Diagnosis concealment is prevalent in MS, and associated with diagnosis experience.

BACKGROUND: Receiving a diagnosis of multiple sclerosis (MS) can be stressful; later, patients may conceal their diagnosis. Here, we aimed to (1) assess prevalence of disclosure and concealment behaviors, and (2) explore whether diagnosis experience is associated with later concealment and if MS provider engagement on this topic modifies concealment. METHODS: In a survey-based study, MS patients completed DISCO-MS assessing disclosure and concealment and responded to questions about diagnosis experience and practitioner attention to disclosure. Frequency analysis and Pearson's correlations were used in exploratory analyses. RESULTS: 428 adults with MS participated. 49% (N = 201) conceal their diagnosis. Higher education [t(405) = 3.66, p < 0.001], younger age (r = -0.15, p = 0.002), and shorter disease duration (r = -0.18, p = 0.010) were associated with higher concealment. 39% (N = 159) anticipate negative consequences of disclosure. Individuals reporting positive diagnosis experience (26%, N = 102) were less likely to conceal later in disease course compared to those with negative experience (34%, N = 136) [t(233) = 2.483, p = 0.014]. Patients whose MS providers discussed disclosure (23%, N = 73) anticipated less negative consequences of disclosure [t(323) = 2.475, p = 0.014]. CONCLUSIONS: Diagnosis concealment is common in MS. Favorable diagnosis experience and provider attention to the topic of disclosure throughout the MS disease course may influence diagnosis concealment.

Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium.

BACKGROUND: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. PATIENTS AND METHODS: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). RESULTS: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. CONCLUSIONS: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.

Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3).

BACKGROUND: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. MATERIALS AND METHODS: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. RESULTS: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). CONCLUSION: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.

Non-opioid analgesic modes of pain management are associated with reduced postoperative complications and resource utilisation: a retrospective study of obstructive sleep apnoea patients undergoing elective joint arthroplasty.

BACKGROUND: Studies on the effectiveness of multimodal analgesia, particularly in patients at higher perioperative risk from obstructive sleep apnoea (OSA), are lacking. We aimed to assess the impact of multimodal analgesia on opioid use and complications in this high-risk cohort. METHODS: We conducted a population-based retrospective cohort study of OSA patients undergoing elective lower extremity joint arthroplasty (2006-16, Premier Healthcare database). Multimodal analgesia was defined as opioid use with the addition of one, two, or more non-opioid analgesic modes including, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, paracetamol/acetaminophen, peripheral nerve blocks, steroids, gabapentin/pregabalin, or ketamine. Multilevel multivariable regression models measured associations between multimodal analgesia and opioid prescription (primary outcome; oral morphine equivalents). Secondary outcomes included opioid- and OSA-related complications, and resource utilisation. Odds ratios (OR) or % change and 95% confidence intervals (CI) are reported. RESULTS: Among 181 182 OSA patients included, 88.5% (n = 160 299) received multimodal analgesia with increasing utilisation trends. Multivariable models showed stepwise beneficial postoperative outcome effects with increasing additional analgesic modes compared with opioid-only analgesia. In patients who received more than two additional analgesia modes (n = 64 174), opioid dose prescription decreased by 14.9% (CI -17.0%; -12.7%), while odds were significantly decreased for gastrointestinal complications (OR 0.65, CI 0.53; 0.78), mechanical ventilation (OR 0.23, CI 0.16; 0.32), and critical care admission (OR 0.60, CI 0.48; 0.75), all P<0.0001. CONCLUSIONS: In a population at high risk for perioperative complications from OSA, multimodal analgesia was associated with a stepwise reduction in opioid use and complications, including critical respiratory failure.

Neuraxial anaesthesia techniques and postoperative outcomes among joint arthroplasty patients: is spinal anaesthesia the best option?

BACKGROUND: Neuraxial anaesthesia is frequently used for lower limb arthroplasty but it is unclear whether benefits vary among patients receiving different subtypes of neuraxial anaesthesia. We evaluated whether differences in risk for adverse postoperative outcomes exist between patients receiving combined spinal and epidural (CSE), epidural, or spinal anaesthesia. METHODS: In this retrospective cohort study, we identified 40 852 patients who underwent total hip and knee arthroplasty (THA and TKA) procedures under neuraxial anaesthesia (34 301 CSE, 2464 epidural, 4087 spinal) between 2005 and 2014 at a single institution. We used multivariable logistic regression to evaluate the following outcomes: cardiac, pulmonary, gastrointestinal, renal/genitourinary, and thromboembolic complications, and prolonged length of stay. RESULTS: Compared with CSE, spinal anaesthesia was associated with reduced adjusted odds for cardiac [odds ratio (OR), 0.68; 95% confidence interval (CI), 0.52-0.89], pulmonary (OR: 0.51; 95% CI: 0.38-0.68), gastrointestinal (OR: 0.50; 95% CI: 0.32-0.78), and thromboembolic complications (OR: 0.40; 95% CI: 0.23-0.73), and prolonged length of stay (OR: 0.72; 95% CI: 0.66-0.80). Patients who received epidural anaesthesia did not have significantly different odds for any outcomes compared with CSE patients. CONCLUSIONS: We identified clear differences in risk for certain postoperative events by subtype of neuraxial anaesthesia, suggesting that spinal anaesthesia is associated with the most favourable outcomes profile.

Proximal femoral growth disturbance in developmental dysplasia of the hip: what do we know?

BACKGROUND: Proximal femoral growth disturbance (PFGD) can be the most devastating complication of the treatment of development dysplasia of the hip. The reported incidence ranges from 0% to 73%. The condition involves varying degrees of growth disturbances of the femoral capital epiphysis, the physeal plate or both. PURPOSE: This manuscript will discuss normal growth and development of the hip, the blood supply to the upper end of the femur, pathological and radiographic changes, classifications used to describe PFGD and, most importantly, the potential causes of these growth disturbances and the authors' strategies for avoiding PFGD.

Ecological and Evolutionary Consequences of Parasite Avoidance.

Predators often cause prey to adopt defensive strategies that reduce predation risk. The 'ecology of fear' examines these trait changes and their consequences. Similarly, parasites can cause hosts to adopt defensive strategies that reduce infection risk. However the ecological and evolutionary consequences of these behaviors (the 'ecology of disgust') are seldom considered. Here we identify direct and indirect effects of parasite avoidance on hosts and parasites, and examine differences between predators and parasites in terms of cost, detectability, and aggregation. We suggest that the nonconsumptive effects of parasites might overshadow their consumptive effects, as has been shown for predators. We emphasize the value of uniting predator-prey and parasite-host theory under a general consumer-resource framework.

No association between circulating concentrations of vitamin D and risk of lung cancer: an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3).

Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3). Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables. Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology. Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.

Postoperative delirium in total knee and hip arthroplasty patients: a study of perioperative modifiable risk factors.

BACKGROUND: Postoperative delirium continues to pose major clinical difficulties. While unmodifiable factors (e.g. age and comorbidity burden) are commonly studied risk factors for delirium, the role of modifiable factors, such as anaesthesia type and commonly used perioperative medications, remains understudied. This study aims to evaluate the role of modifiable factors for delirium after hip and knee arthroplasties. METHODS: We performed a retrospective study of 41 766 patients who underwent hip or knee arthroplasties between 2005 and 2014 at a single institution. Data were collected as part of routine patient care. Multivariable logistic regression models assessed associations between anaesthesia type and commonly used perioperative medications (opioids, benzodiazepines, and ketamine) and postoperative delirium. Odds ratios (OR) and 95% confidence intervals (CI) are reported. Various sensitivity analyses are also considered, including multiple imputation methods to address missing data. RESULTS: Postoperative delirium occurred in 2.21% (n=922) of all patients. While patients who received neuraxial anaesthesia were at lower risk for postoperative delirium (compared with general anaesthesia; epidural OR 0.59 CI 0.38-0.93; spinal OR 0.55 CI 0.37-0.83; combined spinal/epidural OR 0.56 CI 0.40-0.80), those given intraoperative ketamine (OR 1.27 CI 1.01-1.59), opioids (OR 1.25 CI 1.09-1.44), postoperative benzodiazepines (OR 2.47 CI 2.04-2.97), and ketamine infusion (OR 10.59 CI 5.26-19.91) were at a higher risk. CONCLUSIONS: In this cohort of hip and knee arthroplasty patients, anaesthesia type and perioperative medications were associated with increased odds for postoperative delirium. Our results support the notion that modifiable risk factors may exacerbate or attenuate risk for postoperative delirium.

Serum pepsinogen 1 and anti-Helicobacter pylori IgG antibodies as predictors of gastric cancer risk in Finnish males.

BACKGROUND: Serum pepsinogen 1 (SPG1) and anti-Helicobacter pylori serology have been used for gastric risk stratification in Asia. AIM: To assess utility of these markers in a Western population. METHODS: SPG1 measurements were available for 21 895 Finnish male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We used Cox proportional hazards models adjusted for potential confounders to estimate gastric cancer hazard ratios (HR) and 95% confidence intervals (95% CI) for low SPG1 (<25 µg/L). In a subset (n = 3555) with anti-H. pylori serology, these markers jointly defined the following: Group A (H. pylori[-], SPG1[normal]; reference group), Group B (H. pylori[+], SPG1[normal]), Group C (H. pylori[+], SPG1[low]) and Group D (H. pylori[-], SPG1[low]). Odds ratios (ORs) and 95% CI were calculated using multivariate logistic regression. RESULTS: There were 329 gastric cancers diagnosed an average of 13.9 years after baseline. Pre-diagnostic low SPG1 was significantly associated with increased gastric cancer risk (HR 2.68, 95% CI 1.99-3.61). Among subjects with both SPG1 and H. pylori serology, groups B, C and D had increased gastric cancer ORs (95% CI) of 1.79 (1.21-2.64), 3.85 (2.36-6.28) and 6.35 (2.20-18.34), respectively. CagA seropositives had significantly higher ORs than CagA seronegatives within group B (Pheterogeneity  = 0.01). For groups B and C, repeat SPG1 level at 3 years did not further stratify gastric cancer risk. CONCLUSIONS: Low SPG1 was associated with increased gastric cancer risk in our large Finnish cohort. A single measurement of SPG1 along with H. pylori whole cell and CagA serology provides potentially useful prediction of gastric cancer risk.

Special symposium issue: slipped capital femoral epiphysis (SCFE).

Up-date on the pathogenesis, epidemiology, pathology, histopathology, clinical findings, diagnosis & classification, imaging modalities and all treatment options in slipped capital femoral epiphysis. This symposium issue of JCO is based on lectures presented at the Pre-Course at the 35th Annual Congress of the European Paediatric Orthopaedic Society (EPOS) in 2016.

Assessment of disease extent on contrast-enhanced MRI in breast cancer detected at digital breast tomosynthesis versus digital mammography alone.

AIM: To compare the utility of breast magnetic resonance imaging (MRI) in determining the extent of disease in patients with newly diagnosed breast cancer detected on combination digital breast tomosynthesis (DBT) versus digital screening mammography (DM). MATERIALS AND METHODS: Review of 24,563 DBT-screened patients and 10,751 DM-screened patients was performed. Two hundred and thirty-five DBT patients underwent subsequent MRI examinations; 82 to determine extent of disease after newly diagnosed breast cancer. Eighty-three DM patients underwent subsequent MRI examinations; 23 to determine extent of disease. MRI examinations performed to assess disease extent were considered true positives if additional disease was discovered in the contralateral breast or >2 cm away from the index malignancy. Differences in cancer subtypes and MRI outcomes between the DM and DBT cohorts were compared using chi-squared tests and post-hoc Bonferroni-adjusted tests for equal proportions. RESULTS: No differences in cancer subtype findings were observed between the two cohorts; however, MRI outcomes were found to differ between the DBT and DM cohorts (p=0.024). Specifically, the DBT cohort had significantly (p=0.013) fewer true-positive findings (7/82, 8.5%) than did the DM cohort (7/23; 30%), whereas the false-positive rate was similar between the cohorts (not statistically significant). When stratifying by breast density, this difference in true-positive rates was primarily observed when evaluating women with non-dense breasts (p=0.001). CONCLUSION: In both the DM- and DBT-screened populations with new cancer diagnoses, MRI is able to detect additional cancer; however, in those patients who have DBT screen-detected cancers the positive impact of preoperative MRI is diminished, particularly in those women with non-dense breasts.

Baylisascaris procyonis Demography and Egg Production in a California Raccoon Population.

California has more reported human raccoon roundworm cases than any other state due to large and overlapping human and raccoon populations. Infection by this parasite, Baylisascaris procyonis , is relatively benign in raccoons but can cause severe pathology in other species. Disease risk is driven by environmental egg contamination which increases with raccoon density, worm intensity, and worm prevalence. To improve knowledge about risk to humans and other species, 189 raccoons from southern California were examined to investigate how host age and season affect worm abundance, demography, and fecundity. Adult worms were present in animals as young as 10 wk and 100% of 4-mo-old raccoons were infected. Although 80% of sampled raccoons hosted adult B. procyonis , prevalence and abundance were lower in older animals. There were more worms in juvenile than in adult raccoons, resulting in a convex age-intensity profile. Coupled with raccoon demography, this drove fall peaks in parasite abundance and egg production. Eggs per-gram feces averaged 4,606 ± 661 (SE), and this output increased with worm intensity, with no evidence that crowding reduced parasite size or fecundity. High parasite egg outputs from hosts in this California raccoon population increase human exposure risk, and this risk could be reduced by management strategies that target heavily infected juvenile raccoons.

Local envenomation from the bite of a juvenile false water cobra (Hydrodynastes gigas; Dipsadidae).

The false water cobra (Hydrodynastes gigas) is a non-front-fanged colubroid snake frequently exhibited in zoos, and maintained by amateur collectors. Little detailed documentation regarding the time-course of symptoms development and the consequences of their bites to humans has been published. Reported here is a case of envenoming in a 25 yo male that occurred after the bite of a juvenile H. gigas. The victim was bitten on the fourth digit of the left hand while processing the snake for sex determination, and the snake remained attached to the digit for approximately 30 s; there was no jaw advancement. Within 5 min, intense local pain developed, and at 4hr post bite the entire dorsal aspect of the hand was significantly edematous, The local effects progressed and involved the entire forearm, and the local pain referred to the axillary region. Mild paresthesia and local blanching ("pallor") were noted in the affected digit, but resolved within 7 days. The clinical course in the patient showed that moderate localized symptoms may result from the bite of a juvenile H.gigas.

Association of 4p14 TLR locus with antibodies to Helicobacter pylori.

A genome-wide association study among Europeans related polymorphisms of the Toll-like receptor (TLR) locus at 4p14 and the Fcγ receptor 2a locus at 1q23.3 to Helicobacter pylori serologic status. We replicated associations of 4p14 but not 1q23.3 with anti-Helicobacter pylori antibodies in 1402 Finnish males. Importantly, our analysis clarified that the phenotype affected by 4p14 is quantitative level of these antibodies rather than association with seropositivity per se. In addition, we annotated variants at 4p14 as expression quantitative trait loci (eQTL) associated with TLR6/10 and FAM114A1. Our findings suggest that 4p14 polymorphisms are linked to host immune response to H. pylori infection but not to its acquisition.

Incidental biliary adenofibroma with dysplastic features.

We present a case of an incidentally detected cystic liver mass on CT scan, with histology showing biliary epithelium embedded in fibrous stroma and dysplastic features, consistent with an adenofibroma. This is only the third case described in the literature with malignant histology and the first case with angiographic imaging and subsequent management with preoperative embolization prior to surgical resection. We discuss the differential of the imaging findings and the features of this rare entity. Because of the risk of malignant transformation, consideration of this tumour is important to ensure early detection and ultimately resection for improved survival.

Gravity-driven instability of a thin liquid film underneath a soft solid.

The gravity-driven instability of a thin liquid film located underneath a soft solid material is considered. The equations and boundary conditions governing the solid deformation are systematically converted from a Lagrangian representation to an Eulerian representation, which is the natural framework for describing the liquid motion. This systematic conversion reveals that the continuity-of-velocity boundary condition at the liquid-solid interface is more complicated than has previously been assumed, even in the small-strain limit. We then make clear the conditions under which the commonly used simplified version of this boundary condition is valid. The small-strain approximation, lubrication theory, and linear stability analysis are applied to derive an expression for the growth rate of small-amplitude perturbations. Asymptotic analysis reveals that the coupling between the liquid and solid manifests itself as a lower effective liquid-air interfacial tension that leads to larger instability growth rates. Although this suggests that it is more difficult to maintain a stable liquid coating underneath a soft solid, the effect is expected to be weak for cases of practical interest.

Association of serum α-tocopherol, ß-carotene, and retinol with liver cancer incidence and chronic liver disease mortality.

BACKGROUND: Micronutrients may influence the development or progression of liver cancer and liver disease. We evaluated the association of serum α-tocopherol, ß-carotene, and retinol with incident liver cancer and chronic liver disease (CLD) mortality in a prospective cohort of middle-aged Finnish male smokers. METHODS: Baseline and 3-year follow-up serum were available from 29,046 and 22,805 men, respectively. After 24 years of follow-up, 208 men were diagnosed with liver cancer and 237 died from CLD. Hazards ratios and 95% confidence intervals were calculated for highest vs lowest quartiles from multivariate proportional hazards models. RESULTS: Higher ß-carotene and retinol levels were associated with less liver cancer (ß-carotene: 0.35, 0.22-0.55, P-trend <0.0001; retinol: 0.58, 0.39-0.85, P-trend=0.0009) and CLD mortality (ß-carotene: 0.47, 0.30-0.75, P-trend=0.001; retinol: 0.55, 0.38-0.78, P-trend=0.0007). α-Tocopherol was associated with CLD mortality (0.63, 0.40-0.99, P-trend=0.06), but not with liver cancer (1.06, 0.64-1.74, P-trend=0.77). Participants with higher levels of ß-carotene and retinol, but not α-tocopherol, at both baseline and year 3 had lower risk of each outcome than those with lower levels. CONCLUSIONS: Our findings suggest that higher concentrations of ß-carotene and retinol are associated with incident liver cancer and CLD. However, such data do not indicate that supplementation should be considered for these diseases.

Effects of α-tocopherol and ß-carotene supplementation on liver cancer incidence and chronic liver disease mortality in the ATBC study.

BACKGROUND: Recent data suggest the possible benefits of α-tocopherol and ß-carotene supplementation on liver cancer and chronic liver disease (CLD), but the long-term trial data are limited. METHODS: We evaluated the efficacy of supplemental 50 mg day(-1) α-tocopherol and 20 mg day(-1) ß-carotene on incident liver cancer and CLD mortality in a randomised trial of 29,105 Finnish male smokers, who received supplementation for 5-8 years and were followed for 16 additional years for outcomes. RESULTS: Supplemental α-tocopherol, ß-carotene, or both, relative to placebo, did not reduce the risk of liver cancer or CLD, either overall, during the intervention or during the post-intervention period. CONCLUSIONS: Long-term supplemental α-tocopherol or ß-carotene had no effect on liver cancer or CLD mortality over 24 years of follow-up.