Responsiveness of the PROMIS physical function measure in orthopaedic trauma patients.

OBJECTIVES: To compare the responsiveness of the Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) to the 36-Item Short Form Survey Physical Component Score (SF36-PCS) in orthopaedic trauma patients from pre-injury to one year recovery. DESIGN AND SETTING: Prospective cohort study at a Level 1 trauma centre. PARTICIPANTS: Patients over the age of 18 with orthopaedic trauma injuries to the pelvis, lower extremity or upper extremity between 2017 and 2018. MAIN OUTCOMES MEASUREMENTS: The PROMIS-PF and SF36-PCS assessments were conducted at baseline, 3 months, 6 months and 12 months. Responsiveness of each measure was assessed between time points by calculating the standardized response mean (SRM), the proportions of patients exceeding minimal clinically important difference (MCID), and the floor and ceiling effects. RESULTS: Sixty-eight patients with completed assessments at every timepoint were included: mean age 44.7 years, 39 were male and mean Injury Severity Score (ISS) was 7.4 (range: 4-16). Mean time of completion for the SF-36 at all the time points was 5.6 min vs 1.7 min for the PROMIS-PF (p<0.01). The SRM was comparable between measures at all the time points. Although a greater proportion of patients achieved MCID for SF36-PCS between all the time points, this only approached statistical significance between the 6- and 12-month assessments (47.1% vs 33.8%; p = 0.15). There was a significant ceiling effect demonstrated with the PROMIS-PF at baseline and 12-month assessments, with 34 (50.0%) patients and 7 (10.3%) patients achieving the maximum scores at each time point, respectively. DISCUSSION AND CONCLUSIONS: PROMIS-PF has a more favourable responder burden based on lower time to completion and comparable responsiveness to the SF-36 PCS. However, there are limitations in responsiveness with the PROMIS-PF in patients who are higher functioning as demonstrated by the ceiling effects in patients at baseline pre-injury and at 12 months post-injury timepoints.

Comparing the responsiveness of a generic and a musculoskeletal specific functional outcome measure in orthopaedic patients with operative fixation of pelvic ring, acetabulum, or tibia fractures: a comparison between single injury and multiply injured patients.

OBJECTIVES: This study compares the responsiveness, or the ability to detect clinical change in a disease, between the generic Short Form-36 (SF-36) and musculoskeletal specific Short Musculoskeletal Functional Assessment (SMFA) patient-reported outcome measures (PROMs) in the orthopaedic trauma population. Stratified analysis was performed to compare whether responsiveness differs between patients with single or multiple orthopaedic injuries. DESIGN: Prospective case series. SETTING: Level 1 Trauma Center. PATIENTS: A total of 659 patients with orthopaedic trauma injuries to the pelvis, acetabulum, or tibia were included for analysis. There were 485 patients with a single isolated injury and 174 patients with multiple orthopaedic injuries. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: Responsiveness was calculated through the standard response mean (SRM), the proportion meeting a minimal clinically important difference, and floor and ceiling effects. RESULTS: Between baseline and 6 months the magnitude of the SRM for SF-36 was consistently greater than that of SMFA in patients with single (P < .01) and multiple injuries (P < .01). Between 6 and 12 months, there were no differences in SRM across all cohorts. The proportion of patients who achieved minimal clinically important difference was consistently higher when assessed with SF-36 compared with SMFA between baseline and 6 months (81.8% vs 68.1%, P < .0001) and between 6 and 12 months (63.3% vs 55.4%, P = .01).A ceiling effect was only observed at baseline for the SMFA with 16.6% of patients achieving the maximal level of functioning detectable. No floor effects were seen in either PROM. CONCLUSION: This study demonstrates that SF-36 has superior responsiveness versus SMFA in both polytrauma and isolated injury patients and supports the collection of SF-36 as the primary PROM in prospective orthopaedic trauma studies irrespective of whether the patient has an isolated injury or multiple injuries.

DNA Damage Repair in Huntington's Disease and Other Neurodegenerative Diseases.

Recent genome-wide association studies of Huntington's disease (HD) primarily highlighted genes involved in DNA damage repair mechanisms as modifiers of age at onset and disease severity, consistent with evidence that more DNA repair genes are being implicated in late age-onset neurodegenerative diseases. This provides an exciting opportunity to advance therapeutic development in HD, as these pathways have already been under intense investigation in cancer research. Also emerging are the roles of other polyglutamine disease proteins in DNA damage repair mechanisms. A potential universal trigger of oxidative DNA damage shared in these late age-onset diseases is the increase of reactive oxygen species (ROS) in human aging, defining an age-related mechanism that has defied other hypotheses of neurodegeneration. We discuss the potential commonality of DNA damage repair pathways in HD and other neurodegenerative diseases. Potential targets for therapy that may prove beneficial across many of these diseases are also identified, defining nodes in the ataxia telangiectasia-mutated (ATM) complex, mismatch repair, and poly ADP-ribose polymerases (PARPs).

Predicting completion of follow-up in prospective orthopaedic trauma research.

OBJECTIVE: Orthopaedic trauma studies that collect long-term outcomes are expensive and maintaining high rates of follow-up can be challenging. Knowing what factors influence completion of follow-up could allow interventions to improve this. We aimed to assess which factors influence completion of follow-up in the 12 months following surgery in prospective orthopaedic trauma research. DESIGN: Prospective Cohort Study. SETTING: Level 1 Trauma Center, Vancouver, Canada. PARTICIPANTS: Eight hundred seventy patients recruited to 4 prospective studies investigating the outcomes of operatively treated lower extremity fractures. MAIN OUTCOME MEASUREMENTS: Completion of follow-up defined as completion of all outcome measures at all time points up to 12 months following injury. RESULTS: Univariate analysis and subsequent analysis by building a reductive multivariate regression model allowed for estimation of the influence of factors in completion of follow-up.Eight hundred seventy patients with complete data had previously been recruited and were included in the analysis. Seven hundred seven patients (81.2%) completed follow-up to 12 months. Factors associated with completion of follow up included higher physical component score of SF-36 at baseline, not being on social assistance at the time of injury, being married and having a higher level of educational attainment. CONCLUSIONS: Our study has demonstrated several important factors identifiable at baseline which are associated with a failure to complete follow-up. Although these factors are not modifiable themselves, we advocate that researchers designing studies should plan for additional follow-up resources and interventions for at risk patients. LEVEL OF EVIDENCE: Level IV.

Reproductive biology of the greeneye spurdog Squalus chloroculus (Squaliformes, Squalidae).

The reproduction of the greeneye spurdog Squalus chloroculus was studied based on animals caught in the multispecies and multi-gear southern and eastern scalefish and shark fishery on the upper continental slope off southern Australia. One hundred and ninety-nine females (502-990 mm, total length, LT ) and 189 males (515-810 mm LT ) were examined. The female reproductive cycle, based on 41 breeding animals, is continuous and triennial, with the pregnancy period estimated to be 31-34 months, seasonal and synchronous with the ovarian cycle; a third of the breeding female population is estimated to give birth between September and December each year. The estimated LT at which 50% of females are mature is 799 mm (95% c.i.: 794, 804), whereas the LT at which 50% are maternal is 825 mm (95% c.i.: 817-833), but these estimates are probably biased by the phenomenon of apparent change of LT at maternity and LT at maturity following severe length-selective fishing mortality. Litters ranged from four to 15 embryos with a 1:1 sex ratio, and litter size increased with maternal length. The breeding cycle of males is neither seasonal nor synchronous with the female cycle. The estimated LT of males where 50% are mature was 629 mm (95% c.i.: 603, 645).

Resolution of life-threatening dysphagia caused by caudal occipital malformation syndrome following foramen magnum decompressive surgery.

A Cavalier King Charles Spaniel was presented with acute onset, life-threatening dysphagia suspected to be secondary to medulla oblongata compression caused by caudal occipital malformation syndrome. The patient required urgent tracheostomy tube placement to remain stable and was subsequently cured of the presenting neurological deficits by foramen magnum decompressive surgery. Neurogenic dysphagia is a relatively common presenting sign in human Chiari malformation syndromes, but has not been described as a major clinical sign in veterinary patients. Caudal occipital malformation syndrome should be included in the differential diagnosis list for susceptible breeds presenting with dysphagia. Early recognition favours expeditious surgical intervention and a positive outcome in human patients, and this may also be the case in veterinary patients.

Intraoperative parathyroid hormone concentration to confirm removal of hypersecretory parathyroid tissue and time to postoperative normocalcaemia in nine dogs with primary hyperparathyroidism.

OBJECTIVE: To determine (1) whether the intraoperative parathyroid hormone concentration ([PTH]) during parathyroidectomy (PTX) can be used to indicate cure in dogs with primary hyperparathyroidism and (2) the time taken for postoperative serum calcium concentration to normalise. DESIGN: Retrospective study (2005-10) from a private referral hospital in Sydney, New South Wales, Australia. PROCEDURE: Nine client-owned dogs underwent surgical PTX for naturally occurring primary hyperparathyroidism. [PTH] was measured from serum samples taken immediately post-induction (pre-PTX]) and at least 20 min after adenoma removal (post-PTX) for all dogs, and during parathyroid gland manipulation (intra-PTX) for six dogs. The concentration of ionised calcium (iCa) was measured at various time points postoperatively until it normalised, then stabilised or decreased below reference ranges. Statistical analysis compared the mean pre-, intra- and post-PTX [PTH] and the average rate of decline of iCa concentration postoperatively. RESULTS: All dogs demonstrated a significant decrease from mean pre-PTX [PTH] (168.51 pg/mL) to mean post-PTX [PTH] (29.20 pg/mL). There was a significant increase in mean intra-PTX [PTH] (279.78 pg/mL). The average rate of decline of iCa concentration postoperatively to within the reference range (1.12-1.40 mmol/L) occurred after 24 h. CONCLUSION: Intraoperative measurements of [PTH] can be used clinically to determine cure of primary hyperparathyroidism. Parathyroid hormone increases significantly during parathyroid gland manipulation. Plasma iCa concentration returns to within the reference range on average 24 h after successful PTX. Not all dogs require vitamin D or calcium supplementation pre- or postoperatively.

Biological vulnerability of two exploited sharks of the genus Deania (Centrophoridae).

Life-history parameters of Deania calcea and Deania quadrispinosa suggested that their productivity was very low. Maturity (L(T50) ) occurs at c. 80% of maximum observed total lengths (L(T) ) for both species and sexes. A large proportion of mature females were neither pre-ovulatory nor pregnant, and the reproductive cycle included a distinct resting phase after pregnancy. For D. calcea, mean ovarian fecundity was 12 and maximum observed litter size was 10 (average of six); D. quadrispinosa averaged 17 pups per litter. Birth L(T) was 28-33 cm for D. calcea and 23-25 cm for D. quadrispinosa. The male and female reproductive cycles were aseasonal, and consequently, the length of the reproductive cycle could not be determined. Preliminary ageing data from dorsal-spine growth bands suggested that female D. calcea lived to 31-36 years and males to 24-32 years. The L(T) -at-age data using external bands on the spines showed maturity occurring at 15·5 years (males) and 21·5 years (females), whereas banding on the internal dentine indicated maturity at 10·5 and 17·5 years for males and females. Thus, a female lifetime of 31-36 years allowed for a maximum of 7 litters if a 2 year cycle is assumed or only five litters with a 3 year cycle, resulting in a lifetime fecundity of only 42 pups (2 year cycle) or even lower (3 year cycle).

Outcome measures in major trauma care: a review of current international trauma registry practice.

Multiple reports over the past 20 years have criticised the care delivered to major trauma patients in England. The setting up of regional trauma networks is well underway to address these deficiencies. Outcomes currently collected in major trauma are restricted to mortality rates and process measures; however, many patients are left with long-term disabilities and reduced quality of life (QoL), which are not measured at present. Trauma systems need to develop outcome measures that capture this important information to judge the quality of care and influence the development of services. This review aimed to identify the current practice of international trauma registries with regard to outcome measurement and review the literature surrounding these measures. An internet-based search of international trauma registry websites including data dictionaries and annual reports was carried out as well as a literature review to determine what outcome measures are routinely collected by trauma registries. All registries were found to look at mortality and process measures, but only one registry routinely collected morbidity outcome measures for both adults and children. There is a considerable amount of disability and reduced QoL in survivors of major trauma that lasts for years following the injury. At present only the Victorian State Trauma Registry collects outcome measures that evaluate the extent of this. English regional trauma networks and the Trauma Audit and Research Network have the opportunity to learn from this experience and routinely start to collect measures of outcome that can drive service improvement and reduce patient morbidity.

Uterine adenomyosis in an orang-utan (Pongo abelii/pygmaeus).

A 48-year-old, multiparous, female hybrid orang-utan (Pongo abelii/pygmaeus) was investigated after a 3-year history of irregular and excessively heavy menstrual bleeding. Opportunistic pelvic examinations over a 2.5-year period were non-diagnostic. Medical therapy was not effective. A subtotal hysterectomy with bilateral salpingo-ovariectomy was performed. A pedunculated mass spanning 90% of the uterine lumen was seen grossly, and histopathology confirmed uterine adenomyosis. Adenomyosis is defined as the ectopic occurrence or diffuse implantation of endometrial tissue, including glands and stroma, into the myometrium. It is common in older, usually premenopausal, multiparous women and is frequently associated with other uterine pathology, including endometrial hyperplasia and leiomyomas. The most common clinical signs are dysmenorrhoea and heavy menstrual bleeding; however, up to 35% of women are asymptomatic. Diagnosis is difficult and requires myometrial sampling and an experienced pathologist. A hysterectomy in this case was diagnostic and curative. There have been few reports of uterine adenomyosis in non-human primates and none reported in an orang-utan. Uterine adenomyosis should be considered in the differential diagnosis in any multiparous, aged, non-human female primate with irregular and excessively heavy menstrual bleeding, and hysterectomy with bilateral salpingo-ovariectomy is recommended as a diagnostic and therapeutic solution.

Thrombotic risk in patients with aortic bioprostheses.

Thrombosis of Mosaic aortic valve bioprostheses occurring at more than one month after surgery occurs in 0.8% (95% CI 0.33-1.67%) of patients. In the two cases reported here, each patient had risk factors for thrombus formation, namely severe left ventricular impairment in one patient, while the other patient was heterozygous for prothrombin variant G20210A. The cases were treated successfully, by thrombolytic therapy with streptokinase in the first case, and by repeat aortic valve replacement in the second case. Thrombosis of bioprosthetic valves in the aortic position is rare, and a period of anticoagulation postoperatively does not invariably protect against this serious complication. In conclusion, patients with risk factors for thrombus formation should be considered for long-term anticoagulation.

Soil water content and organic carbon availability are major determinants of soil microbial community composition.

Exploration of environmental factors governing soil microbial community composition is long overdue and now possible with improved methods for characterizing microbial communities. Previously, we observed that rice soil microbial communities were distinctly different from tomato soil microbial communities, despite management and seasonal variations within soil type. Potential contributing factors included types and amounts of organic inputs, organic carbon content, and timing and amounts of water inputs. Of these, both soil water content and organic carbon availability were highly correlated with observed differences in composition. We examined how organic carbon amendment (compost, vetch, or no amendment) and water additions (from air dry to flooded) affect microbial community composition. Using canonical correspondence analysis of phospholipid fatty acid data, we determined flooded, carbon-amended (+C) microcosm samples were distinctly different from other +C samples and unamended (-C) samples. Although flooding without organic carbon addition influenced composition some, organic carbon addition was necessary to substantially alter community composition. Organic carbon availability had the same general effects on microbial communities regardless of whether it was compost or vetch in origin. In addition, flooded samples, regardless of organic carbon inputs, had significantly lower ratios of fungal to bacterial biomarkers, whereas under drier conditions and increased organic carbon availability the microbial communities had higher proportions of fungal biomass. When comparing field and microcosm soil, flooded +C microcosm samples were most similar to field-collected rice soil, whereas all other treatments were more similar to field-collected tomato soil. Overall, manipulating water and carbon content selected for microbial communities similar to those observed when the same factors were manipulated at the field scale.

Fatty acid composition and dynamics of selected fungal-feeding nematodes and fungi.

Fatty acid profiles of fungal-feeding nematodes, Aphelenchus avenae and Aphelenchoides composticola, and selected fungi were determined in microcosm cultures of agar, broth, or sand amended with organic matter. Fatty acids of A. avenae and A. composticola included 16:0 18:0, 18:1omega7, 18:1omega9, 18:2, 20:0, 20:1, 20:2, 20:3 and 20:4 phospholipid fatty acids (PLFAs) and neutral lipid fatty acids (NLFAs). The nematodes differed in relative amounts of saturated and C(18) fatty acids. Similar C(16) and C(18) PLFAs and whole-cell fatty acids were found in Rhizoctonia solani, Fusarium oxysporum and Trichoderma sp. with 18:2omega6 as the major component. The C(20) fatty acids were not found in these fungi. Although only present in the nematodes, C(20) PLFAs were only detected when nematode population levels were > or =22 per gram of sand, suggesting that there is a detection threshold that might limit their use as biomarkers in the soil community. After removal of nematodes from a food source, the relative amount of C(20) PLFAs (structural components of nematode cell membranes) decreased more slowly than the C(16) and C(18) PLFAs, which may have reflected ingested fungal cytoplasm in the nematode intestine. In the early stage of organic matter decomposition, total and fungal PLFAs were lower in the presence of A. composticola then in its absence at C:N ratios > or =30:1.

Epidemiology of hypertrophic cardiomyopathy-related death: revisited in a large non-referral-based patient population.

BACKGROUND: Death resulting from hypertrophic cardiomyopathy (HCM), particularly when sudden, has been reported to be largely confined to young persons. These data emanated from tertiary HCM centers with highly selected referral patterns skewed toward high-risk patients. METHODS AND RESULTS: The present analysis was undertaken in an international population of 744 consecutively enrolled and largely unselected patients more representative of the overall HCM spectrum. HCM-related death occurred in 86 patients (12%) over 8+/-7 years (mean+/-SD). Three distinctive modes of death were as follows: (1) sudden and unexpected (51%; age, 45+/-20 years); (2) progressive heart failure (36%; age, 56+/-19 years); and (3) HCM-related stroke associated with atrial fibrillation (13%; age, 73+/-14 years). Sudden death was most common in young patients, whereas heart failure- and stroke-related deaths occurred more frequently in midlife and beyond. However, neither sudden nor heart failure-related death showed a statistically significant, disproportionate age distribution (P=0.06 and 0.5, respectively). Stroke-related deaths did occur disproportionately in older patients (P=0.002). Of the 45 patients who died suddenly, most (71%) had no or mild symptoms, and 7 (16%) participated in moderate to severe physical activities at the time of death. CONCLUSIONS: HCM-related cardiovascular death occurred suddenly, or as a result of heart failure or stroke, largely during different phases of life in a prospectively assembled, regionally based, and predominantly unselected patient cohort. Although most sudden deaths occurred in adolescents and young adults, such catastrophes were not confined to patients of these ages and extended to later phases of life. This revised clinical profile suggests that generally held epidemiological tenants for HCM have been influenced considerably by skewed reporting from highly selected populations. These data are likely to importantly affect risk stratification and treatment strategies importantly for the prevention of sudden death in HCM.

Polygenic influence on plasma homocysteine: association of two prevalent mutations, the 844ins68 of cystathionine beta-synthase and A(2756)G of methionine synthase, with lowered plasma homocysteine levels.

A moderately elevated plasma total homocysteine (tHcy), whether measured during fasting or post-methionine load (PML), is increasingly being recognized as a risk factor for coronary artery diseases (CAD). However, etiologies for moderately elevated plasma tHcy, particularly with regard to the role of genetic influence on plasma tHcy levels, are still not well understood. In the current investigation, we studied 1025 individuals with respect to the effect of the 68-bp insertion (844ins68 variant) of the cystathionine beta-synthase (CBS) gene, the A(2756)G transition of the B(12)-dependent methionine synthase (MS) gene and the C(677)T transition of the methylenetetrahydrofolate reductase (MTHFR) gene on fasting and 4 h PML tHcy. Of these individuals, 153 (14.9%) were heterozygous for the 68-bp insertion, 329 (32.1%) were heterozygous for the G(2756) allele and 122 (11.9%) were homozygous for the C(677)T transition. Individuals heterozygous for the insertion had significantly lower PML increase in tHcy concentrations, while individuals homozygous for the A(2756)G transition had significantly lower fasting tHcy levels. A 2-way ANOVA showed that there was no interaction between the 844ins68 and the A(2756)G transition for either fasting tHcy or PML increase in tHcy, confirming the fact that the effect of these two genotypes on plasma tHcy levels are additive. The effects are opposite but additive with the C(677)50% of all individuals in this study carried polymorphic traits, which predisposed them to either higher or lower plasma tHcy concentrations, thus providing new evidence of the importance of genetic influences as determinants of tHcy levels.

Blunt chest trauma and the heart.

The Green Lane Hospital experience of patients presenting with cardiac damage as a result of chest trauma has been reviewed following the recent referral of a patient with tricuspid regurgitation due to trauma. A retrospective search of surgical records was made over the preceding 28 years which yielded a further nine patients. Our group has experienced a number of unusual causes of non-fatal cardiac trauma that have followed accidents. In nine out of ten cases closed chest injury resulted in damage to the heart. In some, diagnosis had been delayed for years. Echocardiography is a very useful diagnostic tool. Surgery was undertaken in all cases.

Genetic causes of mild hyperhomocysteinemia in patients with premature occlusive coronary artery diseases.

Elevated plasma homocysteine is increasingly being recognized as a risk factor for coronary artery disease (CAD). Although there is general agreement on the importance of micronutrients and genetic predisposition to elevated plasma homocysteine, the exact influence of the known prevalent mutations in genes which regulate homocysteine metabolism is not clear. We studied 376 cases of individuals with premature CAD with respect to their fasting and post-methionine load (PML) total homocysteine (tHcy) concentrations. We also determined the presence or absence of the T833C and G919A mutations of the cystathionine-beta-synthase (CBS) gene, the C677T mutation of the methylene tetrahydrofolate reductase (MTHFR) gene, and the A2756G transition of the B12 dependent methionine synthase (MS) gene. Our objectives were therefore both to confirm the relationship of plasma homocysteine with premature CAD and to examine the importance of genetic influence on both fasting and PML homocysteine. Approximately 32% of the CAD patients had fasting hyperhomocysteinemia and 16% had PML hyperhomocysteinemia. Of these, 8.5% had both forms of hyperhomocysteinemia (combined hyperhomocysteinemia). The T133C mutation in the CBS gene and the thermolabile C677T mutation in the MTHFR gene seem to play an important role in the subset of individuals with combined hyperhomocysteinemia. The A2756G transition in the MS gene is not associated with elevated plasma tHcy. Many cases (47%) of hyperhomocysteinemia are not associated with micronutrient deficiencies, impaired renal function, and/or currently known genetic mutations. Further work is needed to study whether unknown mutations, particularly those residing in the intronic sequences of the genes involved in homocysteine metabolism, other environmental factors, or interaction of gene, nutrient, and environmental factors may be the cause of currently unexplained cases of mild hyperhomocysteinemia.