Low-intensity pulsed ultrasound does not influence bone healing by distraction osteogenesis: a multicentre double-blind randomised control trial.

AIMS: The aim of this double-blind prospective randomised controlled trial was to assess whether low intensity pulsed ultrasound (LIPUS) accelerated or enhanced the rate of bone healing in adult patients undergoing distraction osteogenesis. PATIENTS AND METHODS: A total of 62 adult patients undergoing limb lengthening or bone transport by distraction osteogenesis were randomised to treatment with either an active (n = 32) or a placebo (n = 30) ultrasound device. A standardised corticotomy was performed in the proximal tibial metaphysis and a circular Ilizarov frame was used in all patients. The rate of distraction was also standardised. The primary outcome measure was the time to removal of the frame after adjusting for the length of distraction in days/cm for both the per protocol (PP) and the intention-to-treat (ITT) groups. The assessor was blinded to the form of treatment. A secondary outcome was to identify covariates affecting the time to removal of the frame. RESULTS: There was no difference in the time to removal of the frame between the PP (difference in favour of the control group was 10.1 days/cm, 95% confidence interval (CI) -3.2 to 23.4, p = 0.054) or ITT (difference 5.0 days/cm, 95% CI -8.2 to 18.21, p = 0.226) groups. The smoking status was the only covariate which increased the time to removal of the frame (hazard ratio 0.47, 95% CI 0.22 to 0.97, p = 0.042). CONCLUSION: LIPUS does not influence the rate of bone healing in patients who undergo distraction osteogenesis. Smoking may influence bone healing. Cite this article: Bone Joint J 2017;99-B:494-502.

The multifactorial aetiology of fracture nonunion and the importance of searching for latent infection.

OBJECTIVES: A successful outcome following treatment of nonunion requires the correct identification of all of the underlying cause(s) and addressing them appropriately. The aim of this study was to assess the distribution and frequency of causative factors in a consecutive cohort of nonunion patients in order to optimise the management strategy for individual patients presenting with nonunion. METHODS: Causes of the nonunion were divided into four categories: mechanical; infection; dead bone with a gap; and host. Prospective and retrospective data of 100 consecutive patients who had undergone surgery for long bone fracture nonunion were analysed. RESULTS: A total of 31% of patients had a single attributable cause, 55% had two causes, 14% had three causes and 1% had all four. Of those (31%) with only a single attributable cause, half were due to a mechanical factor and a quarter had dead bone with a gap. Mechanical causation was found in 59% of all patients, dead bone and a gap was present in 47%, host factors in 43% and infection was a causative factor in 38% of patients.In all, three of 58 patients (5%) thought to be aseptic and two of nine (22%) suspected of possible infection were found to be infected. A total of 100% of previously treated patients no longer considered to have ongoing infection, had multiple positive microbiology results. CONCLUSION: Two thirds of patients had multiple contributing factors for their nonunion and 5% had entirely unexpected infection. This study highlights the importance of identifying all of the aetiological factors and routinely testing tissue for infection in treating nonunion. It raises key points regarding the inadequacy of a purely radiographic nonunion classification system and the variety of different definitions for atrophic nonunion in the current mainstream classifications used for nonunion.Cite this article: L. Mills, J. Tsang, G. Hopper, G. Keenan, A. H. R. W. Simpson. The multifactorial aetiology of fracture nonunion and the importance of searching for latent infection. Bone Joint Res 2016;5:512-519. DOI: 10.1302/2046-3758.510.BJR-2016-0138.

Standard methods based on last menstrual period dates misclassify and overestimate US preterm births.

OBJECTIVE: To compare number of US preterm births based on obstetric versus last menstrual period (LMP) estimates and evaluate their correlations with clinical risk indicators associated with prematurity. STUDY DESIGN: Preterm births were assessed from LMP, per standard practice, and, separately, from obstetric estimates using the 2012 Natality Public Use File. Percentages of infants with neonatal intensive care unit (NICU) admission and low birth weight (LBW) were calculated. RESULT: More births were <37 weeks gestational age (GA) by reported LMP (11.4%) versus obstetric estimates (9.5%). Among infants preterm by LMP, but born at 37-41 weeks by obstetric estimates, there were 5.7% NICU admission and 7.7% LBW rates versus 25.2% and 35.4%, respectively, of those preterm by obstetric estimates but born 37-41 weeks by LMP assessments. CONCLUSION: Obstetric estimates provide the most clinically relevant estimates of US preterm births. Assessments calculated from LMP alone may overestimate prematurity incidence by ~20%.

Femoral lengthening with the Intramedullary Skeletal Kinetic Distractor.

Femoral lengthening using the Intramedullary Skeletal Kinetic Distractor is a new technique. However, with intramedullary distraction the surgeon has less control over the lengthening process. Therefore, 33 femora lengthened with this device were assessed to evaluate the effect of operative variables under the surgeon's control on the course of lengthening. The desired lengthening was achieved in 32 of 33 limbs. Problems encountered included difficulty in achieving length in eight femora (24%) and uncontrolled lengthening in seven (21%). Uncontrolled lengthening was more likely if the osteotomy was placed with less than 80 mm of the thick portion of the nail in the distal fragment (p = 0.052), and a failure to lengthen was more likely if there was over 125 mm in the distal fragment (p = 0.008). The latter problem was reduced with over-reaming by 2.5 mm to 3 mm. Previous intramedullary nailing also predisposed to uncontrolled lengthening (p = 0.042), and these patients required less reaming. Using the Intramedullary Skeletal Kinetic Distractor, good outcomes were obtained; problems were minimised by optimising the position of the osteotomy and the amount of over-reaming performed.

Necrotising myositis: a surgical emergency that may have minimal changes in the skin.

Necrotising myositis is a surgical emergency. It is underappreciated that it may present without changes in the skin. Diagnosis is therefore often delayed. We describe a case of necrotising myositis necessitating glenohumeral disarticulation. Remarkable features were the absence of skin signs and the rapidity with which the patient became extremely septic. A review of the literature has shown the importance of early diagnosis and quick decision making to minimise mortality.

The Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT): results of radiographic analyses after 1 year.

OBJECTIVE: Infliximab is effective in improving signs and symptoms of joint/skin involvement, functional status, and quality of life in patients with psoriatic arthritis (PsA). Using IMPACT trial data, we assessed the effect of infliximab (IFX) on structural damage in PsA. METHODS: Patients with active PsA were randomly assigned to receive placebo (PBO/IFX) or infliximab 5 mg/kg (IFX/IFX) at weeks 0, 2, 6, and 14, with the primary endpoint at week 16. The PBO group received infliximab loading doses at weeks 16, 18, and 22. Thereafter, all patients received infliximab 5 mg/kg every 8 weeks through week 50. Hand/feet radiographs were obtained at weeks 0 and 50. Total radiographic scores were determined using the PsA modified van der Heijde-Sharp (vdH-S) score. Projected annual rate of progression was calculated by dividing x ray score by disease duration (years). RESULTS: As reported previously, 65% of infliximab treated patients versus 10% of PBO treated patients achieved an ACR20 response at week 16 (p<0.001). At week 50, 69% of patients achieved an ACR20 response. Radiographs (baseline and week 50) were available for 72/104 patients. At baseline, estimated mean annual rate of progression was 5.8 modified vdH-S points/year. Mean (median) changes from baseline to week 50 in the total modified vdH-S score were -1.95 (-0.50) for PBO/IFX and -1.52 (-0.50) for IFX/IFX patients (p = NS). At week 50, 85% and 84% of patients in the PBO/IFX and IFX/IFX groups had no worsening in the total modified vdH-S score. CONCLUSION: Infliximab inhibits radiographic progression in patients with PsA through week 50.

Methotrexate dosage reduction in patients with rheumatoid arthritis beginning therapy with infliximab: the Infliximab Rheumatoid Arthritis Methotrexate Tapering (iRAMT) trial.

OBJECTIVE: Infliximab plus methotrexate (MTX) is approved for the treatment of rheumatoid arthritis (RA). Based on the benefit/risk profile of this combination therapy, lower doses of MTX would be preferable when infliximab efficacy can be maintained. We evaluated the ability of patients receiving infliximab plus MTX to achieve and maintain a clinical response while the dose of MTX was tapered. METHODS: Infliximab infusions were administered at a minimum dosage of 3 mg/kg at 8-week intervals (following three loading doses at weeks 0, 2, and 6) to patients who had an inadequate response to MTX. MTX tapering was initiated at week 22 or later when at least a 40% improvement in the combined tender and swollen joint count was achieved; dosages were reduced by 5 mg every 8 weeks to a protocol-specified minimum dosage of 5 mg per week. If the required dosage of MTX after a flare was greater than the baseline dosage, the patient was considered a treatment failure. RESULTS: Of the 210 patients enrolled, 159 (76%) achieved a 40% or better improvement in the combined tender and swollen joint count and had their MTX doses tapered. In these 159 responders, the median (mean) dose of MTX was reduced from 15 (16.5) mg per week at baseline to 5 (7.1) mg per week at week 54. From the time of initial response, 79% of these patients had a zero- or a one-vial increase in infliximab, corresponding to an approximate dose increase of 1 mg/kg, through week 54. CONCLUSION: Approximately 75% of the patients participating in this trial achieved at least a 40% reduction in the combined swollen and tender joint count (correlating with an American College of Rheumatology 20% [ACR20] response in 83% of patients) while reducing the mean MTX dose by 57%.

Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate.

OBJECTIVE: To evaluate the efficacy and safety of repeated administration of infliximab plus methotrexate (MTX) over a 2-year period in patients with rheumatoid arthritis (RA) who previously experienced an incomplete response to MTX. METHODS: Four hundred twenty-eight patients were randomly assigned to receive MTX plus placebo or infliximab at a dose of 3 or 10 mg/kg plus MTX for 54 weeks, with an additional year of followup. The protocol was later amended to allow for continued treatment during the second year. Of 259 patients who entered the second year of treatment, 216 continued to receive infliximab plus MTX for 102 weeks. Ninety-four of these 259 patients experienced a gap in therapy of >8 weeks before continuing therapy. Infusions were administered at weeks 0, 2, and 6, followed by treatment every 4 weeks or every 8 weeks (alternating with placebo infusions in the interim 4-week visits) at a dose of 3 or 10 mg/kg for a total of 102 weeks (including the gap in therapy). For safety and efficacy assessments, data on the patients who were randomized to receive treatment, irrespective of whether treatment was administered for 102 weeks, were evaluated using all actual observations available. The efficacy measures included the Health Assessment Questionnaire (HAQ) (physical function), Short Form 36 health survey (SF-36) (health-related quality of life), total radiographic scores (structural damage), and the American College of Rheumatology 20% improvement criteria (ACR20) (signs and symptoms). RESULTS: The infliximab plus MTX regimens resulted in significantly greater improvement in HAQ scores (P < or = 0.006) and SF-36 physical component summary scores (P < or = 0.011) compared with the MTX-only group. There also was stability in the SF-36 mental component summary score among patients who received the infliximab plus MTX regimens. Median changes from baseline to week 102 in the total radiographic score were 4.25 for patients who received the MTX-only regimen and 0.50 for patients who received the infliximab plus MTX regimen. The proportion of patients achieving an ACR20 response at week 102 varied from 40% to 48% for the infliximab plus MTX groups compared with 16% for the MTX-only group. CONCLUSION: Throughout 102 weeks of therapy, infliximab plus MTX provided significant, clinically relevant improvement in physical function and quality of life, accompanied by inhibition of progressive joint damage and sustained improvement in the signs and symptoms of RA among patients who previously had an incomplete response to MTX alone.

Sleep and periodic limb movement in sleep in juvenile fibromyalgia.

OBJECTIVES: Fibromyalgia has been recently recognized in children and adolescents as juvenile fibromyalgia (JF). In adult fibromyalgia, subjective complaints of nonrestorative sleep and fatigue are supported by altered polysomnographic findings including a primary sleep disorder known as periodic limb movements in sleep (PLMS) in some subjects. Although poor sleep is a diagnostic criterion for JF, few reports in the literature have evaluated specific sleep disturbances. Our objectives were to evaluate in a controlled study the polysomnographic findings of children and adolescents with JF for alterations in sleep architecture as well as possible PLMS not previously noted in this age group. METHODS: Sixteen consecutive children and adolescents (15.0 +/- 2.6 years of age) diagnosed with JF underwent overnight polysomnography. Polysomnography was also performed on 14 controls (14.0 +/- 2.2 years of age) with no history of an underlying medical condition that could impact on sleep architecture. Respiratory variables, sleep stages, and limb movements were measured during sleep in all subjects. RESULTS: JF subjects differed significantly from controls in sleep architecture. JF subjects presented with prolonged sleep latency, shortened total sleep time, decreased sleep efficiency, and increased wakefulness during sleep. In addition, JF subjects exhibited excessive movement activity during sleep. Six of the JF subjects (38%) were noted to have an abnormally elevated PLMS index (>5/hour), indicating PLMS in these subjects. CONCLUSION: Our study demonstrated abnormalities in sleep architecture in children with JF. We also noted PLMS in a significant number of subjects. This has not been reported previously in children with this disorder. We recommend that children who are evaluated for JF undergo polysomnography including PLMS assessment. juvenile fibromyalgia; periodic limb movement in sleep; restless legs syndrome.

Novel gastrointestinal tract manifestations in juvenile dermatomyositis.

We report a case of juvenile dermatomyositis in which a dilated atonic esophagus was associated with delayed gastric emptying and intestinal mucosal thickening, resulting in a radiographic "stacked coin" appearance. These findings, which can also occur in infectious, neoplastic, or other immune-mediated diseases, broaden the spectrum of gastrointestinal tract manifestations in juvenile dermatomyositis. Physicians should be alert for these treatable manifestations in children with myositis who present with unexplained gastrointestinal symptoms, which are reversible with immunosuppressive therapy.

Evolution of a light-harvesting protein by addition of new subunits and rearrangement of conserved elements: crystal structure of a cryptophyte phycoerythrin at 1.63-A resolution.

Cryptophytes are unicellular photosynthetic algae that use a lumenally located light-harvesting system, which is distinct from the phycobilisome structure found in cyanobacteria and red algae. One of the key components of this system is water-soluble phycoerythrin (PE) 545 whose expression is enhanced by low light levels. The crystal structure of the heterodimeric alpha(1)alpha(2)betabeta PE 545 from the marine cryptophyte Rhodomonas CS24 has been determined at 1.63-A resolution. Although the beta-chain structure is similar to the alpha and beta chains of other known phycobiliproteins, the overall structure of PE 545 is novel with the alpha chains forming a simple extended fold with an antiparallel beta-ribbon followed by an alpha-helix. The two doubly linked beta50/beta61 chromophores (one on each beta subunit) are in van der Waals contact, suggesting that exciton-coupling mechanisms may alter their spectral properties. Each alpha subunit carries a covalently linked 15,16-dihydrobiliverdin chromophore that is likely to be the final energy acceptor. The architecture of the heterodimer suggests that PE 545 may dock to an acceptor protein via a deep cleft and that energy may be transferred via this intermediary protein to the reaction center.

Standardized nomenclatures: keys to continuity of care, nursing accountability and nursing effectiveness.

Standardized nursing nomenclatures must be included in clinical documentation systems to generate data that more accurately represent nursing practice than outcomes-related measures currently used to support important policy decisions. NANDA, NIC, and NOC--comprehensive nomenclatures for the needed variables of nursing diagnoses, interventions, and outcomes--are described. Added benefits of using NANDA, NIC, and NOC in everyday practice are outlined, including facilitation of the continuity of care of patients in integrated health systems.

Lyme disease: diagnosis & management.

Lyme disease is the most common vector borne illness occurring in the United States. Most cases occur in the East. Prompt recognition of typical features and understanding the limitations of laboratory testing are essential in order to provide appropriate management. Outcome in cases treated early is uniformly good.

Norms and nurse management of conflicts: keys to understanding nurse-physician collaboration.

In this cross-sectional study, registered nurses from 36 emergency rooms completed an abridged version of the Organizational Culture Inventory (Cooke & Lafferty, 1989) and responded to nine hypothetical conflict vignettes. Stepwise regressions were performed with nurse conflict style intentions as dependent variables and 10 independent variable (three sets of norms, five measures of conflict styles expected to be used by the physician, gender, and education). Nurses' expectations for physicians to collaborate and strong constructive and aggressive norms were found to explain a moderate amount of variance (32%) in nurses' intentions to collaborate in conflicts conducive to nurse-physician collaboration. The findings of this study provide support for the proposed theoretical framework and can be used to design interventions that promote nurse-physician collaboration.

Polymerase chain reaction as a diagnostic tool.

Although the method of polymerase chain reaction (PCR) is technical, the concept is simple: PCR is a sequential process that explores a sample for the presence of a known sequence of DNA or RNA. Chapter sections cover specific applications of PCR to infectious diseases with rheumatic manifestations.

Discontinuation of methotrexate treatment in juvenile rheumatoid arthritis.

OBJECTIVE: Children with juvenile rheumatoid arthritis (JRA) treated with methotrexate (MTX) were examined for their course after the discontinuation of the drug to define the relapse and remission rates and to identify predictors of relapse. METHODOLOGY: A retrospective chart review of all patients with JRA was conducted in two pediatric rheumatology centers. A total of 101 patients being treated with MTX were identified. Dose, response to the drug, and length of time until reaching a state of complete control were noted. The outcome of patients with a complete response in whom the drug was discontinued was examined with regards to length of time to relapse or continued remission. RESULTS: In 25 patients, MTX was discontinued after reaching complete control of the disease. There were no statistically significant predictors of response to MTX identified. Of 25 whose MTX was discontinued, relapse occurred in 13 (52%) after a mean of 11 months after discontinuation. There was no significant difference among patients who relapsed or those who remained in remission as to sex, subtype of JRA, number of months to complete control, or number of months in complete control until discontinuing MTX. Patients younger than 41/2 years at diagnosis were found to be more likely to relapse than patients diagnosed at a later age. In 10 of the patients who relapsed, complete control was induced within a mean of 7 months after restarting MTX. CONCLUSION: The optimal time for discontinuing MTX in children with JRA who have achieved complete control is unknown. Relapse occurred in approximately half of the patients in whom MTX was discontinued. Because response to reinstitution of the drug is good, it is reasonable to discontinue MTX after prolonged complete control. It remains to be seen whether the relapse rate can be improved by waiting for longer periods of time in complete control before its discontinuation.