Study Outcome Parameters Research Articles

The impact of expiratory muscle strength training on voluntary cough effectiveness in Huntington's disease.

Dysfunction of the airway defence system in Huntington's disease (HD) is a significant but often overlooked problem. Although expiratory muscle strength training (EMST) is frequently utilized in cough effectiveness treatment, its specific impact in HD patients has not yet been explored. This study investigated the effects of EMST on voluntary peak cough flow (vPCF) in HD patients and evaluated the retention of potential gains post-intervention. In this prospective case-controlled trial, 29 HD patients completed an 8-week wait-to-start period, which served to identify the natural development of expiratory muscle strength and vPCF. This was followed by 8 weeks of EMST training and an additional 8 weeks of follow-up. The study's outcome parameters, vPCF and maximum expiratory pressure (MEP), were measured against those of age- and sex-matched healthy controls. Huntington's disease patients had significantly lower MEP (p < 0.001) and vPCF (p = 0.012) compared to healthy controls at baseline. Following the EMST, significant improvements in MEP (d = 1.39, p < 0.001) and vPCF (d = 0.77, p = 0.001) were observed, with HD patients reaching the cough performance levels of healthy subjects. However, these gains diminished during the follow-up, with a significant decline in vPCF (d = -0.451, p = 0.03) and in MEP (d = -0.71; p = 0.002). Expiratory muscle strength training improves expiratory muscle strength and voluntary cough effectiveness in HD patients, but an ongoing maintenance programme is necessary to sustain the improvements.

Effects of anesthesia with sevoflurane on outcome parameters in murine experimental studies.

Multiple murine studies modelling the immuno-pathophysiological consequences of trauma, shock, burn or sepsis were performed during the last decades. Almost every animal model requires anesthesia for practical and ethical reasons. Furthermore, often, corresponding control groups involve untreated animals without or with a limited exposure to anesthetics. However, the influences of anesthetic drugs on immuno-pathophysiological reactions remain insufficiently investigated. Therefore, we aimed to closer characterize the anesthetic impact exemplified by sevoflurane on the organ performance in mice and thereby investigate the influence of anesthesia itself on major outcome parameters in animal studies. C57/BL6 mice were subjected either to 270min of sevoflurane narcosis or directly euthanized. Plasma, BAL-fluids, lungs, kidneys, liver and intestine were collected and examined for immunological, functional and morphological changes. Systemic levels of the cytokine keratinocyte chemoattractant (KC) were raised in the narcosis group, while concentrations of high mobility group box protein 1 (HMGB-1) as a major inflammatory marker were reduced. In the lungs, levels of HMGB-1 and interleukin 6 (IL-6) were reduced. In contrast, systemic concentrations of intestinal fatty acid binding-protein (i-FABP) as an intestinal damage marker were elevated. Furthermore, liver-type fatty acid binding-protein (L-FABP) levels were lower in the narcosis animals, and inflammatory markers were reduced in liver tissues. Anesthesia also ameliorated the inflammatory reaction in renal tissues, while plasma levels of urea and creatinine were elevated, reflecting either dehydration and/or impaired renal function. As anesthesia with sevoflurane exhibited distinct effects in different organs, it is difficult to predict its specific impact on targets of interest in in vivo studies. Therefore, further studies are required to clarify the effects of different anesthetic drugs. Overall, the inclusion of a control group subjected to the same anesthesia protocol as the experimental groups of interest seems helpful to precisely define the inherent impact of the anesthetic when investigating immuno-pathophysiologic conditions in vivo.

Efficacy and safety of robotic vs. laparoscopic gastrectomy for patients with gastric cancer: systematic review and meta-analysis.

The emergence of robotic surgical systems compensated for the technological shortcomings of laparoscopic approaches. However, whether robotic gastrectomy (RG) has better perioperative outcomes and survival than laparoscopic gastrectomy (LG) for gastric cancer is still unclear but increasingly drawing attention. In this systematic review and meta-analysis, we searched the PubMed, EMBASE, Web of Science, and Cochrane Library as of January 20, 2024 and referenced list of eligible articles for all published studies comparing RG and LG for patients with gastric cancer, Data on study characteristics, individual characteristics, and outcome parameters were extracted. The quality of studies was assessed using the Revised Cochrane risk-of-bias 2 tool and the risk of bias in non-randomized studies of interventions tool. The main outcome measures were overall survival (OS) and disease-free survival (DFS). We identified 3641 articles, of which 72 studies (30081 patients) were included in the meta-analysis. Compared with LG, RG was associated with higher OS [hazard ratio (HR)=0.89, 95% CI=0.83 to 0.96), lower rate of overall postoperative complications [odds ratio (OR)=0.77, 95% CI=0.71 to 0.84], longer operating time [mean difference (MD)=35.53, 95% CI=29.23 to 41.83], less estimated blood loss (MD=-37.45, 95% CI=-46.24 to -28.67), a higher number of retrieved lymph nodes (MD=1.88, 95% CI=0.77 to 3.00), faster postoperative recovery, and lower rate of conversion (OR=0.44, 95% CI=0.36 to 0.55). Mortality and DFS were not significantly different between the two groups. The subgroup of meta-analysis results also showed the advantages of robotic surgery over laparoscopic surgery in intracorporeal reconstruction, total gastrectomy, Ⅰ/Ⅱ stage, and BMI≥25, especially for patients with stage Ⅰ/Ⅱ, there is better overall survival and disease-free survival. Our findings point to robotic surgery having great benefits compared with laparoscopic surgery in gastric cancer. Our study may help inform decision-making in applying robotic surgical systems to clinical treatment.

Hyaluronic acid in tooth extraction: a systematic review and meta-analysis of preclinical and clinical trials

ObjectivesTo assess whether in animals or patients with ≥ 1 tooth extracted, hyaluronic acid (HyA) application results in superior healing and/or improved complication management compared to any other treatment or no treatment.Materials and methodsThree databases were searched until April 2022. The most relevant eligibility criteria were (1) local application of HyA as adjunct to tooth extraction or as treatment of alveolar osteitis, and (2) reporting of clinical, radiographic, histological, or patient-reported data. New bone formation and/or quality were considered main outcome parameters in preclinical studies, while pain, swelling, and trismus were defined as main outcome parameters in clinical studies.ResultsFive preclinical and 22 clinical studies (1062 patients at final evaluation) were included. In preclinical trials, HyA was applied into the extraction socket. Although a positive effect of HyA was seen in all individual studies on bone formation, this effect was not confirmed by meta-analysis. In clinical studies, HyA was applied into the extraction socket or used as spray or mouthwash. HyA application after non-surgical extraction of normally erupted teeth may have a positive effect on soft tissue healing. Based on meta-analyses, HyA application after surgical removal of lower third molars (LM3) resulted in significant reduction in pain perception 7 days postoperatively compared to either no additional wound manipulation or the application of a placebo/carrier. Early post-operative pain, trismus, and extent of swelling were unaffected.ConclusionsHyA application may have a positive effect in pain reduction after LM3 removal, but not after extraction of normally erupted teeth.Clinical relevanceHyA application may have a positive effect in pain reduction after surgical LM3 removal, but it does not seem to have any impact on other complications or after extraction of normally erupted teeth. Furthermore, it seems not to reduce post-extraction alveolar ridge modeling, even though preclinical studies show enhanced bone formation.

A critical analysis of clinical research methods to study regenerative endodontics.

Regenerative endodontic treatment such as revitalization provides a treatment option for immature teeth with pulp necrosis. The main difference to the alternative procedure, the apical plug, is the induction of a blood clot inside the canal as a scaffold for healing and new tissue formation. Due to the biology-based and minimally-invasive nature of the treatment, revitalization has raised considerable interest in recent years. Whereas the procedure is fairly new and recommendations from endodontic societies have been in place only for a few years, the treatment protocol has evolved over the past two decades. Evidence has been created, not only from laboratory and animal work, but also from clinical studies including case reports, cohort studies and eventually prospective randomized controlled clinical trials, systematic reviews and meta-analyses. However, the research methods and clinical studies with subsequent reports oftentimes present with methodical limitations, which makes it difficult to objectively assess the value of this treatment modality. Several open questions remain, including the need for a more differentiated indication of revitalization after different traumatic injuries, the long-term prognosis of treated teeth and the true benefits for the patient. Therefore, this review aims to identify and reflect on such limitations, scrutinizing study design, diagnostic tools, procedural details and outcome parameters. A core outcome set is also proposed in this context, which can be considered in future clinical investigations. These considerations may lead to a more detailed and stringent planning and execution of future studies in order to create high-quality evidence for the treatment modality of revitalization and thus provide more robust data, create a larger body of knowledge for clinicians and further specify current recommendations.

Comparison and validation of EuroQol-5 Dimension level and Short Form-6 Dimension in cataract patients

Background: EuroQol-5 Dimension (EQ-5D) and Short Form-6 dimension (SF-6D) are instruments that have been widely used to assess utility index as an outcome parameter in pharmacoeconomic studies. The choice of an instrument will have an important effect and can influence the decision making of an economic health evaluation. Objectives: The aim of this study was to compare the SF-6D and EQ-5D instruments to assess utility index in cataract patients. Methods: The study was conducted with on 448 cataract patients in a hospital in Yogyakarta. The subjects of the study were outpatient cataract patients over 45 years of age. The patient's health-related quality of life (HRQoL) was assessed using the SF-6D, EQ-5D, and visual function questionnaire instruments. The construct validity was tested including known group validity using the independent sample t test and ANOVA, convergent validity with the Spearman correlation, ceiling effect, and bland and Altmand plots. Results: A total of 448 cataract patients, mean age 64.7 (10.1) years, showed utility index assessed using the EQ-5D-5L and SF-6D instruments, which were 0.7 (0.2) and 0.8 (0.1), respectively. Convergent validity shows that the EQ-5D-5L dimensions have a moderate to very strong correlation (0.4-0.9) with the dimensions on VFQ-25, as well as the SF-6D (0.4-0.8). The known group validity shows that both EQ-5D-5L and SF-6D can differentiate the patient's health status based on cataract surgery, visual acuity, and comorbidity. The Bland Altman plot shows the level of agreement between EQ-5D-5L and SF-6D of 91.7%. In better health status, the utility index of EQ-5D-5L is higher and vice versa, in the worse health status the utility index of SF-6D is higher. Conclusion: Both the EQ-5D-5L and SF-6D instruments are valid for assessing the utility index in cataract patients. By using different instruments, there are differences in the utility value of cataract patients based on their health status. Therefore it is necessary to consider in choosing the instrument in assessing utility as an outcome parameter in pharmacoeconomic study.

A critical appraisal of tools for delivery room assessment of the newborn infant.

Assessment of an infant's condition in the delivery room represents a prerequisite to adequately initiate medical support. In her seminal paper, Virginia Apgar described five parameters to be used for such an assessment. However, since that time maternal and neonatal care has changed; interventions were improved and infants are even more premature. Nevertheless, the Apgar score is assigned to infants worldwide but there are concerns about low interobserver reliability, especially in preterm infants. Also, resuscitative interventions may preclude the interpretation of the score, which is of concern when used as an outcome parameter in delivery room intervention studies. Within the context of these changes, we performed a critical appraisal on how to assess postnatal condition of the newborn including the clinical parameters of the Apgar score, as well as selected additional parameters and a proposed new scoring system. The development of a new scoring system that guide clinicians in assessing infants and help to decide how to support postnatal adaptation is discussed. IMPACT: This critical paper discusses the reliability of the Apgar score, as well as additional parameters, in order to improve assessment of a newborn's postnatal condition. A revised neonatal scoring system should account for infant maturity and the interventions administered. Delivery room assessment should be directed toward determining how much medical support is needed and how the infant responds to these interventions.

The value of LH supplementation in young women with diminished ovarian reserve treated with GnRH Antagonist Protocol for ovarian hyperstimulation in ICSI-cycles.

To compare the success of two controlled ovarian hyperstimulation protocols; rFSH + hp-hMG with only rFSH in the GnRH antagonist protocol in diminished ovarian reserve under 35 years of age. Data from January 2015 to June 2019 were abstracted from the hospital records of IVF Clinic. The women younger than 35 years of age who were diagnosed as diminished ovarian reserve and underwent standard GnRH antagonist protocol were included. Patients in Group-1 underwent controlled ovarian stimulation with rFSH alone and Group-2 with rFSH in combination with hp-hMG. Patients in both groups were divided into three subgroups according to their antral follicle count at Day 3: < 4 (a), 4-6 (b), and 7-10 (c). Demographic features and IVF outcomes of the patients were extracted. Total number of retrieved oocytes, was higher in Group-1 than Group-2 (6.5 ± 2.1 vs 5.5 ± 2.3, respectively, p < 0.001). However, there were no significant differences between the two groups in terms of clinical pregnancy rate, implantation rate, miscarriage rate and live birth rate. Although the main study outcome parameters did not show significant difference between Group-1a and Group-2a, the number of mature oocytes (5 ± 2.8 vs 1.8 ± 1.2, respectively, p = 0.006) was higher in Group-1a. We observed no beneficial effect of LH supplementation during IVF for the treatment of women under 35 years old with diminished ovarian reserve in the first treatment cycle when compared with rFSH only in the antagonist protocols.

Mitochondrial and glycolytic extracellular flux analysis optimization for isolated pig intestinal epithelial cells

Intestinal epithelial cells (IECs) are crucial to maintain intestinal function and the barrier against the outside world. To support their function they rely on energy production, and failure to produce enough energy can lead to IEC malfunction and thus decrease intestinal barrier function. However, IEC metabolic function is not often used as an outcome parameter in intervention studies, perhaps because of the lack of available methods. We therefore developed a method to isolate viable IECs, suitable to faithfully measure their metabolic function by determining extracellular glycolytic and mitochondrial flux. First, various methods were assessed to obtain viable IECs. We then adapted a previously in-house generated image-analysis algorithm to quantify the amount of seeded IECs. Correcting basal respiration data of a group of piglets using this algorithm reduced the variation, showing that this algorithm allows for more accurate analysis of metabolic function. We found that delay in metabolic analysis after IEC isolation decreases their metabolic function and should therefore be prevented. The presence of antibiotics during isolation and metabolic assessment also decreased the metabolic function of IECs. Finally, we found that primary pig IECs did not respond to Oligomycin, a drug that inhibits complex V of the electron transport chain, which may be because of the presence of drug exporters. A method was established to faithfully measure extracellular glycolytic and mitochondrial flux of pig primary IECs. This tool is suitable to gain a better understanding of how interventions affect IEC metabolic function.

Effect of Digital Care Platforms on Quality of Care for Oncological Patients and Barriers and Facilitators for Their Implementation: Systematic Review.

BackgroundOncological health care services are challenged by the increasing number of cancer survivors, long-term follow-up care, and fragmentation of care. Digital care platforms are potential tools to deliver affordable, patient-centered oncological care. Previous reviews evaluated only one feature of a digital care platform or did not evaluate the effect on enhancement of information, self-efficacy, continuity of care, or patient- and health care provider–reported experiences. Additionally, they have not focused on the barriers and facilitators for implementation of a digital care platform in oncological care.ObjectiveThe aim of this systematic review was to collect the best available evidence of the effect of a digital care platform on quality of care parameters such as enhancement of available information, self-efficacy, continuity of care, and patient- and health care provider–reported experiences. Additionally, barriers and facilitators for implementation of digital care platforms were analyzed.MethodsThe PubMed (Medline), Embase, CINAHL, and Cochrane Library databases were searched for the period from January 2000 to May 2020 for studies assessing the effect of a digital care platform on the predefined outcome parameters in oncological patients and studies describing barriers and facilitators for implementation. Synthesis of the results was performed qualitatively. Barriers and facilitators were categorized according to the framework of Grol and Wensing. The Mixed Methods Appraisal Tool was used for critical appraisal of the studies.ResultsSeventeen studies were included for final analysis, comprising 8 clinical studies on the effectiveness of the digital care platform and 13 studies describing barriers and facilitators. Usage of a digital care platform appeared to enhance the availability of information and self-efficacy. There were no data available on the effect of a digital care platform on the continuity of care. However, based on focus group interviews, digital care platforms could potentially improve continuity of care by optimizing the exchange of patient information across institutes. Patient-reported experiences such as satisfaction with the platform were considerably positive. Most barriers for implementation were identified at the professional level, such as the concern for increased workload and unattended release of medical information to patients. Most facilitators were found at the patient and innovation levels, such as improved patient-doctor communication and patient empowerment. There were few barriers and facilitators mentioned at the economic and political levels.ConclusionsThe use of digital care platforms is associated with better quality of care through enhancement of availability of information and increased self-efficacy for oncological patients. The numerous facilitators identified at the patient level illustrate that patients are positive toward a digital care platform. However, despite these favorable results, robust evidence concerning the effectiveness of digital care platforms, especially from high-quality studies, is still lacking. Future studies should therefore aim to further investigate the effectiveness of digital care platforms, and the barriers and facilitators to their implementation at the economic and political levels.

Safety and Tolerability of Sodium Glucose Co-transporter -2 Inhibitors (SGLT2i) During Ramadan Fasting

Background: Diabetic management during Ramadan fasting is a significant clinical challenge. Sodium glucose co-transporter -2 inhibitors (SGLT2i) are new class of antidiabetic medications known for low frequency of associated hypoglycemia. The present study aimed to evaluate efficacy, safety and tolerability of SGLT2i in diabetic patients practicing Ramadan fasting. Patients and methods: The study included 94 patients. They comprised 51 patients who received metformin and sulfonylureas (SU): glimepiride (1-6 mg/d) or gliclazide MR (60-120mg/d) and 43 patients who received metformin and SGLT2i: empagliflozin (25 mg), dapagliflozin (10 mg) or canagliflozin (300 mg). The study outcome parameters were frequency of hypoglycemia episodes, volume depletion episodes, number of days with early breaking of fasting and missed fasting days. Results: It was found that patients in SGLTi group experiences significantly fewer symptomatic (9.3 % versus 35.3 %, p=0.003) and documented (7.0 % versus 25.5 %, p=0.017) hypoglycemic episodes as compared to the SU group. However, there were no significant differences between the studied groups regarding the frequency of patients with volume depletion episodes (5.9 % versus 16.3 %, p= 0.1). Moreover, there were no significant differences between groups regarding the frequency of patients with early breaking of fasting (11.8 % versus 9.3 %, p=0.7) or missed fasting (3.9 % versus 2.3 %, p=0.66). None of the studied patients discontinued the prescribed medications. Conclusions: SGLT2i combined with metformin for diabetic patients during Ramadan fasting are effective, safe and well-tolerated with the advantage of reduced hypoglycemic events.

353-P: Safety and Tolerability of Sodium-Glucose Cotransporter 2 Inhibitors during Ramadan Fasting

Background: Diabetic management during Ramadan fasting is a significant clinical challenge. Sodium glucose co-transporter -2 (SGLT-2) inhibitors are new class of antidiabetic medications known for low frequency of associated hypoglycemia. The present study aimed to evaluate efficacy, safety and tolerability of SGLT-2 inhibitors in diabetic patients practicing Ramadan fasting. Patients and Methods: The study included 94 patients. They comprised 51 patients who received metformin and sulfonylureas: Glimepiride (1mg-6mg/d) or Gliclazide MR (60-120mg/d) and 43 patients who received SGLT2 inhibitors: Empagliflozin (25 mg), Dapagliflozin (10 mg) or Canagliflozin (300 mg). The study outcome parameters were frequency of hypoglycemia episodes, volume depletion episodes, number of days with early breaking of fasting and missed fasting days. Results: It was found that patients in SGLTI group experiences significantly fewer symptomatic (9.3 % versus 35.3 %, p=0.003) and documented (7.0 % versus 25.5 %, p=0.017) hypoglycemic episodes as compared to the SU group. However, there were no significant differences between the studied groups regarding the frequency of patients with volume depletion episodes (5.9 % versus 16.3 %, p= 0.1). Moreover, there were no significant differences between groups regarding the frequency of patients with early breaking of fasting (11.8 % versus 9.3 %, p=0.7) or missed fasting (3.9 % versus 2.3 %, p=0.66). None of the studied patients discontinued the prescribed medications. Conclusions: SGLT-2 inhibitors combined with metformin for diabetic patients during Ramadan fasting are effective, safe and well-tolerated with the advantage of reduced hypoglycemic events. Disclosure E. M. A. Eid: None. A. Hussein: None. H. A. Ghazi: None.

Sex-Related Differences in Cardiac Channelopathies: Implications for Clinical Practice.

Sex-related differences in prevalence, clinical presentation, and outcome of cardiac channelopathies are increasingly recognized, despite their autosomal transmission and hence equal genetic predisposition among sexes. In congenital long-QT syndrome, adult women carry a greater risk for Torsades de pointes and sudden cardiac death than do men. In contrast, Brugada syndrome is observed predominantly in adult men, with a considerably higher risk of arrhythmic sudden cardiac death in adult men than in women. In both conditions, the risk for arrhythmias varies with age. Sex-associated differences appear less evident in other cardiac channelopathies, likely a reflection of their rare(r) occurrence and our limited knowledge. In several cardiac channelopathies, sex-specific predictors of outcome have been identified. Together with genetic and environmental factors, sex hormones contribute to the sex-related disparities in cardiac channelopathies through modulation of the expression and function of cardiac ion channels. Despite these insights, essential knowledge gaps exist in the mechanistic understanding of these differences, warranting further investigation. Precise application of the available knowledge may improve the individualized care of patients with cardiac channelopathies. Promoting the reporting of sex-related phenotype and outcome parameters in clinical and experimental studies and advancing research on cardiac channelopathy animal models should translate into improved patient outcomes. This review provides a critical digest of the current evidence for sex-related differences in cardiac channelopathies and emphasizes their clinical implications and remaining gaps requiring further research.

A Comparative Study of 23-Gauge and 27-Gauge Vitrectomy for Puckers or Floaters, Including Evaluation of the Effect of Combined Phaco-Vitrectomy Surgery on Postoperative Outcome

Introduction: A single-center, prospective randomized comparison of postoperative recovery between 23-gauge and 27-gauge surgical approaches in vitrectomy was performed. Methods: A single-center, prospective randomized comparison of postoperative recovery between 23-gauge and 27-gauge surgical approaches to evaluate efficiencies and postoperative outcomes of the two surgical gauges. Eighty patients who were scheduled to undergo pars plana vitrectomy (PPV) for floaters or macular surgery were treated with either 27-gauge or 23-gauge techniques and assessed for efficiency of the procedures as well as a variety of postop indicators of pain and inflammation. Results: 27-Gauge vitrectomy took 90 s more time compared to 23-gauge surgery. Wound closure was significantly easier in 27-gauge than 23-gauge. Less postoperative eye reddishness was seen in 27-gauge compared to 23-gauge. A trend towards less inflammation was seen in 27-gauge. Conclusion: Overall, the trial showed that 27-gauge has the better postoperative outcome compared to 23-gauge PPV. Combining vitrectomy with phaco-surgery did not influence the study outcome parameters.

Malnutrition as predictor of poor outcome after total hip arthroplasty

IntroductionThe aim of this study was to assess the prevalence of protein energy malnutrition (PEM) and correlation with poor post-operative outcome in the elderly undergoing primary total hip arthroplasty (THA).HypothesisPatients with PEM would have inferior post-operative outcome after THA.Materials and methodWe retrospectively evaluated the nutritional status of 220 hospitalized patients undergoing THA, 65 years and older. PEM was assessed using serum albumin and total lymphocyte count (TLC). Studied outcome parameters were length of pre-operative and post-operative stay, complications up to six months after surgery and 12-month mortality. Clinical and demographic data were retrieved from medical records from the hospital database.ResultsThe prevalence of PEM among patients undergoing THA was 12.3% (27/220). Patients with PEM were significantly older (mean age 81.3 ± 7.0, p < 0.001), had a lower BMI (24.7 ± 4.1 kg/m 2, p = 0.022), and showed more comorbid conditions (mean CCI 2.8 ± 2.0, p = 0.002) compared with well-nourished patients (age 75.6 ± 6.2, BMI 26.8 ± 4.3 kg/m 2, CCI: 1.7 ± 1.7). Length of pre-operative stay differed significantly (p < 0.001) between PEM (median 7, range 1–36 days) and non PEM (median 1, range 1–22 days). In the PEM group, 12 (44.4%) patients had post-operative complications within six months after OP and 15 (7.8%) patients in the non PEM group (HR = 6.3, 95% CI 1.7–23.1).ConclusionWe observed a higher post-operative complication rate for malnourished patients undergoing elective THA. These results underline the importance of pre-operative nutritional assessment in the elderly. Therefore, serum albumin and TLC are valuable clinical markers of PEM and the post-operative outcome.

Disease-specific gait deviations in pediatric patients with X-linked hypophosphatemia

BackgroundX-linked hypophosphatemia (XLH) represents the most common genetic form of rickets featuring profound hypophosphatemia with associated skeletal and non-skeletal manifestations. Early onset gait disturbances contribute strongly to the burden of disease. However, no study has comprehensively characterized naturally occurring gait deviations in pediatric patients with XLH. Research questionsCan disease-specific gait deviations and potentially influencing factors be identified by gait analysis in non-surgically treated children with XLH? MethodsGait laboratory assessments of 12 pediatric patients with XLH without previous long bone surgery was retrospectively analyzed and compared to age-matched healthy controls. Radiologic and clinical parameters of XLH patients were correlated with kinematic gait variables and gait scores. ResultsReduced external knee rotation and increased external hip orientation was ubiquitous in children with XLH. Increased lateral trunk lean, or “waddling gait”, occurred in five children and was associated with varus knee deformities. Overall, children with XLH showed a reduced Gait Deviation Index (GDI) compared to controls. Radiologic and gait analysis revealed complex combined frontal and torsional deformity of the lower limbs as a common feature in XLH. Higher Body Mass Index (BMI) was associated with both lateral trunk lean and impaired GDI. SignificanceGait analysis is feasible to quantify gait deviations and lower limb deformities in pediatric patients with XLH. Specific gait characteristics including internal knee rotation and external hip rotation are common among patients with XLH and contribute to impaired gait scores. Our data suggest the use of gait and deformity data assessment as outcome parameters in future observational and interventional studies. Standardized assessment might contribute to targeted treatments to improve life quality in XLH patients.

Is Exercise-Induced Fatigue a Problem in Children with Duchenne Muscular Dystrophy?

Duchenne muscular dystrophy (DMD) is a devastating X-linked muscular disorder. The number of studies investigating new therapeutic approaches is substantially increasing. This study aims to investigate the impact and diagnostic value of exercise-induced fatigue in DMD, which has been proposed as a suitable outcome parameter in other conditions like spinal muscular atrophy. A cohort of 55 DMD patients (49 of them treated with steroids and 9 with ataluren) underwent a total of 241 6MWT (mean 4.4 tests/patient) which were retrospectively analyzed. Exercise-induced fatigue was assessed by the ratio between the distance achieved in the sixth minute and the distance in the second minute of the 6MWT. In previous studies a quotient above 1 was defined as a sign of fatigue. The average fatigue quotient in the whole cohort of patients was 1.0. In a further analysis no impact of age, steroid therapy, ataluren therapy, overall disability, and distance in the 6-minute walk test (6MWT) on fatigue in DMD patients could be shown. Our data show that fatigue does not play a relevant role in DMD. Analysis of fatigue is not a useful outcome parameter in DMD studies. For this reason we suggest the 2MWT, which is better accepted by the patients, as an alternative to the commonly 6MWT.

Translation, Cultural Adaptation, and Validation of Short-Form 6D on the General Population in Indonesia

ObjectivesThis study aims to translate, culturally adapt, and validate the Short-Form 6D (SF-6D) instruments for measuring quality of life as outcome parameters in pharmacoeconomic studies. MethodsThe forward-backward methods were applied to translate the SF-6D questionnaire. A preliminary Indonesian version of SF-6D questionnaire was field tested in samples of 470 adult general population. Test–retest reliability was assessed by using Spearman rank correlation coefficient and internal consistency with Cronbach α. Face validity was assessed descriptively based on the response of the respondents to all items in SF-6D. The construct validity test included internal construct validity and convergent validity, which was assessed by examining the correlation between the questionnaire and Euro-Quality of life-5D based on the scale of each domain. The known group method was used to test discriminant validity. Mann-Whitney U test was employed for comparing the utility score on dichotomous variables and Kruskal-Wallis H test was used for polychromatic variables. ResultsThe SF-6D was a valid and reliable questionnaire, indicated by the reliability coefficient of 0.725 and the value of each item ranging from 0.698 to 0.750. Construct validity indicated a strong correlation between physical functioning, role limitation, social functioning, pain, and mental health with the SF-6D utility score. Convergent validity showed a weak and moderate correlation between dimensions on SF-6D and Euro-Quality of life-5D. ConclusionsThe SF-6D questionnaire has been translated into Indonesian version. The SF-6D questionnaire is valid and reliable. Known group validity shows that the SF-6D could differentiate utility scores by age group and history present illness.

Perbandingan EQ-5D-5L dan SF-6D Untuk Mengukur Index Utility Kesehatan Pada Populasi Umum di Yogyakarta

The EuroQuality of life-5 dimension 5 level (EQ-5D-5L) and Short Form-6 Dimension (SF-6D) are the most widely used generic instruments for assessing utility as an outcome parameter in pharmacoeconomic studies. Different instruments cause different utility values and influence the decision making. The purpose of this study was to compare the utility score index measured using EuroQuality of life-5 dimension 5 levels (EQ-5D-5L) and Short Form-6 Dimension (SF-6D) in general population. The study was conducted cross sectional design in general population in the Yogyakarta. EQ-5D-5L and SF-6D questionnaires were given to 470 respondents to measure the utility score index. Differences of utility index scores based on demographic characteristics were analyzed using Mann Whitney and Kruskal Wallis test, while correlations between EQ-5D and SF-6D domains with utility scores were analyzed using Pearson Correlation. Limits of agreement were described by Bland and Altman Plot. The results of the study showed the utility scores measured using EQ-5D-5L, EQ-VAS, and SF-6D were 0.944 (SD = 0.093), 0.829 (SD = 0.089) and 0.915 (SD = 0.081) respectively. EQ-5D-5L and EQ-VAS can distinguish utility values based on age. There is a strong correlation (&gt; 0.700) between the domain of mobility and pain with the EQ-5D-5L utility index, and the domain of physical function and pain with the SF-6D utility index. Ceiling effect of EQ-5D-5L (59%) is greater than SF-6D (22.4%). The Bland and Altman plot shows the difference in utility scores of EQ-5D-5L with SF-6D, SF-6D with EQ-VAS, and EQ-5D-5L with VAS, respectively at the limit of agreement 92.98%, 96 , 38%, and 95.74%. EQ-5D-5L can distinguish utility scores based on age, but showed higher ceiling effect. Both EQ-5D-5L and SF-6D showed a strong correlation between the domain of mobility (physical function) and pain with the utility score.

Proposed Definition of Experimental Secondary Ischemia for Mouse Subarachnoid Hemorrhage

Inconsistency in outcome parameters for delayed cerebral ischemia (DCI) makes it difficult to compare results between mouse studies, in the same way inconsistency in outcome parameters in human studies has for long obstructed adequate comparison. The absence of an established definition may in part be responsible for the failed translational results. The present article proposes a standardized definition for DCI in experimental mouse models, which can be used as outcome measure in future animal studies. We used a consensus-building approach to propose a definition for “experimental secondary ischemia” (ESI) in experimental mouse subarachnoid hemorrhage that can be used as an outcome measure in preclinical studies. We propose that the outcome measure should be as follows: occurrence of focal neurological impairment or a general neurological impairment compared with a control group and that neurological impairment should occur secondarily following subarachnoid hemorrhage (SAH) induction compared with an initial assessment following SAH induction. ESI should not be used if the condition can be explained by general anesthesia or if other means of assessments sufficiently explain function impairment. If neurological impairment cannot reliably be evaluated, due to scientific setup. Verification of a significant secondary impairment of the cerebral perfusion compared with a control group is mandatory. This requires longitudinal examination in the same animal. The primary aim is that ESI should be distinguished from intervention-related ischemia or neurological deficits, in order establish a uniform definition for experimental SAH in mice that is in alignment with outcome measures in human studies.