The experience of using prompting technology from the perspective of people with Dementia and their primary carers.

OBJECTIVES: People who are living with dementia typically experience difficulties in completing multi-step, everyday tasks. However, digital technology such as touchscreen tablets provide a means of delivering concise personalised prompts that combine audio, text and pictures. This study was one component of a broader, mixed methods study that tested how an application (app) -based prompter running on a touchscreen tablet computer could support everyday activities in individuals with mild to moderate dementia. In this study we set out to understand the experiences of people living with dementia and their primary carer in using the prompter over a four-week period. METHOD: We collected qualitative data using semi-structured interviews from 26 dyads, composed of a person living with dementia and their carer. Dyads were interviewed at the start and end of this period. Transcripts were then analysed using thematic analysis. RESULTS: The study identified three overarching themes related to: participants' attitudes towards the technology; their judgements about how useful the prompter would be; and the emotional impact of using it. CONCLUSION: Consistent with the Technology Acceptance Model, carers and participants were influenced by their approaches to technology and determined the usefulness of the prompter according to whether it worked for them and fitted into their routines. In addition, participants' decisions about using the prompter were also determined by the extent to which doing so would impact on their self-identity.

Subtalar coalition resection utilizing live navigation: a technique tip.

PURPOSE: Describe the surgical technique of talocalcaneal coalition resection using live CT navigation. METHODS: A ten-year-old female with left talocalcaneal coalition hindfoot pain refractory to conservative management underwent surgical coalition resection using live CT navigation. The procedure and discussion of this technique is described in detail. RESULTS: With minimal radiation exposure to the patient, CT navigation for this complex talocalcaneal coalition was both helpful and potentially timesaving by allowing immediate localization and guided resection of the coalition. CONCLUSION: In the case of a complex subtalar coalition resection, CT navigation poses minimal patient radiation exposure and allows immediate localization and guided resection of the coalition. LEVEL OF EVIDENCE: Level V.

Availability of global health opportunities in North American Paediatric Orthopaedic Fellowship Programmes.

PURPOSE: Orthopaedic residents are increasingly seeking international health electives (IHEs) during training, many of which involve providing paediatric orthopaedic care. However, little is known about the availability of IHEs during orthopaedic fellowship training. Our study sought to assess the global health opportunities available to North American paediatric orthopaedic fellows. METHODS: We conducted an online, REDCap-based survey of paediatric orthopaedic fellowship programme directors (PDs) in the United States and Canada. The survey link was sent by the Pediatric Orthopaedic Society of North America (POSNA) Evidence-Based Medicine Committee to all POSNA-approved paediatric orthopaedic fellowship PDs. Follow-up reminder emails were delivered at set time intervals. RESULTS: The overall response rate was 55% (26/47). Only three of 26 responding programmes (11.5%) offered a structured global health programme but 42.3% of programmes (11/26) reported fellow IHE participation within the last ten years. In all, 91% of PDs reported that fellows were extremely satisfied with their IHE, and 91% agreed that IHEs are valuable for trainees. Perceived barriers to fellow participation in IHEs included lack of funding, lack of established partner sites, lack of interest among fellows and concerns related to time away compromising clinical/call coverage. In all, 65.4% of PDs agree that IHE participation during training plays a major role in shaping fellows' future volunteer activities. CONCLUSION: There are limited global health opportunities among North American paediatric orthopaedic fellowship programmes, with only 11.5% offering a structured global health programme. Greater efforts to establish sustainable funding and international partnerships may increase opportunities for IHEs during paediatric orthopaedic fellowship training. LEVEL OF EVIDENCE: Level II.

Experience is more important than technology in paediatric post-tonsillectomy bleeding.

BACKGROUND: Paediatric tonsillectomy is a common procedure and one of the first skills acquired by surgical trainees. Post-tonsillectomy bleeding is one of the most significant complications. This study examined post-tonsillectomy bleed rates associated with technology and level of surgical experience. METHODS: Data were collected on all tonsillectomies performed by surgical consultants (n = 6) and trainees (n = 10) at affiliated hospitals over a nine-month period. Hospital records were audited for post-tonsillectomy bleeding re-admissions and returns to the operating theatre. RESULTS: A total of 1396 tonsillectomies were performed (279 by trainees, 1117 by consultant surgeons). Primary post-tonsillectomy bleed rates were equivalent between trainees and consultants. Secondary bleed rates were significantly greater for trainees (10.0 per cent) compared to consultants (3.3 per cent), as were return to operating theatre rates (2.5 per cent vs 0.7 per cent). Amongst consultants, technology used was not associated with differences in secondary post-tonsillectomy bleeding and returns to the operating theatre. CONCLUSION: Our data suggest that experience of the surgeon may have greater bearing on post-tonsillectomy bleed rates than the technology used.

Phase I/II trial of everolimus in combination with bortezomib and rituximab (RVR) in relapsed/refractory Waldenstrom macroglobulinemia.

We examined the combination of the mammalian target of rapamycin inhibitor everolimus with bortezomib and rituximab in patients with relapsed/refractory Waldenstrom macroglobulinemia (WM) in a phase I/II study. All patients received six cycles of the combination of everolimus/rituximab or everolimus/bortezomib/rituximab followed by maintenance with everolimus until progression. Forty-six patients were treated; 98% received prior rituximab and 57% received prior bortezomib. No dose-limiting toxicities were observed in the phase I. The most common treatment-related toxicities of all grades were fatigue (63%), anemia (54%), leucopenia (52%), neutropenia (48%) and diarrhea (43%). Thirty-six (78%) of the 46 patients received full dose therapy (FDT) of the three drugs. Of these 36, 2 (6%) had complete response (90% confidence interval (CI): 1-16). In all, 32/36 (89%) of patients experienced at least a minimal response (90% CI: 76-96%). The observed partial response or better response rate was 19/36 (53, 90 CI: 38-67%). For the 36 FDT patients, the median progression-free survival was 21 months (95% CI: 12-not estimable). In summary, this study demonstrates that the combination of everolimus, bortezomib and rituximab is well tolerated and achieved 89% response rate even in patients previously treated, making it a possible model of non-chemotherapeutic-based combination therapy in WM.

Evaluation of a 'Watch and Wait' Approach for Chemotherapy in Patients with Newly Diagnosed Advanced Non-small Cell Lung Cancer from a Diverse Community Population.

AIMS: Systemic therapy in advanced non-small cell lung cancer (NSCLC) is the standard of care. The time of treatment administration has not been examined in the metastatic setting. A 'watch and wait' approach for the initiation of chemotherapy is sometimes used in clinical practice, either because of patient preference, presumed indolent disease behaviour, upfront radiotherapy or other interventions. We propose to evaluate the effect of a watch and wait approach on systemic treatment deliverability and patients' outcomes in a population-based study. MATERIALS AND METHODS: A retrospective analysis of stage IIIB/IV NSCLC patients referred to medical oncology at the British Columbia Cancer Agency in 2009 was conducted. We defined the following: immediate chemotherapy (ICT) - chemotherapy ≤ 8 weeks from medical oncology consult; watch and wait chemotherapy (WWC) - initial observation with chemotherapy > 8 weeks from medical oncology consultation; watch and wait missed (WWM) - watch and wait patients who did not receive chemotherapy; best supportive care (BSC) - patients deemed chemotherapy ineligible. Statistical methods included Kaplan-Meier analysis, Log-rank tests and Cox proportional hazards modelling. RESULTS: In total, 744 patients were seen by medical oncology; 355 (48%) received ICT, 173 (23%) watch and wait and 216 (29%) BSC. Of the 173 patients on a watch and wait approach, 42% missed an opportunity for chemotherapy due to poor performance status (50%), death (49%) and comorbidity (1%). The median overall survival was as follows: watch and wait 11.5 months, ICT 12.8 months and BSC 4.3 months (P < 0.0001). Controlling for confounding factors (age, gender, performance status), overall survival was longer in WWC (hazard ratio 0.73, confidence interval 0.81-1.07, P = 0.023) and lower in WWM (hazard ratio 1.68, 95% confidence interval 1.27-2.22, P < 0.0001), compared with ICT. CONCLUSIONS: A significant proportion of watch and wait patients never receive systemic therapy, predominantly due to a decline in performance status. Patients in the ICT group were younger, had a better performance status and had non-squamous histology compared with the watch and wait group. The overall survival was longer in the patients who received ICT versus watch and wait. The watch and wait strategy is associated with a high risk of missing the opportunity for any chemotherapy and should be judiciously implemented only in carefully selected patients.

Clinical activity of abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after enzalutamide.

BACKGROUND: Abiraterone acetate and enzalutamide both improve outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). Optimal sequencing for these agents and whether cross-resistance occurs is unknown. METHODS: Multicentre review of patients with mCRPC treated with abiraterone acetate and prednisone after progressing on enzalutamide. Primary objective was to determine abiraterone acetate response. RESULTS: Thirty patients identified from four North American centres. At abiraterone initiation, median age was 70 years (56-84 years); 70% had ECOG performance status of 0-1; all had prior docetaxel. Median prior enzalutamide treatment duration was 41 weeks (6-95 weeks), with 70% (21 of 30) having a ≥30% prostate-specific antigen (PSA) decline. Median abiraterone acetate treatment duration was 13 weeks (1-52). No objective radiographic responses were observed. Median abiraterone time to progression (PSA, objective or symptomatic) was 15.4 weeks [95% confidence interval (CI) 10.7-20.2]. Median overall survival was 50.1 weeks (95% CI 28.3-72.0). Three patients had a ≥30% PSA decline with abiraterone. Two of these patients had PSA progression as best response with prior enzalutamide. CONCLUSIONS: In this study of patients progressing after enzalutamide, treatment with abiraterone was associated with a modest response rate and brief duration of effect. Primary progression on enzalutamide may not preclude a response to abiraterone.

Cytogenetic and array-CGH characterization of a complex de novo rearrangement involving duplication and deletion of 9p and clinical findings in a 4-month-old female.

Approximately 15 patients with partial trisomy 9p involving de novo duplications have been previously described. Here, we present clinical, cytogenetic, FISH and aCGH findings in a patient with a de novo complex rearrangement in the short arm of chromosome 9 involving an inverted duplication at 9p24-->p21.3 and a deletion at 9pter-->p24.2. FISH probes generated from BACs selected from the UCSC genome browser were utilized to verify this rearrangement. It is likely that some previously described duplications of 9p may also be products of complex chromosomal aberrations. This report in which FISH and aCGH were used to more comprehensively characterize the genomic rearrangement in a patient with clinical manifestations of 9p duplication syndrome underscores the importance of further characterizing cytogenetically detected rearrangements.

Vitamin D insufficiency is common in Indian mothers but is not associated with gestational diabetes or variation in newborn size.

BACKGROUND/OBJECTIVES: Vitamin D is required for bone growth and normal insulin secretion. Maternal hypovitaminosis D may impair fetal growth and increase the risk of gestational diabetes. We have related maternal vitamin D status in pregnancy to maternal and newborn glucose and insulin concentrations, and newborn size, in a South Indian population. SUBJECTS/METHODS: Serum 25 hydroxy vitamin D (25(OH)D) concentrations, glucose tolerance, and plasma insulin, proinsulin and 32-33 split proinsulin concentrations were measured at 30 weeks gestation in 559 women who delivered at the Holdsworth Memorial Hospital, Mysore. The babies' anthropometry and cord plasma glucose, insulin and insulin precursor concentrations were measured. RESULTS: In total 66% of women had hypovitaminosis D (25(OH)D concentrations <50 nmol l(-1)) and 31% were below 28 nmol l(-1). There was seasonal variation in 25(OH)D concentrations (P<0.0001). There was no association between maternal 25(OH)D and gestational diabetes (incidence 7% in women with and without hypovitaminosis D). Maternal 25(OH)D concentrations were unrelated to newborn anthropometry or cord plasma variables. In mothers with hypovitaminosis D, higher 25(OH)D concentrations were associated with lower 30-min glucose concentrations (P=0.03) and higher fasting proinsulin concentrations (P=0.04). CONCLUSIONS: Hypovitaminosis D at 30 weeks gestation is common in Mysore mothers. It is not associated with an increased risk of gestational diabetes, impaired fetal growth or altered neonatal cord plasma insulin secretory profile.

The coconut condyle: occipital condylar dysplasia causing torticollis and leading to c1 fracture.

In this report we discuss the case of a child who was initially diagnosed at 1 month of age with congenital muscular torticollis. After falling off a slide at 22 months of age, the patient had onset of pain and an abrupt worsening of his torticollis. After a full workup, it was found that the patient had a C1 fracture and a disproportionately large ipsilateral occipital "coconut" condyle. We believe this congenital anomaly to be the cause of his original head tilt and also predisposed him to C1 fracture and worsening head tilt.

Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders?

BACKGROUND: Vitamin-D deficiency and vitamin-D receptor genotype (VDR) are risk factors for several disorders with inflammatory components, including coronary heart disease (CHD) and diabetes, though the mechanisms involved are unclear. AIM: To examine the hypothesis that vitamin D status modulates the matrix metalloproteinase (MMP) system in a population with a high prevalence of vitamin D deficiency, a situation affecting susceptibility to CHD and diabetes. DESIGN: Prospective cross-sectional, interventional and embedded studies. METHODS: Circulating MMP2,9, the inhibitor TIMP-1 and C-reactive protein (CRP) were measured during studies of vitamin-D deficiency as a risk factor for type 2 diabetes and CHD in 171 healthy British Bangladeshi adults, free of known diabetes or major illness. Vitamin D status, VDR genotype, body-build, blood pressure, lipid and insulin profiles, glucose tolerance, fibrinogen, PAI-1, folate and homocysteine were measured. Vitamin-D-deficient subjects were re-assessed after 1 years' supplementation. MMP, TIMP-1 and CRP levels were measured in 41 subjects halfway through 5-year follow-up. Independent determinants of circulating concentrations of MMP9, TIMP-1 and CRP were assessed by multiple regression analysis. RESULTS: Vitamin D status was the sole determinant of circulating MMP9 (inversely) and an independent determinant of CRP (inversely). Determinants of TIMP-1 were MMP9, systolic blood-pressure (directly) and VDR genotype (TaqI). Significant reductions in MMP9 (-68%), TIMP-1 (-38%) and CRP (-23%) concentrations followed vitamin-D supplementation. DISCUSSION: Vitamin-D insufficiency is associated with increased circulating MMP2,9 and CRP, correctable by supplementation. This finding provides a possible mechanism for tissue damage in chronic inflammatory conditions, including CHD and diabetes.

Varus derotation osteotomy for the treatment of hip subluxation and dislocation in cerebral palsy: statistical analysis in 73 hips.

The purpose of this study is to review the results of varus osteotomy in patients with cerebral palsy and to determine factors that influence the rates of residual hip displacement. A retrospective chart review of 65 patients who underwent 79 varus osteotomies was performed. Preoperative, postoperative and follow-up radiographs were analyzed for routine radiographic measurements, pelvic obliquity, osteonecrosis (avascular necrosis), joint incongruity or degenerative joint disease. The average follow-up was 5.2 years (range, 1.1-18.4 years). At follow-up, 3 hips were dislocated, 19 were subluxated and 57 were stable (72%). Age at surgery and the degree of preoperative hip displacement had significant effects on outcome. The average age at surgery for initially subluxated hips, which were located at follow-up, was 7.2 years. This was significantly younger (P = 0.008) than initially subluxated hips, which were displaced (10 years of age). Subluxated hips at surgery were also more likely to be located at follow-up than dislocated hips.

Salvage reconstruction with vascularized fibular strut graft fusion using posterior approach in the treatment of severe spondylolisthesis.

STUDY DESIGN: One case is reported in which a failed anterior fusion for Grade 4 spondylolisthesis was treated with a vascularized fibular strut graft using a posterior approach. OBJECTIVES: To demonstrate the applicability of this technique for salvage cases or patients with systemic conditions that may decrease the success of more standard techniques. SUMMARY OF BACKGROUND DATA: Surgical stabilization of spondylolisthesis through posterior approach with a fibular strut graft has been previously described. A vascularized strut graft can be used in the treatment of spondylolisthesis and may have applicability in those patients with underlying disease that may impair the use of more standard techniques or in salvage reconstruction. METHODS: With the patient under general anesthesia, through a posterior approach S1 and L4 were decompressed. The fibula with its vascularity intact was harvested and anastomosed with the superior gluteal artery and vein. The fibular strut was placed into the space formed by reaming between L5 and S1. Ilial autograft was used to augment the posterior fusion. After the procedure the patient was placed in a hip spica cast. RESULTS: At the 2-year follow-up the patient has incorporation of the graft, with no evidence of fracture and no significant progression of anterior slip. CONCLUSION: A vascularized fibular strut graft is a feasible alternative in the treatment of severe spondylolisthesis. No complications were encountered in the involved patient. Future application may include salvage reconstruction of failed arthrodesis or in individuals with systemic conditions that may impair graft incorporation using more standard techniques.

The release of leptin and its effect on hormone release from human pituitary adenomas.

BACKGROUND: Leptin is the protein product of the obese gene, known to play an important role in body energy balance. The leptin receptor exists in numerous isoforms, the long isoform being the major form involved in signal transduction. Leptin expression has recently been demonstrated in the human pituitary, both in normal tissue and in pituitary adenomas. The long isoform of the leptin receptor has also been shown to be present in pituitary adenomas; however, contrasting results have been obtained regarding its expression in the normal human pituitary. AIM: The aim of this study was (i) to investigate the presence and pattern of distribution of leptin mRNA and the long isoform of its receptor mRNA in the normal pituitary and in different types of pituitary adenomas with RT-PCR; (ii) to study leptin secretion from human pituitary tumours in culture and (iii) to assess in vitro pituitary hormone release following stimulation with human leptin. RESULTS: Leptin receptor long isoform expression was detected in 2/4 GH-secreting adenomas, 12/17 non-functioning adenomas, 5/9 ACTH-secreting adenomas, 1/2 prolactinomas, 2/2 FSH-secreting adenomas and 5/5 normal pituitaries. The receptor long isoform did not segregate with any particular tumour type, and varying levels of expression were detected between the tissues studied. Leptin mRNA was detected at a low level of expression in 2/7 GH-secreting adenomas, 9/14 non-functioning adenomas, 2/3 ACTH-secreting adenomas, 1/3 prolactinomas and 1/3 FSH-secreting adenomas. We were unable to detect leptin mRNA in any of the five normal pituitaries removed at autopsy; however, immunostaining of a non-tumorous pituitary adjacent to an adenoma removed at transsphenoidal surgery showed scattered leptin positive cells. Culture of pituitary adenomas showed that 16/47 released leptin into the incubation media. Leptin release did not correlate with tumour type or with any of the other pituitary hormones released. In vitro leptin stimulation of pituitary tumours caused stimulation of FSH and alpha-subunit secretion from a non-functioning adenoma and TSH secretion from a somatotroph adenoma. CONCLUSION: We conclude that not only is leptin stored within the pituitary, but it may also be released from pituitary cells and modulate other pituitary hormone secretion. Pituitary leptin may therefore be a novel paracrine regulator of pituitary function.

Decontamination issues for chemical and biological warfare agents: how clean is clean enough?

The objective of this assessment is to determine what level of cleanup will be required to meet regulatory and stakeholder needs in the case of a chemical and/or biological incident at a civilian facility. A literature review for selected, potential chemical and biological warfare agents shows that dose information is often lacking or controversial. Environmental regulatory limits or other industrial health guidelines that could be used to help establish cleanup concentration levels for such agents are generally unavailable or not applicable for a public setting. Although dose information, cleanup criteria, and decontamination protocols all present challenges to effective planning, several decontamination approaches are available. Such approaches should be combined with risk-informed decision making to establish reasonable cleanup goals for protecting health, property, and resources. Key issues during a risk assessment are to determine exactly what constitutes a safety hazard and whether decontamination is necessary or not for a particular scenario. An important conclusion is that cleanup criteria are site dependent and stakeholder specific. The results of a modeling exercise for two outdoor scenarios are presented to reinforce this conclusion. Public perception of risk to health, public acceptance of recommendations based on scientific criteria, political support, time constraints, and economic concerns must all be addressed in the context of a specific scenario to yield effective and acceptable decontamination.

Results of femoral varus osteotomy in children older than 9 years of age with Perthes disease.

We review the results of varus osteotomy in 17 patients older than 9 years of age with 18 hips affected by Perthes disease. Seventeen hips were judged as Catterall 3 or 4, and 14 hips had partial or complete loss of the lateral pillar. At an average follow-up of 10 years (4.2-17.8 years), 3 hips were rated Stulberg 1, 3 were Stulberg 2, 4 were Stulberg 3, and 8 were Stulberg 4 or 5. At follow-up, 7 hips were considered good or fair based on the use of Mose circles. Statistical analysis indicated better results in patients younger than 10 years of age compared with those older than 10 years of age. Varus osteotomy as a method of containment for Perthes disease provides improved results in children older than 9 years compared with natural history studies or studies of noncontainment methods. However, it seems likely that there is an upper age limit for effectiveness of containment treatment.

Recurrent supracondylar humerus fracture following prior malunion.

In this report, two patients sustained a recurrent supracondylar humerus fracture following malunion of a previous supracondylar humerus fracture. The patients were treated for their first fracture at 5 and 6 years of age, respectively. One underwent open reduction with percutaneous pinning, and the other was treated with closed reduction with casting. Both patients healed in a moderate degree of extension after the first fracture. Two years later, both sustained a second fracture of the supracondylar humerus. Both had closed reduction with percutaneous pinning and went on to heal uneventfully. We speculate that ensuing post-traumatic extension deformity may accentuate a child's tendency for elbow hyperextension. Extension malunion may place the child at increased risk for a second fracture via similar mechanisms of injury.