US of the Penis: Beyond Erectile Dysfunction.

High-frequency US, with a linear transducer and gray-scale, color, and spectral Doppler US techniques, is the primary imaging modality for evaluation of the penis. It can allow delineation of anatomy and assessment of dynamic blood flow; it is easily available and noninvasive or minimally invasive; it is cost effective; and it is well tolerated by patients. US assessment after pharmacologic induction of erection is an additional tool in assessing patients with suspected vasculogenic impotence, and also in selected patients with penile trauma and suspected Peyronie disease. Penile injuries, life-threatening infections, and vascular conditions such as priapism warrant rapid diagnosis to prevent long-term morbidities due to clinical misdiagnosis or delayed treatment. US can facilitate a timely diagnosis in these emergency conditions, even at the point of care such as the emergency department, which can facilitate timely treatment. In addition, color and spectral Doppler US are valuable applications in the follow-up of patients treated with endovascular revascularization procedures for vasculogenic erectile dysfunction. Image optimization and attention to meticulous techniques including Doppler US is vital to improve diagnostic accuracy. Radiologists should be familiar with the detailed US anatomy, pathophysiologic characteristics, scanning techniques, potential pitfalls, and US manifestations of a wide spectrum of vascular and nonvascular penile conditions to suggest an accurate diagnosis and direct further management. The authors review a range of common and uncommon abnormalities of the penis, highlight their key US features, discuss differential diagnosis considerations, and briefly review management. ©RSNA, 2024 Supplemental material is available for this article.

SARS-CoV-2 rapidly evolves lineage-specific phenotypic differences when passaged repeatedly in immune-naïve mice.

The persistence of SARS-CoV-2 despite the development of vaccines and a degree of herd immunity is partly due to viral evolution reducing vaccine and treatment efficacy. Serial infections of wild-type (WT) SARS-CoV-2 in Balb/c mice yield mouse-adapted strains with greater infectivity and mortality. We investigate if passaging unmodified B.1.351 (Beta) and B.1.617.2 (Delta) 20 times in K18-ACE2 mice, expressing the human ACE2 receptor, in a BSL-3 laboratory without selective pressures, drives human health-relevant evolution and if evolution is lineage-dependent. Late-passage virus causes more severe disease, at organism and lung tissue scales, with late-passage Delta demonstrating antibody resistance and interferon suppression. This resistance co-occurs with a de novo spike S371F mutation, linked with both traits. S371F, an Omicron-characteristic mutation, is co-inherited at times with spike E1182G per Nanopore sequencing, existing in different within-sample viral variants at others. Both S371F and E1182G are linked to mammalian GOLGA7 and ZDHHC5 interactions, which mediate viral-cell entry and antiviral response. This study demonstrates SARS-CoV-2's tendency to evolve with phenotypic consequences, its evolution varying by lineage, and suggests non-dominant quasi-species contribution.

How do we ensure a safe ABO recheck process?

BACKGROUND: Collecting a patient's blood in a correctly labeled pretransfusion specimen tube is essential for accurate ABO typing and safe transfusion. Noncompliance with specimen collection procedures can lead to wrong blood in tube (WBIT) incidents with potentially fatal consequences. Recent WBIT events inspired the investigation of how various institutions currently reduce the risk of these errors and ensure accurate ABO typing of patient samples. MATERIALS AND METHODS: This article describes the techniques employed at various institutions across the United States to mitigate the risk of misidentified pretransfusion patient specimens. Details and considerations for each of these measures are provided. RESULTS: Several institutions require the order for an ABO confirmation specimen, if indicated, to be generated from the transfusion medicine (TM) laboratory. Others issue a dedicated collection tube that is available exclusively from the TM service. Many institutions employ barcoding for electronic positive patient identification. Some use a combination of these strategies, depending on the locations or service lines from which the specimens are collected. CONCLUSION: The description of various WBIT mitigation strategies will inform TM services on practices that may be effective at their respective institutions. Irrespective of the method(s) utilized, institutions should continue to monitor and mitigate specimen misidentification errors to promote sustained safe transfusion practices.

Angiotensin II Type 1 Receptor Antibody-Mediated Kidney Rejection Unresponsive to Treatment.

Allograft rejection is a significant cause of renal transplant failure which needs prompt diagnosis and treatment for graft salvage. Angiotensin II type 1 receptor antibody-mediated rejection (AT1R-AMR) is increasingly being identified as the etiology of antibody-mediated rejection in kidney transplant recipients with allograft rejection but without detectable human leukocyte antigen (HLA) antibodies. While some reports have suggested that AT1R-AMR may be refractory to standard therapy, others have reported improvement or stabilization of graft function. We present two patients in which anti-rejection therapy including therapeutic plasma exchange was unable to salvage the allograft.

Hemolysis dictates monocyte differentiation via two distinct pathways in sickle cell disease vaso-occlusion.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by painful vaso-occlusive crises (VOC) and chronic hemolysis. The mononuclear phagocyte system is pivotal to SCD pathophysiology, but the mechanisms governing monocyte/macrophage differentiation remain unknown. This study examined the influence of hemolysis on circulating monocyte trajectories in SCD. We discovered that hemolysis stimulated CSF-1 production, partly by endothelial cells via Nrf2, promoting classical monocyte (CMo) differentiation into blood patrolling monocytes (PMo) in SCD mice. However, hemolysis also upregulated CCL-2 through IFN-I, inducing CMo transmigration and differentiation into tissue monocyte-derived macrophages. Blocking CMo transmigration by anti-P selectin antibody in SCD mice increased circulating PMo, corroborating that CMo-to-tissue macrophage differentiation occurs at the expense of CMo-to-blood PMo differentiation. We observed a positive correlation between plasma CSF-1/CCL-2 ratios and blood PMo levels in patients with SCD, underscoring the clinical significance of these two opposing factors in monocyte differentiation. Combined treatment with CSF-1 and anti-P selectin antibody more effectively increased PMo numbers and reduced stasis compared with single-agent therapies in SCD mice. Altogether, these data indicate that monocyte fates are regulated by the balance between two heme pathways, Nrf2/CSF-1 and IFN-I/CCL-2, and suggest that the CSF-1/CCL-2 ratio may present a diagnostic and therapeutic target in SCD.

How do we operate a large monthly red blood cell exchange program.

BACKGROUND: Red blood cell (RBC) exchange for sickle cell disease presents unique difficulties due to RBC phenotyping, complex antibody work-ups, large number of RBC units required, and vascular access considerations, any of which can delay the procedure. Multidisciplinary coordination and systemic processes ensure that monthly appointments remain on schedule. STUDY DESIGN AND METHODS: A high-volume chronic RBC exchange program is described, highlighting the importance of multidisciplinary coordination and process improvement strategies involving initial referral, vascular access, order sets, and allocation of antigen-negative or phenotypically matched RBCs. RESULTS: Approximately 50 outpatient RBC exchanges are performed each month with an 82% kept-appointment rate. Specific factors for program success include open communication across services and improvements to referrals and standardized order sets. CONCLUSION: A combination of multidisciplinary coordination and process improvement can ensure the success of a high volume RBC exchange program. Frequent communication of upcoming appointments between the referring hematologists, the hemapheresis clinic, transfusion service, and interventional radiology is critical. Advance notice to the immunohematology reference lab of upcoming appointments is needed to allow enough time for allocating antigen-negative RBCs. Order sets can be leveraged to standardize and streamline RBC exchanges. Lastly, numerous mechanisms help patients compensate for the cognitive sequelae of stroke.

A comparison of four leukapheresis methods to harvest an optimal dose of CD34+ cells: A single center experience.

BACKGROUND: Chemokine receptor CXCR4 antagonist plerixafor (Px) as well as high volume (HV) leukapheresis have been shown to reduce hematopoietic stem progenitor cell (HSPC) mobilization failure rates. However, no direct comparisons of such methods currently exists. METHODS AND MATERIALS: We compared the HSPC collection yield based on basal peripheral blood CD34+ cell numbers in patients diagnosed with multiple myeloma or non-Hodgkin's lymphoma undergoing autologous stem cell transplantation in a retrospective chart review. The leukapheresis methods used included HV versus regular volume (RV) with or without Px. There were 116 patients in the study group while the historical control group had 34 patients. RESULTS AND CONCLUSIONS: Control group underwent RV leukapheresis without Px. Addition of Px or HV in the study group failed to display significant improvement in CD34+ cell collection yield; however, when basal CD34+ cell numbers were taken into account, both Px + RV and HV without Px increased CD34+ cell collection yield. The collection failure rates of HV without Px group were comparable to Px + RV when the basal CD34+ cell numbers were over 20/µl. Of interest, multivariate linear regression analysis did not detect any significant difference between HV versus Px + RV or other leukapheresis methods in CD34 yields or collection failure rates from a single collection after controlling for other factors (sex, age, or underlying disease). In multivariate analysis, pre apheresis CD34+ cell number was significantly and positively associated with the CD34+ cell yields from a single apheresis. In our studies, the majority of patients can be rescued without Px by HV alone as a potential cost saving approach. In summary, trend in our studies reflects that both Px and HV are capable of reducing the mobilization failure rates except the poorest mobilizers, which will need to be validated in larger studies.

3D Printed Osteoblast-Alginate/Collagen Hydrogels Promote Survival, Proliferation and Mineralization at Low Doses of Strontium Calcium Polyphosphate.

The generation of biomaterials via 3D printing is an emerging biotechnology with novel methods that seeks to enhance bone regeneration. Alginate and collagen are two commonly used biomaterials for bone tissue engineering and have demonstrated biocompatibility. Strontium (Sr) and Calcium phosphate (CaP) are vital elements of bone and their incorporation in composite materials has shown promising results for skeletal repair. In this study, we investigated strontium calcium polyphosphate (SCPP) doped 3D printed alginate/collagen hydrogels loaded with MC3T3-E1 osteoblasts. These cell-laden scaffolds were crosslinked with different concentrations of 1% SCPP to evaluate the effect of strontium ions on cell behavior and the biomaterial properties of the scaffolds. Through scanning electron microscopy and Raman spectroscopy, we showed that the scaffolds had a granular surface topography with the banding pattern of alginate around 1100 cm-1 and of collagen around 1430 cm-1. Our results revealed that 2 mg/mL of SCPP induced the greatest scaffold degradation after 7 days and least amount of swelling after 24 h. Exposure of osteoblasts to SCPP induced severe cytotoxic effects after 1 mg/mL. pH analysis demonstrated acidity in the presence of SCPP at a pH between 2 and 4 at 0.1, 0.3, 0.5, and 1 mg/mL, which can be buffered with cell culture medium. However, when the SCPP was added to the scaffolds, the overall pH increased indicating intrinsic activity of the scaffold to buffer the SCPP. Moreover, cell viability was observed for up to 21 days in scaffolds with early mineralization at 0.3, 0.5, and 1 mg/mL of SCPP. Overall, low doses of SCPP proved to be a potential additive in biomaterial approaches for bone tissue engineering; however, the cytotoxic effects due to its pH must be monitored closely.

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

Race/ethnicity and underlying disease influences hematopoietic stem/progenitor cell mobilization response: A single center experience.

BACKGROUND: Whether race/ethnicity plays a role in hematopoietic stem/progenitor cells (HSPC) mobilization in autologous donors has not been studied. We hypothesize that donor characteristic including race/ethnicity, age, sex, body mass index, and diagnostic groups influences HSPC mobilization. Diagnostic groups include healthy allogeneic donors, autologous multiple myeloma (MM) and non-MM donors. STUDY DESIGN AND METHODS: Here, we conducted a single-center retrospective study in 64 autologous patients and 48 allogeneic donors. Autologous donors were patients diagnosed with MM or non-MM. All donors were grouped as African American (AA), White (W), or "Other"(O). RESULTS: Multivariate analysis demonstrated diagnostic group differences for CD34+ cell yields between race/ethnicity. Specifically, non-MM patients had the lowest CD34+ cell yields in AA and O, but not in W. For pre-apheresis peripheral blood (PB) CD34+ cell numbers, race/ethnicity had a significant effect both in bivariate and multivariate analyses. Non-MM patients had the lowest, and AA patients had the highest PB CD34+ cells. The results support the view that past therapies used in MM are likely more conducive of recovery of HSPC. CONCLUSIONS: Our study shows that race/ethnicity and diagnostic group differences influenced CD34+ cell mobilization response across donor types. Interestingly, autologous MM donors with the aid of plerixafor displayed comparable CD34 yields to allogeneic donors. Even though both MM and non-MM donors received plerixafor, non-MM donors had significantly lower CD34 yields among AA and O donors but not in W donors. Larger studies would be required to validate the role of diagnostic groups and race/ethnicity interactions.

Removal of Anti-Thymocyte Globulin by Plasma Exchange in ABO-Incompatible and Positive Crossmatch Kidney Transplant Recipients.

BACKGROUND: Recipients of ABO-incompatible (ABOI) and positive crossmatch (PXM) kidney transplants are at high risk for antibody-mediated acute rejection. Despite aggressive immunosuppression in high-risk patients, the incidence of acute rejection remains considerably higher than in other groups. No published studies have examined plasma concentrations of anti-thymocyte globulin (ATG) in patients undergoing plasma exchange. The objectives of this study were to compare plasma ATG concentrations before and after plasma exchange in ABOI and PXM kidney transplant patients to determine the amount removed. MATERIALS AND METHODS: This prospective pharmacokinetic evaluation enrolled 10 patients undergoing ABOI or PXM kidney transplant at an academic medical center. Blood and waste plasma samples from 5 patients were assayed for total and active ATG concentrations. Patient records were monitored for renal function and rejection rates in the first 6 months post-transplant. RESULTS: Total ATG concentrations decreased a mean of 59.78 ± 13.91% after each plasma exchange session, and active ATG levels decreased a mean of 56.8 ± 17.08%. Mean daily concentrations reflect a lack of expected ATG accumulation. Only 1 of 4 patients had detectable ATG concentrations after 30 days. After 6 months, the incidence of acute rejection in this sample was 44% and graft survival was 89%. CONCLUSIONS: This is the first study to show that plasma exchange removes a substantial amount of ATG in high-risk kidney transplant patients. Based on these results, we believe these high-risk patients have been traditionally underdosed.

Restoring carbapenem efficacy: a novel carbapenem companion targeting metallo-ß-lactamases in carbapenem-resistant Enterobacterales.

BACKGROUND: The dissemination of MBLs compromises effective use of many ß-lactams in the treatment of patients with life-threatening bacterial infections. Predicted global increases in the prevalence of MBL-producing carbapenem-resistant Enterobacterales (CRE) are being realized, yielding infections that are untreatable with existing therapies including newly approved ß-lactam/ß-lactamase inhibitor combinations. Developing MBL inhibitors (MBLIs) now is essential to address the growing threat that MBL-producing CRE pose to patients. METHODS: A novel MBLI series was assessed by susceptibility testing and time-kill assays. Target activity and selectivity was evaluated using bacterial NDM, VIM and IMP enzyme assays and human matrix metallopeptidase enzyme assays, respectively, and cytotoxicity was assessed in HepG2 cells. In vivo efficacy of meropenem/MBLI combinations was evaluated in a mouse thigh infection model using an NDM-1-producing Escherichia coli strain. RESULTS: Combination of MBLIs with carbapenems reduced MICs for NDM/IMP/VIM-producing Enterobacterales by up to 128-fold compared with the carbapenems alone. Supplementation of meropenem with the promising compound 272 reduced the MIC90 from 128 to 0.25 mg/L in a panel of MBL-producing CRE clinical isolates (n = 115). Compound 272 restored the bactericidal activity of meropenem and was non-cytotoxic, potentiating the antimicrobial action of meropenem through specific inhibition of NDM, IMP and VIM. In vivo efficacy was achieved in a mouse thigh infection model with meropenem/272 dosed subcutaneously. CONCLUSIONS: We have developed a series of rationally designed MBLIs that restore activity of carbapenems against NDM/IMP/VIM-producing Enterobacterales. This series warrants further development towards a novel combination therapy that combats antibiotic-resistant organisms, which pose a critical threat to human health.

Non-infectious comorbidity in patients with multiple sclerosis: A national cohort study in Sweden.

BACKGROUND: Comorbidity is of significant concern in multiple sclerosis (MS). Few population-based studies have reported conditions occurring in MS after diagnosis, especially in contemporary cohorts. OBJECTIVE: To explore incident comorbidity, mortality and hospitalizations in MS, stratified by age and sex. METHODS: In a Swedish population-based cohort study 6602 incident MS patients (aged ≥18 years) and 61,828 matched MS-free individuals were identified between 1 January 2008 and 31 December 2016, using national registers. Incidence rates (IRs) and incidence rate ratios (IRRs) with 95% CI were calculated for each outcome. RESULTS: IRs of cardiovascular disease (CVD) were higher among MS patients than MS-free individuals, (major adverse CVD: IRR 1.42; 95% CI 1.12-1.82; hemorrhagic/ischemic stroke: 1.46; 1.05-2.02; transient ischemic attack: 1.65; 1.09-2.50; heart failure: 1.55; 1.15-2.10); venous thromboembolism: 1.42; 1.14-1.77). MS patients also had higher risks of several non-CVDs such as autoimmune conditions (IRR 3.83; 3.01-4.87), bowel dysfunction (2.16; 1.86-2.50), depression (2.38; 2.11-2.68), and fractures (1.32; 1.19-1.47), as well as being hospitalized and to suffer from CVD-related deaths ((1.91; 1.00-3.65), particularly in females (3.57; 1.58-8.06)). CONCLUSION: MS-patients experience a notable comorbidity burden which emphasizes the need for integrated disease management in order to improve patient care and long-term outcomes of MS.

Comparison of blur and magnification effects on stereopsis: overall and meridional, monocularly- and binocularly-induced.

PURPOSE: To determine whether monocularly- and binocularly-induced spherical and meridional blur and aniseikonia had similar effects on stereopsis thresholds. METHODS: Twelve participants with normal binocular vision viewed McGill modified random dot stereograms to determine stereoacuities in a four-alternative forced-choice procedure. Astigmatism was induced by placing trial lenses in front of the eyes. Twenty-three conditions were used, consisting of zero (no lens), +1 D and +2 D spheres and cylinders at axes 180, 45 and 90 in front of the right eye, and the following binocular combinations of both lens powers: R × 180/L × 180, R × 45/L × 45, R × 90/L × 90, R sphere/L sphere, R × 180/L × 90, R × 45/L × 135, R × 90/L × 180. Aniseikonia was induced by placing magnifying lenses in front of the eyes. Twenty-three conditions were used, consisting of zero, 6% and 12% overall magnification and both magnifications at axes 180, 45 and 90 in front of the right eye only, and the following binocular combinations using 3% and 6% lenses: R × 90/L × 90, R × 45/L × 45, R × 180/L × 180, R overall/L overall, R × 90/L × 180, R × 45/L × 135, and R × 180/L × 90. RESULTS: Stereopsis losses for binocular blur effects with parallel axes (non-anisometropic) were the same as for monocular blur effects of the same axes, and these were strongly dependent on axis (spherical blur and ×90 had the greatest effects). Binocular blur effects with orthogonal axes had greater effects than with parallel axes, with the axis combination of the former having no effect (e.g. R × 90/L × 180 was similar to R × 45/L × 135). For induced aniseikonia, splitting the magnifications between the eyes improved stereopsis slightly, and the effects were not dependent on axis. CONCLUSION: Binocular blur affects stereopsis similarly to monocular meridional blur if axes in the two eyes are parallel, whereas the effect is greater if the axes are orthogonal. In meridional aniseikonia, splitting magnification between the right and left lenses produces a small improvement in stereopsis that is independent of axis direction and right/left combination.

Infections in patients with multiple sclerosis: A national cohort study in Sweden.

BACKGROUND: Multiple sclerosis (MS) patients have an increased risk of infections, but few population-based studies have reported infections occurring in MS in the years immediately after diagnosis. OBJECTIVE: To explore incident infections in MS, stratified by age and sex. METHODS: In a Swedish population-based cohort study 6602 incident MS patients (aged ≥18 years), matched at diagnosis with 61,828 matched MS-free individuals were identified between 1st January 2008 and 31st December 2016, using national registers. Incidence rates (IR) and incidence rate ratios (IRR) with 95% CI were calculated for each outcome. RESULTS: The IRRs were 2.54 (95% CI 2.28-2.83) for first serious infection and 1.61 (1.52-1.71) for first non-serious infection. Compared with MS-free individuals, MS patients had higher IRs for skin, respiratory/throat infections, pneumonia/influenza, bacterial, viral, and fungal infections, with the highest IRR observed for urinary tract/kidney infections (2.44; 2.24-2.66). The cumulative incidence for most of these infections was higher among MS patients than MS-free individuals, both 0 to <5 and 5 to <9 years after index date. CONCLUSION: The burden of infections around the time of MS diagnosis and subsequent infection risk, underscore the need for careful considerations regarding the risk-benefit across different disease-modifying therapies.

Red blood cell exchange to avoid intubating a COVID-19 positive patient with sickle cell disease?

As the COVID-19 pandemic continues to claim lives across the globe, insufficient data exists regarding the optimal treatment. It is well known that patients 55 years of age or older and patients with certain chronic diseases are at higher risk of severe illness, including acute respiratory distress syndrome and death. A potentially fatal pulmonary complication of sickle cell disease, acute chest syndrome, can be precipitated by acute infections, including respiratory viruses. We report the case of a patient with sickle cell disease (HbSC) who developed COVID-19 pneumonia and acute chest syndrome who was treated with emergent red blood cell exchange in order to avoid endotracheal intubation.

Diagnostic Ultrasound Services During the Coronavirus Disease (COVID-19) Pandemic.

OBJECTIVE. Nosocomial transmission of coronavirus disease (COVID-19) to frontline health care workers is well known, and health care workers may inadvertently become vectors for onward transmission. Ultrasound (US) service providers are at significant risk because scanning usually requires prolonged close patient contact. The bulky US equipment may also facilitate fomite transmission of disease. With increasing use of point-of-care and portable diagnostic US services, the risk is substantial. CONCLUSION. Our experience and protocols may help service providers with their own effective response against COVID-19.

Development and validation of the Karitane Family Outcomes Tool.

PURPOSE: The purpose of this study was to develop the Karitane Family Outcomes Tool (KFOT), a brief parent-report questionnaire to measure outcomes of Australian Early Parenting Centres (EPCs) and similar programmes worldwide. DESIGN AND METHODS: The study was conducted in two stages. In Stage One, an initial item pool (80 items) was developed via focus group discussions with clinical experts and parents. In Stage Two, three samples of parents were recruited (online community sample: n = 849, clinical sample 1: n = 141, clinical sample 2: n = 109). The online community sample completed the 80-items and then non-normally distributed items were culled, leaving a total item pool of 57 items. The online community sample was then split into two subsamples (subsample 1: n = 650, subsample 2: n = 199). Exploratory factor analysis (EFA) was then conducted on online community subsample 1 and confirmatory factor analysis (CFA) on online community subsample 2 and clinical sample 1. Using clinical sample 2, concurrent validity was assessed by examining correlations between KFOT factor scores with scores on the Parenting Stress Index. Finally, discriminant validity was assessed by examining the KFOTs sensitivity to change following EPC intervention and by comparing KFOT scores of clinical and community samples. RESULTS: EFA revealed 13 items loading onto three factors: "Parental feelings," "Reading cues & meeting the child's needs" and "Perceptions of child behaviour." The factor structure was confirmed using CFA in both the community and clinical samples. Significant differences on all three KFOT factors and on the total score were found between the clinical and community samples, suggesting that the scale is able to discriminate between clinical and nonclinical groups. Significant differences were also found between pre- and postintervention scores, and between pre- and follow-up scores, on all three KFOT factors, providing further indication of discriminant validity. The KFOT factors correlated in the expected direction with scores on the Parenting Stress Index, showing concurrent validity. PRACTICAL IMPLICATIONS: Results indicate that the KFOT is a brief, valid and reliable parent-report scale that can be used by nurses to evaluate outcomes of EPC and similar parenting programmes.

Incident cardiovascular disease in patients diagnosed with multiple sclerosis: A multi-database study.

BACKGROUND: Recent data on rates of cardiovascular disease (CVD) in patients after MS diagnosis are sparse. OBJECTIVE: To describe incident CVD in MS patients after diagnosis compared with a matched non-MS population. METHODS: We conducted a matched cohort study in two separate electronic medical databases, the United States Department of Defense military health care system and the United Kingdom's Clinical Practice Research Datalink GOLD. The study population included all patients with a first recorded diagnosis of MS and no history of CVD or selected measurable comorbidities associated with CVD and matched non-MS patients who were also free of CVD and the CVD associated comorbidities. We identified incident CVD outcomes first recorded after the MS diagnosis / matched date and calculated incidence rates and incidence rate ratios by type of CVD. RESULTS: Rates of venous thromboembolism and peripheral vascular disease were 2-fold higher among MS than non-MS patients in both databases and the risk of myocardial infarction was 2.5 times higher among female MS patients compared with non-MS females in both databases. Other CVD outcomes were not consistent between databases. CONCLUSION: MS patients in the UK and the US have increased risk of venous thromboembolism and peripheral vascular disease. The risk of myocardial infarction is increased among female MS patients.