycin for antibiotic lock in animal models and adults, there are no data on its use in children.

Methods

A descriptive study was conducted in a tertiary hospital, including patients younger than 16 years in whom daptomycin lock therapy was employed between 2018 and 2022.

Results

We report three pediatric patients in whom CRB was confirmed on admission by paired blood cultures positive for CoNS sensitive to vancomycin, daptomycin and linezolid. All patients started vancomycin lock therapy and systemic antibiotic therapy with proven sensitivity for the isolated bacteria, without achieving negative blood cultures. Due to the persistence of positive cultures, vancomycin lock therapy was replaced by daptomycin, and blood cultures turned negative, with no relapses or need for catheter removal.

Conclusion

The use of daptomycin lock therapy could be considered in children with CoNS catheter infection, especially when other antibiotic lock therapy had failed.
Associations between change in physical activity and sedentary time and health-related quality of life in older english adults: the EPIC-Norfolk cohort study
Authors: Yerrakalva Dharani , Hajna Samantha , Suhrcke Marc , Wijndaele Katrien , Westgate Kate , Khaw Kay-Tee , Wareham Nick , Brage Soren , Griffin Simon
Published: June 2023

Background

No previous studies have examined the associations between changes in objectively-measured physical behaviours with follow-up QoL in older adults. Based on cross-sectional evidence, it is biologically plausible that such associations exist. If so, this bolsters the case for the commissioning of activity interventions and for including QoL as an outcome in trials of such interventions.

Methods

We assessed physical behaviours (total physical activity, moderate-to-vigorous physical activity (MVPA), light physical activity, total sedentary time and prolonged sedentary bout time) for 7 days using hip-worn accelerometers at baseline (2006–2011) and follow-up (2012–2016) and health-related quality-of-life (QoL) using EQ-5D questionnaires at follow-up in 1433 participants (≥ 60 years) of the EPIC (European Prospective Investigation into Cancer)-Norfolk study. The EQ-5D summary score was used, with 0 as the worst to 1 as best perceived quality-of-life. We evaluated the prospective associations of baseline physical behaviours with follow-up QoL, and of changes in behaviours with follow-up QoL using multi-level regression.

Results

On average, MVPA decreased by 4.0 min/day/year (SD 8.3) for men and 4.0 min/day/year for women (SD 12.0) between baseline and follow-up. Total sedentary time increased by an average 5.5 min/day/yr (SD 16.0) for men and 6.4 min/day/yr (SD 15.0) for women between baseline and follow-up. Mean (SD) follow-up time was 5.8 (1.8) years.

We found that higher baseline MVPA and lower sedentary time was associated with higher subsequent QoL (e.g. 1 h/day greater baseline MVPA was associated with 0.02 higher EQ-5D score, 95% CI 0.06, 0.36). More pronounced declines in activity were associated with worse Hr-QoL (0.005 (95% CI 0.003, 0.008) lower EQ-5D per min/day/yr decrease in MVPA). Increases in sedentary behaviours were also associated with poorer QoL (0.002 lower EQ-5D, 95% CI -0.003, -0.0007 per hour/day/yr increase in total sedentary time).

Conclusions

Promotion of physical activity and limiting sedentary time among older adults may improve quality-of-life, and therefore this relationship ought to be included in future cost effectiveness analyses so that greater commissioning of activity interventions can be considered.
Right heart thrombus in transit and peripherally inserted central catheters
Authors: Hussain Rezwan N , Mandal Amit K J , Li Nick , Kafsi Jihène El , Sioftanos Anastasis , Missouris Constantinos G
Published: June 2023

Right heart thrombus in transit or “free-floating right heart thrombus” is defined as thrombus(i) arising from the deep veins that embolises to the right atrium or right ventricle before reaching the pulmonary vasculature. It is almost always associated with pulmonary thromboembolism and is a medical emergency with reported mortality rates of over 40%. We present two cases of right heart thrombus in transit with pulmonary thromboembolism resulting from venous thrombosis associated with peripherally inserted central catheters that were managed with different approaches. The cases highlight that clinicians should have a low threshold to utilise imaging modalities such as computerised tomography and transthoracic echocardiography when there is an untoward change in physiological parameters among patients with peripherally inserted central catheters, particularly those with risk factors for peripherally inserted central catheter associated venous thrombosis. Furthermore, procedural optimisation surrounding peripherally inserted central catheters, such as insertion technique and choice of lumen size, is underscored.
Construction and validation of prognostic models in critically Ill patients with sepsis-associated acute kidney injury: interpretable machine learning approach
Authors: Fan Zhiyan , Jiang Jiamei , Xiao Chen , Chen Youlei , Xia Quan , Wang Juan , Fang Mengjuan , Wu Zesheng , Chen Fanghui
Published: June 2023

Background

Acute kidney injury (AKI) is a common complication in critically ill patients with sepsis and is often associated with a poor prognosis. We aimed to construct and validate an interpretable prognostic prediction model for patients with sepsis-associated AKI (S-AKI) using machine learning (ML) methods.

Methods

Data on the training cohort were collected from the Medical Information Mart for Intensive Care IV database version 2.2 to build the model, and data of patients were extracted from Hangzhou First People's Hospital Affiliated to Zhejiang University School of Medicine for external validation of model. Predictors of mortality were identified using Recursive Feature Elimination (RFE). Then, random forest, extreme gradient boosting (XGBoost), multilayer perceptron classifier, support vector classifier, and logistic regression were used to establish a prognosis prediction model for 7, 14, and 28 days after intensive care unit (ICU) admission, respectively. Prediction performance was assessed using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) were used to interpret the ML models.

Results

In total, 2599 patients with S-AKI were included in the analysis. Forty variables were selected for the model development. According to the areas under the ROC curve (AUC) and DCA results for the training cohort, XGBoost model exhibited excellent performance with F1 Score of 0.847, 0.715, 0.765 and AUC (95% CI) of 0.91 (0.90, 0.92), 0.78 (0.76, 0.80), and 0.83 (0.81, 0.85) in 7 days, 14 days and 28 days group, respectively. It also demonstrated excellent discrimination in the external validation cohort. Its AUC (95% CI) was 0.81 (0.79, 0.83), 0.75 (0.73, 0.77), 0.79 (0.77, 0.81) in 7 days, 14 days and 28 days group, respectively. SHAP-based summary plot and force plot were used to interpret the XGBoost model globally and locally.

Conclusions

ML is a reliable tool for predicting the prognosis of patients with S-AKI. SHAP methods were used to explain intrinsic information of the XGBoost model, which may prove clinically useful and help clinicians tailor precise management.