Firearm legislation and firearm mortality in the USA: a cross-sectional, state-level study.

BACKGROUND In an effort to reduce firearm mortality rates in the USA, US states have enacted a range of firearm laws to either strengthen or deregulate the existing main federal gun control law, the Brady Law. We set out to determine the independent association of different firearm laws with overall firearm mortality, homicide firearm mortality, and suicide firearm mortality across all US states. We also projected the potential reduction of firearm mortality if the three most strongly associated firearm laws were enacted at the federal level. METHODS We constructed a cross-sectional, state-level dataset from Nov 1, 2014, to May 15, 2015, using counts of firearm-related deaths in each US state for the years 2008-10 (stratified by intent [homicide and suicide]) from the US Centers for Disease Control and Prevention's Web-based Injury Statistics Query and Reporting System, data about 25 firearm state laws implemented in 2009, and state-specific characteristics such as firearm ownership for 2013, firearm export rates, and non-firearm homicide rates for 2009, and unemployment rates for 2010. Our primary outcome measure was overall firearm-related mortality per 100 000 people in the USA in 2010. We used Poisson regression with robust variances to derive incidence rate ratios (IRRs) and 95% CIs. FINDINGS 31 672 firearm-related deaths occurred in 2010 in the USA (10·1 per 100 000 people; mean state-specific count 631·5 [SD 629·1]). Of 25 firearm laws, nine were associated with reduced firearm mortality, nine were associated with increased firearm mortality, and seven had an inconclusive association. After adjustment for relevant covariates, the three state laws most strongly associated with reduced overall firearm mortality were universal background checks for firearm purchase (multivariable IRR 0·39 [95% CI 0·23-0·67]; p=0·001), ammunition background checks (0·18 [0·09-0·36]; p<0·0001), and identification requirement for firearms (0·16 [0·09-0·29]; p<0·0001). Projected federal-level implementation of universal background checks for firearm purchase could reduce national firearm mortality from 10·35 to 4·46 deaths per 100 000 people, background checks for ammunition purchase could reduce it to 1·99 per 100 000, and firearm identification to 1·81 per 100 000. INTERPRETATION Very few of the existing state-specific firearm laws are associated with reduced firearm mortality, and this evidence underscores the importance of focusing on relevant and effective firearms legislation. Implementation of universal background checks for the purchase of firearms or ammunition, and firearm identification nationally could substantially reduce firearm mortality in the USA. FUNDING None.

Network Analysis Reveals Sex- and Antibiotic Resistance-Associated Antivirulence Targets in Clinical Uropathogens.

Increasing antibiotic resistance among uropathogenic Escherichia coli (UPEC) is driving interest in therapeutic targeting of nonconserved virulence factor (VF) genes. The ability to formulate efficacious combinations of antivirulence agents requires an improved understanding of how UPEC deploy these genes. To identify clinically relevant VF combinations, we applied contemporary network analysis and biclustering algorithms to VF profiles from a large, previously characterized inpatient clinical cohort. These mathematical approaches identified four stereotypical VF combinations with distinctive relationships to antibiotic resistance and patient sex that are independent of traditional phylogenetic grouping. Targeting resistance- or sex-associated VFs based upon these contemporary mathematical approaches may facilitate individualized anti-infective therapies and identify synergistic VF combinations in bacterial pathogens.

Incorporation of tissue-based genomic biomarkers into localized prostate cancer clinics.

Localized prostate cancer (PCa) is a clinically heterogeneous disease, which presents with variability in patient outcomes within the same risk stratification (low, intermediate or high) and even within the same Gleason scores. Genomic tools have been developed with the purpose of stratifying patients affected by this disease to help physicians personalize therapies and follow-up schemes. This review focuses on these tissue-based tools. At present, four genomic tools are commercially available: Decipher™, Oncotype DX®, Prolaris® and ProMark®. Decipher™ is a tool based on 22 genes and evaluates the risk of adverse outcomes (metastasis) after radical prostatectomy (RP). Oncotype DX® is based on 17 genes and focuses on the ability to predict outcomes (adverse pathology) in very low-low and low-intermediate PCa patients, while Prolaris® is built on a panel of 46 genes and is validated to evaluate outcomes for patients at low risk as well as patients who are affected by high risk PCa and post-RP. Finally, ProMark® is based on a multiplexed proteomics assay and predicts PCa aggressiveness in patients found with similar features to Oncotype DX®. These biomarkers can be helpful for post-biopsy decision-making in low risk patients and post-radical prostatectomy in selected risk groups. Further studies are needed to investigate the clinical benefit of these new technologies, the financial ramifications and how they should be utilized in clinics.

Older patients with low Charlson score and high-risk prostate cancer benefit from radical prostatectomy

INTRODUCTION The aim of the study was to identify the appropriate level of Charlson comorbidity index (CCI) in older patients (>70 years) with high-risk prostate cancer (PCa) to achieve survival benefit following radical prostatectomy (RP). METHODS We retrospectively analyzed 1008 older patients (>70 years) who underwent RP with pelvic lymph node dissection for high-risk prostate cancer (preoperative prostate-specific antigen >20 ng/mL or clinical stage ≥T2c or Gleason ≥8) from 14 tertiary institutions between 1988 and 2014. The study population was further grouped into CCI < 2 and ≥2 for analysis. Survival rate for each group was estimated with Kaplan-Meier method and competitive risk Fine-Gray regression to estimate the best explanatory multivariable model. Area under the curve (AUC) and Akaike information criterion were used to identify ideal 'Cut off' for CCI. RESULTS The clinical and cancer characteristics were similar between the two groups. Comparison of the survival analysis using the Kaplan-Meier curve between two groups for non-cancer death and survival estimations for 5 and 10 years shows significant worst outcomes for patients with CCI ≥ 2. In multivariate model to decide the appropriate CCI cut-off point, we found CCI 2 has better AUC and p value in log rank test. CONCLUSION Older patients with fewer comorbidities harboring high-risk PCa appears to benefit from RP. Sicker patients are more likely to die due to non-prostate cancer-related causes and are less likely to benefit from RP.

Nonlesions, misdiagnoses, missed diagnoses, and other interpretive challenges in fish histopathology studies: a guide for investigators, authors, reviewers, and readers.

Differentiating salient histopathologic changes from normal anatomic features or tissue artifacts can be decidedly challenging, especially for the novice fish pathologist. As a consequence, findings of questionable accuracy may be reported inadvertently, and the potential negative impacts of publishing inaccurate histopathologic interpretations are not always fully appreciated. The objectives of this article are to illustrate a number of specific morphologic findings in commonly examined fish tissues (e.g., gills, liver, kidney, and gonads) that are frequently either misdiagnosed or underdiagnosed, and to address related issues involving the interpretation of histopathologic data. To enhance the utility of this article as a guide, photomicrographs of normal and abnormal specimens are presented. General recommendations for generating and publishing results from histopathology studies are additionally provided. It is hoped that the furnished information will be a useful resource for manuscript generation, by helping authors, reviewers, and readers to critically assess fish histopathologic data.

Low correlation between self-report and medical record documentation of urinary tract infection symptoms.

BACKGROUND Correlations between symptom documentation in medical records and patient self-report (SR) vary depending on the condition studied. Patient symptoms are particularly important in urinary tract infection (UTI) diagnosis, and this correlation for UTI symptoms is currently unknown. METHODS This is a cross-sectional survey study in hospitalized patients with Escherichia coli bacteriuria. Patients were interviewed within 24 hours of diagnosis for the SR of UTI symptoms. We reviewed medical records for UTI symptoms documented by admitting or treating inpatient physicians (IPs), nurses (RNs), and emergency physicians (EPs). The level of agreement between groups was assessed using Cohen κ coefficient. RESULTS Out of 43 patients, 34 (79%) self-reported at least 1 of 6 primary symptoms. The most common self-reported symptoms were urinary frequency (53.5%); retention (41.9%); flank pain, suprapubic pain, and fatigue (37.2% each); and dysuria (30.2%). Correlation between SR and medical record documentation was slight to fair (κ, 0.06-0.4 between SR and IPs and 0.09-0.5 between SR and EDs). Positive agreement was highest for dysuria and frequency. CONCLUSION Correlation between self-reported UTI symptoms and health care providers' documentation was low to fair. Because medical records are a vital source of information for clinicians and researchers and symptom assessment and documentation are vital in distinguishing UTI from asymptomatic bacteriuria, efforts must be made to improve documentation.

Methods for assessment of keel bone damage in poultry

Keel bone damage (KBD) is a critical issue facing the laying hen industry today as a result of the likely pain leading to compromised welfare and the potential for reduced productivity. Recent reports suggest that damage, while highly variable and likely dependent on a host of factors, extends to all systems (including battery cages, furnished cages, and non-cage systems), genetic lines, and management styles. Despite the extent of the problem, the research community remains uncertain as to the causes and influencing factors of KBD. Although progress has been made investigating these factors, the overall effort is hindered by several issues related to the assessment of KBD, including quality and variation in the methods used between research groups. These issues prevent effective comparison of studies, as well as difficulties in identifying the presence of damage leading to poor accuracy and reliability. The current manuscript seeks to resolve these issues by offering precise definitions for types of KBD, reviewing methods for assessment, and providing recommendations that can improve the accuracy and reliability of those assessments.

Causes of keel bone damage and their solutions in laying hens

Keel bone damage (KBD) is a critical issue facing the contemporary laying hen industry due to the likely pain leading to compromised welfare and reduced productivity. Recent reports suggest that KBD, while highly variable and likely dependent on a host of factors, extends to all housing systems (including traditional battery cages, furnished cages and non-cage systems), genetic lines, and management styles. Despite the extent of the problem, the research community remains uncertain as to the causes and influencing factors of KBD. To combat these issues, the current review was produced following discussions from the 1st International Keel Bone Damage Workshop held in Switzerland in April 2014. This exercise sought to assess current knowledge, foster novel collaborations, propose unique methodologies and highlight the key areas where innovative research is needed. The following paper is based on the content of those discussions and presents nine recommendations for future research efforts.

Effects of divergent selection for growth on egg quality traits in Japanese quail

The experiment was designed to investigate the impact of selection for increased body mass on external and internal egg quality traits of Japanese quail. Three hundred and sixty Japanese quail, divergently selected over three generations for different body mass at 4 weeks of age, were used. Quail were homogeneously divided into three groups each consisting of 120 birds: high body mass (HBM), low body mass (LBM) and Control. ANOVA was used to detect the effect of selection on egg quality. In addition, correlation between external and internal egg quality traits was measured. Our results revealed thatHBMquail laid heavier eggs (P = 0.03 compared with LBM but not significantly different with Control quail) with a higher external (shell thickness, shell weight, eggshell ratio and eggshell density, P = 0.0001) and internal egg quality score (albumen weight, P = 0.003; albumen ratio, P = 0.01; albumen height, yolk height, yolk index and Haugh unit, P = 0.0001) when compared with both the Control and LBM. The egg surface area and yolk diameter were significantly higher in HBM when compared with the LBM but not with the Control line. Egg weight was positively correlated with albumen weight (r = 0.54, P = 0.0001), albumen ratio (r = 0.14, P = 0.05), yolk height (r = 0.27, P = 0.0001), yolk weight (r = 0.23, P = 0.002), yolk diameter (r = 0.14, P = 0.05) and yolk index (r = 0.21, P = 0.005) but was negatively correlated with yolk ratio (r = –0.16, P = 0.03). Our results indicate that selection for higher body mass might result in heavier eggs and superior egg quality.

Effects of variation in nest curtain design on pre-laying behaviour of domestic hens

Laying hens in loose-housing systems select a nest daily in which to lay their eggs among many identical looking nests, they often prefer corner nests. We investigated whether heterogeneity in nest curtain appearance – via colours and symbols – would influence nest selection and result in an even distribution of eggs among nests. We studied pre-laying behaviour in groups of 30 LSL hens across two consecutive trials with eight groups per trial. Half of the groups had access to six identical rollaway group-nests, while the others had access to six nests of the same type differing in outer appearance. Three colours (red, green, yellow) and three black symbols (cross, circle, rectangle) were used to create three different nest curtain designs per pen. Nest position and the side of entrance to the pens were changed at 28 and 30 weeks of age, respectively, whereby the order of changes was counterbalanced across trials. Nest positions were numbered 1–6, with nest position 1 representing the nest closest to the pen entrance. Eggs were counted per nest daily from week of age 18 to 33. Nest visits were recorded individually with an RFID system for the first 5 h of light throughout weeks 24–33. Hens with access to nests differing in curtain appearance entered fewer nests daily than hens with identical nests throughout the study but both groups entered more nests with increasing age. We found no other evidence that curtain appearance affected nest choice and hens were inconsistent in their daily nest selection. A high proportion of eggs were laid in corner nests especially during the first three weeks of lay. The number of visits per egg depended upon nest position and age: it increased with age and was higher after the nest position change than before in nest position 1, whereas it stayed stable over time in nest position 6. At 24 weeks of age, gregarious nest visits (hens visiting an occupied nest when there was at least one unoccupied nest) and solitary nest visits (hens visiting an unoccupied nest when there was at least one occupied nest) accounted for a similar amount of nest visits, however, after the door switch, gregarious nest visits made up more than half of all nest visits, while the number of solitary nest visits had decreased. The visual cues were too subtle or inadequate for hens to develop individual preferences while nest position, entrance side, age and nest occupancy affected the quantity and type of nest visits.

Modification of aviary design reduces incidence of falls, collisions and keel bone damage in laying hens

Non-cage housing systems for laying hens such as aviaries provide greater freedom to perform species-specific behavior and thus are thought to improve welfare of the birds; however, aviaries are associated with a high prevalence of keel bone damage (fractures and deviations), which is a major welfare problem in commercial laying hens. Potential causes of keel bone damage are falls and collisions with internal housing structures that occur as birds move between tiers or perches in the aviary. The aim of this study was to investigate the scope for reducing keel bone damage by reducing falls and collisions through modifications of aviary design. Birds were kept in 20 pens in a laying hen house (225 hens per pen) that were assigned to four different treatments (n = 5 pens per treatment group) including (1) control pens and pens modified by the addition of (2) perches, (3) platforms and (4) ramps. Video recordings at 19, 22, 29, 36 and 43 weeks of age were used to analyze controlled movements and falls (including details on occurrence of collision, cause of fall, height of fall and behavior after fall) during the transitional dusk and subsequent dark phase. Palpation assessments (focusing on fractures and deviations) using 20 focal hens per pen were conducted at 18, 20, 23, 30, 37, 44, 52 and 60 weeks of age. In comparison to the control group, we found 44% more controlled movements in the ramp (P = 0.003) and 47% more controlled movements in the platform treatments (P = 0.014) as well as 45% fewer falls (P = 0.006) and 59% fewer collisions (P < 0.001) in the ramp treatment. There were no significant differences between the control and perch treatments. Also, at 60 weeks of age, 23% fewer fractured keel bones were found in the ramp compared with the control treatment (P = 0.0053). After slaughter at 66 weeks of age, no difference in keel bone damage was found between treatment groups and the prevalence of fractures increased to an average of 86%. As a potential mechanism to explain the differences in locomotion, we suggest that ramps facilitated movement in the vertical plane by providing a continuous path between the tiers and thus supported more natural behavior (i.e. walking and running) of the birds. As a consequence of reducing events that potentially damage keel bones, the installation of ramps may have reduced the prevalence of keel fractures for a major portion of the flock cycle. We conclude that aviary design and installation of specific internal housing structures (i.e. ramps and platforms) have considerable potential to reduce keel bone damage of laying hens in aviary systems.

Pitfalls of practicing cancer epidemiology in resource-limited settings: the case of survival and loss to follow-up after a diagnosis of Kaposi's sarcoma in five countries across sub-Saharan Africa.

BACKGROUND Survival after diagnosis is a fundamental concern in cancer epidemiology. In resource-rich settings, ambient clinical databases, municipal data and cancer registries make survival estimation in real-world populations relatively straightforward. In resource-poor settings, given the deficiencies in a variety of health-related data systems, it is less clear how well we can determine cancer survival from ambient data. METHODS We addressed this issue in sub-Saharan Africa for Kaposi's sarcoma (KS), a cancer for which incidence has exploded with the HIV epidemic but for which survival in the region may be changing with the recent advent of antiretroviral therapy (ART). From 33 primary care HIV Clinics in Kenya, Uganda, Malawi, Nigeria and Cameroon participating in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortia in 2009-2012, we identified 1328 adults with newly diagnosed KS. Patients were evaluated from KS diagnosis until death, transfer to another facility or database closure. RESULTS Nominally, 22% of patients were estimated to be dead by 2 years, but this estimate was clouded by 45% cumulative lost to follow-up with unknown vital status by 2 years. After adjustment for site and CD4 count, age <30 years and male sex were independently associated with becoming lost. CONCLUSIONS In this community-based sample of patients diagnosed with KS in sub-Saharan Africa, almost half became lost to follow-up by 2 years. This precluded accurate estimation of survival. Until we either generally strengthen data systems or implement cancer-specific enhancements (e.g., tracking of the lost) in the region, insights from cancer epidemiology will be limited.

Total disc arthroplasty versus anterior cervical interbody fusion: use of the Spine Tango registry to supplement the evidence from randomized control trials.

BACKGROUND CONTEXT Several randomized controlled trials (RCTs) have compared patient outcomes of anterior (cervical) interbody fusion (AIF) with those of total disc arthroplasty (TDA). Because RCTs have known limitations with regard to their external validity, the comparative effectiveness of the two therapies in daily practice remains unknown. PURPOSE This study aimed to compare patient-reported outcomes after TDA versus AIF based on data from an international spine registry. STUDY DESIGN AND SETTING A retrospective analysis of registry data was carried out. PATIENT SAMPLE Inclusion criteria were degenerative disc or disc herniation of the cervical spine treated by single-level TDA or AIF, no previous surgery, and a Core Outcome Measures Index (COMI) completed at baseline and at least 3 months' follow-up. Overall, 987 patients were identified. OUTCOME MEASURES Neck and arm pain relief and COMI score improvement were the outcome measures. METHODS Three separate analyses were performed to compare TDA and AIF surgical outcomes: (1) mimicking an RCT setting, with admission criteria typical of those in published RCTs, a 1:1 matched analysis was carried out in 739 patients; (2) an analysis was performed on 248 patients outside the classic RCT spectrum, that is, with one or more typical RCT exclusion criteria; (3) a subgroup analysis of all patients with additional follow-up longer than 2 years (n=149). RESULTS Matching resulted in 190 pairs with an average follow-up of 17 months that had no residual significant differences for any patient characteristics. Small but statistically significant differences in outcome were observed in favor of TDA, which are potentially clinically relevant. Subgroup analyses of atypical patients and of patients with longer-term follow-up showed no significant differences in outcome between the treatments. CONCLUSIONS The results of this observational study were in accordance with those of the published RCTs, suggesting substantial pain reduction both after AIF and TDA, with slightly greater benefit after arthroplasty. The analysis of atypical patients suggested that, in patients outside the spectrum of clinical trials, both surgical interventions appeared to work to a similar extent to that shown for the cohort in the matched study. Also, in the longer-term perspective, both therapies resulted in similar benefits to the patients.