Colchicine is not effective for reducing osteoarthritic hand pain compared to placebo: a randomised, placebo-controlled trial (COLAH).

BACKGROUND: Colchicine may offer relief in osteoarthritis. This has never been investigated for hand osteoarthritis. OBJECTIVES: To investigate the effect of 1 mg daily colchicine vs placebo on hand pain and function over 12 weeks in older adults with hand osteoarthritis. METHODS: Community-dwelling adults with diagnosed osteoarthritis of the hand aged 40-80 years were randomised to receive colchicine (0.5 mg twice daily) or matching placebo. Primary outcome measure was VAS hand pain score (0-100 mm). Secondary outcome measures included tender and swollen joint count, grip strength, C-reactive protein, and Michigan Hand Questionnaire total, function and pain scores. In an exploratory assessment, we compared synovial grade and power Doppler. All outcome measures were obtained at baseline and week 12. Stata v16 was used to perform constrained longitudinal data analysis models. RESULTS: 64 adults (54 females, 10 males) aged 48-79 years of age were enrolled. 59 participants completed the study (N = 28 colchicine, N = 31 placebo) (withdrawal rate 8%). Adverse reactions to the study medication occurred in nine patients. VAS score was not significantly different at baseline (61 ± 17 mm in the colchicine, 64 ± 17 mm in the placebo group). Between-group difference for VAS score at week 12 was 7.6 mm (95% CI -3.5-18.7, p-value 0.18). There were no significant differences between groups for any secondary outcomes at baseline or week 12. CONCLUSIONS: 1 mg colchicine daily for 12 weeks was not effective for reducing pain, tender and swollen joint count or increasing grip strength in symptomatic hand osteoarthritis. Our results do not support the use of colchicine in hand osteoarthritis.

Systematic review of clinical outcomes after prophylactic surgery.

Introduction Prophylactic appendicectomy is performed prior to military, polar and space expeditions to prevent acute appendicitis in the field. However, the risk-benefit ratio of prophylactic surgery is controversial. This study aimed to systematically review the evidence for prophylactic appendicectomy. It is supplemented by a clinical example of prophylactic surgery resulting in life-threatening complications. Methods A systematic review was performed using MEDLINE(®) and the Cochrane Central Register of Controlled Trials. Keyword variants of 'prophylaxis' and 'appendicectomy' were combined to identify potential papers for inclusion. Papers related to prophylactic appendicectomy risks and benefits were reviewed. Results Overall, 511 papers were identified, with 37 papers satisfying the inclusion criteria. Nine reported outcomes after incidental appendicectomy during concurrent surgical procedures. No papers focused explicitly on prophylactic appendicectomy in asymptomatic patients. The clinical example outlined acute obstruction secondary to adhesions from a prophylactic appendicectomy. Complications after elective appendicectomy versus the natural history of acute appendicitis in scenarios such as polar expeditions or covert operations suggest prophylactic appendicectomy may be appropriate prior to extreme situations. Nevertheless, the long-term risk of adhesion related complications render prophylactic appendicectomy feasible only when the short-term risk of acute appendicitis outweighs the long-term risks of surgery. Conclusions Prophylactic appendicectomy is rarely performed and not without risk. This is the first documented evidence of long-term complications following prophylactic appendicectomy. Surgery should be considered on an individual basis by balancing the risks of acute appendicitis in the field with the potential consequences of an otherwise unnecessary surgical procedure in a healthy patient.

Posttraumatic stress disorder, alone or additively with early life adversity, is associated with obesity and cardiometabolic risk.

BACKGROUND AND AIMS: There is some evidence that posttraumatic stress disorder (PTSD) and early life adversity may influence metabolic outcomes such as obesity, diabetes, and cardiovascular disease. However, whether and how these interact is not clear. METHODS: We analyzed data from a cross-sectional and longitudinal study to determine how PTSD severity influences obesity, insulin sensitivity, and key measures and biomarkers of cardiovascular risk. We then looked at how PTSD and early life adversity may interact to impact these same outcomes. RESULTS: PTSD severity is associated with increasing risk of obesity, diabetes, and cardiovascular disease, with higher symptoms correlating with higher values of BMI, leptin, fibrinogen, and blood pressure, and lower values of insulin sensitivity. PTSD and early life adversity have an additive effect on these metabolic outcomes. The longitudinal study confirmed findings from the cross sectional study and showed that fat mass, leptin, CRP, sICAM-1, and sTNFRII were significantly increased with higher PTSD severity during a 2.5 year follow-up period. CONCLUSIONS: Individuals with early life adversity and PTSD are at high risk and should be monitored carefully for obesity, insulin resistance, and cardiometabolic risk.

Painful, palpable and pathological: anomalous flexor digitorum superficialis brevis in the palm, comparative anatomical context, and an updated classification of anomalies of the flexor digitorum superficialis.

Anomalies of the flexor digitorum superficialis are rare and can present a diagnostic dilemma. Patients present with a painful or palpable mass, or symptoms of carpal tunnel syndrome. This review article summarizes previously reported anomalies of the flexor digitorum superficialis, reports a further case, and proposes a new classification.

Patient-reported outcome measures in nonmelanoma skin cancer of the face: a systematic review.

Nonmelanoma skin cancer (NMSC) is the most common malignancy in the western world, with an incidence of 98,000 in the U.K. Since 2009 the Department of Health (DoH) has collected patient-reported outcome measure (PROM) data following four common surgical procedures. However, a DoH PROM for NMSC does not exist. A systematic review of questionnaires published on patient concerns due to NMSC of the face was conducted. Keywords relevant to PROMs, NMSC and the facial region were comprehensively searched in medical databases. Inclusion criteria stipulated that questionnaires from relevant papers recruited patients with NMSC for both the item formulation and subsequent validation. Questionnaires were then discussed by a multispecialty skin cancer research team. Initially 2548 papers were found; after exclusion criteria were applied, 73 articles were retrieved. Four patient questionnaires for NMSC featured adequate development and validation according to the inclusion criteria. The Facial Skin Cancer Index (FSCI) was the only PROM specific to facial NMSC. Additional questionnaires identified included the Skin Cancer Quality of Life Impact Tool, Skindex, and Dermatology Life Quality Index. There is a scarcity of data relating to NMSC PROMs and appearance concerns. Only one questionnaire--the FSCI--was specific to patients with facial NMSC. We recommend nationally standardized data collection from patients with NMSC in order to create an evidence-based validated PROM for patients with facial skin cancer.

Meningoencephalitis associated with Carnobacterium maltaromaticum-like bacteria in stranded juvenile salmon sharks (Lamna ditropis).

Juvenile salmon sharks beach yearly along the California coast, primarily during late summer and early fall. Fresh, frozen, and formalin-fixed tissues from 19 stranded salmon sharks were collected for examination. Histopathology revealed meningitis or meningoencephalitis in 18 of 19 shark brains with intralesional bacteria observed in 6 of the affected brains. Bacterial culture of fresh or frozen brain, liver, and/or heart blood from 13 sharks yielded pure cultures characterized molecularly and/or biochemically as belonging to the genus Carnobacterium. The 16s ribosomal DNA sequence of 7 tissue isolates from 7 separate sharks was 99% homologous to C. maltaromaticum (GenBank FJ656722.1). Sequence of the large ribosomal DNA intergenic spacer region (ISR) was 97% homologous to C. maltaromaticum (AF374295.1). This is the first report of Carnobacterium infection in any shark species, and the authors posit that brain infection caused by Carnobacterium is a significant cause of morbidity and mortality in juvenile salmon sharks found stranded along the Pacific coast of California.

ß-Cryptoxanthin biofortified maize (Zea mays) increases ß-cryptoxanthin concentration and enhances the color of chicken egg yolk.

The laying hen has a natural ability to deposit carotenoids into its egg yolks, especially the xanthophyll carotenoid lutein that is used commercially as an egg colorant. Can this ability to deposit carotenoids be used to enrich egg yolk provitamin A value? After a 10-d carotenoid depletion period in hens (n = 24), the effects of a 20-d intervention with high-ß-cryptoxanthin, high-ß-carotene, or typical yellow maize on color and carotenoid profile were compared with the effects of a white maize diet (n = 6/treatment). Eggs were collected every other day and yolks were analyzed by using a portable colorimeter to define the color space and by using an HPLC to determine the carotenoid profile. The high-ß-cryptoxanthin and yellow maize increased ß-cryptoxanthin in the yolk (0.55 ± 0.08 to 4.20 ± 0.56 nmol/g and 0.55 ± 0.08 to 1.06 ± 0.12 nmol/g, respectively; P < 0.001). Provitamin A equivalents increased in eggs from hens fed high-ß-cryptoxanthin maize (P < 0.001) but not the high-ß-carotene maize. The color (L*, a*, and b*) assessment of the yolks showed an increase in the high-ß-cryptoxanthin treatment for the red-green a* scale (P < 0.001) and a decrease for the light-dark L* scale (P < 0.001). No appreciable change was noted in the yellow-blue b* scale for the high-ß-cryptoxanthin treatment; but significant changes were noted for the yellow (P = 0.002) and high-ß-carotene maize (P = 0.005) treatments, which were most evident at the end of the washout period with white maize. ß-Cryptoxanthin-biofortified maize is a potential vehicle to elevate provitamin A equivalents and to enhance the color of yolks. This could lead to a human health benefit if widely adopted.

Scars and satisfaction: do smaller scars improve patient-reported outcome?

Thyroidectomy has few complications, as a result, many patients are concerned about the prominence of their scar. Performing thyroid surgery through excessively small incisions in order to maximise cosmesis may increase the likelihood of complications. This study investigates the relationship between conventional approach thyroidectomy scar length and patient satisfaction. A validation of self-measurement of neck circumference and thyroidectomy scar was carried out with the measurements taken by patients compared with those taken by an investigator. One hundred consecutive patients who had undergone conventional thyroidectomy and total thyroidectomy within 24 months were invited to measure their scars and neck circumference, and to score their satisfaction on a Likert scale of 1-10. Spearman's correlation was calculated for the relationship between absolute and relative scar length, and patient satisfaction. Thirty-four patients entered the preliminary study and 80 patients entered the main study (80% response rate). Measurements by patients and investigators were closely associated: Spearman's Rank correlation coefficient for neck circumference and for scar length were ρ = 0.9, p < 0.0001 and ρ = 0.93, p < 0.0001 respectively. No significant correlation was evident between scar length and patient satisfaction (ρ = 0.068, p = 0.55), or between relative scar length ratio and patient satisfaction (ρ = -0.045, p = 0.69). Mean scar length was 6.96 cm [standard deviation (SD) 2.70], and mean satisfaction score 8.62 (SD 2.04). Thyroidectomy scar length appears to have no association with patient satisfaction. Thyroid surgery should, therefore, not be performed through unnecessarily small incisions for purely aesthetic reasons.

Optimising methods for communicating survival data to patients undergoing cancer surgery.

BACKGROUND: Patients undergoing cancer surgery require outcome data to inform decisions, but communication of numerical risk is difficult. This study assessed patient understanding of survival data presented in different formats. METHODS: Semi-structured interviews in which patients interpreted four presentation formats of survival data (three graphical and one narrative) were audio-recorded. The interviewer and a blinded observer (listening to the audio-recordings) scored patients' understanding of each format. Logistic regression examined associations between understanding and clinical and socio-demographic details. RESULTS: Seventy participants with colorectal cancer were interviewed and 67 [95.7%, 95% confidence intervals (CIs) 90.9-100%] correctly interpreted a simplified Kaplan-Meier survival curve. A high proportion accurately understood data presented as a bar chart or pictograph (94.3%, 95% CIs 88.7-99.9% and 92.9%, 95% CIs 86.7-99.0% respectively). Standard narrative alone was least well understood (n = 53, 75.7%, 95% CIs 65.4-86.0%). Multivariable analyses demonstrated that older and female patients had poorer overall understanding (OR 0.93 per year, 95% CIs 0.87-0.98, p = 0.01 and OR 0.24, 95% CIs 0.07-0.86, p = 0.03). CONCLUSION: Patient understanding of survival data was higher when presented with graphs compared to narrative alone. Further work examining understanding in the clinical context and before surgery is recommended before this can be used routinely.

Infection-free surgery: how to improve hand-hygiene compliance and eradicate methicillin-resistant Staphylococcus aureus from surgical wards.

INTRODUCTION: Healthcare-associated infections cost the UK National Health Service 1 billion UK pounds per annum. Poor hand hygiene is the main route of transmission for methicillin-resistant Staphylococcus aureus (MRSA), leading to increased mortality and morbidity for infected patients. This study aims to quantify MRSA infection rates and compliance of alcohol gel application at the entrance to a surgical ward and assess how a simple intervention affects compliance. SUBJECTS AND METHODS: Compliance was assessed via a discretely positioned close-surveillance camera at the ward entrance. Footage was reviewed to monitor compliance of all persons entering the ward over a 12-month period. RESULTS: For the initial 6 months, mean alcohol gel compliance was 24% for all persons entering the ward. After this period, a conspicuous strip of bright red tape was positioned along the corridor approaching the ward entrance. The red line continued up the wall to an arrow head pointing to the two alcohol gel dispensers on the wall. Mean compliance over the subsequent 6 months significantly improved to 62% (P < 0.0001). Compliance improved for all persons entering the ward as follows (before - after, significance): doctors (0% - 54%, P < 0.01); nurses (24% - 75%, P < 0.05); porters (21% - 67%, P < 0.05); visitors (35% - 68%, P < 0.01); patients (23% - 44%, P > 0.05). There were two cases of MRSA bacteraemia in the initial 6 months and no cases in the following 6 months with the red line in situ. CONCLUSIONS: This study demonstrates how a simple intervention significantly improves hand-hygiene compliance with associated eradication of MRSA.

How to improve plastic surgery knowledge, skills and career interest in undergraduates in one day.

INTRODUCTION: Plastic surgery now occupies a negligible component of many undergraduate curricula. The British Association of Plastic, Reconstructive and Aesthetic Surgeons Undergraduate Course aimed to introduce and improve students' plastic surgery knowledge and skills, as well as develop personal career interests. This research aims to quantify whether this was achieved. METHODS: Students attending the one-day course were invited to complete a questionnaire before and after the course. Questions were self-reflective and incorporated four key themes: (1) plastic surgery knowledge; (2) awareness of the work of a plastic surgeon; (3) ability to perform basic plastic surgical skills; (4) career interest in plastic surgery. Non-medical students were given an identical questionnaire to quantify public perception of the work of a plastic surgeon. RESULTS: 121 students attended from 17 universities across the UK, with 93 completing the questionnaire (77% response rate). Paired analyses compared mean or median scores of the students' answers before and after the course. After completing the course, medical students significantly improved in all four key themes (p<0.01). 93 non-medical students completed questionnaires. Medical students were significantly more accurate at identifying plastic surgery procedures than non-medical students (P < 0.01), which was further strengthened after completing the course (P < 0.001). CONCLUSION: This study demonstrates the positive educational impact of a one-day plastic surgery event for medical students and supports the need for plastic surgery education at an undergraduate level.

Can biochemical markers serve as surrogates for imaging in knee osteoarthritis?

OBJECTIVE: Osteoarthritis (OA) is a complex heterogeneous joint disease affecting more than 35 million people worldwide. The current gold standard diagnostic investigation is the plain radiograph, which lacks sensitivity. Biochemical markers have the potential to act as adjunct markers for imaging in the assessment of knee OA. We undertook this study to determine the association between individual biochemical markers and radiographic features, and to establish whether the association is strengthened when selected biochemical markers are combined into a single factor (a theoretical marker). METHODS: Twenty serum and urinary biochemical markers were analyzed in 119 patients with predominantly tibiofemoral knee OA. Pearson's correlation was performed, and corresponding coefficients of determination (R(2)) were calculated to determine the association between biochemical markers and a range of imaging features from radiographs and dual x-ray absorptiometry of the knee. Biochemical markers demonstrating a significant association (P < 0.05) with a specific imaging feature were combined by principal components analysis (PCA). Pearson's correlation was repeated to establish whether the combined panel of biochemical markers showed a stronger association with imaging than the best single marker. RESULTS: Fourteen biochemical markers showed significant associations with one or more imaging features. By combining specific panels of biochemical markers to form factors, the association of markers with imaging features (R(2)) increased from 11.9% to 22.7% for the Kellgren/Lawrence (K/L) score, from 5.9% to 9.2% for joint space width (JSW), from 6.6% to 10.8% for sclerosis, from 13.5% to 22.6% for osteophytes, and from 12.0% to 14.2% for bone mineral density (BMD). Biochemical markers identifying patients with osteophytes overlapped with those correlated with a high K/L score, while markers of subchondral BMD formed a completely separate group. Biochemical markers of JSW included markers associated with both osteophytes and BMD. CONCLUSION: The PCA results suggest that biochemical marker combinations may be more sensitive than individual biochemical markers for reflecting structural damage in patients with knee OA. The differences in biochemical marker profiles associated with osteophytes compared with those associated with subchondral BMD raise the possibility that these 2 processes, commonly seen in bone in knee OA, have underlying biologic differences.

Endovascular embolization of the swine rete mirabile with Eudragit-E 100 polymer.

BACKGROUND AND PURPOSE: Both adhesive and nonabrasive embolic agents are available for arteriovenous malformation (AVM) embolization. The purpose of this study was to evaluate a novel ethanol-based nonadhesive liquid embolic material in a swine AVM model. MATERIALS AND METHODS: Eudragit (copolymer of methyl and butyl methacrylate and dimethylaminoethyl methacrylate) was dissolved in 50% ethanol and 50% iopamidol. Eudragit was injected into 9 retia mirabilia (RMs). Ethanol and iopamidol mixture were injected into 4 RMs for comparison. Three RMs embolized with Eudragit mixture were evaluated both angiographically and histopathologically acutely (3-24 hours) and at 30 days and 90 days after embolization. RESULTS: No procedural complications from Eudragrit embolization were noted, including retention or adhesion of the microcatheter. Various degrees of inflammation were observed in the acute and 30-day specimens. Two RMs showed partial recanalization on both histopathology and follow-up angiography in the 30-day group. Arterial fibrosis and calcification were observed in the 30- and 90-day specimens. The internal elastic lamina was disrupted in the 30- and 90-day specimens, but there was no evidence of Eudragit extravasation or hemorrhage. Endothelial damage was seen in all specimens and was particularly severe in the 30- and 90-day specimens. CONCLUSION: Eudragit polymer induced inflammation in thrombosis similar to n-butyl 2-cyanoacrylate, but without the disadvantages of perivascular hemorrhage and extravasation of embolization material. Although recanalization of some embolized RMs was noted, further investigation into Eudragit as a potentially useful embolic material for brain AVMs is warranted.

Causes of failure of the Kinemax Plus total knee replacement in the first five years.

In order to investigate whether any single batch of polyethylene inserts was responsible for premature failure of total knee replacements (TKR), we performed a retrospective database review of 1133 consecutive primary Kinemax Plus TKR performed by 2 surgical teams between January 1992 and January 2001 at our institution. Cases re-operated in any way within 5 years of the index arthroplasty were identified, case notes studied and radiographs reviewed. The causes contributing to the premature failure of the implants were identified where possible and the polyethylene lot numbers were recorded. Nineteen cases were known to have been revised, 7 cases for deep infection of the prosthesis and 12 for aseptic failure. In 10 cases, an identifiable technical error had contributed to the early failure of the implant. In 4 of these cases, there was inadequate tissue balancing in patients with a significant pre-operative valgus deformity. In 2 cases, the tibial base plate was inserted in a varus mal-alignment. There was one extended tibial component, one internally rotated femoral component, one oversized femoral component and one femoral component with inadequate fixation. Two further cases failed aseptically, one with a fracture of the medial tibial plateau and one idiopathic. The lot numbers of the polyethylene inserts were all different. This study confirms that the premature failure rate of the Kinemax Plus TKR is low. Although a "bad batch" of polyethylene has been suggested as a cause for early failure in TKR, in this series, surgical error was the predominant cause.

2,3,7,8-Tetrachlorodibenzo-p-dioxin affects fluctuating asymmetry of molar shape in mice, and an epistatic interaction of two genes for molar size.

Fluctuating asymmetry (FA), random variation between left and right sides in a bilaterally symmetrical character, is a commonly used measure of developmental instability that is expected to increase with increasing environmental stress. One potential stressor is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a powerful toxicant known to disturb tooth development. In this study, mice in the F(2) generation produced from an intercross between two inbred strains (C57BL/6J and AKR/J) were exposed in utero to TCDD. We hypothesized that TCDD would increase FA in the molars of exposed mice over that of the control mice. In addition, we hypothesized that we would discover genes for molar size, shape or asymmetry whose expression would be affected by TCDD. We detected a very small, but significant, increase in FA of molar shape (but not size) in the TCDD-exposed mice compared to the control mice, although molar size and shape did not differ between these groups. Although we did not uncover any genes that acted differently in the TCDD exposed and control groups, we did identify two genes whose dominance by additive epistatic effect on molar size was affected by TCDD. We concluded that although TCDD may be affecting the expression of some genes governing the development of molars in our population of mice, FA of molar size and shape is not a particularly sensitive indicator of this effect.

Absence of neurotoxic effects in leopard sharks, Triakis semifasciata, following domoic acid exposure.

Domoic acid (DA), a potent neurotoxin produced by select species of algae and diatoms, kills neurons bearing kainic acid-type glutamate receptors. Studies have shown that DA bioaccumulates in invertebrates and fish that consume the diatoms. In every vertebrate species tested or observed in the wild, dietary or systemic DA causes neuronal damage or clinical signs of neurotoxicity. Sharks, like marine birds and mammals, are exposed to DA through their diet; however, no research has demonstrated the effect of DA on shark behavior or physiology. In this study, juvenile leopard sharks (Triakis semifasciata) were given DA by intracoelomic injection at doses of 0, 1, 3, 9, and 27 mg/kg and observed for 7 days. The sharks failed to demonstrate behavioral or histological changes in response to the toxin. We identified putative brain glutamate receptors by probing western blots with an antibody specific for kainic acid-type glutamate receptors and demonstrated receptor localization in the cerebellum with immunohistochemistry. Blood levels of DA in three sharks dosed at 9 mg/kg fell rapidly within 1.5h of injection. We show that leopard sharks possess the molecular target for DA but are resistant to doses of DA known to be toxic to other vertebrates.

Systemically and topically administered leptin both accelerate wound healing in diabetic ob/ob mice.

Leptin is a 16 kD protein that is produced by adipocytes and induces weight loss in both normal and genetically obese ob/ob mice. ob/ob mice are obese, have multiple metabolic abnormalities, and exhibit impaired wound healing. Exogenous administration of leptin to these animals induces weight loss and corrects their metabolic defects. Leptin's effect on wound repair, however, has not been studied. Systemic administration of leptin at doses ranging from 0.1 to 10 mg/kg/day induced a highly significant acceleration in wound repair in ob/ob mice (p<0.0001), but not in db/db mice, indicating that leptin's effects on wound repair were mediated through the leptin receptor. We then investigated the possibility that leptin was acting directly at the wound site by administering leptin topically, and found that topical leptin also induced a dose dependent acceleration in wound repair (p<0.0001). In addition, we found that all forms of leptin receptor, including the signal transducing long form, were present in skin by RNase protection assay, and that leptin receptor localized to subcutaneous vessels of wounded skin by in situ hybridization. Finally, we investigated the possibility that leptin stimulated angiogenesis in wounds by analyzing wound hemoglobin and wound vessel density. Neither systemic nor topical leptin induced any significant changes in either parameter, suggesting that leptin accelerates wound repair by a mechanism other than stimulation of angiogenesis. In summary, both systemic and topical leptin accelerate wound repair in diabetic ob/ob mice, possibly via the direct interaction of leptin with its receptors in wounded skin, but do not appear to significantly stimulate wound angiogenesis. Further studies to better elucidate the mechanisms of leptin's effects on wound repair are warranted.