Running-Related Injury Incidence: Does It Correlate with Kinematic Sub-groups of Runners? A Scoping Review.

BACKGROUND: Historically, kinematic measures have been compared across injured and non-injured groups of runners, failing to take into account variability in kinematic patterns that exist independent of injury, and resulting in false positives. Research led by gait patterns and not pre-defined injury status is called for, to better understand running-related injury (RRI) aetiology and within- and between-group variability. OBJECTIVES: Synthesise evidence for the existence of distinct kinematic sub-groups across a population of injured and healthy runners and assess between-group variability in kinematics, demographics and injury incidence. DATA SOURCES: Electronic database search: PubMed, Web of Science, Cochrane Central Register of Controlled Trials (Wiley), Embase, OVID, Scopus. ELIGIBILITY CRITERIA: Original, peer-reviewed, research articles, published from database start to August 2022 and limited to English language were searched for quantitative and mixed-methods full-text studies that clustered injured runners according to kinematic variables. RESULTS: Five studies (n = 690) were included in the review. All studies detected the presence of distinct kinematic sub-groups of runners through cluster analysis. Sub-groups were defined by multiple differences in hip, knee and foot kinematics. Sex, step rate and running speed also varied significantly between groups. Random injury dispersal across sub-groups suggests no strong evidence for an association between kinematic sub-groups and injury type or location. CONCLUSION: Sub-groups containing homogeneous gait patterns exist across healthy and injured populations of runners. It is likely that a single injury may be represented by multiple movement patterns, and therefore kinematics may not predict injury risk. Research to better understand the underlying causes of kinematic variability, and their associations with RRI, is warranted.

Predicting the outcome of plantar heel pain in adults: a systematic review of prognostic factors.

BACKGROUND: Plantar Heel Pain (PHP) is a common disorder with many treatment pathways and is not self-limiting, hence prognostic information concerning recovery or recalcitrance is needed to guide practice. In this systematic review, we investigate which prognostic factors are associated with favourable or unfavourable PHP outcomes. METHODS: MEDLINE, Web of Science, EMBASE, Scopus and PubMed electronic bibliographic databases were searched for studies evaluating baseline patient characteristics associated with outcomes in prospective longitudinal cohorts or after specific interventions. Cohort, clinical prediction rule derivation and single arms of randomised controlled trials were included. Risk of bias was evaluated with method-specific tools and evidence certainty with GRADE. RESULTS: The review included five studies which evaluated 98 variables in 811 participants. Prognostic factors could be categorised as demographics, pain, physical and activity-related. Three factors including sex and bilateral symptoms (HR: 0.49[0.30-0.80], 0.33[0.15-0.72], respectively) were associated with a poor outcome in a single cohort study. The remaining four studies reported twenty factors associated with a favourable outcome following shockwave therapy, anti-pronation taping and orthoses. Heel spur (AUC = 0.88[0.82-0.93]), ankle plantar-flexor strength (Likelihood ratio (LR): 2.17[1.20-3.95]) and response to taping (LR = 2.17[1.19-3.90]) were the strongest factors predicting medium-term improvement. Overall, the study quality was low. A gap map analysis revealed an absence of research that included psychosocial factors. CONCLUSIONS: A limited number of biomedical factors predict favourable or unfavourable PHP outcomes. High quality, adequately powered, prospective studies are required to better understand PHP recovery and should evaluate the prognostic value of a wide range of variables, including psychosocial factors.

Running shoes for preventing lower limb running injuries in adults.

BACKGROUND: Lower-limb running injuries are common. Running shoes have been proposed as one means of reducing injury risk. However, there is uncertainty as to how effective running shoes are for the prevention of injury. It is also unclear how the effects of different characteristics of running shoes prevent injury. OBJECTIVES: To assess the effects (benefits and harms) of running shoes for preventing lower-limb running injuries in adult runners. SEARCH METHODS: We searched the following databases: CENTRAL, MEDLINE, Embase, AMED, CINAHL Plus and SPORTDiscus plus trial registers WHO ICTRP and ClinicalTrials.gov. We also searched additional sources for published and unpublished trials. The date of the search was June 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs involving runners or military personnel in basic training that either compared a) a running shoe with a non-running shoe; b) different types of running shoes (minimalist, neutral/cushioned, motion control, stability, soft midsole, hard midsole); or c) footwear recommended and selected on foot posture versus footwear not recommended and not selected on foot posture for preventing lower-limb running injuries. Our primary outcomes were number of people sustaining a lower-limb running injury and number of lower-limb running injuries. Our secondary outcomes were number of runners who failed to return to running or their previous level of running, runner satisfaction with footwear, adverse events other than musculoskeletal injuries, and number of runners requiring hospital admission or surgery, or both, for musculoskeletal injury or adverse event. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility and performed data extraction and risk of bias assessment. The certainty of the included evidence was assessed using GRADE methodology. MAIN RESULTS: We included 12 trials in the analysis which included a total of 11,240 participants, in trials that lasted from 6 to 26 weeks and were carried out in North America, Europe, Australia and South Africa. Most of the evidence was low or very low certainty as it was not possible to blind runners to their allocated running shoe, there was variation in the definition of an injury and characteristics of footwear, and there were too few studies for most comparisons. We did not find any trials that compared running shoes with non-running shoes. Neutral/cushioned versus minimalist (5 studies, 766 participants) Neutral/cushioned shoes may make little or no difference to the number of runners sustaining a lower-limb running injuries when compared with minimalist shoes (low-certainty evidence) (risk ratio (RR) 0.77, 95% confidence interval (CI) 0.59 to 1.01). One trial reported that 67% and 92% of runners were satisfied with their neutral/cushioned or minimalist running shoes, respectively (RR 0.73, 95% CI 0.47 to 1.12). Another trial reported mean satisfaction scores ranged from 4.0 to 4.3 in the neutral/ cushioned group and 3.6 to 3.9 in the minimalist running shoe group out of a total of 5. Hence neutral/cushioned running shoes may make little or no difference to runner satisfaction with footwear (low-certainty evidence). Motion control versus neutral / cushioned (2 studies, 421 participants) It is uncertain whether or not motion control shoes reduce the number of runners sustaining a lower-limb running injuries when compared with neutral / cushioned shoes because the quality of the evidence has been assessed as very low certainty (RR 0.92, 95% CI 0.30 to 2.81). Soft midsole versus hard midsole (2 studies, 1095 participants) Soft midsole shoes may make little or no difference to the number of runners sustaining a lower-limb running injuries when compared with hard midsole shoes (low-certainty of evidence) (RR 0.82, 95% CI 0.61 to 1.10). Stability versus neutral / cushioned (1 study, 57 participants) It is uncertain whether or not stability shoes reduce the number of runners sustaining a lower-limb running injuries when compared with neutral/cushioned shoes because the quality of the evidence has been assessed as very low certainty (RR 0.49, 95% CI 0.18 to 1.31). Motion control versus stability (1 study, 56 participants) It is uncertain whether or not motion control shoes reduce the number of runners sustaining a lower-limb running injuries when compared with stability shoes because the quality of the evidence has been assessed as very low certainty (RR 3.47, 95% CI 1.43 to 8.40). Running shoes prescribed and selected on foot posture (3 studies, 7203 participants) There was no evidence that running shoes prescribed based on static foot posture reduced the number of injuries compared with those who received a shoe not prescribed based on foot posture in military recruits (Rate Ratio 1.03, 95% CI 0.94 to 1.13). Subgroup analysis confirmed these findings were consistent between males and females. Therefore, prescribing running shoes and selecting on foot posture probably makes little or no difference to lower-limb running injuries (moderate-certainty evidence). Data were not available for all other review outcomes. AUTHORS' CONCLUSIONS: Most evidence demonstrates no reduction in lower-limb running injuries in adults when comparing different types of running shoes. Overall, the certainty of the evidence determining whether different types of running shoes influence running injury rates was very low to low, and as such we are uncertain as to the true effects of different types of running shoes upon injury rates. There is no evidence that prescribing footwear based on foot type reduces running-related lower-limb injures in adults. The evidence for this comparison was rated as moderate and as such we can have more certainty when interpreting these findings. However, all three trials included in this comparison used military populations and as such the findings may differ in recreational runners.  Future researchers should develop a consensus definition of running shoe design to help standardise classification. The definition of a running injury should also be used consistently and confirmed via health practitioners. More researchers should consider a RCT design to increase the evidence in this area. Lastly, future work should look to explore the influence of different types or running shoes upon injury rates in specific subgroups.

Online questionnaire, clinical and biomechanical measurements for outcome prediction of plantar heel pain: feasibility for a cohort study.

BACKGROUND: Plantar heel pain (PHP) accounts for 11-15% of foot symptoms requiring professional care in adults. Recovery is variable, with no robust prognostic guides for sufferers, clinicians or researchers. Therefore, we aimed to determine the validity, reliability and feasibility of questionnaire, clinical and biomechanical measures selected to generate a prognostic model in a subsequent cohort study. METHODS: Thirty-six people (19 females & 17 males; 20-63 years) were recruited with equal numbers in each of three groups: people with PHP (PwPHP), other foot pain (PwOP) and healthy (H) controls. Eighteen people performed a questionnaire battery twice in a randomised order to determine online and face-to-face agreement. The remaining 18 completed the online questionnaire once, plus clinical measurements including strength and range of motion, mid-foot mobility, palpation and ultrasound assessment of plantar fascia. Nine of the same people underwent biomechanical assessment in the form of a graded loaded challenge augmenting walking with added external weight and amended step length on two occasions. Outcome measures were (1) feasibility of the data collection procedure, measurement time and other feedback; (2) establishing equivalence to usual procedures for the questionnaire battery; known-group validity for clinical and imaging measures; and initial validation and reliability of biomechanical measures. RESULTS: There were no systematic differences between online and face-to-face administration of questionnaires (p-values all > .05) nor an administration order effect (d = - 0.31-0.25). Questionnaire reliability was good or excellent (ICC2,1_absolute)(ICC 0.86-0.99), except for two subscales. Full completion of the survey took 29 ± 14 min. Clinically, PwPHP had significantly less ankle-dorsiflexion and hip internal-rotation compared to healthy controls [mean (±SD) for PwPHP-PwOP-H = 14°(±6)-18°(±8)-28°(±10); 43°(±4)- 45°(±9)-57°(±12) respectively; p < .02 for both]. Plantar fascia thickness was significantly higher in PwPHP (3.6(0.4) mm vs 2.9(0.4) mm, p = .01) than the other groups. The graded loading challenge demonstrated progressively increasing ground reaction forces. CONCLUSION: Online questionnaire administration was valid therefore facilitating large cohort recruitment and being relevant to remote service evaluation and research. The physical and ultrasound examination revealed the expected differences between groups, while the graded loaded challenge progressively increases load and warrants future research. Clinician and researchers can be confident about these methodological approaches and the cohort study, from which useful clinical tools should result, is feasible. LEVEL OF EVIDENCE: IV.

Management of plantar heel pain: a best practice guide informed by a systematic review, expert clinical reasoning and patient values.

OBJECTIVE: To develop a best practice guide for managing people with plantar heel pain (PHP). METHODS: Mixed-methods design including systematic review, expert interviews and patient survey. DATA SOURCES: Medline, Embase, CINAHL, SPORTDiscus, Cochrane Central Register of Controlled Trials, trial registries, reference lists and citation tracking. Semi-structured interviews with world experts and a patient survey. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) evaluating any intervention for people with PHP in any language were included subject to strict quality criteria. Trials with a sample size greater than n=38 were considered for proof of efficacy. International experts were interviewed using a semi-structured approach and people with PHP were surveyed online. RESULTS: Fifty-one eligible trials enrolled 4351 participants, with 9 RCTs suitable to determine proof of efficacy for 10 interventions. Forty people with PHP completed the online survey and 14 experts were interviewed resulting in 7 themes and 38 subthemes. There was good agreement between the systematic review findings and interview data about taping (SMD: 0.47, 95% CI 0.05 to 0.88) and plantar fascia stretching (SMD: 1.21, 95% CI 0.78 to 1.63) for first step pain in the short term. Clinical reasoning advocated combining these interventions with education and footwear advice as the core self-management approach. There was good expert agreement with systematic review findings recommending stepped care management with focused shockwave for first step pain in the short-term (OR: 1.89, 95% CI 1.18 to 3.04), medium-term (SMD 1.31, 95% CI 0.61 to 2.01) and long-term (SMD 1.67, 95% CI 0.88 to 2.45) and radial shockwave for first step pain in the short term (OR: 1.66, 95% CI 1.00 to 2.76) and long term (OR: 1.78, 95% CI 1.07 to 2.96). We found good agreement to 'step care' using custom foot orthoses for general pain in the short term (SMD: 0.41, 95% CI 0.07 to 0.74) and medium term (SMD: 0.55, 95% CI 0.09 to 1.02). CONCLUSION: Best practice from a mixed-methods study synthesising systematic review with expert opinion and patient feedback suggests core treatment for people with PHP should include taping, stretching and individualised education. Patients who do not optimally improve may be offered shockwave therapy, followed by custom orthoses.

Case Study: An intraoperative finding of black bone disease in a podiatric surgery patient.

Black bone disease has been recognised as a potential consequence of long-term treatment with tetracycline antibiotics. Largely documented affecting structures in the head and skull, there are few reported cases of black bone disease in the foot and ankle. The case of a 55 years old patient, who as a teenager, had undergone treatment with minocycline hydrochloride for chronic acne, and was found to have bone discolouration consistent with minocycline induced black bone disease (MIBBD) during the course of hallux valgus corrective surgery some 40 years later, is presented. In spite of the intraoperative findings, the patient's post-operative recovery and bone healing was uneventful. The literature on minocycline induced black bone disease is reviewed.

WITHDRAWN: Interventions for treating hallux valgus (abductovalgus) and bunions.

BACKGROUND: Hallux valgus is classified as an abnormal deviation of the great toe (hallux) towards the midline of the foot. OBJECTIVES: To identify and evaluate the evidence from randomised trials of interventions used to correct hallux valgus. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauama Group trials register (2003/1), the Cochrane Central Register of Controlled Trials (The Cochrane Library issue 1, 2003), MEDLINE (January 1966 to March 2003) and EMBASE (1980 to January 2003). No language restrictions were applied. Hand searching of specific foot journals was also undertaken.Date of the most recent search: 31st March 2003. SELECTION CRITERIA: Randomised or quasi-randomised trials of both conservative and surgical treatments of hallux valgus. Excluded were studies comparing areas of surgery not specific to the control of the deformity such as use of anaesthetics or tourniquet placement. DATA COLLECTION AND ANALYSIS: Methodological quality of trials which met the inclusion criteria was independently assessed by two reviewers. Data extraction was undertaken by two reviewers. The trials were grouped according to the interventions being compared, but the dissimilarity in the comparisons prevented pooling of results. MAIN RESULTS: The methodological quality of the 21 included trials was generally poor and trial sizes were small.Three trials involving 332 participants evaluated conservative treatments versus no treatment. There was no evidence of a difference in outcomes between treatment and no treatment.One good quality trial involving 140 participants compared surgery to conservative treatment. Evidence was shown of an improvement in all outcomes in patients receiving chevron osteotomy compared with those receiving orthoses. The same trial also compared surgery to no treatment in 140 participants. Evidence was shown of an improvement in all outcomes in patients receiving chevron osteotomy compared with those receiving no treatment.Two trials involving 133 people with hallux valgus compared Keller's arthroplasty with other surgical techniques. In general, there was no advantage or disadvantage using Keller's over the other techniques. When the distal osteotomy was compared to Keller's arthroplasty, the osteotomy showed evidence of improving the intermetatarsal angle and preserving joint range of motion. The arthroplasty was found to have less of an impact on walking ability compared to the arthrodesis.Six trials involving 309 participants compared chevron (and chevron-type) osteotomy with other techniques. The chevron osteotomy offered no advantages in these trials. For some outcomes, other techniques gave better results. Two of these trials (94 participants) compared a type of proximal osteotomy to a proximal chevron osteotomy and found no evidence of a difference in outcomes between techniques.Three trials involving 157 participants compared outcomes between original operations and surgeon's adaptations. There was no advantage found for any of the adaptations.Three trials involving 71 people with hallux valgus compared new methods of fixation to traditional methods. There was no evidence that the new methods of fixation were detrimental to the outcome of the patients.Four trials involving 162 participants evaluated methods of post-operative rehabilitation. The use of continuous passive motion appeared to give an improved range of motion and earlier recovery following surgery. Early weightbearing or the use of a crepe bandage were not found to be detrimental to final outcome. AUTHORS' CONCLUSIONS: Only a few studies had considered conservative treatments. The evidence from these suggested that orthoses and night splints did not appear to be any more beneficial in improving outcomes than no treatment. Surgery (chevron osteotomy) was shown to be beneficial compared to orthoses or no treatment, but when compared to other osteotomies, no technique was shown to be superior to any other. Only one trial had compared an osteotomy to an arthroplasty. There was limited evidence to suggest that the osteotomy gave the better outcomes. It was notable that the numbers of participants in some trials remaining dissatisfied at follow-up were consistently high (25 to 33%), even when the hallux valgus angle and pain had improved. A few of the more recent trials used assessment scores that combine several aspects of the patients outcomes. These scoring systems are useful to the clinician when comparing techniques but are of dubious relevance to the patient if they do not address their main concern and such scoring systems are frequently unvalidated. Only one study simply asked the patient if they were better than before the treatment. Final outcomes were most frequently measured at one year, with a few trials maintaining follow-up for 3 years. Such time-scales are minimal given that the patients will be on their feet for at least another 20-30 years after treatment. Future research should include patient-focused outcomes, standardised assessment criteria and longer surveillance periods, more usefully in the region of 5-10 years.

Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions.

The involvement of cytochrome P450 (CYP) enzymes in the metabolism of the atypical (second-generation) antipsychotics clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone and amisulpride is reviewed, and the possible relevance of this metabolism to drug-drug interactions is discussed. Clozapine is metabolized primarily by CYP1A2, with additional contributions by CYP2C19, CYP2D6 and CYP3A4. Risperidone is metabolized primarily by CYP2D6 and to a lesser extent by CYP3A4; the 9-hydroxy metabolite of risperidone (paliperidone) is now marketed as an antipsychotic in its own right. Olanzapine is metabolized primarily by direct glucuronidation and CYP1A2 and to a lesser extent by CYP2D6 and CYP3A4. Quetiapine is metabolized by CYP3A4, as is ziprasidone, although in the latter case aldehyde oxidase is the enzyme responsible for most of the metabolism. CYP2D6 and CYP3A4 are important in the metabolism of aripiprazole, and CYP-catalyzed metabolism of paliperidone and amisulpride appears to be minor. At the usual clinical doses, these drugs appear to not generally affect markedly the metabolism of other coadministered medications. However, as indicated above, several of atypical antipsychotics are metabolized by CYP enzymes, and physicians should be aware of coadministered drugs that may inhibit or induce these CYP enzymes; examples of such possible interactions are presented in this review.

The relevance of neuroactive steroids in schizophrenia, depression, and anxiety disorders.

1. Neuroactive steroids are steroid hormones that exert rapid, nongenomic effects at ligand-gated ion channels. There is increasing awareness of the possible role of these steroids in the pathology and manifestation of symptoms of psychiatric disorders. The aim of this paper is to review the current knowledge of neuroactive steroid functioning in the central nervous system, and to assess the role of neuroactive steroids in the pathophysiology and treatment of symptoms of schizophrenia, depression, and anxiety disorders. Particular emphasis will be placed on GABAA receptor modulation, given the extensive knowledge of the interactions between this receptor complex, neuroactive steroids, and psychiatric illness. 2. A brief description of neuroactive steroid metabolism is followed by a discussion of the interactions of neuroactive steroids with acute and chronic stress and the HPA axis. Preclinical and clinical studies related to psychiatric disorders that have been conducted on neuroactive steroids are also described. 3. Plasma concentrations of some neuroactive steroids are altered in individuals suffering from schizophrenia, depression, or anxiety disorders compared to values in healthy controls. Some drugs used to treat these disorders have been reported to alter plasma and brain concentrations in clinical and preclinical studies, respectively. 4. Further research is warranted into the role of neuroactive steroids in the pathophysiology of psychiatric illnesses and the possible role of these steroids in the successful treatment of these disorders.

Examining the validity of selected measures of foot type: a preliminary study.

The rationale that subtalar joint position, reflected by calcaneal alignment, determines foot morphology was used to formulate an approach to examination of the validity of three measures of "foot type": the Staheli Arch Index, the Chippaux-Smirak Index, and navicular height. Each measure was calculated in five positions, progressively inverting from a reference position of maximal comfortable eversion. Pearson product moment correlations (Staheli Arch Index: r = 0.5; Chippaux-Smirak Index: r = 0.6; and navicular height: r = 0.8) indicated that each measure progressively increased with inversion. The change in calcaneal position required to produce significant changes in each measure was investigated using analysis of variance with Scheffé post hoc analysis. This analysis revealed that changes of 15 degrees and 20 degrees were required to produce significant differences in Chippaux-Smirak Index and Staheli Arch Index scores, respectively, threatening their validity. Navicular height was sensitive to smaller changes of 10 degrees and thus displays greater sensitivity to changes in calcaneal position than the footprint parameters tested.

Interactions between the cytochrome P450 system and the second-generation antipsychotics.

Awareness of the metabolism of second-generation antipsychotics by the cytochrome P450 (CYP) system can inform the clinician about how to avoid and manage drug-drug interactions involving these enzymes. Clozapine is metabolized primarily by CYP1A2, with additional contributions by CYP2C19, CYP2D6 and CYP3A4. Risperidone is metabolized primarily by CYP2D6 and to a lesser extent by CYP3A4. Olanzapine is metabolized primarily by CYP1A2 and to a lesser extent by CYP2D6. Quetiapine and ziprasidone are metabolized by CYP3A4. At the usual clinical doses, these drugs appear not to significantly affect the metabolism of other medications. There is, however, a lack of in vivo metabolic data, especially for the 3 newest second-generation antipsychotics: olanzapine, quetiapine and ziprasidone.

Stereochemistry and drug efficacy and development: relevance of chirality to antidepressant and antipsychotic drugs.

Many drugs contain a chiral center or a center of unsaturation, or such centers result during metabolism of these drugs. Often such drugs are marketed as a mixture of the resultant enantiomers (racemates) or of geometric isomers, respectively. These enantiomers (molecules that are not superimposible on their mirror image) or geometric isomers may differ markedly from each other with regard to their pharmacodynamic and/or pharmacokinetic properties. This review deals primarily with drugs with chiral centers, and possible complications arising from the use of racemates are discussed. Recent developments in resolution of enantiomers, increased knowledge of the molecular structure of specific drug targets and a heightened awareness of several possible advantages of using single enantiomers rather than racemic mixtures of drugs have led to an increased emphasis on understanding the role of chirality in drug development. This has resulted in increased investigation of individual enantiomers early on in the development of drugs and in 'chiral switching', i.e. the replacement of a racemate of a drug which has already been approved or marketed by a single enantiomer. Although stereochemistry is an important matter to consider in drugs of virtually all classes, this review focuses on the relevance of chirality to antidepressant and antipsychotic drugs. Examples of the effects of chiral centers on the properties of antidepressants (tricyclics, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, viloxazine, bupropion, mianserin, venlafaxine, mirtazapine and reboxetine), antipsychotics and/or some of their metabolites are discussed.