Real Clinical Practice Setting Research Articles

Retrospective study of germline variants in patients with hereditary melanoma study criteria in a real clinical practice setting.

Five to twelve percent of melanomas show aggregation of melanomas or other related tumors within the same family or individual. Genes such as CDKN2A, or BAP1, among others, have been involved in this condition. Retrospective descriptive study that includes patients from Cruces University Hospital (2016-2023) who met any of the following criteria: presence of two or more melanomas (1), or a melanoma and a pancreatic cancer (2) in the same individual; presence of a melanoma in an individual and one or more first- or second-degree relatives with melanoma or pancreatic cancer (3); first- or second-degree relationship with an individual with a known deleterious variant in genes related to melanoma predisposition (4); or incidental discovery of deleterious variants in genes related to predisposition to melanoma, within hereditary cancer panels carried out for reasons other than melanoma (5). 59 families were included (69 patients; 63.8% women), of which 8.5% (13% of patients) presented pathogenic/likely pathogenic variants (PV/LPV) in CDKN2A (6% of families and patients, excluding criteria 4 and 5), and 1.7% of families (1.4% of patients) presented PV/LPV in BAP1, BRCA2 and TERF2IP. The frequencies of PV/LPV in CDKN2A are similar to those previously described. This study could contribute to the knowledge of the characteristics of patients who meet genetic study criteria for hereditary melanoma, in a setting of real clinical practice.

Anatomical outcomes and complications of sacrocolpopexy using Surelift Uplift mesh: A multicentric observational study.

The study evaluated the anatomical and functional outcomes, as well as the safety data of laparoscopic sacrocolpopexy (LSC) for pelvic organ prolapse (POP) using a lightweight macroporous mesh. A multicentric observational study was developed including five expert centers between March 2011 and December 2019. Inclusion criteria were female patients with symptomatic ≥stage II POP (POP-Q classification), who underwent a LSC. A lightweight and macroporous mesh device (Surelift Uplift) was used. Baseline anatomical positions were evaluated using POP-Q stage. The anatomical outcomes and procedural complications were assessed during the postoperative period. Primary outcomes were anatomical success, defined as POP-Q stage ≤I, and subjective success, defined as no bothersome bulge symptoms, and no repeat surgery or pessary use for recurrent prolapse. A total of 325 LSCs were analyzed with a median patient age of 66 (interquartile range [IQR] 61-73). After a median follow-up of 68 months (IQR 46.5-89), anatomical success was found in 88.9%, whereas subjective success was seen in 98.5% of the patients. Recurrent prolapse presented as cystocele (1.5%). Reported complications were bladder (4.6%) or rectum lesions (0.6%), de novo urinary incontinence (12.9%), and mesh extrusion (1.2%). LSC provides significant clinical improvement and excellent anatomical results, with a low risk of serious complications for women with ≥2 grade POP in a real clinical practice setting.

Progress in methodological research on bridging the efficacy-effectiveness gap of clinical interventions(2): to improve the extrapolation of efficacy

Objective: Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings. Methods: Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results: A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics. Conclusions: Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.

Effects of an Electronic Medical Records-Linked Diabetes Self-Management System on Treatment Targets in Real Clinical Practice: Retrospective, Observational Cohort Study.

This study evaluated the effects of a mobile diabetes management program called "iCareD" (College of Medicine, The Catholic University of Korea) which was integrated into the hospital's electronic medical records system to minimize the workload of the healthcare team in the real clinical practice setting. In this retrospective observational study, we recruited 308 patients. We categorized these patients based on their compliance regarding their use of the iCareD program at home; compliance was determined through self-monitored blood glucose inputs and message subscription rates. We analyzed changes in the ABC (hemoglobin A1c, blood pressure, and low-density lipoprotein cholesterol) levels from the baseline to 12 months thereafter, based on the patients' iCareD usage patterns. The patients comprised 92 (30%) non-users, 170 (55%) poor-compliance users, and 46 (15%) good-compliance users; the ABC target achievement rate showed prominent changes in good-compliance groups from baseline to 12 months (10.9% vs. 23.9%, P<0.05), whereas no significant changes were observed for poor-compliance users and non-users (13.5% vs. 18.8%, P=0.106; 20.7% vs. 14.1%, P=0.201; respectively). Implementing the iCareD can improve the ABC levels of patients with diabetes with minimal efforts of the healthcare team in real clinical settings. However, the improvement of patients' compliance concerning the use of the system without the vigorous intervention of the healthcare team needs to be solved in the future.

Effect of Concomitant Use of Proton Pump Inhibitors on Immunotherapy Clinical Response in Advanced Cancer Patients: Real-Life Setting.

The alteration of the gut microbiota mediated by proton pump inhibitor (PPI) drugs could be involved in the clinical response associated with immunotherapy [immunocheckpoint inhibitors (ICIs)] in cancer patients. Due to the current controversy in the scientific evidence, it has been proposed to evaluate the correlation between the concomitant use of PPIs and the effectiveness of immunotherapy in a real clinical practice setting. Single-center retrospective cohort study that included patients treated with anti-PD-1 or anti-CTLA4, including nivolumab, pembrolizumab, atezolizumab, or the combination ipilimumab-nivolumab in metastatic neoplastic disease. The clinical effectiveness of ICI, measured in progression-free survival (PFS) and overall survival (OS), was compared between the PPI-use versus PPI-no-use group. PPI-use group was associated with lower PFS [hazard ratio (HR):1.89 (1.38-2.59), P<0.001] and OS [HR: 2.02 (1.45-2.82), P<0.001] versus PPI-no-use group. However, this difference was not observed for pembrolizumab PFS [HR: 1.38 (0.93-2.39), P=0.160] and OS [HR: 1.41 (0.81-2.44), P=0.187]. The study showed significantly lower PFS and OS in the chronic PPI-use group (P<0.001), recent PPI-use group (P<0.001) and concomitant PPI-use group (P=0.001, 0.007) versus PPI-no-use group. However, late PPI use >30 days after the onset of ICI has no significant effect on the efficacy of treatment [HR: 0.92 (0.49-1.70), P=0.791; HR: 1.10 (0.59-2.05), P=0.756]. The concomitant use of PPIs in immunotherapy is associated with worse clinical outcomes compared with the group without PPI use. In addition, the study shows how the late use of PPIs does not have a significant effect on clinical benefit.

Efficacy of Enhanced Recovery After Surgery Program for Patients Undergoing Lobectomy for Lung Cancer: A Scoping Review and Single-Center Initial Result in Vietnam.

Surgery for lung cancer can be invasive and the recovery process is often slow with many complications. To address this, the enhanced recovery after surgery (ERAS) program aims tominimize adverse clinical events for surgical patients. This is achieved through a multimodal perioperative care protocol that aims to preserve preoperative organ function and reduce postoperative complications. Initially applied to gastrointestinal surgery, this model has now been expanded to other major surgeries, including lung surgery. Through a review of seven retrospective and prospective cohort observational studies, we have examined the effects of the ERAS program on patients undergoing lobectomy for lung cancer treatment. Our analysis focused on outcomes such as length of stay, re-operation rate, re-admission rate, postoperative mortality, and costs, providing valuable insights into the real clinical practice setting. We also report on some initial results when applying ERAS at University Medical Center Ho Chi Minh City.

Clinical utility of a personalized and long-term monitoring device for Parkinson's disease in a real clinical practice setting: An expert opinion survey on STAT-ON™

BackgroundSTAT-ON™ is an objective tool that registers ON-OFF fluctuations making possible to know the state of the patient at every moment of the day in normal life. Our aim was to analyze the opinion of different Parkinson's disease experts about the STAT-ON™ tool after using the device in a real clinical practice setting (RCPS). MethodsSTAT-ON™ was provided by the Company Sense4Care to Spanish neurologists for using it in a RCPS. Each neurologist had the device for at least three months and could use it in PD patients at his/her own discretion. In February 2020, a survey with 30 questions was sent to all participants. ResultsTwo thirds of neurologists (53.8% females; mean age 44.9±9 years old) worked in a Movement Disorders Unit, the average experience in PD was 16±6.9 years, and 40.7% of them had previously used other devices. A total of 119 evaluations were performed in 114 patients (range 2–9 by neurologist; mean 4.5±2.3). STAT-ON™ was considered “quite” to “very useful” by 74% of the neurologists with an overall opinion of 6.9±1.7 (0, worst; 10, best). STAT-ON™ was considered better than diaries by 70.3% of neurologists and a useful tool for the identification of patients with advanced PD by 81.5%. Proper identification of freezing of gait episodes and falls were frequent limitations reported. ConclusionSTAT-ON™ could be a useful device for using in PD patients in clinical practice.

Plasma cell dyscrasia: monoclonal gammopathies, AL-amyloidosis, multiple myeloma Clinical case study

This study was performed in real clinical practice settings. Our paper describes two case studies which show the difficulty of differential diagnosis of monoclonal gammopathies, multiple myeloma associated with AL-amyloidosis and primary AL-amyloidosis.

Abstract P2-07-02: Effects of different duration of prophylactic antibiotic use on unplanned reoperation in breast cancer patients undergoing implant-based breast reconstruction: A retrospective study with overlap weighting analysis

Abstract Background: Some special consensus recommended the duration of perioperative antibiotic prophylaxis was within 24 hours postoperatively in breast cancer undergoing postmastectomy implant breast reconstruction. However, surgeons in practice favored to prolong the duration. The aim of this study was to estimate the effects of duration of antibiotics on major adverse outcomes in real clinical practice setting with diverse population using overlap weighting model. Methods: In this retrospective study, patients with breast cancer undergoing breast implant reconstructions were collected in Fudan University Shanghai Cancer Center from 1 January 2008 to 31 December 2021. Cases were divided into two groups according to the duration of perioperative antibiotic prophylaxis: short-term group (≤ 24 hours) and long-term group (&amp;gt;24 and≤48 hours). The primary outcomes were unplanned reoperations and complication-related unplanned reoperations. Unplanned reoperation was defined as debridement, expander removal without prosthesis implantation, expander removal and expander implantation, prosthesis removal and prosthesis implantation, prosthesis removal, prosthesis removal and expander implantation. By reviewing the patients’ detailed medical history, all unplanned reoperations were divided into non-complication-related unplanned reoperations and complication-related unplanned reoperations. Non-complication-related unplanned reoperations included: patients voluntarily gave up continuing reconstruction, suspected recurrence of cancer, changed reconstruction methods, unsatisfactory appearance, and unknown reasons. Complication-related unplanned reoperations included: infection, exposure of prosthesis or expander, poor wound healing, rupture of expander, necrosis of skin flap, bleeding. The secondary outcomes were infections that required intervention. It was defined as both met with white blood cells elevation and physician antibiotic prescription during outpatient follow-up. To adjust confounders, propensity score overlap weighting was used, and subgroup analysis and sensitive test were conducted to demonstrate the robustness of results. A P value less than 0.05 was considered statistically significant. Results: In 4367 cases of unilateral implant reconstructions, 4128 (95%) were included in this study. Among them, 1689 were expander implantation, 1124 were prosthesis implantation and 1315 were expander removal and prosthetic implantation. At inclusion, only 283 cases (6.9%) received antibiotics prophylaxis ≤24 hours, 3090 cases (74.9%) with duration &amp;gt;24 and≤48 hours, and 755 cases (18.3%) with duration &amp;gt;48 hours. Of them, 230 cases (5.6%) underwent unplanned reoperation, including 131 (3.2%) complication-related unplanned reoperations, and 99 (2.4%) non-complication-related unplanned reoperations. And there were 110 cases (2.7%) with infections that required intervention. In unweighted or weighted data set, short-term antibiotic use did not significantly increase the risk of adverse outcomes, including unplanned reoperation, complication-related unplanned reoperation, and infection required intervention, compared with long-term antibiotic use with or without patients with duration more than 48 hours. Most subgroup analysis showed no evidence of heterogeneity of the effects of duration of antibiotic use on adverse outcomes. Conclusion: In clinical setting with diverse population, prolong antibiotic prophylaxis with more than 24 hours is not necessary to reduce major adverse outcomes, even in some critical conditions. Appropriating and accessible prophylactic initiatives should be developed and implemented with shorten the duration of antibiotic prophylaxis and minimized adverse outcomes. Key words: perioperative antibiotic prophylaxis, breast cancer, postmastectomy implant reconstruction, unplanned reoperation Citation Format: Zeqing Li, Jiajian Chen, Shuang Hao, A-Yong Cao, Xiaoyan Huang, Zhiming Shao, Jiong Wu. Effects of different duration of prophylactic antibiotic use on unplanned reoperation in breast cancer patients undergoing implant-based breast reconstruction: A retrospective study with overlap weighting analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-07-02.

Faecal Microbiota Transplantation is a simple, effective and safe treatment in the management of C. difficile infection in daily clinical practice

IntroductionFaecal microbiota transplantation (FMT) is a treatment supported by wide scientific evidence and proved to be very effective in the management of Clostridioides difficile infection (CDI). The objective of this study is to analyze its effectiveness and safety in a real clinical practice setting. MethodsRetrospective, single-center and descriptive observational study in which all FMT performed between May 2016 and December 2020 were included. Technical success was defined as the successful administration of the faecal preparation in the patient's gastrointestinal tract and clinical success the disappearance of diarrhoea in the first 72 h after the procedure with no relapse within the following 8 weeks after the therapy was started. Results15 FMT were performed in 13 patients. Median age was 79 years (range: 40–98 years); being 60% women and 33.3% depedent persons. The indication for FMT was recurrent CDI in 84.6%. All FMTs were performed by colonoscopy and from related donors. With a first procedure, the FMT was effective in 11 of 13 patients (84.61%; 95% CI; 54.55–98.07). Time until resolution of symptoms was less than 48 h in all cases. Post-transplant follow-up was 25.66 ± 17.5 months. No significant short or long-term complications were recorded at follow-up. ConclusionTMF is a simple, effective and safe procedure in CD infection, even in elderly patients or those with great comorbidities.

Abbreviated perioperative fasting management for elective fresh fracture surgery: guideline adherence analysis

BackgroundLong-term fasting for elective surgery has been proven unnecessary based on established guidelines. Instead, preoperative carbohydrate loading 2 h before surgery and recommencing oral nutrition intake as soon as possible after surgery is recommended. This study was performed to analyze the compliance with and effect of abbreviated perioperative fasting management in patients undergoing surgical repair of fresh fractures based on current guidelines.MethodsPatients with fresh fractures were retrospectively analyzed from the prospectively collected database about perioperative managements based on enhanced recovery of surgery (ERAS) from May 2019 to July 2019 at our hospital. A carbohydrate-enriched beverage was recommended up to 2 h before surgery for all surgical patients except those with contraindications. Postoperatively, oral clear liquids were allowed once the patients had regained full consciousness, and solid food was allowed 1 to 2 h later according to the patients’ willingness. The perioperative fasting time was recorded and the patients’ subjective comfort with respect to thirst and hunger was assessed using an interview-assisted questionnaire.ResultsIn total, 306 patients were enrolled in this study. The compliance rate of preoperative carbohydrate loading was 71.6%, and 93.5% of patients began ingestion of oral liquids within 2 h after surgery. The median (interquartile range) preoperative fasting time for liquids and solids was 8 (5.2–12.9) and 19 (15.7–22) hours, respectively. The median postoperative fasting time for liquids and solids was 1 (0.5–1.9) and 2.8 (2.2–3.5) hours, respectively. A total of 70.3% and 74.2% of patients reported no thirst and hunger during the perioperative period, respectively. Logistic regression analysis showed that the preoperative fasting time for liquids was an independent risk factor for perioperative hunger. No risk factor was identified for perioperative thirst. No adverse events such as aspiration pneumonia or gastroesophageal reflux were observed.ConclusionsIn this study of a real clinical practice setting, abbreviated perioperative fasting management was carried out with high compliance in patients with fresh fractures. The preoperative fasting time should be further shortened to further improve patients’ subjective comfort.

Olaparib maintenance therapy after frontline chemotherapy in patients with BRCA-mutated ovarian cancer: real-world results in expanded access program

Introduction. Olaparib is the only PARP inhibitor approved in Russia for the maintenance therapy for BRCA-positive ovarian cancer after frontline chemotherapy. We conducted a real-world analysis of olaparib efficacy and safety for this indication.Aim. To assess the efficacy of PARP inhibitors in real-world clinical practice.Materials and methods. Patients with stage III-IV BRCA-mutated ovarian cancer who received olaparib maintenance therapy in expanded access program in 03.2019-12.2020 timeframe. Briefly, key inclusion criteria were: serous or endometrioid highgrade ovarian cancer; pathogenic BRCA1/2 mutation; primary or interval debulking; complete or partial response to frontline platinum-based therapy. Olaparib was administered as tablets (300 mg BID) up to 2-years, disease progression or unacceptable toxicity, whichever occurred first. The primary endpoint of the study was progression-free survival (PFS), overall survival (OS) and safety were key secondary endpoints. Statistical analysis was done with R and RStudio software.Results and discussion. 23 patients were enrolled. Median age was 49 years, all patients had high-grade serous adenocarcinoma histology. Complete debulking at primary or interval surgery was achieved in 30% of patients. With median follow-up time equal to 22 months, median PFS and OS were not reached. The 2-year PFS and OS were 65 and 84%, respectively. Grade 3-4 adverse events was detected in 7 (30.4%) patients.Conclusion. Our results supports high efficacy of olaparib in real clinical practice setting reported in the SOLO1 trial.

Secukinumab is effective in the treatment of recalcitrant palmoplantar psoriasis and palmoplantar pustular psoriasis in a daily practice setting

Secukinumab is effective in the treatment of recalcitrant palmoplantar psoriasis and palmoplantar pustular psoriasis in a daily practice setting

El trasplante de microbiota fecal es un tratamiento sencillo, efectivo y seguro en el manejo de la infección por C.difficile en la práctica clínica diaria

IntroductionFaecal microbiota transplantation (FMT) is a treatment supported by wide scientific evidence and proved to be very effective in the management of Clostridioides difficile (CD) infection. The objective of this study is to analyze its effectiveness and safety in a real clinical practice setting. MethodsRetrospective, single-center and descriptive observational study in which all FMT performed between May 2016 and December 2020 were included. Technical success was defined as the successful administration of the fecal preparation in the patient's gastrointestinal tract and clinical success the disappearance of diarrhea in the first 72 h after the procedure with no relapse within the following 8 weeks after the therapy was started. Results15 FMT were performed in 13 patients. The mean age of the patients was 73 ± 19,4 years (range: 40–98 years); being 60% women. The indication for FMT was relapsing colitis due to CD in 84.6%. All FMTs were performed by colonoscopy and from related donors. With a first procedure, the TMF was effective in 11 of 13 patients (84.61%; 95% CI; 54.55–98.07). Time until resolution of symptoms was less than 48h in all cases. Post-transplant follow-up was 25.66 ± 17.5 months. No significant short or long-term complications were recorded at follow-up. ConclusionTMF is a simple, effective and safe procedure in CD infection, even in elderly patients or those with great comorbidities.

Super responders to guselkumab treatment in moderate-to-severe psoriasis: a real clinical practice pilot series.

The term super responders defines a subset of patients with moderate-to-severe psoriasis that present a rapid and higher rate of response to biological treatments in comparison to the general population. Little scientific evidence to explain the behavior and clinical characteristics of these psoriatic patients has been published thus far. Its characterization could be important to improve therapeutic optimization and to identify the profile of patients that will respond efficiently to biological treatments. The main objective of this study was to evaluate and characterize the proportion of super-responder patients (who achieved PASI = 0 at week 12 and 24) in a total of 87 patients with moderate-to-severe psoriasis treated with guselkumab. Also, our intent was to analyze and evaluate differences in response to guselkumab in absolute PASI, PASI 75, PASI 90, PASI 100, BSA, VAS pruritus, and DLQI between groups. A total of 14 out of 87 patients treated with guselkumab were characterized as SR. No differences in demographic characteristics were found. The percentage of patients reaching PASI 75, PASI 90, and PASI 100 were numerically greater for SR than N-SR at week 12, 24, 36, and 52. These differences were more pronounced for PASI 100 > PASI 90 > PASI 75. SR performed better and faster to guselkumab treatment as assessed by absolute PASI, BSA, VAS pruritus, and DLQI. Statistically significant differences were found in absolute PASI, BSA, VAS pruritus, and DLQI between groups along the 52 weeks of study. No differences in drug survival were found between groups (P = 0.3326). Our study demonstrated for the first time, in a real clinical practice setting, the presence of a subpopulation of patients that super respond to guselkumab at week 12 and 24 and maintain this efficacy for 52 weeks. Further research must be performed to identify basal specific characteristics of this SR population.

Real-world evidence on the strategy of olmesartan-based triple single-pill combination in Korean hypertensive patients: a prospective, multicenter, observational study (RESOLVE-PRO)

BackgroundIn this prospective, multicenter, non-comparative observational study, the effectiveness and safety of the triple single-pill combination (SPC) of olmesartan/amlodipine/hydrochlorothiazide (OM/AML/HCTZ) were evaluated in a real clinical practice setting in Korean patients with essential hypertension.MethodsA total of 3752 patients were enrolled and followed for 12 months after administration of OM/AML/HCTZ. Primary endpoint was change from baseline to month 6 in the mean systolic blood pressure (SBP). Secondary endpoints included changes from baseline in the mean SBP at month 3, 9, 12 and the mean diastolic blood pressure (DBP) at month 3, 6, 9, 12; changes in the mean SBP/DBP according to age and underlying risk factors; and blood pressure control rate (%) at different time points. Adherence to and satisfaction with OM/AML/HCTZ treatment among patients and physicians were assessed by medication possession ratio (MPR) and numeric rating scale, respectively, as exploratory endpoints. Safety was evaluated by the incidence and severity of adverse events (AEs) as well as the discontinuation rate due to AEs.ResultsOM/AML/HCTZ administration led to significant reductions in the mean SBP/DBP by 11.5/6.6, 12.3/7.0, 12.3/7.2, and 12.8/7.4 mmHg from baseline to month 3, 6, 9 and 12, respectively (P < 0.0001). The BP reductions were maintained throughout the 1-year observation period in all patients with different age groups and risk factors (diabetes mellitus, cardiovascular disease, and renal disease). The BP control rate (%) of < 140/90 mmHg was 65.9, 67.9, 68.9, and 70.6% at month 3, 6, 9, and 12, respectively. The mean MPR during the observation period was 0.96. The safety results were consistent with the previously reported safety profile of OM/AML/HCTZ.ConclusionsTreatment with the triple SPC of OM/AML/HCTZ demonstrated significant effectiveness in reducing SBP/DBP and achieving target BP control with high adherence over the 1-year observation period in Korean hypertensive patients and was well-tolerated.Trial registrationCRIS, KCT0002196, Registered 3 May 2016.

Clinical utility of a personalized and long-term monitoring device for Parkinson's disease in a real clinical practice setting: An expert opinion survey on STAT-ON™

BackgroundSTAT-ON™ is an objective tool that registers ON-OFF fluctuations making possible to know the state of the patient at every moment of the day in normal life. Our aim was to analyze the opinion of different Parkinson's disease experts about the STAT-ON™ tool after using the device in a real clinical practice setting (RCPS). MethodsSTAT-ON™ was provided by the Company Sense4Care to Spanish neurologists for using it in a RCPS. Each neurologist had the device for at least three months and could use it in PD patients at his/her own discretion. In February 2020, a survey with 30 questions was sent to all participants. ResultsTwo thirds of neurologists (53.8% females; mean age 44.9±9 years old) worked in a Movement Disorders Unit, the average experience in PD was 16±6.9 years, and 40.7% of them had previously used other devices. A total of 119 evaluations were performed in 114 patients (range 2–9 by neurologist; mean 4.5±2.3). STAT-ON™ was considered “quite” to “very useful” by 74% of the neurologists with an overall opinion of 6.9±1.7 (0, worst; 10, best). STAT-ON™ was considered better than diaries by 70.3% of neurologists and a useful tool for the identification of patients with advanced PD by 81.5%. Proper identification of freezing of gait episodes and falls were frequent limitations reported. ConclusionSTAT-ON™ could be a useful device for using in PD patients in clinical practice.

A Primer on the Military Health System's Approach to Medical Research and Development.

The Military Health System (MHS) has a medical research program aimed at a wide range of health-, disease-, and injury-related topic areas that works with civilian academic institutions and the biomedical industry to accomplish its goals. There are many opportunities for civilian academic institutions and the biomedical industry to engage with this program, but its unique features are important to understand to optimize the chances for successful partnerships. Unlike the National Institutes of Health, which uses an "investigator-initiated" approach, the Department of Defense (DoD) aligns its funding with specific needs, also referred to as requirements; thus, DoD research is often described as "requirements-driven" research. At the highest level, requirements are aligned with the National Security Strategy and National Defense Strategy, though requirements documents list specific areas in medicine with unmet needs. Military labs and the Uniformed Services University of the Health Sciences, which can also receive DoD appropriations to conduct medical research, serve as hubs that interface with civilian academic institutions and the biomedical industry and organize and track the overall progress of DoD investments. As a mechanism to propel findings from "bench to bedside," the military budgets funds for the various phases of research and development for a given topic area. Research programs are most effective when they are integrated into the MHS learning health system, which allows MHS clinical communities to inform and track research investments and evaluate the utility of research products in real clinical practice settings. This Perspective provides introductory information and a basic framework for those interested in performing DoD-funded medical research or collaborating with researchers in military labs. It is hoped that as academic institutions and the biomedical industry look to increase efficiency in medical research, they will find ways to engage with DoD research opportunities and consider elements of the military's approach useful.

Real-life Bioequivalence of Tacrolimus in Patients With Living-Related Donor De Novo Renal Transplantation: An Observational Study

Tacrolimus is a narrow therapeutic index drug. As a result, regulatory agencies worldwide recommend stringent bioequivalence evaluation criteria for approval of generics. Despite this, the professional transplantation societies have raised concerns over the safety and efficacy of generic substitutions. We conducted this pragmatic real-life bioequivalence study to assess the effect of generic substitutions of tacrolimus. This was an observational study including recipients of renal transplantation who were considered for generic medication substitution. Transplanted organs were from living-related donors and were performed at least 1 month before the study. Time of administration of the drug, time of dosing with respect to meals, and time of blood sample collection were controlled; however, the lot number of the generic drugs was not controlled. The participants were allowed to use their usual supplies irrespective of the lot number. Concentration (C0) was quantified by liquid chromatography with tandem mass spectrometry after the generic substitution from ABC brand to XYZ brand. The average C0 ± SD with generic ABC was 11.09 ± 4.26 ng/mL and generic ABC was 9.7 ± 4.12 ng/mL. Though there was no statistically significant difference observed between the concentrations, when the individual patient data was examined, 2 patients were found to have a very high concentration of tacrolimus and at least 7 patients fell below the therapeutic range. These derangements called for retitration with the new generic tacrolimus (40%). The results of our study suggest that generic-to-generic substitutions should be carried out very carefully in a closely observed setting in patients with renal transplants. The strength of our study is that it matched the real clinical practice setting as much as possible unlike a bioequivalence study. Therefore, we recommend repeating C0 at least 3 times over a period of 7 to 10 days with a generic substitution to prevent untoward consequences.

Improvement of Function and Its Determinants in a Group of Axial Spondyloarthritis Patients Treated with TNF Inhibitors: A Real-Life Study.

IntroductionThe aim of this work is to investigate the improvement of physical function and its determinants in axial spondyloarthritis (SpA) patients treated with tumor necrosis factor (TNF) inhibitors in a real clinical practice setting.MethodsAn observational study was conducted in patients with axial SpA treated with anti-TNF from 2010 to 2018 with a minimum 6 months of follow-up. All patients fulfilled ASAS or the modified New York criteria. The Bath Ankylosing Spondylitis Metrology Index (BASMI) and the Bath Ankylosing Spondylitis Functional Index (BASFI) were used as objective and self-reported functional indices. The improvement of function and factors associated were evaluated for the present study, as well as disease activity and patient-reported outcome measures.ResultsA total of 183 patients with axial SpA were examined. Among them, 27 were non-radiographic axial SpA, while the remaining 156 were ankylosing spondylitis patients. BASFI and BASMI significantly improved during follow-up. Improvement of metrology index BASMI inverse correlated with disease duration (rho − 0.2, p = 0.009) and directly correlated with the improvement of BASDAI (rho 0.26, p = 0.003) and CRP (rho 0.26, p = 0.0003). Improvement of BASFI significantly inversely correlated with disease duration and directly correlated with the improvement of BASDAI, CRP, and baseline ESR. Male sex, lower disease duration, high ESR, and the improvement of BASDAI were found to be associated with the improvement of BASFI.ConclusionsOur results showed that in real-life settings, patients improve in BASMI and BASFI. Furthermore, factors associated with this improvement were identified.