Clinical Outcome Measures Research Articles

Design and Validation of a Clinical Outcome Measure for Adolescents and Adult Patients with Spinal Muscular Atrophy: SMA Life Study Protocol.

The objective of this study is to develop a clinical tool for the evaluation and follow-up of adolescent and adult patients with 5q spinal muscular atrophy (SMA) and to design its validation. This prospective, non-interventional study will be carried out at five centres in Spain and will include patients aged 16years or older with a confirmed diagnosis of 5q SMA (biallelic mutation of the survival motor neuron 1 [SMN1] gene). A panel of experts made up of neurologists, physiatrists and Spanish patients' association (FundAME), participated in the design of the clinical tool. Physicians will administer the tool at three time points (baseline, 12months and 24months). Additionally, data from other questionnaires and scales will be collected. Once recruitment is achieved, an interim statistical analysis will be performed to assess its psychometric properties by applying Rasch analysis and classical statistical tests. The tool will consist of up to 53 items to assess functional status from a clinical perspective in seven key dimensions (bulbar, respiratory, axial, lower, upper, fatigability and other symptoms), which will be collected together with objective clinical measures (body mass index, forced vital capacity, pinch strength and 6-minute walk test). The validation of this tool will facilitate the clinical evaluation of adult and adolescent patients with SMA and the quantification of their response to new treatments in both clinical practice and research.

Evaluation of the impact of a health-system specialty pharmacy patient management program on achieving predefined clinical outcome measures.

Specialty medications often have high costs, pose difficulties with payor approval, and require additional monitoring. Earlier articles have defined various examples of clinical outcome measures (COMs); however, goals and benchmarks have not been well defined, and a gap in the literature exists. This study evaluated the effectiveness of our health-system specialty pharmacy (HSSP) patient management program (PMP) in achieving predefined COM goals. Disease state protocols were developed within the HSSP, and clinical and adherence goals were created for each COM based on primary literature. This retrospective, single-center review examined outcomes and adherence data on patients enrolled in the PMP during 2022. The primary outcome was the number of predefined disease state COM goals met. Secondary outcomes included the number of predefined adherence goals met and annual financial impact. Of 1,431 patients whose records were reviewed, 1,053 met criteria for inclusion. The primary outcome analysis showed that 85% (33 of 39) of the predefined disease state goals were met. Predefined adherence goals were met, with an average proportion of days covered (PDC) for all specialty medications of >90%. The PMP yielded $5,167,043 in direct patient cost savings and $167,260 in cost avoidance. The PMP yielded positive results in meeting goals set for the COMs in the disease states managed within the HSSP. COMs will remain a focus for HSSPs to help patients achieve desired clinical outcomes and HSSPs adhere to accreditation standards. More research in this field and standardization of COM goals may benefit the larger HSSP community.

Combined Cabazitaxel and Carboplatin Treatment of Metastatic Castration Resistant Prostate Cancer Patients, With Innate or Acquired Resistance to Cabazitaxel Monotherapy

BackgroundThere is new interest in platinum-based treatment of patients with metastatic castration resistant prostate cancer (mCRPC), to which a subgroup responds. Although platinum sensitivity is suggested to be associated with aggressive disease features and distinct molecular profiles, identification of responders is a clinical challenge. In this study, we selected patients who displayed PSA progression during cabazitaxel monotherapy, for combined cabazitaxel and carboplatin treatment. MethodsIn this retrospective study, mCRPC patients received carboplatin and cabazitaxel after biochemical progression following at least 2 cabazitaxel monotherapy cycles. We assessed PSA response, Time to PSA Progression (TTpsa) and Time to Radiographic Progression (TTrad). For a subset of patients, mutational analysis of BRCA-1, BRCA-2, ATM, PTEN, P53 and RB1 was performed. ResultsForty-five patients were included, after a median of 4 (3-6) cycles of cabazitaxel monotherapy. Patients received a median of 3 (2-5) cycles of combined cabazitaxel and carboplatin, on which 12 (26.6%) patients had a PSA decline ≥ 50% from baseline. TTpsa was 2 (1-5) months and TTrad 3 (2-6) months. Adverse events were predominantly grade 1-2. Of the 29 (64.4%) patients evaluable for molecular signature, 6 (13.3%) had BRCA1, BRCA2 or ATM mutations and 12 (26.7%) had a PTEN, P53 or RB1 mutations. The occurrence of these mutations was not associated with any clinical outcome measure. ConclusionsIn this study we showed that patients with PSA progression during cabazitaxel monotherapy could benefit from the addition of carboplatin to cabazitaxel, while prospective identification of these patients remains a clinical challenge.

Significant improvements in clinical outcome measures and patient satisfaction after combined all-arthroscopic meniscal allograft transplantation and autologous chondrocyte implantation: A single-centre longitudinal study.

The optimal treatment approach for the complex pathology of meniscal insufficiency and coexisting full-thickness cartilage defects remains unclear. The purpose of this study was to evaluate the viability, safety, and efficacy of this combined surgical approach at medium-term follow-up. This is a single-centre longitudinal study with blinded outcome assessment. All consecutive patients treated with combined all-arthroscopic meniscal allograft transplantation (MAT) with bone bridge fixation and ACI using chondrospheres at our institution between 2001 and 2021 were eligible for inclusion. Twenty patients with an average follow-up of 72.6 ± 34.4 months were included in the statistical analysis. Clinical outcomes were assessed pre- and postoperatively using the IKDC Subjective Knee Form, Lysholm Score, Tegner Activity Scale, KOOS, and Visual Analog Scale (VAS) for patient satisfaction. Failure and reoperation rates were assessed, and cartilage regeneration tissue was evaluated on postoperative MRI. IKDC scores significantly improved from 52.1 ± 16.9 to 68.5 ± 16.3 (p = 0.003). Lysholm scores improved from 61.5 ± 21.7 to 78.5 ± 12.9 (p = 0.004). Tegner scores improved from 3.5 (1-4) to 4.0 (2-6) (p = 0.014). KOOS scores improved significantly across all subcategories, except 'symptoms', where improvements did not reach statistical significance. VAS for overall patient satisfaction showed improvements but did not reach statistical significance. The combined procedure was successful in 17 patients (85%). Eight patients had to undergo reoperation (40%), comprising mostly small, arthroscopic procedures. Seven reoperations were directly attributable to meniscal allograft transplantation (46.7%). Postoperative Magnetic Resonance Observation of Cartilage Repair Tissue scores were 68.9 ± 16.8 (n = 14). Combined arthroscopic MAT and autologous chondrocyte implantation (ACI) is a viable, safe, and effective treatment approach for younger patients with meniscal insufficiency and coexisting full-thickness cartilage damage, where alternative treatment options are limited. The combined surgical procedure achieved significant improvements in clinical outcome measures and patient satisfaction with acceptable failure and high arthroscopic reoperation rates. MAT is the limiting part of this combined procedure, with most failures and reoperations being attributable to MAT, as opposed to ACI. Level III.

Effectiveness of Immersive Virtual Reality-Based Hand Rehabilitation Games for Improving Hand Motor Functions in Subacute Stroke Patients.

Stroke rehabilitation faces challenges in attaining enduring improvements in hand motor function and is frequently constrained by interventional limitations. This research aims to present an innovative approach to the integration of cognitive engagement within visual feedback incorporated into fully immersive virtual reality (VR) based games to achieve enduring improvements. These innovative aspects of interaction provide more functional advantages beyond motivation to efficiently execute repeatedly hand motor tasks. The effectiveness of virtual reality games incorporated with innovative aspects has been investigated for improvements in hand motor functions. A randomized controlled trial was conducted, a total of (n=56) subacute stroke patients were assessed for eligibility and (n=52) patients fulfilled the inclusion criteria. (n=26) patients were assigned to the experimental group and (n=26) patients were assigned to the control group. VR intervention involves four VR based games, developed based on hand movements including flexion/extension, close/open, supination/pronation and pinch. All patients got therapy of 24 sessions, lasting 4 days/week for a total of 6 weeks. Five clinical outcome measures were Fugl- Meyer Assessment-Upper Extremity, Action Research Arm Test, Box and Block Test, Modified Barthel Index, and Stroke-Specific Quality of Life were assessed to evaluate patients' performance. Results revealed that after therapy there was significant improvement between the groups (p<0.05) and within groups (p<0.05) in all assessment weeks in all clinical outcome measures however, improvement was observed significantly greater in the experimental group due to fully immersive VR-based games. Results indicated that cognitive engagement within visual feedback incorporated in VR-based hand games effectively improved hand motor functions.

Incidence, risk factors, and clinical outcomes of acute brain swelling associated with traumatic acute subdural hematoma: a retrospective study utilizing novel diagnostic criteria.

Post-traumatic acute brain swelling (ABS) is a major cause of elevated intracranial pressure and thus mortality. The current definition of post-traumatic ABS has certain limitations, and there is limited information available regarding ABS associated with traumatic acute subdural hematoma (ASDH). To investigate the incidence, risk factors, and clinical outcomes of ABS associated with traumatic ASDH. Retrospective study. Data for 161 patients diagnosed with traumatic ASDH were retrospectively collected. Novel computed tomography-based criteria were proposed for diagnosing ABS in patients with ASDH and determining its incidence. Univariate and multivariate logistic regression analyses were performed to explore the risk factors of post-traumatic ABS. The Glasgow Outcome Scale (GOS) score, mortality, and functional prognosis of all patients at discharge and the proportion of intraoperative malignant brain bulge in surgical patients were taken as clinical outcome measures. A total of 45 (28%) patients experienced post-traumatic ABS, exhibiting significantly lower Glasgow Coma Scale scores on admission (p < 0.001). The incidence of hemispheric and whole-brain swelling was 8.1% and 19.9%, respectively. Risk factors independently associated with post-traumatic ABS were: (1) age [odds ratio (OR) = 0.917, p < 0.001]; (2) platelet to white blood cell ratio (PWR) (OR = 0.887, p = 0.012); and (3) traumatic subarachnoid hemorrhage (SAH) (OR = 4.346, p = 0.005). The ABS cohort had a lower GOS score [2 (1-3) versus 4 (3-5); p < 0.001], higher mortality (46.7% versus 6.9%; p < 0.001), and higher proportion of unfavorable functional prognosis (75.6% versus 34.5%; p < 0.001) upon discharge compared to the no ABS cohort, along with higher proportion of intraoperative malignant brain bulge (43.8% versus 0%; p < 0.001). The incidence of ABS associated with ASDH is significantly high overall. Patients with ASDH who have young age, low PWR, and traumatic SAH are at an increased risk of developing post-traumatic ABS, and therefore of poor clinical outcomes.

A feasibility randomised waitlist-controlled trial of a personalised multi-level language treatment for people with aphasia: The remote LUNA study.

Stroke survivors with aphasia want to improve their everyday talking (discourse). In current UK practice, 90% of speech and language therapists believe discourse assessment and treatment is part of their role but are hampered by barriers in resources, time and expertise. There is a clinical need for well-articulated discourse assessment and treatments. LUNA is a multi-level treatment targeting words, sentences and discourse macrostructure in personal stories that addresses this clinical need. This study aimed to assess the feasibility and acceptability of LUNA trial procedures in a randomised waitlist-controlled trial; and to evaluate preliminary efficacy. This paper reports a phase II, waitlist-controlled, proof-of-concept feasibility trial. Participants with chronic aphasia (n = 28) were recruited from the community and randomised to an Immediate (n = 14) or Delayed (n = 14) group. LUNA treatment was delivered twice weekly for 10 weeks via the videoconferencing technology, Zoom. Feasibility was assessed in terms of participant recruitment and retention, adherence, missing data, and treatment fidelity. Preliminary treatment efficacy was assessed in terms of between group differences in outcome measures relating to discourse, language, and psychosocial state. The remote LUNA trial was feasible: 85% of those eligible consented to the trial; trial retention was 86%; 87% of treatment sessions were delivered as scheduled, and 79% of participants completed 80%+ of the treatment programme; data was missing only for participants who withdrew; treatment fidelity was high at 92% adherence; and only one clinical outcome measure demonstrated ceiling effects. ANCOVA analysis of the clinical outcome measures revealed group differences with medium and large effect sizes, indicating, improvements in the production of words, sentences, discourse macrostructure, overall language functioning (WAB-R), and psychosocial state (VAMS) following LUNA treatment. For most outcomes measured, similar treatment benefits were suggested in a secondary, non-parametric analysis. Large-scale evaluation of the clinical efficacy and cost-effectiveness of LUNA is warranted and supported by these findings. Clinical trials registration: NCT05847023 (clinical trials.gov).

Factors Influencing Social and Community Participation of People with Spinal Cord Injury in Karnataka, India.

Social and community participation are major indicators to assess the adequacy of treatment and rehabilitation in patients with spinal cord injury (SCI). This study examined the relationship between functional independence, level of disability, and social and community participation among people with SCI in India. In this cross sectional study, 110 persons with SCI, aged 18 years and above participated in a community setting, in Karnataka, India. Spinal Cord Independence Measure Version III-self-reporting (SCIM III-SR), Craig Handicap Assessment and Reporting Technique (CHART), and WHO Disability Assessment Schedule 2.0 (WHODAS) were the clinical outcome measures. Spearman's correlation and stepwise multiple linear regression were done to determine association and identify the factors determining the community participation of people with SCI. CHART physical independence had a positive correlation with SCIM self-care (R = 0.446) and SCIM mobility (r = 0.434). CHART cognitive independence (R = -0.38) and CHART mobility (R = -0.396) had a weak correlation with WHODAS. SCIM self-care and SCIM mobility (R2 = 0.34) were determinants of CHART cognitive independence. SCIM respiratory and sphincter management and SCIM self-care (R2 = 0.327) were determinants of CHART mobility. Self-care and mobility of people with SCI determine their ability to successfully reintegrate into the community, warranting a comprehensive community rehabilitation program.

Development and Validation of a Risk Prediction Model for NAFLD: A Study Based on a Physical Examination Population.

To construct and validate a precise and personalized predictive model for non-alcoholic fatty liver disease (NAFLD) to enhance NAFLD screening and healthcare administration. A total of 730 participants' clinical information and outcome measurements were gathered and randomly divided into training and validation sets in a ratio of 3:7. Using the least absolute shrinkage and selection operator (LASSO) regression and multiple logistic regression, a nomogram was established to select risk predictor variables. The NAFLD prediction model was validated through the receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA). After random grouping, the cohort comprised 517 in the training set and 213 in the validation set. The prediction model employed nine of the 20 selected variables, namely gender, hypertension, waist circumference, body mass index, blood platelet, triglycerides, high-density lipoprotein cholesterol, plasma glucose, and alanine aminotransferase. ROC curve analysis yielded an area under the curve values of 0.877 (95% Confidence Interval [CI]: 0.848-0.907) for the training set and 0.871 (95% CI: 0.825-0.917) for the validation set. Optimal critical values were determined as 0.472 (0.786, 0.825) in the training set and 0.457 (0.743, 0.839) in the validation set. Calibration curves for both sets showed proximity to the ideal diagonal, with P-values of 0.972 and 0.370 for the training and validation sets, respectively (P > 0.05). DCA indicated favorable clinical applicability of the model. We constructed a nomogram model that could complement traditional NAFLD detection methods, aiding in individualized risk assessment for NAFLD.

Use of biomarkers in clinical trials and future developments that will help identify novel biomarkers.

Engineering new solutions for therapeutic benefit in Amyotrophic Lateral Sclerosis (ALS) has proved a difficult task to accomplish. This is largely the reflection of complexities at multiple levels, that require solutions to improve cost-effectiveness and outcomes. The main obstacle related to the condition's clinical heterogeneity, chiefly the broad difference in survival observed among ALS patients, imposes large populations studies and long follow-up to evaluate any efficacy. The emerging solution is composite clinical and biological parameters enabling prognostic stratification into homogeneous phenotypes for more affordable studies. From a therapeutic development perspective, the choice of a medicinal product requires the availability of treatment-specific biomarkers of target engagement to identify off-target effects based on the compound's putative modality of action. More importantly, there are no established biomarkers of treatment response that can complement clinical outcome measures and support futility and end of treatment analyses of efficacy. Ultimately the onus rests on the development of biomarkers encompassing the unmet needs of clinical trial design, from inclusion to efficacy. These readouts of the pathological process may be used in combination with clinical and paraclinical outcome measured, significantly reducing the time and financial burden of clinical studies. Progress towards a biomarker-driven clinical trial design in ALS has been possible thanks to the accurate detection of neurofilaments and of other immunological mediators in biological fluids with the disease progression, a step change enabling the testing of novel therapeutic agents in a new clinical trial setting. However, further progress remains to be made to find treatment specific target engagement biomarkers along with readouts of treatment response that can be reliably applied to all emerging therapies and clinical studies. Here we will cover the basic notions of biomarker development in ALS clinical trials, the most crucial unanswered questions and the unmet needs in the ALS biomarkers space.

Feasibility and acceptability of a dengue self-monitoring system to reduce treatment delay in Malaysia: A single-centre pilot randomised controlled trial.

Most dengue cases are managed in an outpatient setting, where patients are advised to return to the clinic daily for monitoring. Some patients can develop severe dengue at home and fail to recognise the deterioration. An application called DengueAid was designed as a self-monitoring tool for patients to reduce delay in seeking timely treatment. This study aimed to assess the feasibility of conducting a randomised controlled trial to determine the effectiveness of the DengueAid application. Dengue patients were recruited from a public health clinic in Malaysia and randomised to either use the DengueAid application plus standard care for dengue or receive only the standard care. The outcomes evaluated were the (1) feasibility of recruitment, data collection and follow-up procedures; (2) preliminary clinical outcome measures; and (3) acceptability of DengueAid. Qualitative interviews were conducted for participants in the intervention arm to assess the acceptability of DengueAid. Thirty-seven patients were recruited with 97% (n = 36) retention rates. The recruitment rate was low (63% refusal rate, n = 62/99) with difficulty in data collection and follow-up due to the variable interval of care for dengue in an outpatient setting. DengueAid application was acceptable to the participants, but preliminary clinical outcomes and qualitative data suggested limited utility of the application. Unwell conditions of patients and limited access to healthcare are important factors impacting the application's utility. The feasibility trial uncovered issues with recruitment, data collection and follow-up processes. Further research and modification to the application are needed to improve its utility and usability.

An Internet Mantram Repetition Program to Promote Well-being in Breast Cancer Survivors: A Feasibility Randomized Controlled Trial.

Introduction: The primary objective of this study was to assess the feasibility of a 6-week internet-delivered Mantram Repetition Program (MRP) for women recently treated for breast cancer. A secondary objective explored changes in perceived stress, psycho-spiritual measures, and cytokines in the treatment group compared to a waitlist. Methods: A feasibility study (ORBIT model Phase IIa) with a randomized controlled trial pilot was conducted. Eligible women recently treated for breast cancer were randomized to the treatment group (n = 14) or a waitlist group (n = 12) and participated for 12 weeks. During weeks 1-6, the treatment group received the MRP intervention while the waitlisted group was inactive. During weeks 7-12, the treatment group was inactive while the waitlisted group received the MRP intervention. The primary outcomes were feasibility and acceptability of the internet-delivered MRP intervention protocol. Participants completed pre and post-intervention psycho-spiritual health assessments. A subset of participants provided serum for cytokine analyses at enrollment and week 6, coinciding with the period in which the treatment group receiving the MRP intervention. Results: Overall study attrition was 19.2%. MRP adherence for both groups was 86% at post-intervention and 90% in the treatment group at 6-week follow-up. Pre-to-post-intervention analyses pooling both groups' data demonstrated decreased perceived stress (p = .045) and increased spiritual well-being (p =.004). IFN-γ and IL-17A were increased in the waitlisted group and decreased in the treatment group (p = 0.048). Conclusion: Feasibility of a 6-week, internet-delivered MRP intervention for breast cancer survivors was established. Psycho-spiritual variables and serum cytokines are suitable clinical outcome measures for future MRP studies with breast cancer survivors. Data suggest MRP may reduce perceived stress and support spiritual well-being in women with breast cancer; however, additional studies are needed.

Protocol for a Pilot Study on the Neurocardiac Mechanism of an Interoceptive Compassion-Based Heart-Smile Training for Depression.

Heart-Smile Training (HST) is an interoceptive compassion-based behavioral intervention that in case reports has been beneficial for depression. Interoception refers to the awareness and regulation of physiological signals from inside the body. Depressed patients often have diminished interoceptive awareness and often experience disconnection from bodily needs and sensations. In addition to interoceptive dysfunction, depression often involves negative self-evaluation and self-critical rumination. HST is a compassion-based meditation training program that explicitly cultivates interoceptive awareness of the heart area. This study aims to investigate the possible neurocardiac mechanisms engaged through HST for depression patients. We plan to enroll 50 subjects to be randomized into a 4-week HST intervention group and a waitlist group. A battery of psychological questionnaires will be administered at baseline and post-intervention timepoints, and electroencephalography (EEG) will be collected during compassion meditation guided by pre-recorded audio. The primary clinical outcome measures are on the feasibility of the intervention and research procedures, the primary mechanistic outcome measure is the post-intervention change in Heartbeat Evoked Potential (HEP) amplitude. Secondary outcome measures include changes in depression severity and EEG gamma spectral activity. Exploratory outcome measures include effects of HST on skin conductance response, heart rate variability, EEG spectral properties in other frequency bands, as well as a list of psychological questionnaires that measure depression and anxiety symptoms, emotion regulation, mindfulness, interoceptive awareness, self-compassion, gratitude, sleep quality, quality of life and social connectedness. Results not yet available. This is the first study on the feasibility and interoceptive neurocardiac mechanism of HST. Our findings will provide frontier knowledge on the physiological working mechanism of behavioral interventions with an interoception-based meditative approach. https://clinicaltrials.gov/study/NCT05564533.

Comparison of bilateral ligaments after unilateral anterior cruciate ligament reconstruction: Based on magnetic resonance imaging analysis.

This study quantitatively assessed postoperative changes in graft inclination angle and femorotibial position after ACL reconstruction using MRI, to identify reliable indicators for evaluating knee stability. A retrospective analysis of 50 cases of ACL reconstruction from June 2019 to June 2020 included clinical outcome measures. MRI assessed graft/ACL inclination angles, medial/lateral anterior tibial translation (ATT), and femoral/tibial rotation angles on both surgical and contralateral sides. Femorotibial angle (FTA) and rotational tibial subluxation (RTS) were calculated for comparing MRI results. Following ACL reconstruction, graft inclination angles, ATT, and FA/TA were significantly greater than those of the contralateral knee joint (P<0.05). FTA and RTS did not differ significantly between sides, but exhibited significant correlation. Graft inclination angles could not fully recover to normal levels post-ACL reconstruction, while notable medial/lateral ATT occurred on the surgical side. Additionally, a significant correlation was observed between FTA and RTS, suggesting their potential as combined clinical indicators for assessing knee joint rotation stability.

Percutaneous Fifth Metatarsal Osteotomy for Bunionette Deformity Without Fixation or Strapping: A Retrospective Study.

Bunionette deformity (BD) is a painful condition of the fifth metatarsal characterized by an osseous prominence and fifth toe varus deformity. The purpose of this study is to assess the clinical, functional, and radiographic outcomes of percutaneous distal metatarsal metaphyseal osteotomy (DMMO) without fixation or postoperative strapping of the foot. A retrospective case series was performed on 111 patients (132 feet) with symptomatic BD who underwent percutaneous DMMO of the fifth metatarsal from September 2020 to January 2022 by an experienced minimally invasive surgeon. According to the Shimobayashi classification, we treated 1 type I deformity, 37 type II deformities, 52 type III deformities, 42 feet with type IV deformity, and no patient with a type V deformity. Ninety patients (81%) underwent unilateral osteotomy, and 21 (19%) had bilateral osteotomies. Most cases included other procedures including treatment of 114 associated deformities of the same feet: 68 bunions, 12 lesser metatarsal osteotomies (2-3-4 metatarsals), and 34 hammertoes (20 second hammertoes, 10 third hammertoes, 1 fourth hammertoes, 2 fifth hammertoes). Patient-reported clinical outcome measures, including the Foot Function Index (FFI) questionnaire, the visual analog score (VAS), and overall satisfaction were collected. Fourth-to-fifth intermetatarsal angle (IMA) correction, time to bone union, and complication rates were assessed in all patients. Mean follow-up was 24.1 months (range, 14-39 months). Both radiographic parameters and patient-reported outcome measures significantly improved after DMMO procedure. The average fourth-to-fifth IMA improved from 12.2 degrees, preoperatively, to 4.4 degrees, postoperatively (P < .001). Patient outcomes reflect the overall outcomes of the combined surgeries on a per-patient basis. Preoperatively, patients had a mean VAS score of 7.6, which improved to 0.6 at the last follow-up (P < .001). Furthermore, the average FFI significantly decreased from pre- to postoperation from 19.2 to 4.4, respectively (P < .001). Overall, 108 of 111 patients reported being satisfied with the outcomes of the procedure. Average bone union was achieved at 12.6 weeks postoperation, with a minimum of 12 and a maximum of 25 weeks. The complication rate was 1.5%, including 1 case of an asymptomatic cock-up deformity and 1 case of lateral fifth metatarsal shaft bone overhang pain, which resolved with an exostectomy. The results of this study of patients who had minimally invasive surgery from an experienced surgeon suggest that percutaneous DMMO of the fifth metatarsal without internal fixation or postoperative immobilization or strapping can be effective at improving radiographic alignment, pain, function, and overall satisfaction with minimal rates of complication. Level IV, case series.

The Impact of Antifungal Stewardship on Clinical and Performance Measures: A Global Systematic Review.

Antimicrobial stewardship programs (ASP) have been proposed as an opportunity to optimize antifungal use. The antifungal resistance is a significant and emerging threat. The literature on antifungal stewardship (AFS) and its influence on performance and clinical outcome measures is scarce. This study aimed to examine global evidence of the impact of AFS on patients and performance measures. The "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) was used for the flow of identification, screening, eligibility, and inclusion. PubMed and MEDLINE were searched using the term ''antifungal stewardship'' on 15 February 2023. Search terms included antifungal stewardship, antimicrobial stewardship, candida, candidemia, candiduria, and invasive fungal disease. Of the 1366 records, 1304 were removed since they did not describe an antifungal stewardship intervention. Among the 62 full texts assessed, 21 articles were excluded since they were non-interventional studies and did not include the outcome of interest. Thus, 41 articles were eligible for systematic review. Eligible studies were those that described an AFS program and evaluated clinical or performance measures. Of the 41 included studies, the primary performance measure collected was antifungal consumption (22 of 41), and mortality (22 of 41), followed by length of stay (11 of 41) and cost (9 of 41). Most studies were single-center, quasi-experimental, with varying interventions across studies. The principal finding from most of the studies in this systematic review is a reduction in mortality expressed in different units and the use of antifungal agents (13 studies out of 22 reporting mortality). Antifungal consumption was significantly blunted or reduced following stewardship initiation (10 of 22). Comparing studies was impossible due to a lack of standard units, making conducting a meta-analysis unfeasible, which would be a limitation of our study. It has been shown that AFS interventions may improve antifungal consumption and other performance measures. According to available published studies, antifungal consumption and mortality appear to be the possible performance measures to evaluate the impact of AFS.

Evaluation Metrics for Augmented Reality in Neurosurgical Preoperative Planning, Surgical Navigation, and Surgical Treatment Guidance: A Systematic Review.

Recent years have shown an advancement in the development of augmented reality (AR) technologies for preoperative visualization, surgical navigation, and intraoperative guidance for neurosurgery. However, proving added value for AR in clinical practice is challenging, partly because of a lack of standardized evaluation metrics. We performed a systematic review to provide an overview of the reported evaluation metrics for AR technologies in neurosurgical practice and to establish a foundation for assessment and comparison of such technologies. PubMed, Embase, and Cochrane were searched systematically for publications on assessment of AR for cranial neurosurgery on September 22, 2022. The findings were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The systematic search yielded 830 publications; 114 were screened full text, and 80 were included for analysis. Among the included studies, 5% dealt with preoperative visualization using AR, with user perception as the most frequently reported metric. The majority (75%) researched AR technology for surgical navigation, with registration accuracy, clinical outcome, and time measurements as the most frequently reported metrics. In addition, 20% studied the use of AR for intraoperative guidance, with registration accuracy, task outcome, and user perception as the most frequently reported metrics. For quality benchmarking of AR technologies in neurosurgery, evaluation metrics should be specific to the risk profile and clinical objectives of the technology. A key focus should be on using validated questionnaires to assess user perception; ensuring clear and unambiguous reporting of registration accuracy, precision, robustness, and system stability; and accurately measuring task performance in clinical studies. We provided an overview suggesting which evaluation metrics to use per AR application and innovation phase, aiming to improve the assessment of added value of AR for neurosurgical practice and to facilitate the integration in the clinical workflow.

Outcomes of total ankle replacement – Current evidence

Total ankle replacement surgery is gaining popularity and is beginning to establish itself as a viable alternative to arthrodesis in the treatment of end-stage ankle arthritis. Only a few studies exist directly comparing these 2 techniques. Also lacking are the long-term outcome studies of ankle replacement surgery. A better understanding of clinical and patient-reported outcome measures after ankle fusion and replacement will enable the surgeon to better counsel the patient and help choose the right treatment. This article will summarise the reported clinical outcomes after total ankle replacements and survivorship analysis from the various national arthroplasty registers.

Discovery of plasma proteome markers associated with clinical outcome and immunological stress after cardiac surgery.

Molecular mechanisms underlying perioperative acute phase reactions in cardiac surgery are largely unknown. We aimed to characterise perioperative alterations of the acute phase plasma proteome in a cohort of adult patients undergoing on-pump cardiac surgery using high-throughput mass spectrometry and to identify candidate proteins potentially relevant to postoperative clinical outcome through a novel, multi-step approach. This study is an analysis of the Bern Perioperative Biobank, a prospective cohort of adults who underwent cardiac surgery with the use of cardiopulmonary bypass (CPB) at Bern University Hospital between January and December 2019. Blood samples were taken before induction of anaesthesia and on postoperative day one. Proteomic analyses were performed by mass spectrometry. Through a multi-step, exploratory approach, hit-proteins were first identified according to their perioperative prevalence and dynamics. The set of hit-proteins were associated with predefined clinical outcome measures (all-cause one-year mortality, length of hospital stay, postoperative myocardial infarction and stroke until hospital discharge). 192 patients [75.5% male, median age 67.0 (IQR 60.0-73.0)] undergoing cardiac surgery with the use of CPB were included in this analysis. In total, we identified and quantified 402 proteins across all samples, whereof 30/402 (7%) proteins were identified as hit-proteins. Three hit-proteins-LDHB, VCAM1 and IGFBP2-demonstrated the strongest associations with clinical outcomes. After adjustment both for age, sex, BMI and for multiple comparisons, the scaled preoperative levels of IGFBP2 were associated with 1-year all-cause mortality (OR 10.63; 95% CI: 2.93-64.00; p = 0.046). Additionally, scaled preoperative levels of LDHB (OR 5.58; 95% CI: 2.58-8.57; p = 0.009) and VCAM1 (OR 2.32; 95% CI: 0.88-3.77; p = 0.05) were found to be associated with length of hospital stay. We identified a subset of promising candidate plasma proteins relevant to outcome after on-pump cardiac surgery. IGFBP2 showed a strong association with clinical outcome measures and a significant association of preoperative levels with 1-year all-cause mortality. Other proteins strongly associated with outcome were LDHB and VCAM1, reflecting the dynamics in the acute phase response, inflammation and myocardial injury. We recommend further investigation of these proteins as potential outcome markers after cardiac surgery. ClinicalTrials.gov; NCT04767685, data are available via ProteomeXchange with identifier PXD046496.

Investigation of perfusion impairment in degenerative cervical myelopathy beyond the site of cord compression

The aim of this study was to determine tissue-specific blood perfusion impairment of the cervical cord above the compression site in patients with degenerative cervical myelopathy (DCM) using intravoxel incoherent motion (IVIM) imaging. A quantitative MRI protocol, including structural and IVIM imaging, was conducted in healthy controls and patients. In patients, T2-weighted scans were acquired to quantify intramedullary signal changes, the maximal canal compromise, and the maximal cord compression. T2*-weighted MRI and IVIM were applied in all participants in the cervical cord (covering C1–C3 levels) to determine white matter (WM) and grey matter (GM) cross-sectional areas (as a marker of atrophy), and tissue-specific perfusion indices, respectively. IVIM imaging resulted in microvascular volume fraction (F\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$F$$\\end{document}), blood velocity (D∗\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$D^{*}$$\\end{document}), and blood flow (F·D∗\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$F \\cdot D^{*}$$\\end{document}) indices. DCM patients additionally underwent a standard neurological clinical assessment. Regression analysis assessed associations between perfusion parameters, clinical outcome measures, and remote spinal cord atrophy. Twenty-nine DCM patients and 30 healthy controls were enrolled in the study. At the level of stenosis, 11 patients showed focal radiological evidence of cervical myelopathy. Above the stenosis level, cord atrophy was observed in the WM (− 9.3%; p = 0.005) and GM (− 6.3%; p = 0.008) in patients compared to healthy controls. Blood velocity (BV) and blood flow (BF) indices were decreased in the ventral horns of the GM (BV: − 20.1%, p = 0.0009; BF: − 28.2%, p = 0.0008), in the ventral funiculi (BV: − 18.2%, p = 0.01; BF: − 21.5%, p = 0.04) and lateral funiculi (BV: − 8.5%, p = 0.03; BF: − 16.5%, p = 0.03) of the WM, across C1–C3 levels. A decrease in microvascular volume fraction was associated with GM atrophy (R = 0.46, p = 0.02). This study demonstrates tissue-specific cervical perfusion impairment rostral to the compression site in DCM patients. IVIM indices are sensitive to remote perfusion changes in the cervical cord in DCM and may serve as neuroimaging biomarkers of hemodynamic impairment in future studies. The association between perfusion impairment and cervical cord atrophy indicates that changes in hemodynamics caused by compression may contribute to the neurodegenerative processes in DCM.