Post-diagnosis adiposity, physical activity, sedentary behaviour, dietary factors, supplement use and colorectal cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading.

Based on the World Cancer Research Fund Global Cancer Update Programme, we performed systematic reviews and meta-analyses to investigate the association of post-diagnosis adiposity, physical activity, sedentary behaviour, and dietary factors with colorectal cancer prognosis. We searched PubMed and Embase until 28th February, 2022. An independent expert committee and expert panel graded the quality of evidence. A total of 167 unique publications were reviewed, and all but five were observational studies. The quality of the evidence was graded conservatively due to the high risk of several biases. There was evidence of non-linearity in the associations between body mass index and colorectal cancer prognosis. The associations appeared reverse J-shaped, and the quality of this evidence was graded as limited (likelihood of causality: limited-no conclusion). The evidence on recreational physical activity and lower risk of all-cause mortality (relative risk [RR] highest vs. lowest: 0.69, 95% confidence interval [CI]: 0.62-0.77) and recurrence/disease-free survival (RR: 0.80, 95% CI: 0.70-0.92) was graded as limited-suggestive. There was limited-suggestive evidence for the associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), intake of whole grains and coffee with lower risk of all-cause mortality, and between unhealthy dietary patterns and intake of sugary drinks with higher risk of all-cause mortality. The evidence for other exposures on colorectal cancer outcomes was sparse and graded as limited-no conclusion. Analyses were conducted excluding cancer patients with metastases without substantial changes in the findings. Well-designed intervention and cohort studies are needed to support the development of lifestyle recommendations for colorectal cancer patients.

Post-diagnosis physical activity and sedentary behaviour and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

Low physical activity and high sedentary behaviour have been clearly linked with colorectal cancer development, yet data on their potential role in colorectal cancer survival is limited. Better characterisation of these relationships is needed for the development of post-diagnosis physical activity and sedentary behaviour guidance for colorectal cancer survivors. We searched PubMed and Embase through 28 February 2022 for studies assessing post-diagnosis physical activity, and/or sedentary behaviour in relation to all-cause and cause-specific mortality and recurrence after colorectal cancer diagnosis. Total and recreational physical activity were assessed overall and by frequency, duration, intensity, and volume using categorical, linear, and non-linear dose-response random-effects meta-analyses. The Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel interpreted and graded the likelihood of causality. We identified 16 observational studies on 82,220 non-overlapping patients from six countries. Physical activity was consistently inversely associated with colorectal cancer morbidity and mortality outcomes, with 13%-60% estimated reductions in risk. Sedentary behaviour was positively associated with all-cause mortality. The evidence had methodological limitations including potential confounding, selection bias and reverse causation, coupled with a limited number of studies for most associations. The CUP Global Expert panel concluded limited-suggestive evidence for recreational physical activity with all-cause mortality and cancer recurrence. Total physical activity and its specific domains and dimensions, and sedentary behaviour were all graded as limited-no conclusion for all outcomes. Future research should focus on randomised trials, while observational studies should obtain objective and repeated physical activity measures and better adjustment for confounders.

Post-diagnosis dietary factors, supplement use and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

The role of diet in colorectal cancer prognosis is not well understood and specific lifestyle recommendations are lacking. We searched for randomised controlled trials (RCTs) and longitudinal observational studies on post-diagnosis dietary factors, supplement use and colorectal cancer survival outcomes in PubMed and Embase from inception until 28th February 2022. Random-effects dose-response meta-analyses were conducted when at least three studies had sufficient information. The evidence was interpreted and graded by the CUP Global independent Expert Committee on Cancer Survivorship and Expert Panel. Five RCTs and 35 observational studies were included (30,242 cases, over 8700 all-cause and 2100 colorectal cancer deaths, 3700 progression, recurrence, or disease-free events). Meta-analyses, including 3-10 observational studies each, were conducted for: whole grains, nuts/peanuts, red and processed meat, dairy products, sugary drinks, artificially sweetened beverages, coffee, alcohol, dietary glycaemic load/index, insulin load/index, marine omega-3 polyunsaturated fatty acids, supplemental calcium, circulating 25-hydroxyvitamin D (25[OH]D) and all-cause mortality; for alcohol, supplemental calcium, circulating 25(OH)D and colorectal cancer-specific mortality; and for circulating 25(OH)D and recurrence/disease-free survival. The overall evidence was graded as 'limited'. The inverse associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), whole grains, total, caffeinated, or decaffeinated coffee and all-cause mortality and the positive associations between unhealthy dietary patterns, sugary drinks and all-cause mortality provided 'limited-suggestive' evidence. All other exposure-outcome associations provided 'limited-no conclusion' evidence. Additional, well-conducted cohort studies and carefully designed RCTs are needed to develop specific lifestyle recommendations for colorectal cancer survivors.

Post-diagnosis adiposity and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

The adiposity influence on colorectal cancer prognosis remains poorly characterised. We performed a systematic review and meta-analysis on post-diagnosis adiposity measures (body mass index [BMI], waist circumference, waist-to-hip ratio, weight) or their changes and colorectal cancer outcomes. PubMed and Embase were searched through 28 February 2022. Random-effects meta-analyses were conducted when at least three studies had sufficient information. The quality of evidence was interpreted and graded by the Global Cancer Update Programme (CUP Global) independent Expert Committee on Cancer Survivorship and Expert Panel. We reviewed 124 observational studies (85 publications). Meta-analyses were possible for BMI and all-cause mortality, colorectal cancer-specific mortality, and cancer recurrence/disease-free survival. Non-linear meta-analysis indicated a reverse J-shaped association between BMI and colorectal cancer outcomes (nadir at BMI 28 kg/m2). The highest risk, relative to the nadir, was observed at both ends of the BMI distribution (18 and 38 kg/m2), namely 60% and 23% higher risk for all-cause mortality; 95% and 26% for colorectal cancer-specific mortality; and 37% and 24% for cancer recurrence/disease-free survival, respectively. The higher risk with low BMI was attenuated in secondary analyses of RCTs (compared to cohort studies), among studies with longer follow-up, and in women suggesting potential methodological limitations and/or altered physiological state. Descriptively synthesised studies on other adiposity-outcome associations of interest were limited in number and methodological quality. All the associations were graded as limited (likelihood of causality: no conclusion) due to potential methodological limitations (reverse causation, confounding, selection bias). Additional well-designed observational studies and interventional trials are needed to provide further clarification.

Fascia Iliaca Blocks Performed in the Emergency Department Decrease Opioid Consumption and Length of Stay in Patients with Hip Fracture.

OBJECTIVES: To examine the impact of fascia iliaca (FI) blocks performed in the emergency department on patients with hip fracture on opioid consumption, length of stay, and readmission rate. DESIGN: Prospective cohort study. SETTING: Community-based Level 1 trauma center. PATIENTS/PARTICIPANTS: Ninety-eight patients with isolated femoral neck, intertrochanteric, and subtrochanteric femur fractures (OTA/AO 31-A and 31-B) presenting from January 1, 2020, to June 30, 2020. INTERVENTION: Ultrasound-guided FI compartment block using 40 mL of 0.25% bupivacaine. MAIN OUTCOME MEASUREMENTS: Opioid consumption, length of stay, discharge disposition, and 30-day readmission rate. RESULTS: Thirty-three patients had contraindication to FI block. Thirty-nine of 65 patients (60%) without contraindications to undergoing FIB received FI block. Mean age, body mass index, fracture type, and surgical procedure were similar between patients undergoing FIB and not receiving FIB. The FIB group had significantly lower opioid consumption preoperatively [17.4 vs. 32.0 morphine milliequivalents (MMEs)], postoperatively (37.1 vs. 85.5 MMEs), over total hospital stay (54.5 vs. 117.5 MMEs), and mean opioid consumption per day of hospital stay (13.3 vs. 24.0 MMEs). Patients in the FIB group had shorter length of stay compared with the control group (4.3 vs. 5.2 days). There was no significant difference in discharge disposition destination between groups. No patients reported complications of FI block. CONCLUSIONS: Undergoing FI block in the emergency department was associated with decreased opioid consumption, decreased length of stay, and decreased hospital readmission within 30 days of hip fracture. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Microfluidic processing of synovial fluid for cytological analysis.

Cytological analysis of synovial fluid is widely used in the clinic to assess joint health and disease. However, in general practice, only the total number of white blood cells (WBCs) are available for cytologic evaluation of the joint. Moreover, sufficient volume of synovial aspirates is critical to run conventional analyses, despite limited volume of aspiration that can normally be obtained from a joint. Therefore, there is a lack of consistent and standardized synovial fluid cytological tests in the clinic. To address these shortcomings, we developed a microfluidic platform (Synovial Chip), for the first time in the literature, to achieve repeatable, cost- and time-efficient, and standardized synovial fluid cytological analysis based on specific cell surface markers. Microfluidic channels functionalized with antibodies against specific cell surface antigens are connected in series to capture WBC subpopulations, including CD4+, CD8+, and CD66b+ cells, simultaneously from miniscule volumes (100 µL) of synovial fluid aspirates. Cell capture specificity was evaluated by fluorescent labeling of isolated cells in microchannels and was around 90% for all three WBC subpopulations. Furthermore, we investigated the effect of synovial fluid viscosity on capture efficiency in the microfluidic channels and utilized hyaluronidase enzyme treatment to reduce viscosity and to improve cell capture efficiency (>60%) from synovial fluid samples. Synovial Chip allows efficient and standardized point-of-care isolation and analysis of WBC subpopulations in miniscule volumes of patient synovial fluid samples in the clinic.

Fission-Produced 99Mo Without a Nuclear Reactor.

99Mo, the parent of the widely used medical isotope 99mTc, is currently produced by irradiation of enriched uranium in nuclear reactors. The supply of this isotope is encumbered by the aging of these reactors and concerns about international transportation and nuclear proliferation. Methods: We report results for the production of 99Mo from the accelerator-driven subcritical fission of an aqueous solution containing low enriched uranium. The predominately fast neutrons generated by impinging high-energy electrons onto a tantalum convertor are moderated to thermal energies to increase fission processes. The separation, recovery, and purification of 99Mo were demonstrated using a recycled uranyl sulfate solution. Conclusion: The 99Mo yield and purity were found to be unaffected by reuse of the previously irradiated and processed uranyl sulfate solution. Results from a 51.8-GBq 99Mo production run are presented.

The influence of emotional facial expressions on gaze-following in grouped and solitary pedestrians.

The mechanisms contributing to collective attention in humans remain unclear. Research indicates that pedestrians utilise the gaze direction of others nearby to acquire environmentally relevant information, but it is not known which, if any, additional social cues influence this transmission. Extending upon previous field studies, we investigated whether gaze cues paired with emotional facial expressions (neutral, happy, suspicious and fearsome) of an oncoming walking confederate modulate gaze-following by pedestrians moving in a natural corridor. We found that pedestrians walking alone were not sensitive to this manipulation, while individuals traveling together in groups did reliably alter their response in relation to emotional cues. In particular, members of a collective were more likely to follow gaze cues indicative of a potential threat (i.e., suspicious or fearful facial expression). This modulation of visual attention dependent on whether pedestrians are in social aggregates may be important to drive adaptive exploitation of social information, and particularly emotional stimuli within natural contexts.

Visual attention and the acquisition of information in human crowds.

Pedestrian crowds can form the substrate of important socially contagious behaviors, including propagation of visual attention, violence, opinions, and emotional state. However, relating individual to collective behavior is often difficult, and quantitative studies have largely used laboratory experimentation. We present two studies in which we tracked the motion and head direction of 3,325 pedestrians in natural crowds to quantify the extent, influence, and context dependence of socially transmitted visual attention. In our first study, we instructed stimulus groups of confederates within a crowd to gaze up to a single point atop of a building. Analysis of passersby shows that visual attention spreads unevenly in space and that the probability of pedestrians adopting this behavior increases as a function of stimulus group size before saturating for larger groups. We develop a model that predicts that this gaze response will lead to the transfer of visual attention between crowd members, but it is not sufficiently strong to produce a tipping point or critical mass of gaze-following that has previously been predicted for crowd dynamics. A second experiment, in which passersby were presented with two stimulus confederates performing suspicious/irregular activity, supports the predictions of our model. This experiment reveals that visual interactions between pedestrians occur primarily within a 2-m range and that gaze-copying, although relatively weak, can facilitate response to relevant stimuli. Although the above aspects of gaze-following response are reproduced robustly between experimental setups, the overall tendency to respond to a stimulus is dependent on spatial features, social context, and sex of the passerby.

Risk, uncertainty and regulation.

This paper reviews the relationship between scientific evidence, uncertainty, risk and regulation. Risk has many different meanings. Furthermore, if risk is defined as the likelihood of an event happening multiplied by its impact, subjective perceptions of risk often diverge from the objective assessment. Scientific evidence may be ambiguous. Scientific experts are called upon to assess risks, but there is often uncertainty in their assessment, or disagreement about the magnitude of the risk. The translation of risk assessments into policy is a political judgement that includes consideration of the acceptability of the risk and the costs and benefits of legislation to reduce the risk. These general points are illustrated with reference to three examples: regulation of risk from pesticides, control of bovine tuberculosis and pricing of alcohol as a means to discourage excessive drinking.

Increasing incidence of Ehrlichia chaffeensis and Anaplasma phagocytophilum in the United States, 2000-2007.

Ehrlichia chaffeensis causes human monocytic ehrlichiosis, and Anaplasma phagocytophilum causes human granulocytic anaplasmosis. These related tick-borne rickettsial organisms can cause severe and fatal illness. During 2000-2007, the reported incidence rate of E. chaffeensis increased from 0.80 to 3.0 cases/million persons/year. The case-fatality rate was 1.9%, and the hospitalization rate was 49%. During 2000-2007, the reported incidence of A. phagocytophilum increased from 1.4 to 3.0 cases/million persons/year. The case-fatality rate was 0.6%, and the hospitalization rate was 36%. Rates among female patients were lower than among male patients for ehrlichiosis (rate ratio = 0.68) and anaplasmosis (rate ratio = 0.70). Most (80%) ehrlichiosis and anaplasmosis cases met only a probable case definition, although, use of a polymerase chain reaction to confirm infections increased during 2000-2007. Heightened reporting of these diseases will likely continue with improving recognition, changing surveillance practices, and appropriate application of diagnostic assays.

Rocky mountain spotted fever in the United States, 2000-2007: interpreting contemporary increases in incidence.

Rocky Mountain spotted fever (RMSF), a potentially fatal tick-borne infection caused by Rickettsia rickettsii, is considered a notifiable condition in the United States. During 2000 to 2007, the annual reported incidence of RMSF increased from 1.7 to 7 cases per million persons from 2000 to 2007, the highest rate ever recorded. American Indians had a significantly higher incidence than other race groups. Children 5-9 years of age appeared at highest risk for fatal outcome. Enzyme-linked immunosorbent assays became more widely available beginning in 2004 and were used to diagnose 38% of cases during 2005-2007. The proportion of cases classified as confirmed RMSF decreased from 15% in 2000 to 4% in 2007. Concomitantly, case fatality decreased from 2.2% to 0.3%. The decreasing proportion of confirmed cases and cases with fatal outcome suggests that changes in diagnostic and surveillance practices may be influencing the observed increase in reported incidence rates.

The gourmet ape: evolution and human food preferences.

This review explores the relation between evolution, ecology, and culture in determining human food preferences. The basic physiology and morphology of Homo sapiens sets boundaries to our eating habits, but within these boundaries human food preferences are remarkably varied, both within and between populations. This does not mean that variation is entirely cultural or learned, because genes and culture may coevolve to determine variation in dietary habits. This coevolution has been well elucidated in some cases, such as lactose tolerance (lactase persistence) in adults, but is less well understood in others, such as in favism in the Mediterranean and other regions. Genetic variation in bitter taste sensitivity has been well documented, and it affects food preferences (eg, avoidance of cruciferous vegetables). The selective advantage of this variation is not clear. In African populations, there is an association between insensitivity to bitter taste and the prevalence of malaria, which suggests that insensitivity may have been selected for in regions in which eating bitter plants would confer some protection against malaria. Another, more general, hypothesis is that variation in bitter taste sensitivity has coevolved with the use of spices in cooking, which, in turn, is thought to be a cultural tradition that reduces the dangers of microbial contamination of food. Our evolutionary heritage of food preferences and eating habits leaves us mismatched with the food environments we have created, which leads to problems such as obesity and type 2 diabetes.

Spatial clustering by disease severity among reported Rocky Mountain spotted fever cases in the United States, 2001-2005.

Rocky Mountain spotted fever (RMSF) occurs throughout much of the United States, ranging in clinical severity from moderate to fatal infection. Yet, little is known about possible differences among severity levels across geographic locations. To identify significant spatial clusters of severe and non-severe disease, RMSF cases reported to Centers for Disease Control and Prevention (CDC) were geocoded by county and classified by severity level. The statistical software program SaTScan was used to detect significant spatial clusters. Of 4,533 RMSF cases reported, 1,089 hospitalizations (168 with complications) and 23 deaths occurred. Significant clusters of 6 deaths (P = 0.05, RR = 11.4) and 19 hospitalizations with complications (P = 0.02, RR = 3.45) were detected in southwestern Tennessee. Two geographic areas were identified in north-central North Carolina with unusually low rates of severity (P = 0.001, RR = 0.62 and P = 0.001, RR = 0.45, respectively). Of all hospitalizations, 20% were clustered in central Oklahoma (P = 0.02, RR = 1.43). Significant geographic differences in severity were observed, suggesting that biologic and/or anthropogenic factors may be impacting RMSF epidemiology in the United States.

Should conservation strategies consider spatial generality? Farmland birds show regional not national patterns of habitat association.

A key assumption underlying any management practice implemented to aid wildlife conservation is that it will have similar effects on target species across the range it is applied. However, this basic assumption is rarely tested. We show that predictors [nearly all associated with agri-environment scheme (AES) options known to affect European birds] had similar effects for 11 bird species on sites with differing farming practice (pastoral vs. mixed farming) or which differed in the density at which the species was found. However, predictors from sites in one geographical region tended to have different effects in other areas suggesting that AES options targeted at a regional scale are more likely to yield beneficial results for farmland birds than options applied uniformly in national schemes. Our study has broad implications for designing conservation strategies at an appropriate scale, which we discuss.

Rabies surveillance in the United States during 2005.

During 2005, 49 states and Puerto Rico reported 6,417 cases of rabies in nonhuman animals and 1 case in a human being to the CDC, representing a 6.2% decrease from the 6,836 cases in nonhuman animals and 8 cases in human beings reported in 2004. Approximately 92% of the cases were in wildlife, and 8% were in domestic animals. Relative contributions by the major animal groups were as follows: 2,534 raccoons (39.5%), 1,478 skunks (23%), 1,408 bats (21.9%), 376 foxes (5.9%), 269 cats (4.2%), 93 cattle (1.5%), and 76 dogs (1.2%). Compared with numbers of reported cases in 2004, cases in 2005 decreased among all groups, except bats, horses, and other wild animals. Decreases in numbers of rabid raccoons during 2005 were reported by 10 of the 20 eastern states in which raccoon rabies was enzootic and decreased overall by 1.2%, compared with 2004. On a national level, the number of rabies cases in skunks during 2005 decreased 20.4% from the number reported in 2004. Once again, Texas reported the greatest number (n = 392) of rabid skunks and the greatest overall state total of rabies cases (741). Texas reported no cases of rabies associated with the dog/coyote rabies virus variant and only 8 cases associated with the Texas gray fox rabies virus variant (compared with 22 cases in 2004). The total number of cases of rabies reported nationally in foxes decreased 3.3%, compared with those reported in 2004. The 1,408 cases of rabies reported in bats represented a 3.5% increase over numbers reported in 2005. Cases of rabies in cats, dogs, cattle, and sheep and goats decreased 4.3%, 19.2%, 19.1%, and 10%, respectively, whereas cases reported in horses and mules increased 9.3%. In Puerto Rico, reported cases of rabies in mongooses increased 29.8%, and rabies in domestic animals decreased 37.5%. One case of human rabies was reported from Mississippi during 2005. This case was submitted by the state to the CDC's unexplained deaths project and diagnosed as rabies retrospectively.

Rocky mountain spotted fever in the United States, 1997-2002.

The increased incidence of Rocky Mountain spotted fever (RMSF) in 1997-2002 compared with previous years may be related to enhanced awareness and reporting of RMSF as well as changes in human-vector interaction. However, reports on RMSF mortality underscore the need for physician vigilance in considering a diagnosis of RMSF for febrile individuals potentially exposed to ticks and stress the importance of treating such persons regardless of the presence of a rash.

Rocky Mountain spotted fever in the United States, 1997-2002.

Rocky Mountain spotted fever (RMSF) is the most commonly reported fatal tick-borne disease in the United States. During 1997-2002, 3,649 cases of RMSF were reported to the Centers for Disease Control and Prevention via the National Electronic Telecommunications System for Surveillance; 2,589 case report forms, providing supplemental information, were also submitted. The average annual RMSF incidence during 1997-2002 was 2.2 cases/million persons. The annual incidence increased during 1997-2002 to a rate of 3.8 cases/million persons in 2002. The incidence was lowest among persons aged<5 and 10-29 years, and highest among adults aged 60-69 years. The overall case-fatality rate was 1.4%; the rate peaked in 1998 at 2.9% and declined to 0.7% in 2001 and 2002. Children<5 years of age had a case-fatality rate (5%) that was significantly greater than the rates for age groups<60 years of age, except for that for 40-49 years of age. Continued national surveillance is needed to assess the effectiveness of prevention efforts and early treatment in decreasing severe morbidity and mortality associated with RMSF.