An innovative method for clinical practice guideline contextualisation for chronic musculoskeletal pain in the South African context.

BACKGROUND: Clinical guidelines produced in developed nations may not be appropriate in resource-constrained environments, due to differences in cultural, societal, economic and policy contexts. The purpose of this article is to describe an innovative and resource-efficient method to develop a clinical practice guideline (CPG), using the CPG contextualisation approach. METHODS: The four phased contextualisation framework was applied to produce a contextualised, multidisciplinary CPG for the primary health care of adults with chronic musculoskeletal pain (CMSP) in the South African context. The four phases were: a contextual analysis, evidence synthesis, contextual integration and external evaluation. Qualitative methodology was used to investigate context factors influencing health care in this environment. A systematic review was conducted to identify current, high-quality CPGs on the topic, and to synthesise a core set of clinical recommendations from the CPGs. Consensus methods were used to integrate context information with recommendations. A multidisciplinary panel of local experts authenticated and contextualised recommendations. The resultant CPG was externally reviewed using a survey. RESULTS: The results from the contextual analysis phase indicated a wide range of contextual factors that could influence the applicability and implementability of the recommendations, including: the personal characteristics of the patient and clinician, social and environmental circumstances, healthcare interventions available, and healthcare system factors. During phase two, six existent high quality CPGs were identified and a core set of multidisciplinary recommendations were sourced from them. The contextual integration phase produced the validated recommendations, accompanied by its underpinning body of evidence and context specific information. The outcome of phase four (external review) was that the recommendations were confirmed as relevant for the intended setting. CONCLUSION: CPG contextualisation was found to be a practical approach to develop a contextualised multidisciplinary CPG for the primary health care of adults with CMSP in a South African setting. The contextualisation approach enhanced the integration of multiple stakeholder perspectives and highlighted the importance of considering clinical, social and economic complexities during CPG development. Attention to contextual information is advocated to enhance the uptake of CPG recommendations, particularly in resource constrained settings. TRIAL REGISTRATION: Health Research Ethics Committee of Stellenbosch University, South Africa (S14/01/018); the review protocol was registered on PROSPERO (registration number CRD42015022098 ).

Final Results of the Prospective FH02 Mammographic Surveillance Study of Women Aged 35-39 at Increased Familial Risk of Breast Cancer.

BACKGROUND: Many women who are at increased risk of breast cancer due to a mother or sister diagnosed with breast cancer aged under 40 do not currently qualify for surveillance before 40 years of age. There are almost no available data to assess whether mammography screening aged 35-39 years would be effective in this group, in terms of detection of breast cancer at an early stage or cost effective. METHODS: A cohort screening study (FH02) with annual mammography was devised for women aged 35-39 to assess the sensitivity and screening performance and potential survival of women with identified tumours. FINDINGS: 2899 women were recruited from 12/2006-12/2015. These women underwent 12,086 annual screening mammograms and were followed for 13,365.8 years. A total of 55 breast cancers in 54 women occurred during the study period (one bilateral) with 50 cancers (49 women) (15 CIS) adherent to the screening. Eighty percent (28/35) of invasive cancers were ≤ 2 cm and 80% also lymph node negative. Invasive cancers diagnosed in FH02 were significantly smaller than the comparable (POSH-unscreened prospective) study group (45% (131/293) ≤ 2 cm in POSH vs 80% (28/35) in FH02 p < 0.0001), and were less likely to be lymph-node positive (54% (158/290, 3 unknown) in POSH vs 20% (7/35) in FH02: p = 0.0002. Projected and actual survival were also better than POSH. Overall radiation dose was not higher than in an older screened population at mean dose on study per standard sized breast of 1.5 mGy. INTERPRETATION: Mammography screening aged 35-39 years detects breast cancer at an early stage and is likely to be as effective in reducing mortality as in women at increased breast cancer risk aged 40-49 years.

On the role of the second-order derivative term in the calculation of convergent beam diffraction patterns.

The simulation of (scanning) transmission electron microscopy images and diffraction patterns is most often performed using the forward-scattering approximation where the second-order derivative term in z is assumed to be small with respect to the first-order derivative term in the modified Schrödinger equation. This assumption is very good at high incident electron energies, but breaks down at low energies. In order to study the differences between first- and second-order methods, convergent beam electron diffraction patterns were simulated for silicon at the [111] zone-axis orientation at 20 keV and compared using electron intensity difference maps and integrated intensity profiles. The geometrical differences in the calculated diffraction patterns could be explained by an Ewald surface analysis. Furthermore, it was found that solutions based on the second-order derivative equation contained small amplitude oscillations that need to be resolved in order to ensure numerical integration stability. This required the use of very small integration steps resulting in significantly increased computation time compared to the first-order differential equation solution. Lastly, the efficiency of the numerical integration technique is discussed.

Low-dose dexamethasone as a treatment for women with heavy menstrual bleeding: protocol for response-adaptive randomised placebo-controlled dose-finding parallel group trial (DexFEM).

INTRODUCTION: Heavy menstrual bleeding (HMB) diminishes individual quality-of-life and poses substantial societal burden. In HMB endometrium, inactivation of cortisol (by enzyme 11ß hydroxysteroid dehydrogenase type 2 (11ßHSD2)), may cause local endometrial glucocorticoid deficiency and hence increased angiogenesis and impaired vasoconstriction. We propose that 'rescue' of luteal phase endometrial glucocorticoid deficiency could reduce menstrual bleeding. METHODS AND ANALYSIS: DexFEM is a double-blind response-adaptive parallel-group placebo-controlled trial in women with HMB (108 to be randomised), with active treatment the potent oral synthetic glucocorticoid dexamethasone, which is relatively resistant to 11ßHSD2 inactivation. Participants will be aged over 18 years, with mean measured menstrual blood loss (MBL) for two screening cycles ≥50 mL. The primary outcome is reduction in MBL from screening. Secondary end points are questionnaire assessments of treatment effect and acceptability. Treatment will be for 5 days in the mid-luteal phases of three treatment menstrual cycles. Six doses of low-dose dexamethasone (ranging from 0.2 to 0.9 mg twice daily) will be compared with placebo, to ascertain optimal dose, and whether this has advantage over placebo. Statistical efficiency is maximised by allowing randomisation probabilities to 'adapt' at five points during enrolment phase, based on the response data available so far, to favour doses expected to provide greatest additional information on the dose-response. Bayesian Normal Dynamic Linear Modelling, with baseline MBL included as covariate, will determine optimal dose (re reduction in MBL). Secondary end points will be analysed using generalised dynamic linear models. For each dose for all end points, a 95% credible interval will be calculated for effect versus placebo. ETHICS AND DISSEMINATION: Dexamethasone is widely used and hence well-characterised safety-wise. Ethical approval has been obtained from Scotland A Research Ethics Committee (12/SS/0147). Trial findings will be disseminated via open-access peer-reviewed publications, conferences, clinical networks, public lectures, and our websites. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01769820; EudractCT 2012-003405-98.

A comparison of body composition measurement techniques.

BACKGROUND: An understanding of the reproducibility of body composition measurements is essential for effective intervention studies. Air displacement plethysmography (ADP) and bioelectrical impedance (BIA) are two easy-to-use measures of body composition. The present study aimed to assess the reproducibility of ADP and BIA and compare them with each other, as well as with skinfold measurement. METHODS: Forty-one participants were tested on two occasions following an overnight fast. On test day 1, participants' height, weight and % body fat (BF) were measured using ADP and BIA. Measurements were replicated to assess the within-day reproducibility. On test day 2, participants were again tested using ADP and BIA and had skinfold measurements taken. Three skinfold equations for BF calculation were applied. Comparisons of within- and between-day reproducibility and between measurement techniques were completed using Pearson correlations and Bland-Altman analysis. RESULTS: Both Pearson correlation and Bland-Altman analysis showed good within- and between-day relationships and agreement for BF from ADP and BIA measurements. The two methods had a high correlation between them; however, the mean difference between the two was 3.1% (4.1%). From the skinfold equations used, the best agreement with ADP had a mean difference of 0.3% (0.8%) and, with BIA, had mean differences of 1.9% (4.2%). CONCLUSIONS: The data indicate that ADP and BIA cannot be used interchangeably, although both measurements had good within- and between-day agreement.

An investigation of cellular dynamics during the development of intramembranous bones: the scleral ossicles.

The development of intramembranous bone is a dynamic and complex process requiring highly coordinated cellular activities. Although the literature describes the detailed cellular dynamics of early mesoderm-derived endochondral bone, studies regarding neural crest-derived intramembranous bone have failed to keep pace. We analyzed the development of chick scleral ossicles from the onset of osteoid deposition to mineralization at morphological, histological, and ultrastructural levels. We find that the mesenchymal condensations from which ossicles develop change their shape from ellipsoidal to trapezoidal concurrent with an increase in size. Furthermore, the size of an ossicle is dependent upon its time of induction. Our histological analyses of condensation growth reveal cell migration and osteoid secretion as key cellular processes determining condensation size; these processes occur concomitantly to increase both the area and thickness of condensations. We also describe the formation of the zone of overlap between ossicles and conclude that the process is similar to that of cranial suture formation. Finally, transmission electron microscopy of early condensations demonstrates that early osteoblasts secrete collagen parallel to the long axis of the condensation. This study elucidates fundamental mechanisms of intramembranous bone development at the cellular level, furthering our knowledge of this important process among vertebrates.

Downward migration of radiocaesium in organic soils across a transect in Scotland.

Following the accident at the Chernobyl nuclear power plant in 1986, radioactive materials including (137)Cs were distributed over large parts of the former Soviet Union and Europe. Due to the relatively long physical half-life of (137)Cs (30.1 y) measurable activity concentrations can still be observed in the natural environment. We have determined the depth distribution of (137)Cs from the testing of nuclear weapons in the atmosphere and Chernobyl, in eight highly-organic soils along an approximately east to west transect across the Central Highlands of Scotland. The (137)Cs activity concentrations in the soil profiles, corrected for radioactive decay to May 1986, were between 2.8 and 14.4 kBq m(-2). There were differences in the pattern of distribution of (137)Cs in the soil profiles. The mean migration depth of (137)Cs in the soil profiles was 12.2 cm with a range between 8.2 and 17.4 cm. Quantitative mineralogical analysis of the ash obtained after heating the soil to 400 °C indicated that clay minerals alone did not have a prime role in controlling the migration of (137)Cs down the profile.

A psychophysiological comparison of on-sight lead and top rope ascents in advanced rock climbers.

Research suggests that lead climbing is both physiologically and psychologically more stressful than top rope climbing for intermediate performers. This observation may not be true for advanced climbers, who train regularly on lead routes and are accustomed to leader falls. The aim of this study was to compare the psychophysiological stresses of lead and top rope on-sight ascents in advanced rock climbers. Twenty-one climbers (18 men and three women) ascended routes near or at the best of their ability (22 Ewbank). Psychological stress was measured preclimb using the Revised Comparative State Anxiety Inventory (CSAI-2R). Plasma cortisol was sampled at six intervals. The volume of oxygen (VO2 ) and heart rate (Hr) were measured throughout the climbs. No significant differences were found in self-confidence, somatic, or cognitive anxiety between the conditions lead and top rope. No significant differences in plasma cortisol concentration were found between any time points. No significant relationships were found between cortisol and any CSAI-2R measures. No significant differences were found between conditions for VO2 or blood lactate concentration. During the lead climb, Hr was significantly elevated during the last part of the route. Findings suggest that advanced rock climbers do not find lead climbing to be more stressful than top rope climbing during an on-sight ascent.

Capillary cortisol sampling during high-intensity exercise.

Venepuncture is the established "gold standard" for sampling cortisol, but it is expensive, highly invasive and impractical for many experimental and clinical settings. Salivary free cortisol is a non-invasive and practical alternative; however, when cortisol concentrations exceed 500 nmol · L there is a lack of agreement between salivary (free) and venous (bound) cortisol. No known research has assessed whether capillary cortisol accurately reflects venous blood cortisol across a range of concentrations. The objective of the current study was to determine the agreement between capillary and venous blood samples of total plasma cortisol across a range of concentrations. 11 healthy male subjects (26.1 ± 5.3 years) were recruited. Capillary and venous blood samples were collected pre and post (immediately post and post 5, 10, 15 and 20 min) a treadmill VO2max test. Regression analysis revealed a strong relationship (R2=0.96, y=1.0028x + 1.2964 (P<0.05)) between capillary and venous cortisol concentrations. A Bland-Altman plot showed all data was within the upper and lower bounds of the 95% confidence interval, and no systematic bias was evident. In conclusion, capillary sampling is a valid technique for measuring bound cortisol across a range of concentrations.

The timing and achievement of mobility skills during SCI rehabilitation.

STUDY DESIGN: Retrospective, observational study, with consecutive sampling. OBJECTIVES: To document the frequency and time frames for the achievement of independence in mobility skills for people undergoing rehabilitation following spinal cord injury (SCI). SETTING: The South Australian Spinal Cord Injury Service, Hampstead Rehabilitation Centre, Adelaide, Australia. METHODS: Retrospective data collection from a purpose-designed form. The achievement of independence in nine functional mobility skills, and time lines for this, were documented for people with a new SCI undergoing rehabilitation. Data from 152 participants were analyzed. RESULTS: Of the nine mobility-based goals evaluated, the one most likely to be achieved was sitting on the edge of the bed and the least likely was gait. Time taken to achieve the skills varied from 4 to 10 weeks on average and reflected the degree of difficulty. CONCLUSION: The frequency and time frames to achieve independence in mobility skills documented in this study will be useful when goal setting in a post-acute SCI rehabilitation setting.

Effectiveness of once-weekly gym-based exercise programmes for older adults post discharge from day rehabilitation: a randomised controlled trial.

OBJECTIVE: To determine whether high-intensity, progressive gym-based exercise performed once a week is as effective as twice weekly for maintaining both subjective and objective outcomes in older adults post discharge from a metropolitan day rehabilitation centre (DRC). DESIGN: Randomised controlled trial. SETTING: Community-based exercise centre for older adults, located in Metropolitan Adelaide, South Australia. PARTICIPANTS: 21 men and 85 women who completed the DRC programme were assessed and randomly allocated to a study group. INTERVENTION: The two experimental interventions were gym-based exercise programmes (including resistance, aerobic, flexibility and balance training) varying only in frequency of delivery: either once or twice a week, directly compared with usual care (control). MAIN OUTCOME MEASURES: Lower limb strength (one-repetition maximum), balance (Berg Balance Scale), physical function (gait speed, 30-s chair stand test, timed up and go test (primary outcome) and 6-min walk test), self-reported pain (Glasgow Pain Questionnaire), activities of daily living (Barthel Index and Older Americans Resources and Services Multidimensional Functional Assessment Questionnaire), perceived benefits of and barriers to exercise (Exercise Benefits Barriers Scale), quality of life (Assessment of Quality of Life Questionnaire) and exercise frequency preference. RESULTS: Most of the outcomes (69%, 11/16) were maintained over the intervention period with no significant group effects detected between the two intervention groups or compared to the control group. Physical activity levels recorded in the control group showed a significant proportion of participants were actively exercising once weekly. A per-protocol analysis was undertaken to take this potential contamination effect into account. This showed that the control group participants, who did not exercise, did not maintain outcomes to the extent of the intervention groups, with significant group-by-time effects detected between the two intervention groups and the control group. Most of all participants (66%, 62/94) nominated once a week as their preferred exercise frequency. CONCLUSIONS: The overall finding of no significant differences between the two intervention groups for all outcomes measured gives support to the effectiveness of once-a-week exercise in maintaining outcomes at 3 months post rehabilitation. Further research is warranted given the once-a-week exercise intervention should cost less, had higher compliance and was nominated as the preferred exercise frequency by most of the participants.

Lack of impact of semen quality on fertilization in assisted conception.

BACKGROUND: Defective semen quality is one of the commonest causes of infertility. The diagnosis of male fertility depends upon a descriptive evaluation of human semen, however a normal semen analysis does not necessarily indicate satisfactory fertility potential. AIMS: (i) to examine the semen quality of patients undergoing treatment by assisted conception, (ii) to explore relationships between semen quality and treatment outcomes, and (iii) to look at inter-laboratory variation in the assessment of semen quality. METHODS: Semen quality in patients undergoing assisted conception treatment between 2001 and 2004 was reviewed. Data on female age, egg numbers and fertilization outcomes was obtained by case note review. RESULTS: The thresholds used to direct patients towards IVF or ICSI treatment were comparable with the normal values promulgated by WHO, with the exception of morphology. Semen quality was not predictive of fertilization rates. When the results of independent measurements of the same sample were compared, there was diagnostic disagreement in between 10%-29% of samples. CONCLUSIONS: The conventional criteria of semen quality are used to determine treatment strategy for couples undergoing assisted conception but are not reflected in fertilization rates, emphasising the limited utility of the conventional criteria of semen quality in the assessment of sperm function. There remains significant inter-laboratory variation in the results of semen analysis.

A systematic review of collaborative models for health and education professionals working in school settings and implications for training.

CONTEXT: Collaborative engagement between education and health agencies has become requisite since the establishment of school inclusion policies in many developed countries. For the child with healthcare needs in an educational setting, such collaboration is assumed to be necessary to ensure a coordinated and holistic approach. However, it is less clear how this is best achieved. OBJECTIVES: This secondary research aimed to answer the questions: what are the reported models of best practice to support the collaboration between education and health staff and what are the implications for training strategies at an undergraduate and postgraduate level to affect these models? METHODS: Systematic review of current literature, with narrative summary. FINDINGS: Models of interaction and teamwork are well-described, but not necessarily well-evaluated, in the intersection between schools and health agencies. They include a spectrum from consultative to collaborative and interactive teaming. It is suggested that professionals may not be adequately skilled in, or knowledgeable about, teamwork processes or the unique roles each group can play in collaborations around the health needs of school children. DISCUSSION AND CONCLUSION: There is a need for robust primary research into the questions identified in this paper, as well as a need for educators and health professionals to receive training in interprofessional teamwork and collaboration beyond their traditional domains. It is suggested such training needs to occur at both the undergraduate and postgraduate levels.

Multi-segment trunk kinematics during a loaded lifting task for elderly and young subjects.

The trunk is frequently modelled as one fixed segment ignoring possible multi-segmental contributions during manual handling. This study compared segmental trunk motion in a young and older population during a lifting task. Twelve elderly and 19 young subjects repeatedly lifted a 5 kg box from bench to shelf under two stance conditions. Displacement and angular trunk segment kinematics were recorded with an electromagnetic tracker system and then analysed. The elderly subjects displayed significantly increased pelvic and trunk displacement and significantly reduced pelvic and lower thorax (T10-L1) range of motion in both stance conditions. Upper thorax (C7-T10) motion was at times greater than lumbar motion and opposite to the lower segments and was related to the task while the lower segments contributed to both equilibrium and task requirements. Decreased segmental trunk angular kinematics may contribute to increased displacement kinematics and place the elderly at increased risk of injury and falling. The pelvis, lumbar spine, low thorax (T10-L1), upper thorax (C7-10) contributed uniquely and synchronously to trunk (C7-S2) mechanics during a lifting task. Reduced angular kinematics of the pelvis and low thorax contributed to increased displacement kinematics and hence increased the risk of falling in the elderly compared to the young. Investigations of trunk mechanics should include multi-segment analysis.

A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer.

Prostate specific membrane antigen (PSMA) is a validated molecular marker for prostate cancer. A series of glutamate-urea (Glu-urea-X) heterodimeric inhibitors of PSMA were designed and synthesized where X = epsilon-N-(o-I, m-I, p-I, p-Br, o-Cl, m-Cl, p-Cl, p-F, H)-benzyl-Lys and epsilon-(p-I, p-Br, p-Cl, p-F, H)-phenylureido-Lys. The affinities for PSMA were determined by screening in a competitive binding assay. PSMA binding of the benzyllysine series was significantly affected by the nature of the halogen substituent (IC(50) values, Cl < I = Br << F = H) and the ring position of the halogen atom (IC(50) values, p-I < o-I << m-I). The halogen atom had little affect on the binding affinity in the para substituted phenylureido-Lys series. Two lead iodine compounds were radiolabeled with (123)I and (131)I and demonstrated specific PSMA binding on human prostate cancer cells, warranting evaluation as radioligands for the detection, staging, and monitoring of prostate cancer.

Evidence for the retraining of sensation after stroke: a systematic review.

OBJECTIVE: Retraining of sensory function following stroke is frequently overlooked in rehabilitation protocols despite more than 60% of patients presenting with sensory deficits. Methods to train sensory function include both passive and active training protocols. Here we examined the volume and quality of the evidence available for both passive and active sensory training following stroke. In addition, we aimed to quantify the effect of sensory training on impairment and function. DATA SOURCES: Databases searched included MEDLINE, AMED, CINAHL, Academic search elite, Scopus and the Cochrane library. Unpublished articles were identified using a search engine. REVIEW METHODS: Studies utilizing passive or active sensory training paradigms post stroke were identified. Methodological quality was examined using the National Health and Medical Research Council hierarchy of evidence and the McMaster University critical appraisal tool. RESULTS: Fourteen studies met the inclusion criteria; 8 examined passive and 6 active sensory training. Methodological quality scores ranged from 11 to 18.5 (maximum 20). Meta-analysis was performed using three studies examining hand function, demonstrating a moderate effect in favour of passive sensory training. Other studies were unable to be pooled due to heterogeneity of measures or insufficient data. CONCLUSION: Meta-analyses and single studies offer some support for the effectiveness of passive sensory training in relation to sensory impairment and motor function. However, empirical evidence for active sensory training is limited. Further high-quality studies with greater statistical power and meaningful clinical measures are required in order to accurately determine the effectiveness of sensory retraining following stroke.

Stepwise effects of the BCR sequential chemical extraction procedure on dissolution and metal release from common ferromagnesian clay minerals: a combined solution chemistry and X-ray powder diffraction study.

Sequential extraction procedures (SEPs) are commonly used to determine speciation of trace metals in soils and sediments. However, the non-selectivity of reagents for targeted phases has remained a lingering concern. Furthermore, potentially reactive phases such as phyllosilicate clay minerals often contain trace metals in structural sites, and their reactivity has not been quantified. Accordingly, the objective of this study is to analyze the behavior of trace metal-bearing clay minerals exposed to the revised BCR 3-step plus aqua regia SEP. Mineral quantification based on stoichiometric analysis and quantitative powder X-ray diffraction (XRD) documents progressive dissolution of chlorite (CCa-2 ripidolite) and two varieties of smectite (SapCa-2 saponite and SWa-1 nontronite) during steps 1-3 of the BCR procedure. In total, 8 (+/-1) % of ripidolite, 19 (+/-1) % of saponite, and 19 (+/-3) % of nontronite (% mineral mass) dissolved during extractions assumed by many researchers to release trace metals from exchange sites, carbonates, hydroxides, sulfides and organic matter. For all three reference clays, release of Ni into solution is correlated with clay dissolution. Hydrolysis of relatively weak Mg-O bonds (362 kJ/mol) during all stages, reduction of Fe(III) during hydroxylamine hydrochloride extraction and oxidation of Fe(II) during hydrogen peroxide extraction are the main reasons for clay mineral dissolution. These findings underscore the need for precise mineral quantification when using SEPs to understand the origin/partitioning of trace metals with solid phases.