International Foot and Ankle Osteoarthritis Consortium review and research agenda for diagnosis, epidemiology, burden, outcome assessment and treatment.

OBJECTIVE: To summarise the available evidence relating to the diagnosis, epidemiology, burden, outcome assessment and treatment of foot and ankle osteoarthritis (OA) and to develop an agenda to guide future research. METHOD: Members of the International Foot and Ankle Osteoarthritis Consortium compiled a narrative summary of the literature which formed the basis of an interactive discussion at the Osteoarthritis Research Society International World Congress in 2021, during which a list of 24 research agenda items were generated. Following the meeting, delegates were asked to rank the research agenda items on a 0 to 100 visual analogue rating scale (0 = not at all important to 100 = extremely important). Items scoring a mean of 70 or above were selected for inclusion. RESULTS: Of the 45 delegates who attended the meeting, 31 contributed to the agenda item scoring. Nineteen research agenda items met the required threshold: three related to diagnosis, four to epidemiology, four to burden, three to outcome assessment and five to treatment. CONCLUSIONS: Key knowledge gaps related to foot and ankle OA were identified, and a comprehensive agenda to guide future research planning was developed. Implementation of this agenda will assist in improving the understanding and clinical management of this common and disabling, yet relatively overlooked condition.

Foot structure and lower limb function in individuals with midfoot osteoarthritis: a systematic review.

OBJECTIVE: To determine how foot structure and lower limb function differ between individuals with and without midfoot osteoarthritis (OA). DESIGN: Electronic databases were searched from inception until May 2020. To be eligible, studies needed to (1) include participants with radiographically confirmed midfoot OA, with or without midfoot symptoms, (2) include a control group of participants without radiographic midfoot OA or without midfoot symptoms, and (3) report outcomes of foot structure, alignment, range of motion or any measures of lower limb function during walking. Screening and data extraction were performed by two independent assessors, with disagreements resolved by a third independent assessor. The methodological quality of included studies was assessed using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS: A total of 1,550 records were screened by title and abstract and 11 met the inclusion criteria. Quantitative synthesis indicated that individuals who had midfoot OA had a more pronated foot posture, greater first ray mobility, less range of motion in the subtalar joint and first metatarsophalangeal joints, longer central metatarsals and increased peak plantar pressures, pressure time integrals and contact times in the heel and midfoot during walking. Meta-analysis could not be performed as the data were not sufficiently homogenous. CONCLUSIONS: There are several differences in foot structure and lower limb function between individuals with and without midfoot OA. Future research with more consistent case definitions and detailed biomechanical models would further our understanding of potential mechanisms underlying the development of midfoot OA.

Objectively measured 24-hour activity profiles before and after total hip arthroplasty.

AIMS: The purpose of this exploratory study was to investigate if the 24-hour activity profile (i.e. waking activities and sleep) objectively measured using wrist-worn accelerometry of patients scheduled for total hip arthroplasty (THA) improves postoperatively. PATIENTS AND METHODS: A total of 51 THA patients with a mean age of 64 years (24 to 87) were recruited from a single public hospital. All patients underwent THA using the same surgical approach with the same prosthesis type. The 24-hour activity profiles were captured using wrist-worn accelerometers preoperatively and at 2, 6, 12, and 26 weeks postoperatively. Patient-reported outcomes (Hip Disability and Osteoarthritis Outcome Score (HOOS)) were collected at all timepoints except two weeks postoperatively. Accelerometry data were used to quantify the intensity (sedentary, light, moderate, and vigorous activities) and frequency (bouts) of activity during the day and sleep efficiency. The analysis investigated changes with time and differences between Charnley class. RESULTS: Patients slept or were sedentary for a mean of 19.5 hours/day preoperatively and the 24-hour activity pattern did not improve significantly postoperatively. Outside of sleep, the patients spent their time in sedentary activities for a mean of 620 minutes/day (sd 143) preoperatively and 641 minutes/day (sd 133) six months postoperatively. No significant improvements were observed for light, moderate, and vigorous intensity activities (p = 0.140, p = 0.531, and p = 0.407, respectively). Sleep efficiency was poor (< 85%) at all timepoints. There was no postoperative improvement in sleep efficiency when adjusted for medications (p > 0.05). Patient-reported outcome measures showed a significant improvement with time in all domains when compared with preoperative levels. There were no differences with Charnley class at six months postoperatively. However, Charnley class C patients were more sedentary at two weeks postoperatively when compared with Charnley class A patients (p < 0.05). There were no further differences between Charnley classifications. CONCLUSION: This study describes the 24-hour activity profile of THA patients for the first time. Prior to THA, patients in this cohort were inactive and slept poorly. This cohort shows no improvement in 24-hour activity profiles at six months postoperative. Cite this article: Bone Joint J 2019;101-B:415-425.

Midfoot osteoarthritis: potential phenotypes and their associations with demographic, symptomatic and clinical characteristics.

OBJECTIVE: To investigate the demographic, symptomatic, clinical and structural foot characteristics associated with potential phenotypes of midfoot osteoarthritis (OA). DESIGN: Cross-sectional study of 533 community-dwelling adults aged ≥50 years with foot pain in the past year. Health questionnaires and clinical assessments of symptoms, foot structure and function were undertaken. Potential midfoot OA phenotypes were defined by the pattern of radiographic joint involvement affecting either the medial midfoot (talonavicular, navicular-1st cuneiform, or cuneiform-1st metatarsal joint), central midfoot (2nd cuneiform-metatarsal joint), or both medial and central midfoot joints. Multivariable regression models with generalised estimating equations were used to investigate the associations between patterns of midfoot joint involvement and symptomatic, clinical and structural characteristics compared to those with no or minimal midfoot OA. RESULTS: Of 879 eligible feet, 168 had medial midfoot OA, 103 central midfoot OA, 76 both medial and central midfoot OA and 532 no/minimal OA. Having both medial and central midfoot OA was associated with higher pain scores, dorsally-located midfoot pain (OR 2.54, 95%CI 1.45, 4.45), hallux valgus (OR 1.76, 95%CI 1.02, 3.05), flatter foot posture (ß 0.44, 95%CI 0.12, 0.77), lower medial arch height (ß 0.02, 95%CI 0.01, 0.03) and less subtalar inversion and 1st MTPJ dorsiflexion. Isolated medial midfoot OA and central midfoot OA had few distinguishing clinical characteristics. CONCLUSIONS: Distinct phenotypes of midfoot OA appear challenging to identify, with substantial overlap in symptoms and clinical characteristics. Phenotypic differences in symptoms, foot posture and function were apparent in this study only when both the medial and central midfoot were involved.

Biomechanical changes and recovery of gait function after total hip arthroplasty for osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: To determine the change in walking gait biomechanics after total hip arthroplasty (THA) for osteoarthritis (OA) compared to the pre-operative gait status, and to compare the recovery of gait following THA with healthy individuals. METHODS: Systematic review with meta-analysis of studies investigating changes in gait biomechanics after THA compared to (1) preoperative levels and (2) healthy individuals. Data were pooled at commonly reported time points and standardised mean differences (SMDs) were calculated in meta-analyses for spatiotemporal, kinematic and kinetic parameters. RESULTS: Seventy-four studies with a total of 2,477 patients were included. At 6 weeks postoperative, increases were evident for walking speed (SMD: 0.32, 95% confidence intervals (CI) 0.14, 0.50), stride length (SMD: 0.40, 95% CI 0.19, 0.61), step length (SMD: 0.41, 95% CI 0.23, 0.59), and transverse plane hip range of motion (ROM) (SMD: 0.36, 95% CI 0.05, 0.67) compared to pre-operative gait. Sagittal, coronal and transverse hip ROM was significantly increased at 3 months (SMDs: 0.50 to 1.07). At 12 months postoperative, patients demonstrated deficits compared with healthy individuals for walking speed (SMD: -0.59, 95% CI -1.08 to -0.11), stride length (SMD: -1.27, 95% CI -1.63, -0.91), single limb support time (SMD: -0.82, 95% CI -1.23, -0.41) and sagittal plane hip ROM (SMD: -1.16, 95% CI -1.83, -0.49). Risk of bias scores ranged from seven to 24 out of 26. CONCLUSIONS: Following THA for OA, early improvements were demonstrated for spatiotemporal and kinematic gait patterns compared to the pre-operative levels. Deficits were still observed in THA patients compared to healthy individuals at 12 months.

Qualitative and quantitative evaluation of six algorithms for correcting intensity nonuniformity effects.

The desire to correct intensity nonuniformity in magnetic resonance images has led to the proliferation of nonuniformity-correction (NUC) algorithms with different theoretical underpinnings. In order to provide end users with a rational basis for selecting a given algorithm for a specific neuroscientific application, we evaluated the performance of six NUC algorithms. We used simulated and real MRI data volumes, including six repeat scans of the same subject, in order to rank the accuracy, precision, and stability of the nonuniformity corrections. We also compared algorithms using data volumes from different subjects and different (1.5T and 3.0T) MRI scanners in order to relate differences in algorithmic performance to intersubject variability and/or differences in scanner performance. In phantom studies, the correlation of the extracted with the applied nonuniformity was highest in the transaxial (left-to-right) direction and lowest in the axial (top-to-bottom) direction. Two of the six algorithms demonstrated a high degree of stability, as measured by the iterative application of the algorithm to its corrected output. While none of the algorithms performed ideally under all circumstances, locally adaptive methods generally outperformed nonadaptive methods.

Multivariate predictive relationship between kinematic and functional activation patterns in a PET study of visuomotor learning.

Imaging studies of visuomotor learning have reported practice-related activation in brain regions mediating sensorimotor functions. However, development and testing of functional motor learning models, based on the relationship between imaging and behavioral measures, is complicated by the multidimensional nature of motoric control. In the present study, multivariate techniques were used to analyze [15O]water PET and kinematic correlates of learning in a visuomotor tracing task. Fourteen subjects traced a geometric form over a series of eight tracing trials, preceded and followed by baseline trials in which they passively viewed the geometric form. Simultaneous evaluation of multiple behavioral measures indicated that performance improvement was most strongly associated with a global performance measure and least strongly associated with measures of fine motor control. Results of three independent analytic techniques (i.e., intertrial correlation matrices, power function modeling, iterative canonical variate analysis) indicated that imaging and behavioral measures were most closely related on early learning trials. Performance improvement was associated with covarying increases in normalized activity among superior parietal, postcentral gyrus, and premotor regions and covarying decreases in normalized activity among cerebellar, inferior parietal, pallidal, and medial occipital regions. These findings suggest that performance improvement may be associated with increased activation in neural systems previously implicated in visually guided reaching and decreased activation in neural systems previously implicated in attentive visuospatial processing.

In vivo measurement of regional brain and tumor pH using [14C]dimethyloxazolidinedione and quantitative autoradiography. II: Characterization of the extracellular fluid compartment using pH-sensitive microelectrodes and [14C]sucrose.

We measured the extracellular (interstitial) pH (pHe) of RG-2 rat gliomas using H+-sensitive microelectrodes and estimated the volume of tumor extracellular space based on the tissue-plasma ratio of [14C]sucrose. The average RG-2 pHe was 7.63 +/- 0.15 (mean +/- SD, n = 6), whereas the average pHe of contralateral brain tissue was 7.34 +/- 0.10 (n = 3) and arterial pH was 7.36 +/- 0.02. RG-2 extracellular space water volume was estimated to be 0.3 ml water/g tissue. In separate experiments in normal, nontumored rats, intracellular pH (pHi) was calculated for nine gray and white matter regions based on measurements of tissue and plasma [14C]dimethyloxazolidinedione concentration. pHi values ranged from 6.80 to 6.94, and no consistent gray-white differences were observed. Our data suggest that tumor pHi is not more acidic than that of normal brain tissue and that the observed alkalinity of primary brain tumors is due to the presence of a large alkaline extracellular space.

In vivo measurement of regional brain and tumor pH using [14C]dimethyloxazolidinedione and quantitative autoradiography.

Using [14C]dimethyloxazolidinedione ([14C]-DMO) and quantitative autoradiography, we estimated tissue pH (pHt) and intracellular pH (pHi) in nine regions of the normal rat brain and in intracerebrally implanted RG-2 gliomas. Calculations of regional pHt, based on equilibrium tissue and arterial plasma [14C]DMO concentration, ranged from 6.83 to 6.94; pHi, calculated assuming an extracellular water volume of 0.15 ml/g for gray matter and 0.11 ml/g for white matter, ranged from 6.61 to 6.78. No consistent difference was found in pHt or pHi between white and gray matter regions. Tumor tissue water content was determined by drying to constant weight, and extracellular space water volume (Ve) was estimated with [14C]sucrose in nephrectomized rats using quantitative autoradiography. Tumor pHt ranged from 7.08 to 7.18. For Ve = 0.17 (measured), pHi was 6.94-7.06; for Ve = 0.30 (assumed), the corresponding range for pHi was 6.63-6.90. Thus, the RG-2 glioma is not more "acidic" than adjacent brain tissue and its "alkaline" pHt probably reflects a large extracellular water content and plasma-like extracellular pH.

Low-dose Adriamycin remission maintenance therapy for pediatric solid tumors.

A low-dose maintenance schedule of Adriamycin was evaluated in six children whose metastatic solid tumors regressed following toxic induction therapy with Adriamycin. Three of these children are now disease-free more than one year following discontinuation of therapy. Adriamycin can be given on a low-dose maintenance schedule free from alopecia, fever, stomatitis, myelosuppression and recognizable cardiomyopathy. Further studies of similar schedules are warranted.

Tool feed influence on the machinability of CO(2) laser optics.

Influence of tool feed on reflectivity of diamond-machined surfaces was evaluated using materials (gold, silver, and copper) from which CO(2) laser optics are primarily produced. Fifteen specimens were machined by holding all machining parameters constant, except tool feed. Tool feed was allowed to vary by controlled amounts from one evaluation zone (or part) to another. Past experience has verified that the quality of a diamond-machined surface is not a function of the cutting velocity; therefore, this experiment was conducted on the basis that a variation in cutting velocity was not an influencing factor on the diamondturning process. Inspection results of the specimens indicated that tool feeds significantly higher than 5.1 micro/rev (200 microin./rev) produced detrimental effects on the machined surfaces. In some cases, at feeds as high as 13 microm/rev (500 microin./rev), visible scoring was evident. Those surfaces produced with tool feeds less than 5.1 microm/rev had little difference in reflectivity. Measurements indicat d that their reflectivity existed in a range from 96.7% to 99.3% at 10.6 microm.