Foot kinematics in patients with two patterns of pathological plantar hyperkeratosis

Background: The Root paradigm of foot function continues to underpin the majority of clinical foot biomechanics practice and foot orthotic therapy. There are great number of assumptions in this popular paradigm, most of which have not been thoroughly tested. One component supposes that patterns of plantar pressure and associated hyperkeratosis lesions should be associated with distinct rearfoot, mid foot, first metatarsal and hallux kinematic patterns. Our aim was to investigate the extent to which this was true. Methods: Twenty-seven subjects with planter pathological hyperkeratosis were recruited into one of two groups. Group 1 displayed pathological plantar hyperkeratosis only under metatarsal heads 2, 3 and 4 (n = 14). Group 2 displayed pathological plantar hyperkeratosis only under the 1st and 5th metatarsal heads (n = 13). Foot kinematics were measured using reflective markers on the leg, heel, midfoot, first metatarsal and hallux. Results: The kinematic data failed to identify distinct differences between these two groups of subjects, however there were several subtle (generally <3°) differences in kinematic data between these groups. Group 1 displayed a less everted heel, a less abducted heel and a more plantarflexed heel compared to group 2, which is contrary to the Root paradigm. Conclusions: There was some evidence of small differences between planter pathological hyperkeratosis groups. Nevertheless, there was too much similarity between the kinematic data displayed in each group to classify them as distinct foot types as the current clinical paradigm proposes

Randomized Trial to Compare the Immunogenicity and Safety of a CRM or TT Conjugated Quadrivalent Meningococcal Vaccine in Teenagers who Received a CRM or TT Conjugated Serogroup C Vaccine at Preschool Age

Protection after meningococcal C (MenC) conjugate (MCC) vaccination in early childhood is short-lived. Boosting with a quadrivalent vaccine in teenage years, a high-risk period for MenC disease, should protect against additional serogroups but might compromise MenC response. The carrier protein in the primary MCC vaccine determines the response to MCC booster in toddlers, but the relationship between primary vaccine and booster given later is unclear. This study compared responses to a CRM-conjugated or tetanus toxoid (TT)-conjugated MenACWY vaccine in teenagers primed with different MCC vaccines at preschool age

Randomised trial to compare the immunogenicity and safety of a CRM or TT conjugated quadrivalent meningococcal vaccine in teenagers who received a CRM or TT conjugated serogroup C vaccine at preschool age

Background: Protection after meningococcal C (MenC) conjugate (MCC) vaccination in early childhood is short-lived. Boosting with a quadrivalent vaccine in teenage years, a high-risk period for MenC disease, should protect against additional serogroups but might compromise MenC response. The carrier protein in the primary MCC vaccine determines the response to MCC booster in toddlers, but the relationship between primary vaccine and booster given later is unclear. This study compared responses to a CRM-conjugated or tetanus toxoid (TT)-conjugated MenACWY vaccine in teenagers primed with different MCC vaccines at preschool age. Methods: Ninety-three teenagers (16–19 years), who were previously randomized at age 3–6 years to receive single-dose MCC–CRM or MCC–TT, were randomized to receive either MenACWY–CRM or MenACWY–TT booster. Serum bactericidal antibodies (SBA, protective titer >=8) were measured before, 1 month and 6 or 9 months after boosting. Results: Preboosting, MCC–TT-primed teenagers had significantly higher MenC SBA titers than those MCC–CRM-primed (P = 0.02). Postboosting, both MenACWY vaccines induced protective SBA titers to all 4 serogroups in most participants (>=98% at 1 month and >=90% by 9 months postboost). The highest MenC SBA titers were seen in those MCC–TT-primed and MenACWY–TT-boosted [geometric mean titer (GMT) ~ 22,000] followed by those boosted with MenACWY–CRM irrespective of priming (GMT ~ 12,000) and then those MCC–CRM-primed and MenACWY–TT-boosted (GMT ~ 5500). The estimated postbooster MenC SBA decline beyond 1 month was ~40% as time since booster doubles. Both vaccines were well tolerated with no attributable serious adverse events. Conclusion: Both MenACWY vaccines safely induced protective sustained antibody responses against all targeted serogroups in MCC-primed teenagers

Managing lifestyle change to reduce coronary risk: a synthesis of qualitative research on peoples’ experiences

Background Coronary heart disease is an incurable condition. The only approach known to slow its progression is healthy lifestyle change and concordance with cardio-protective medicines. Few people fully succeed in these daily activities so potential health improvements are not fully realised. Little is known about peoples’ experiences of managing lifestyle change. The aim of this study was to synthesise qualitative research to explain how participants make lifestyle change after a cardiac event and explore this within the wider illness experience. Methods A qualitative synthesis was conducted drawing upon the principles of meta-ethnography. Qualitative studies were identified through a systematic search of 7 databases using explicit criteria. Key concepts were identified and translated across studies. Findings were discussed and diagrammed during a series of audiotaped meetings. Results The final synthesis is grounded in findings from 27 studies, with over 500 participants (56% male) across 8 countries. All participants experienced a change in their self-identity from what was ‘familiar’ to ‘unfamiliar’. The transition process involved ‘finding new limits and a life worth living’ , ‘finding support for self’ and ‘finding a new normal’. Analyses of these concepts led to the generation of a third order construct, namely an ongoing process of ‘reassessing past, present and future lives’ as participants considered their changed identity. Participants experienced a strong urge to get back to ‘normal’. Support from family and friends could enable or constrain life change and lifestyle changes. Lifestyle change was but one small part of a wider ‘life’ change that occurred. Conclusions The final synthesis presents an interpretation, not evident in the primary studies, of a person-centred model to explain how lifestyle change is situated within ‘wider’ life changes. The magnitude of individual responses to a changed health status varied. Participants experienced distress as their notion of self identity shifted and emotions that reflected the various stages of the grief process were evident in participants’ accounts. The process of self-managing lifestyle took place through experiential learning; the level of engagement with lifestyle change reflected an individual’s unique view of the balance needed to manage ‘realistic change’ whilst leading to a life that was perceived as ‘worth living’. Findings highlight the importance of providing person centred care that aligns with both psychological and physical dimensions of recovery which are inextricably linked

A new approach to prevention of knee osteoarthritis: reducing medial load in the contralateral knee

Background. Few if any prevention strategies are available for knee osteoarthritis (OA). In those with symptomatic medial OA, the contralateral knee may be at high risk of disease and a reduction in medial loading in that knee might prevent disease or its progression there. Lateral wedge insoles reduce loading across an affected medial knee but their effect on the contralateral knee is unknown. Methods: To determine the proportion of persons with medial knee OA who had concurrent medial contralateral OA or developed contralateral medial OA later, we examined knee radiographs from the longitudinal Framingham Osteoarthritis Study. Then, to examine an approach to reducing medial load in the contralateral knee, 51 people from a separate study with painful medial tibiofemoral OA underwent gait analysis wearing bilateral controlled shoes with i) no insoles ii) two types of lateral wedge insoles laterally posted by 5 degrees. Primary outcome was the external knee adduction moment (EKAM) in the contralateral knee. Non-parametric confidence intervals were constructed around the median differences in percentage change in the affected and contralateral sides. Results: Of Framingham subjects with medial radiograph knee OA, 137/152 (90%) either had concurrent contralateral medial OA or developed it within 10 years. 43/67 (64%) of those with medial symptomatic knee OA had or developed the same disease state in the contralateral knee. Compared to a control shoe, medial loading was reduced substantially on both the affected (median percentage EKAM change =-4.84%; 95% CI -11.33% to -0.65%) and contralateral sides (median EKAM percentage change -9.34% (95% CI -10.57% to -6.45%). Conclusions: In persons with medial OA, the contralateral knee is also at high risk of medial OA. Bilateral reduction in medial loading in knees by use of strategies such as lateral wedge insoles might not only reduce medial load in affected knees but prevent knee OA or its progression on the contralateral side

Does flip-flop style footwear modify ankle biomechanics and foot loading patterns?

Background Flip-flops are an item of footwear, which are rubber and loosely secured across the dorsal fore-foot. These are popular in warm climates; however are widely criticised for being detrimental to foot health and potentially modifying walking gait. Contemporary alternatives exist including FitFlop, which has a wider strap positioned closer to the ankle and a thicker, ergonomic, multi-density midsole. Therefore the current study investigated gait modifications when wearing flip-flop style footwear compared to barefoot walking. Additionally walking in a flip-flop was compared to that FitFlop alternative. Methods Testing was undertaken on 40 participants (20 male and 20 female, mean ± 1 SD age 35.2 ± 10.2 years, B.M.I 24.8 ± 4.7 kg.m−2). Kinematic, kinetic and electromyographic gait parameters were collected while participants walked through a 3D capture volume over a force plate with the lower limbs defined using retro-reflective markers. Ankle angle in swing, frontal plane motion in stance and force loading rates at initial contact were compared. Statistical analysis utilised ANOVA to compare differences between experimental conditions. Results The flip-flop footwear conditions altered gait parameters when compared to barefoot. Maximum ankle dorsiflexion in swing was greater in the flip-flop (7.6 ± 2.6°, p = 0.004) and FitFlop (8.5 ± 3.4°, p &lt; 0.001) than barefoot (6.7 ± 2.6°). Significantly higher tibialis anterior activation was measured in terminal swing in FitFlop (32.6%, p &lt; 0.001) and flip-flop (31.2%, p &lt; 0.001) compared to barefoot. A faster heel velocity toward the floor was evident in the FitFlop (−.326 ± .068 m.s−1, p &lt; 0.001) and flip-flop (−.342 ± .074 m.s−1, p &lt; 0.001) compared to barefoot (−.170 ± .065 m.s−1). The FitFlop reduced frontal plane ankle peak eversion during stance (−3.5 ± 2.2°) compared to walking in the flip-flop (−4.4 ± 1.9°, p = 0.008) and barefoot (−4.3 ± 2.1°, p = 0.032). The FitFlop more effectively attenuated impact compared to the flip-flop, reducing the maximal instantaneous loading rate by 19% (p &lt; 0.001). Conclusions Modifications to the sagittal plane ankle angle, frontal plane motion and characteristics of initial contact observed in barefoot walking occur in flip-flop footwear. The FitFlop may reduce risks traditionally associated with flip-flop footwear by reducing loading rate at heel strike and frontal plane motion at the ankle during stance

Investigation of correlates of protection against pharyngeal carriage of Neisseria meningitidis genogroups W and Y in the African meningitis belt

BACKGROUND: Serum bactericidal antibody titres that correlate with protection against invasive meningococcal disease have been characterised. However, titres that are associated with protection against acquisition of pharyngeal carriage of Neisseria meningitidis are not known. METHODS: Sera were obtained from the members of a household in seven countries of the African meningitis belt in which a pharyngeal carrier of N. meningitidis had been identified during a cross-sectional survey. Serum bactericidal antibody titres at baseline were compared between individuals in the household of the carrier who became a carrier of a meningococcus of the same genogroup during six months of subsequent follow-up and household members who did not become a carrier of a meningococcus of this genogroup during this period. RESULTS: Serum bacterial antibody titres were significantly higher in carriers of a serogroup W or Y meningococcus at the time of recruitment than in those who were not a carrier of N. meningitidis of the same genogroup. Serum bactericidal antibody titres to a strain of N. meningitis of the same genogroup as the index cases were no different in individuals who acquired carriage with a meningococcus of the same genogroup as the index case than in those who did not become a carrier during six months of follow-up. CONCLUSION: Serum bacterial antibody titres to N. meningitidis of genogroup W or Y in the range of those acquired by natural exposure to meningococci of these genogroups, or with cross-reactive bacteria, are not associated with protection against acquisition of carriage with meningococci of either of these genogroups.The MenAfriCar Consortium was supported by grants from the Wellcome Trust (086546) and the Bill & Melinda Gates Foundation (OPP51251)

Molecular Epidemiology of Neisseria meningitidis Serogroup B in Brazil

Background: Neisseria meningitidis serogroup B has been predominant in Brazil, but no broadly effective vaccine is available to prevent endemic meningococcal disease. To understand genetic diversity among serogroup B strains in Brazil, we selected a nationally representative sample of clinical disease isolates from 2004, and a temporally representative sample for the state of São Paulo (1988-2006) for study (n = 372). Methods: We performed multi-locus sequence typing (MLST) and sequence analysis of five outer membrane protein (OMP) genes, including novel vaccine targets fHbp and nadA. Results: In 2004, strain B:4:P1.15,19 clonal complex ST-32/ET-5 (cc32) predominated throughout Brazil; regional variation in MLST sequence type (ST), fetA, and porB was significant but diversity was limited for nadA and fHbp. Between 1988 and 1996, the São Paulo isolates shifted from clonal complex ST-41/44/Lineage 3 (cc41/44) to cc32. OMP variation was associated with but not predicted by cc or ST. Overall, fHbp variant 1/subfamily B was present in 80% of isolates and showed little diversity. The majority of nadA were similar to reference allele 1. Conclusions: A predominant serogroup B lineage has circulated in Brazil for over a decade with significant regional and temporal diversity in ST, fetA, and porB, but not in nadA and fHbp

The Effect of Human Factor H on Immunogenicity of Meningococcal Native Outer Membrane Vesicle Vaccines with Over-Expressed Factor H Binding Protein

The binding of human complement inhibitors to vaccine antigens in vivo could diminish their immunogenicity. A meningococcal ligand for the complement down-regulator, factor H (fH), is fH-binding protein (fHbp), which is specific for human fH. Vaccines containing recombinant fHbp or native outer membrane vesicles (NOMV) from mutant strains with over-expressed fHbp are in clinical development. In a previous study in transgenic mice, the presence of human fH impaired the immunogenicity of a recombinant fHbp vaccine. In the present study, we prepared two NOMV vaccines from mutant group B strains with over-expressed wild-type fHbp or an R41S mutant fHbp with no detectable fH binding. In wild-type mice in which mouse fH did not bind to fHbp in either vaccine, the NOMV vaccine with wild-type fHbp elicited 2-fold higher serum IgG anti-fHbp titers (P = 0.001) and 4-fold higher complement-mediated bactericidal titers against a PorA-heterologous strain than the NOMV with the mutant fHbp (P = 0.003). By adsorption, the bactericidal antibodies were shown to be directed at fHbp. In transgenic mice in which human fH bound to the wild-type fHbp but not to the R41S fHbp, the NOMV vaccine with the mutant fHbp elicited 5-fold higher serum IgG anti-fHbp titers (P = 0.002), and 19-fold higher bactericidal titers than the NOMV vaccine with wild-type fHbp (P = 0.001). Thus, in mice that differed only by the presence of human fH, the respective results with the two vaccines were opposite. The enhanced bactericidal activity elicited by the mutant fHbp vaccine in the presence of human fH far outweighed the loss of immunogenicity of the mutant protein in wild-type animals. Engineering fHbp not to bind to its cognate complement inhibitor, therefore, may increase vaccine immunogenicity in humans

PCR Improves Diagnostic Yield from Lung Aspiration in Malawian Children with Radiologically Confirmed Pneumonia

Accurate data on childhood pneumonia aetiology are essential especially from regions where mortality is high, in order to inform case-management guidelines and the potential of prevention strategies such as bacterial conjugate vaccines. Yield from blood culture is low, but lung aspirate culture provides a higher diagnostic yield. We aimed to determine if diagnostic yield could be increased further by polymerase chain reaction (PCR) detection of bacteria (Streptococcus pneumoniae and Haemophilus influenzae b) and viruses in lung aspirate fluid.A total of 95 children with radiological focal, lobar or segmental consolidation had lung aspirate performed and sent for bacterial culture and for PCR for detection of bacteria, viruses and Pneumocystis jirovecii. In children with a pneumococcal aetiology, pneumococcal bacterial loads were calculated in blood and lung aspirate fluid.Blood culture identified a bacterial pathogen in only 8 patients (8%). With the addition of PCR on lung aspirate samples, causative pathogens (bacterial, viral, pneumocystis) were identified singly or as co-infections in 59 children (62%). The commonest bacterial organism was S.pneumoniae (41%), followed by H. influenzae b (6%), and the commonest virus identified was adenovirus (16%), followed by human bocavirus (HBoV) (4%), either as single or co-infection.In a select group of African children, lung aspirate PCR significantly improves diagnostic yield. Our study confirms a major role of S.pneumoniae and viruses in the aetiology of childhood pneumonia in Africa