bluuebunny/crossref_metadata_2025 huggingface dataset:
Infection deteriorating hepatitis B virus related acute-on-chronic liver failure: a retrospective cohort study
Authors: Zhai Xing-Ran , Tong Jing-Jing , Wang Hong-Min , Xu Xiang , Mu Xiu-Ying , Chen Jing , Liu Zi-Feng , Wang Yu , Su Hai-Bin , Hu Jin-Hua
Published: September 2020

Background

Infection is common in acute-on-chronic liver failure (ACLF), which may worsen the clinical condition and prognosis. However, the characteristics of infection and its influence on prognosis in hepatitis B virus related ACLF (HBV-ACLF) as defined by the European Association for the Study of the Liver (EASL) have not been clarified. We aimed to investigate the characteristics of infection and its influence on mortality in patients with HBV-ACLF defined by EASL in China.

Methods

We performed a retrospective cohort study in patients with HBV-ACLF defined by EASL in a single center from January 2015 to December 2017. These patients were divided into two groups with and without infection. The incidence, sites of infection, isolated strains, and risk factors associated with mortality were evaluated.

Results

A total of 289 patients were included, among them 185 (64.0%) were diagnosed with an infection. The most common type of infection was pneumonia (55.7%), followed by spontaneous bacterial peritonitis (47.6%) and others. The gram-negative bacteria were the most frequent (58.3%). Patients with one, two, and three or more infection sites had a gradually increasing incidence of sepsis (P < 0.01), septic shock (P < 0.001), and ACLF-3 (P < 0.05). Also, patients with infection isolated one, two, and three or more strains showed a growing incidence of sepsis (P < 0.01) and septic shock (P < 0.001). Patients with infection showed a significantly higher 28-day mortality than those without (P < 0.01), especially in patients with ACLF-3. Infection was identified as an independent risk factor for 28-day mortality in all HBV-ACLF patients. Pneumonia and sepsis were identified as independent predictors of 28-day mortality for patients with infection.

Conclusions

Infection is associated with severe clinical course and high mortality in HBV-ACLF defined by EASL. The increased number of infection sites or isolated strains was associated with the occurrence of sepsis and septic shock. Pneumonia and sepsis were independent predictors for mortality in HBV-ACLF patients with infection.
A case of minimal change disease after the administration of anti receptor activator of nuclear factor kappa B ligand (RANKL) monoclonal antibody: a case report
Authors: Horikoshi Keisuke , Sakai Norihiko , Yamamoto Naoki , Ogura Hisayuki , Sato Koichi , Miyagawa Taro , Kitajima Shinji , Toyama Tadashi , Hara Akinori , Iwata Yasunori , Shimizu Miho , Furuichi Kengo , Wada Takashi
Published: September 2020

Background

Minimal change disease (MCD) is one of the causes of idiopathic nephrotic syndrome in adults. The pathogenesis of proteinuria in MCD has not been fully understood. Recently, it has been reported that the receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL) may contribute to the podocyte biology in kidney diseases. Denosumab is a human anti-RANKL monoclonal antibody used to treat osteoporosis. Here we report a case of MCD after denosumab administration.

Case presentation

A 59-year-old male without any episodes of proteinuria was given denosumab to treat osteoporosis. Two weeks after its administration, he noticed a foamy urine and bilateral pretibial edema. Laboratory tests revealed that he had severe proteinuria (15g/g Cr), hypoproteinemia (4.0g/dL), and hypoalbuminemia (1.5g/dL). Based on the results, he was diagnosed with nephrotic syndrome. The proteinuria selectivity index was 0.05, indicating selective proteinuria. Renal biopsy showed minor glomerular abnormality with less tubulointerstitial damage, and electron microscopy showed extensive foot process effacement, indicating MCD. With all these results, glucocorticoid therapy of 50mg/day prednisolone was started. After 4weeks of treatment, the urinary protein level remains high (3.1g/g Cr). Prednisolone therapy was continued, and the levels of proteinuria decreased gradually to the range of partial remission (1.2g/g Cr) with another 7weeks of prednisolone treatment, but complete remission was not achieved.

Conclusions

This might be a case wherein RANKL inhibition is associated with the pathogenesis of MCD. Further studies will be needed to elucidate the causal relationship of RANK-RANKL signaling to the pathogenesis of MCD.
Shortened red blood cell age in patients with end-stage renal disease who were receiving haemodialysis: a cross-sectional study
Authors: Matsumura Koichiro , Okumiya Toshika , Sugiura Tetsuro , Takahashi Nobuyuki , Yamamoto Yoshihiro , Kikuchi Sanae , Fujii Kenichi , Otagaki Munemitsu , Shiojima Ichiro
Published: September 2020

Background

The causes of anaemia in patients with end-stage renal disease include a relative deficiency in erythropoietin production and complex clinical conditions. We aimed to investigate the underlying mechanisms of anaemia in patients with end-stage renal disease who were undergoing maintenance dialysis by measuring erythrocyte creatine levels.

Methods

In a cross-sectional study, we evaluated 69 patients with end-stage renal disease who were receiving haemodialysis (n = 55) or peritoneal dialysis (n = 14). Erythrocyte creatine level, a quantitative marker of mean red blood cell (RBC) age, was measured.

Results

The mean RBC age was significantly shorter in the haemodialysis group than in the peritoneal dialysis group (47.7 days vs. 59.8 days, p < 0.0001), although the haemoglobin levels were comparable between the groups. A Spearman correlation coefficient analysis revealed that shortened RBC age positively correlated with transferrin saturation (r = 0.54), ferritin level (r = 0.47), and haptoglobin level (r = 0.39) but inversely related with reticulocyte (r = − 0.36), weekly doses of erythropoiesis-stimulating agents (ESAs; r = − 0.62), erythropoietin resistance index (r = − 0.64), and intradialytic ultrafiltration rate (r = − 0.32).

Conclusions

Shortened RBC age was observed in patients who were receiving maintenance haemodialysis and was associated with iron deficiency, greater haptoglobin consumption, higher ESA requirements, and poor erythropoietin responsiveness, as well as with greater intradialytic fluid extraction.
Implementing the Risk Identification (RI) and Modified Early Obstetric Warning Signs (MEOWS) tool in district hospitals in Rwanda: a cross-sectional study
Authors: Tuyishime Eugene , Ingabire Honorine , Mvukiyehe Jean Paul , Durieux Marcel , Twagirumugabe Theogene
Published: September 2020

Background

Despite reaching Millennium Development Goal (MDG) 3, the maternal mortality rate (MMR) is still high in Rwanda. Most deaths occur after transfer of patients with obstetric complications from district hospitals (DHs) to referral hospitals; timely detection and management may improve these outcomes. The RI and MEOWS tool has been designed to predict morbidity and decrease delay of transfer. Our study aimed: 1) to determine if the use of the RI and MEOWS tool is feasible in DHs in Rwanda and 2) to determine the role of the RI and MEOWS tool in predicting morbidity.

Methods

A cross-sectional study enrolled parturient admitted to 4 district hospitals during the study period from April to July 2019. Data was collected on completeness rate (feasibility) to RI and MEOWS tool, and prediction of morbidity (hemorrhage, infection, and pre-eclampsia).

Results

Among 478 RI and MEOWS forms used, 75.9% forms were fully completed suggesting adequate feasibility. In addition, the RI and MEOWS tool showed to predict morbidity with a sensitivity of 28.9%, a specificity of 93.5%, a PPV of 36.1%, a NPV of 91.1%, an accuracy of 86.2%, and a relative risk of 4.1 (95% Confidential Interval (CI), 2.4–7.1). When asked about challenges faced during use of the RI and MEOWS tool, most of the respondents reported that the tool was long, the staff to patient ratio was low, the English language was a barrier, and the printed forms were sometimes unavailable.

Conclusion

The RI and MEOWS tool is a feasible in the DHs of Rwanda. In addition, having moderate or high scores on the RI and MEOWS tool predict morbidity. After consideration of local context, this tool can be considered for scale up to other DHs in Rwanda or other low resources settings.

Trial registration

This is not a clinical trial rather a quality improvement project. It will be registered retrospectively.
Anthropometrical measurements and maternal visceral fat during first half of pregnancy: a cross-sectional survey
Authors: Kretzer Daniela Cortés , Matos Salete , Von Diemen Lisia , de Azevedo Magalhães José Antônio , Schöffel Alice Carvalhal , Goldani Marcelo Zubaran , da Silva Rocha Alexandre , Bernardi Juliana Rombaldi
Published: September 2020

Background

Determining anthropometric measures that indicate different fat deposits can be useful to predict metabolic risk and set specific treatment goals, reducing negative consequences for maternal and fetal health. In cases where pre-gestational weight measure and subsequent body mass index (BMI) values cannot be determined, other anthropometric measurements may be ideal for measuring the nutritional status of pregnant women, especially in low- and middle-income countries. This study aims to identify which anthropometric measurements correlate better with the maternal fat deposits measured by ultrasound.

Methods

A cross-sectional study was conducted with pregnant women from the city of Porto Alegre (city), capital of Rio Grande do Sul (state), southern Brazil, from October 2016 until January 2018. Anthropometrical variables (weight, height, mid-upper arm circumference [MUAC], circumferences of calf and neck and triceps skinfolds [TSF] and subscapular skinfolds [SBSF]), and ultrasound variables (visceral adipose tissue [VAT] and total adipose tissue [TAT]) were collected. To verify the correlation of anthropometric and ultrasound measurements, a non-adjusted and adjusted Spearman correlation was used. The study was approved by the ethics committees.

Results

The age median of the 149 pregnant women was 25 years [21–31], pre-pregnancy BMI was 26.22 kg/m² [22.16–31.21] and gestational age was 16.2 weeks [13.05–18.10]. The best measurements correlated with VAT and TAT were MUAC and SBSF, both of which showed a higher correlation than pre-pregnancy BMI.

Conclusions

It is possible to provide a practical and reliable estimate of VAT and TAT from the anthropometric evaluation (MUAC or SBSF) that is low cost, efficient and replicable in an outpatient clinic environment, especially in low- and middle-income countries.
Efficacy of breast MRI for surgical decision in patients with breast cancer: ductal carcinoma in situ versus invasive ductal carcinoma
Authors: Lee Jeeyeon , Jung Jin Hyang , Kim Wan Wook , Park Chan Sub , Lee Ryu Kyung , Kim Hye Jung , Kim Won Hwa , Park Ho Yong
Published: September 2020

Background

Preoperative breast magnetic resonance imaging (MRI) provides more information than mammography and ultrasonography for determining the surgical plan for patients with breast cancer. This study aimed to determine whether breast MRI is more useful for patients with ductal carcinoma in situ (DCIS) lesions than for those with invasive ductal carcinoma (IDC).

Methods

A total of 1113 patients with breast cancer underwent mammography, ultrasonography, and additional breast MRI before surgery. The patients were divided into 2 groups: DCIS (n = 199) and IDC (n = 914), and their clinicopathological characteristics and oncological outcomes were compared. Breast surgery was classified as follows: conventional breast-conserving surgery (Group 1), partial mastectomy with volume displacement (Group 2), partial mastectomy with volume replacement (Group 3), and total mastectomy with or without reconstruction (Group 4). The initial surgical plan (based on routine mammography and ultrasonography) and final surgical plan (after additional breast MRI) were compared between the 2 groups. The change in surgical plan was defined as group shifting between the initial and final surgical plans.

Results

Changes (both increasing and decreasing) in surgical plans were more common in the DCIS group than in the IDC group (P <  0.001). These changes may be attributed to the increased extent of suspicious lesions on breast MRI, detection of additional daughter nodules, multifocality or multicentricity, and suspicious findings on mammography or ultrasonography but benign findings on breast MRI. Furthermore, the positive margin incidence in frozen biopsy was not different (P = 0.138).

Conclusions

Preoperative breast MRI may provide more information for determining the surgical plan for patients with DCIS than for those with IDC.
A real 3D measurement technique for the tibial slope: differentiation between different articular surfaces and comparison to radiographic slope measurement
Authors: Hoch Armando , Jud Lukas , Roth Tabitha , Vlachopoulos Lazaros , Fürnstahl Philipp , Fucentese Sandro F.
Published: September 2020

Background

The tibial slope plays an important role in knee surgery. However, standard radiographic measurement techniques have a low reproducibility and do not allow differentiation between medial and lateral articular surfaces. Despite availability of three-dimensional imaging, so far, no real 3D measurement technique was introduced and compared to radiographic measurement, which were the purposes of this study.

Methods

Computed tomography scans of 54 knees in 51 patients (41 males and 10 females) with a mean age of 46 years (range 22–67 years) were included. A novel 3D measurement technique was applied by two readers to measure the tibial slope of medial and lateral tibial plateau and rim. A statistical analysis was conducted to determine the intraclass correlation coefficient (ICC) for the new technique and compare it to a standard radiographic measurement.

Results

The mean 3D tibial slope for the medial plateau and rim was 7.4° and 7.6°, for the lateral plateau and rim 7.5° and 8.1°, respectively. The mean radiographic slope was 6.0°. Statistical analysis showed an ICC between both readers of 0.909, 0.987, 0.918, 0.893, for the 3D measurement of medial plateau, medial rim, lateral plateau and lateral rim, respectively, whereas the radiographic technique showed an ICC of 0.733.

Conclusions

The proposed novel measurement technique shows a high intraclass agreement and offers an applicable opportunity to assess the tibial slope three-dimensionally. Furthermore, the medial and lateral articular surfaces can be measured separately and one can differentiate the slope from the plateau and from the rim. As three-dimensional planning becomes successively more important, our measurement technique might deliver a useful supplement to the standard radiographic assessment in slope related knee surgery.

Level of evidence

Level III, diagnostic study.
The mechanism of hamstring injuries – a systematic review
Authors: Danielsson Adam , Horvath Alexandra , Senorski Carl , Alentorn-Geli Eduard , Garrett William E. , Cugat Ramón , Samuelsson Kristian , Hamrin Senorski Eric
Published: September 2020

Background

Injuries to the hamstring muscles are among the most common in sports and account for significant time loss. Despite being so common, the injury mechanism of hamstring injuries remains to be determined.

Purpose

To investigate the hamstring injury mechanism by conducting a systematic review.

Study design

A systematic review following the PRISMA statement.

Methods

A systematic search was conducted using PubMed, EMBASE and the Cochrane Library. Studies 1) written in English and 2) deciding on the mechanism of hamstring injury were eligible for inclusion. Literature reviews, systematic reviews, meta-analyses, conference abstracts, book chapters and editorials were excluded, as well as studies where the full text could not be obtained.

Results

Twenty-six of 2372 screened original studies were included and stratified to the mechanism or methods used to determine hamstring injury: stretch-related injuries, kinematic analysis, electromyography-based kinematic analysis and strength-related injuries. All studies that reported the stretch-type injury mechanism concluded that injury occurs due to extensive hip flexion with a hyperextended knee. The vast majority of studies on injuries during running proposed that these injuries occur during the late swing phase of the running gait cycle.

Conclusion

A stretch-type injury to the hamstrings is caused by extensive hip flexion with an extended knee. Hamstring injuries during sprinting are most likely to occur due to excessive muscle strain caused by eccentric contraction during the late swing phase of the running gait cycle.

Level of evidence

Level IV
Deleterious mutations show increasing negative effects with age in Drosophila melanogaster
Authors: Brengdahl Martin I. , Kimber Christopher M. , Elias Phoebe , Thompson Josephine , Friberg Urban
Published: September 2020

Background

In order for aging to evolve in response to a declining strength of selection with age, a genetic architecture that allows for mutations with age-specific effects on organismal performance is required. Our understanding of how selective effects of individual mutations are distributed across ages is however poor. Established evolutionary theories assume that mutations causing aging have negative late-life effects, coupled to either positive or neutral effects early in life. New theory now suggests evolution of aging may also result from deleterious mutations with increasing negative effects with age, a possibility that has not yet been empirically explored.

Results

To directly test how the effects of deleterious mutations are distributed across ages, we separately measure age-specific effects on fecundity for each of 20 mutations inDrosophila melanogaster. We find that deleterious mutations in general have a negative effect that increases with age and that the rate of increase depends on how deleterious a mutation is early in life.

Conclusions

Our findings suggest that aging does not exclusively depend on genetic variants assumed by the established evolutionary theories of aging. Instead, aging can result from deleterious mutations with negative effects that amplify with age. If increasing negative effect with age is a general property of deleterious mutations, the proportion of mutations with the capacity to contribute towards aging may be considerably larger than previously believed.
Metformin may adversely affect orthostatic blood pressure recovery in patients with type 2 diabetes: substudy from the placebo-controlled Copenhagen Insulin and Metformin Therapy (CIMT) trial
Authors: Hansen Christian Stevns , Lundby-Christiansen Louise , Tarnow Lise , Gluud Christian , Hedetoft Christoffer , Thorsteinsson Birger , Hemmingsen Bianca , Wiinberg Niels , Sneppen Simone B. , Lund Søren S. , Krarup Thure , Madsbad Sten , Almdal Thomas , Carstensen Bendix , Jørgensen Marit E. ,   the CIMT study group, Almdal T. , Boesgaard T. W. , Breum L. , Gade-Rasmussen B. , Duun E. , Gluud C. , Hedetoft C. , Hemmingsen B. , Jensen T. , Krarup T. , Lundby-Christensen L. , Lund S. , Madsbad S. , Mathiesen E. R. , Pedersen O. , Perrild H. , Røder M. , Sneppen S. B. , Snorgaard O. , Tarnow L. , Thorsteinsson B. , Vestergaard H. , Vaag A. , Wiinberg N.
Published: September 2020

Background

Metformin has been shown to have both neuroprotective and neurodegenerative effects. The aim of this study was to investigate the effect of metformin in combination with insulin on cardiovascular autonomic neuropathy (CAN) and distal peripheral neuropathy (DPN) in individuals with type 2 diabetes (T2DM).

Methods

The study is a sub-study of the CIMT trial, a randomized placebo-controlled trial with a 2 × 3 factorial design, where 412 patients with T2DM were randomized to 18 months of metformin or placebo in addition to open-labelled insulin. Outcomes were measures of CAN: Changes in heart rate response to deep breathing (beat-to-beat), orthostatic blood pressure (OBP) and heart rate and vibration detection threshold (VDT) as a marker DPN. Serum levels of vitamin B12 and methyl malonic acid (MMA) were analysed.

Results

After 18 months early drop in OBP (30 s after standing) was increased in the metformin group compared to placebo: systolic blood pressure drop increased by 3.4 mmHg (95% CI 0.6; 6.2, p = 0.02) and diastolic blood pressure drop increased by 1.3 mmHg (95% CI 0.3; 2.6, p = 0.045) compared to placebo. Beat-to-beat variation decreased in the metformin group by 1.1 beats per minute (95% CI − 2.4; 0.2, p = 0.10). Metformin treatment did not affect VDT group difference − 0.33 V (95% CI − 1.99; 1.33, p = 0.39) or other outcomes. Changes in B12, MMA and HbA1c did not confound the associations.

Conclusions

Eighteen months of metformin treatment in combination with insulin compared with insulin alone increased early drop in OBP indicating an adverse effect of metformin on CAN independent of vitamin B12, MMA HbA1c.

Trial registration The protocol was approved by the Regional Committee on Biomedical Research Ethics (H–D-2007-112), the Danish Medicines Agency and registered with ClinicalTrials.gov (NCT00657943).
Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet
Authors: Yoshida Masatoki , Nakamura Kazufumi , Miyoshi Toru , Yoshida Masashi , Kondo Megumi , Akazawa Kaoru , Kimura Tomonari , Ohtsuka Hiroaki , Ohno Yuko , Miura Daiji , Ito Hiroshi
Published: September 2020

Background

Statins suppress the progression of atherosclerosis by reducing low-density lipoprotein (LDL) cholesterol levels. Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor α modulator, is expected to reduce residual risk factors including high triglycerides (TGs) and low high-density lipoprotein (HDL) cholesterol during statin treatment. However, it is not known if statin therapy with add-on pemafibrate improves the progression of atherosclerosis. The aim of this study was to assess the effect of combination therapy with pitavastatin and pemafibrate on lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats.

Methods

Seven-week-old male Dahl salt-sensitive (DS) rats were divided into the following five treatment groups (normal diet (ND) plus vehicle, high-salt and high-fat diet (HD) plus vehicle, HD plus pitavastatin (0.3 mg/kg/day), HD plus pemafibrate (K-877) (0.5 mg/kg/day), and HD plus combination of pitavastatin and pemafibrate) and treated for 12 weeks. At 19 weeks, endothelium-dependent relaxation of the thoracic aorta in response to acetylcholine was evaluated.

Results

After feeding for 12 weeks, systolic blood pressure and plasma levels of total cholesterol were significantly higher in the HD-vehicle group compared with the ND-vehicle group. Combination therapy with pitavastatin and pemafibrate significantly reduced systolic blood pressure, TG levels, including total, chylomicron (CM), very LDL (VLDL), HDL-TG, and cholesterol levels, including total, CM, VLDL, and LDL-cholesterol, compared with vehicle treatment. Acetylcholine caused concentration-dependent relaxation of thoracic aorta rings that were pre-contracted with phenylephrine in all rats. Relaxation rates in the HD-vehicle group were significantly lower compared with the ND-vehicle group. Relaxation rates in the HD-combination of pitavastatin and pemafibrate group significantly increased compared with the HD-vehicle group, although neither medication alone ameliorated relaxation rates significantly. Western blotting experiments showed increased phosphorylated endothelial nitric oxide synthase protein expression in aortas from rats in the HD-pemafibrate group and the HD-combination group compared with the HD-vehicle group. However, the expression levels did not respond significantly to pitavastatin alone.

Conclusions

Combination therapy with pitavastatin and pemafibrate improved lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Pemafibrate as an add-on strategy to statins may be useful for preventing atherosclerosis progression.
The correlation between dietary fat quality indices and lipid profile with Atherogenic index of plasma in obese and non-obese volunteers: a cross-sectional descriptive-analytic case-control study
Authors: Moussavi Javardi Maryam Sadat , Madani Zahra , Movahedi Ariyo , Karandish Majid , Abbasi Behnood
Published: September 2020

Background and aim

Abnormalities in lipid metabolism are commonly observed in patients who were obese. Alongside dyslipidemia, one of the markers in predicting the risk of cardiovascular disease is the Atherogenic Index of Plasma (AIP), which is related to dietary intake. Healthy fat quality indices might affect on AIP. The purpose of this study is to find the possible relationship between dietary fat quality, and AIP and comparison of these indices among obese and non-obese volunteers.

Methods

This study was a cross-sectional descriptive-analytic case-control study with 157 normal and overweight and obese volunteers (n = 71 normal, Age: 38.90 ± 10.976 vsn = 86 overweight/obese, Age: 38.60 ± 9.394) in the age range of 18–65 years. Food intake was measured using FFQ, anthropometric indices (weight, height, body mass index and waist to hip ratio), body composition (visceral fat level, total body water, body fat mass), and lipid profile were measured.

Results

Based on the present results, comparable biochemical parameters including TC (P = 0.580), TG (P = 0.362), LDL (P = 0.687) and HDL (P = 0.151) among overweight/obese volunteers as compared to normal ones were noticed. Effects of dietary fat quality, including Atherogenicity (AI) and Thrombogenicity (TI) hypo/hypercholesterolemic ratio (h/H), the Cholesterol-Saturated Fat Index (CSI) showed significantly higher AI (P = 0.012) in the overweight/obese group as compared to the normal group. Whereas, h/H (P = 0.034) and ω-6/ω-3 ratio (P = 0.004) were significantly higher in normal-weight volunteers. There was a positive correlation between AI, TI, CSI, SFA, MUFA, PUFA and ω-6/ω-3 ratio with AIP and negative correlation between h/H with AIP in both groups. Despite the significances of these correlations no strong relation was observed by doing multiple regression among normal and overweight/obese groups (R2 = 0.210,R2 = 0.387).

Conclusions

In summary, the present work proposes a direct relationship between dietary fat quality, increased BMI, and lipid abnormalities with AIP. Nevertheless, further large-scale studies are required to sustain a clear conclusion in this wish.
Defining key questions for clinical practice guidelines: a novel approach for developing clinically relevant questions
Authors: Chakraborty Samantha , Brijnath Bianca , Dermentzis Jacinta , Mazza Danielle
Published: September 2020

Background

There is no standardised protocol for developing clinically relevant guideline questions. We aimed to create such a protocol and to apply it to developing a new guideline.

Methods

We reviewed international guideline manuals and, through consensus, combined steps for developing clinical questions to produce a best-practice protocol that incorporated qualitative research. The protocol was applied to develop clinical questions for a guideline for general practitioners.

Results

A best-practice protocol incorporating qualitative research was created. Using the protocol, we developed 10 clinical questions that spanned diagnosis, management and follow-up.

Conclusions

Guideline developers can apply this protocol to develop clinically relevant guideline questions.
Virtual reality in pain therapy: a requirements analysis for older adults with chronic back pain
Authors: Stamm Oskar , Dahms Rebecca , Müller-Werdan Ursula
Published: September 2020

Background

Today immersive environments such as Virtual Reality (VR) offer new opportunities for serious gaming in exercise therapy and psychoeducation. Chronic back pain (CBP) patients could benefit from exergames in VR. The requirements in older CBP patients for a VR pain therapy have not yet been determined in studies. The aim of the study was to perform a requirements analysis for the user group of geriatric patients with CBP for a VR exergame. The objective was to find out the expectations, desires, preferences and barriers in order to collect them as requirements for this vulnerable group and to determine frameworks of therapy by physiotherapists and psychotherapists.

Methods

We conducted a requirements analysis through semi-structured interviews with 10 elderly participants with CBP. Furthermore, two focus groups were conducted with three physiotherapists and two psychotherapists to determine frameworks of therapy programs for the target group. The qualitative data were transcribed and examined through a structuring content analysis. Subsequently, the results of the analysis were prioritized by all participants of the study.

Results

The results of the requirements analysis indicate mandatory requirements for the overall system, hardware, software and gamification elements. The key requirements were target-group-specific applications of the VR exergame through e.g. individual briefing, user-friendly handling, inclusion of movement limitations, presentation of everyday scenarios in combination with biofeedback, age-appropriate feedback through praise and awards and a maximum exercise duration of 30 min and 15 min of relaxation.

Conclusion

It should be possible to use the determined requirements productively to create user-friendly VR exergames that motivate elderly chronic back pain patients to perform exercises regularly.

Trial registration

The study is registered in the German Clinical Trials Register (DRKS-ID: DRKS00015294 12.10.2018).
Predicting clinically significant motor function improvement after contemporary task-oriented interventions using machine learning approaches
Authors: Thakkar Hiren Kumar , Liao Wan-wen , Wu Ching-yi , Hsieh Yu-Wei , Lee Tsong-Hai
Published: September 2020

Background

Accurate prediction of motor recovery after stroke is critical for treatment decisions and planning. Machine learning has been proposed to be a promising technique for outcome prediction because of its high accuracy and ability to process large volumes of data. It has been used to predict acute stroke recovery; however, whether machine learning would be effective for predicting rehabilitation outcomes in chronic stroke patients for common contemporary task-oriented interventions remains largely unexplored. This study aimed to determine the accuracy and performance of machine learning to predict clinically significant motor function improvements after contemporary task-oriented intervention in chronic stroke patients and identify important predictors for building machine learning prediction models.

Methods

This study was a secondary analysis of data using two common machine learning approaches, which were the k-nearest neighbor (KNN) and artificial neural network (ANN). Chronic stroke patients (N = 239) that received 30 h of task-oriented training including the constraint-induced movement therapy, bilateral arm training, robot-assisted therapy and mirror therapy were included. The Fugl-Meyer assessment scale (FMA) was the main outcome. Potential predictors include age, gender, side of lesion, time since stroke, baseline functional status, motor function and quality of life. We divided the data set into a training set and a test set and used the cross-validation procedure to construct machine learning models based on the training set. After the models were built, we used the test data set to evaluate the accuracy and prediction performance of the models.

Results

Three important predictors were identified, which were time since stroke, baseline functional independence measure (FIM) and baseline FMA scores. Models for predicting motor function improvements were accurate. The prediction accuracy of the KNN model was 85.42% and area under the receiver operating characteristic curve (AUC-ROC) was 0.89. The prediction accuracy of the ANN model was 81.25% and the AUC-ROC was 0.77.

Conclusions

Incorporating machine learning into clinical outcome prediction using three key predictors including time since stroke, baseline functional and motor ability may help clinicians/therapists to identify patients that are most likely to benefit from contemporary task-oriented interventions. The KNN and ANN models may be potentially useful for predicting clinically significant motor recovery in chronic stroke.
Optimisation of a metabotype approach to deliver targeted dietary advice
Authors: Hillesheim Elaine , Ryan Miriam F. , Gibney Eileen , Roche Helen M. , Brennan Lorraine
Published: September 2020

Background

Targeted nutrition is defined as dietary advice tailored at a group level. Groups known as metabotypes can be identified based on individual metabolic profiles. Metabotypes have been associated with differential responses to diet, which support their use to deliver dietary advice. We aimed to optimise a metabotype approach to deliver targeted dietary advice by encompassing more specific recommendations on nutrient and food intakes and dietary behaviours.

Methods

Participants (n = 207) were classified into three metabotypes based on four biomarkers (triacylglycerol, total cholesterol, HDL-cholesterol and glucose) and using a k-means cluster model. Participants in metabotype-1 had the highest average HDL-cholesterol, in metabotype-2 the lowest triacylglycerol and total cholesterol, and in metabotype-3 the highest triacylglycerol and total cholesterol. For each participant, dietary advice was assigned using decision trees for both metabotype (group level) and personalised (individual level) approaches. Agreement between methods was compared at the message level and the metabotype approach was optimised to incorporate messages exclusively assigned by the personalised approach and current dietary guidelines. The optimised metabotype approach was subsequently compared with individualised advice manually compiled.

Results

The metabotype approach comprised advice for improving the intake of saturated fat (69% of participants), fibre (66%) and salt (18%), while the personalised approach assigned advice for improving the intake of folate (63%), fibre (63%), saturated fat (61%), calcium (34%), monounsaturated fat (24%) and salt (14%). Following the optimisation of the metabotype approach, the most frequent messages assigned to address intake of key nutrients were to increase the intake of fruit and vegetables, beans and pulses, dark green vegetables, and oily fish, to limit processed meats and high-fat food products and to choose fibre-rich carbohydrates, low-fat dairy and lean meats (60–69%). An average agreement of 82.8% between metabotype and manual approaches was revealed, with excellent agreements in metabotype-1 (94.4%) and metabotype-3 (92.3%).

Conclusions

The optimised metabotype approach proved capable of delivering targeted dietary advice for healthy adults, being highly comparable with individualised advice. The next step is to ascertain whether the optimised metabotype approach is effective in changing diet quality.
Treating schizophrenia with cariprazine: from clinical research to clinical practice. Real world experiences and recommendations from an International Panel
Authors: Fagiolini Andrea , Alcalá José Ángel , Aubel Thomas , Bienkiewicz Wojciech , Bogren Mats Magnus Knut , Gago Joaquim , Cerveri Giancarlo , Colla Michael , Sanchez Francisco Collazos , Cuomo Alessandro , Helge Frieling , Iacoponi Eduardo , Karlsson Per-Axel , Peddu Pradeep , Pettorruso Mauro , Pereira Henrique Jorge Ramos , Schölin Johan Sahlsten , Vernaleken Ingo Bernd
Published: September 2020

Background

Management of schizophrenia is sub-optimal in many patients. Targeting negative symptoms, among the most debilitating aspects of schizophrenia, together with positive symptoms, can result in significant functional benefits and dramatically improve quality of life for patients and their carers. Cariprazine, a partial agonist of the dopamine receptors D2/D3 has demonstrated effectiveness across symptom domains in clinical trials, particularly on negative symptoms.

Objective

To obtain a broader insight from clinicians with specific experience with cariprazine, on how it affects patient populations outside the clinical trial setting.

Methods

The panel addressed a series of psychopharmacologic topics not comprehensively addressed by the evidence-based literature, including characteristics of patients treated, dosing and switching strategies, duration of therapy, role of concomitant medications and tolerability as well as recommendations on how to individualize cariprazine treatment for patients with schizophrenia.

Results

Patients recommended for cariprazine treatment are those with first episodes of psychosis, predominant negative symptoms (maintenance/acute phase) and significant side effects (metabolic side effects, hyperprolactinemia, sedation) with other antipsychotics. When the long-term treatment of a lifetime illness is adequately weighted, cariprazine becomes one of the first-line medications, not only for patients with predominant negative symptoms but also for those with relatively severe positive symptoms, especially if they are at the first episodes and if a specific medication is added for symptoms such as agitation or insomnia. For instance, patients with agitation may also benefit from the combination of cariprazine and a benzodiazepine or another sedating agent. Cariprazine may be prescribed as add-on to medications such as clozapine, when that medication alone is ineffective for negative symptoms, and sometimes the first may be discontinued or its dose lowered, after a period of stability, leaving the patient on a better tolerated antipsychotic regimen.

Conclusions

Based on real-world clinical experience, the panel considered that cariprazine, with its distinct advantages including pharmacokinetics/pharmacodynamics, good efficacy and tolerability, represents a drug of choice in the long-term management of schizophrenia not only for patients with predominant negative symptoms but also for those with positive symptoms.
Occupational exposure of platinum-based anti-cancer drugs: five-year monitoring of hair and environmental samples in a single hospital
Authors: Hori Ai , Shimura Mari , Iida Yutaka , Yamada Kazuhiko , Nohara Kyoko , Ichinose Takayuki , Yamashita Ai , Shirataki Junko , Hagiwara Shotaro
Published: September 2020

Background

Occupational exposure to chemotherapeutic agents in hospitals is a critical issue. Here, we focused on occupational exposure to platinum-based anti-cancer drugs (PDs) by evaluating platinum concentrations in hair and environmental workplace samples to monitor the risk among workers.

Methods

Hospital workers who dealt with or without PDs, patients treated with PDs, and non-medical office workers outside the hospital donated hair samples and completed a questionnaire regarding their history of handling PDs, including any incidents. Hair samples were collected and surface wipe sampling was performed in July 2010 and April 2015, before and after moving to a new building and introducing a revised safety program in August 2010. Samples were analyzed by inductively coupled plasma-mass spectrometry.

Results

Platinum concentrations in hair from PDs-handling workers was significantly higher than in non-PDs-handling workers (P = 0.045), although 50 times lower than that from PDs-treated patients. Platinum concentrations in the hospital environment had decreased at the second survey 5 years later but had not changed significantly in the hair samples from hospital workers.

Conclusion

Platinum concentrations in hair are likely dependent on the frequency of handling PDs. Reduced environmental contamination from PDs did not influence platinum levels in hospital workers’ hair. Continuous monitoring by measuring platinum concentrations in the environment and in hair would provide information regarding these issues.
Healthcare cost associations of patients who use illicit drugs in Florida: a retrospective analysis
Authors: Ryan Jessica L. , Rosa Veronica R.
Published: September 2020

Background

Illicit drug use increases visits to the hospital. Research is limited on the costs of these healthcare visits by illicit drug.

Methods

Florida’s Agency for Health Care Administration’s emergency department and inpatient datasets from 2016 to 2018 were analyzed. Adults who used an illicit drug were included in the study population resulting in 709,658 observations. Cost-to-charge ratios were used to estimate healthcare costs. Linear regression analyzed associations of illicit drugs with total healthcare cost.

Results

Total healthcare costs are estimated at $6.4 billion over the 3 year period. Medicare paid for the most patient care ($2.16 billion) with Medicaid and commercial insurance each estimated at $1.36 billion. Cocaine (9.25%) and multiple drug use (6.12%) increased the costs of an ED visit compared to a patient with cannabis SUD. Opioids (23.40%) and inhalants use (16.30%) increased the costs of inpatient compared to cannabis SUD.

Conclusion

Healthcare costs are high of patients with illicit drug SUD and poisoning, over half of which are paid for with tax payer dollars and to an unknown degree hospital write-offs. Injuries and illness of patients using cocaine and multiple drugs are associated with more expensive ED patient care and opioids and inhalants are associated with more expensive inpatient care.
The results of screw augmentation of acetabular cement spacers for the treatment of periprosthetic hip joint infection
Authors: Jin Jing-Yao , Yoon Taek-Rim , Park Kyung-Soon , Jin Sheng-Yu , Jung Dong-Min , Li Qing-Song
Published: September 2020

Introduction

Prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) is widely used in two-stage revision arthroplasty in periprosthetic joint infection (PJI) after total hip arthroplasty (THA). In our institution, we encountered several cases of acetabular cement spacer dislodgement. The aim of this study was to compare the results of two-stage revision arthroplasties with antibiotic-loaded cement spacers with or without screws on the acetabulum for PJI.

Patients and methods

This retrospective study included 44 patients who underwent a two-stage revision THA for PJI from June 2007 to May 2017. We divided the patients into two groups: group 1 consisted of 21 patients (21 hips) who underwent two-stage revision arthroplasty with screw augmentation, while group 2 consisted of 23 patients (23 hips) who underwent the same surgery without screw augmentation at the acetabular cement spacer. We compared the migration and dislodgement of the acetabular cement spacer between the two groups.

Results

Before the second-stage surgery, there was less vertical migration of the cement spacer in group 1 compared to group 2 (1.2 mm vs 3.1 mm,p< 0.001). There was also less medial migration of the cement spacer in group 1 (0.6 mm vs 1.6 mm,p= 0.001). After the first stage, the mean Harris Hip score was significantly higher in group 1 than in group 2 (75 vs 65,p= 0.033). Cement spacer rotation or total movement out of the acetabular area occurred in six patients, all in group 2. After first stage reinfection occurred in two patients, one in each group.

Conclusions

Screw augmentation to the acetabulum in the first-stage surgery provides better stability of acetabular antibiotic cement spacers without increasing reinfection rate.
Incidental retroaortic innominate vein in a patient with acute aortic dissection
Authors: Sasaki Hideki , Harada Takashi , Ishitoya Hiroshi , Sasaki Osamu
Published: September 2020

Background

Retroaortic innominate vein is a rare anomaly. It has been reported in patients with congenital anomalies such as Tetralogy of Fallot or right aortic arch. However, isolated retroaortic innominate vein is quite rare.

Case presentation

A 63-year-old man was transferred to our institution because of Stanford type A acute aortic dissection. Incidentally, we noticed that the left innominate vein coursed under the aortic arch and was directed into the superior vena cava on computed tomography. We performed emergent hemiarch replacement.

Conclusions

Attention must be paid to the cannulation site for venous uptake and the method of myocardial protection.
Structural modelling of the lumenal domain of human GPAA1, the metallo-peptide synthetase subunit of the transamidase complex, reveals zinc-binding mode and two flaps surrounding the active site
Authors: Su Chinh Tran-To , Sinha Swati , Eisenhaber Birgit , Eisenhaber Frank
Published: September 2020

Background

The transamidase complex is a molecular machine in the endoplasmic reticulum of eukaryotes that attaches a glycosylphosphatidylinositol (GPI) lipid anchor to substrate proteins after cleaving a C-terminal propeptide with a defined sequence signal. Its five subunits are very hydrophobic; thus, solubility, heterologous expression and complex reconstruction are difficult. Therefore, theoretical approaches are currently the main source of insight into details of 3D structure and of the catalytic process.

Results

In this work, we generated model 3D structures of the lumenal domain of human GPAA1, the M28-type metallo-peptide-synthetase subunit of the transamidase, including zinc ion and model substrate positions. In comparative molecular dynamics (MD) simulations of M28-type structures and our GPAA1 models, we estimated the metal ion binding energies with evolutionary conserved amino acid residues in the catalytic cleft. We find that canonical zinc binding sites 2 and 3 are strongest binders for Zn1 and, where a second zinc is available, sites 2 and 4 for Zn2. Zinc interaction of site 5 with Zn1 enhances upon substrate binding in structures with only one zinc. Whereas a previously studied glutaminyl cyclase structure, the best known homologue to GPAA1, binds only one zinc ion at the catalytic site, GPAA1 can sterically accommodate two. The M28-type metallopeptidases segregate into two independent branches with regard to one/two zinc ion binding modality in a phylogenetic tree where the GPAA1 family is closer to the joint origin of both groups. For GPAA1 models, MD studies revealed two large loops (flaps) surrounding the active site being involved in an anti-correlated, breathing-like dynamics.

Conclusions

In the light of combined sequence-analytic and phylogenetic arguments as well as 3D structural modelling results, GPAA1 is most likely a single zinc ion metallopeptidase. Two large flaps environ the catalytic site restricting access to large substrates.

Reviewers

This article was reviewed by Thomas Dandekar (MD) and Michael Gromiha.