CDK-independent role of D-type cyclins in regulating DNA mismatch repair.

Although mismatch repair (MMR) is essential for correcting DNA replication errors, it can also recognize other lesions, such as oxidized bases. In G0 and G1, MMR is kept in check through unknown mechanisms as it is error-prone during these cell cycle phases. We show that in mammalian cells, D-type cyclins are recruited to sites of oxidative DNA damage in a PCNA- and p21-dependent manner. D-type cyclins inhibit the proteasomal degradation of p21, which competes with MMR proteins for binding to PCNA, thereby inhibiting MMR. The ability of D-type cyclins to limit MMR is CDK4- and CDK6-independent and is conserved in G0 and G1. At the G1/S transition, the timely, cullin-RING ubiquitin ligase (CRL)-dependent degradation of D-type cyclins and p21 enables MMR activity to efficiently repair DNA replication errors. Persistent expression of D-type cyclins during S-phase inhibits the binding of MMR proteins to PCNA, increases the mutational burden, and promotes microsatellite instability.

Identification of Surgeon Outliers to Improve Cost Efficiency: A Novel Use of the Centers for Medicare and Medicaid Quality Payment Program.

BACKGROUND: Bundled payment programs for total joint arthroplasty (TJA) have become popular among both private and public payers. Because these programs provide surgeons with financial incentives to decrease costs through reconciliation payments, there is an advantage to identifying and emulating cost-efficient surgeons. The objective of this study was to utilize the Centers for Medicare and Medicaid Services (CMS) Quality Payment Program (QPP) in combination with institutional data to identify cost-efficient surgeons within our region and, subsequently, identify cost-saving practice patterns. METHODS: Data was obtained from the CMS QPP for total knee arthroplasty (TKA) and total hip arthroplasty (THA) surgeons within a large metropolitan area from January 2019 to December 2021. A simple linear regression determined the relationship between surgical volume and cost-efficiency. Internal practice financial data determined whether patients of identified surgeons differed with respect to x-ray visits, physical therapy visits, out-of-pocket payments to the practice, and whether surgery was done in hospital or surgical center settings. RESULTS: There were 4 TKA and 3 THA surgeons who were cost-efficiency outliers within our area. Outliers and nonoutlier surgeons had patients who had similar body mass index, American Society of Anesthesiologists Physical Status Score, and age-adjusted Charlson Comorbidity Index scores. Patients of these surgeons had fewer x-ray visits for both TKA and THA (1.06 versus 1.11, P < .001; 0.94 versus 1.15, P < .001) and lower out-of-pocket costs ($86.10 versus $135.46, P < .001; $116.10 versus $177.40, P < .001). If all surgeons performing > 30 CMS cases annually within our practice achieved similar cost-efficiency, the savings to CMS would be $17.2 million for TKA alone ($75,802,705 versus $93,028,477). CONCLUSIONS: The CMS QPP can be used to identify surgeons who perform cost-efficient surgeries. Practice patterns that result in cost savings can be emulated to decrease the cost curve, resulting in reconciliation payments to surgeons and institutions and cost savings to CMS.

Lower Revenue Surplus in Medicare Advantage Versus Private Commercial Insurance for Total Joint Arthroplasty: An Analysis of a Single Payor Source at One Institution.

BACKGROUND: Since the Affordable Care Act was passed in 2010, reductions in Medicare reimbursement have led to larger discrepancies between the relative cost of Medicare patients and privately insured patients. The purpose of this study was to compare reimbursement between Medicare Advantage and other insurance plans in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: Patients of a single commercial payor source who underwent primary unilateral TKA or THA at 1 institution between the dates of January 4 and June 30, 2021, were included (n = 833). Variables included insurance type, medical comorbidities, total costs, and surplus amounts. The primary outcome measure was revenue surplus between Medicare Advantage and Private Commercial plans. t-tests, Analyses of Variance, and Chi-Squared tests were used for analysis. A THA represented 47% of cases and a TKA 53%. Of these patients, 31.5% had Medicare Advantage and 68.5% had Private Commercial insurance. Medicare Advantage patients were older and had higher medical comorbidity risk for both TKA and THA. RESULTS: Significant differences were observed in medical costs between Medicare Advantage and Private Commercial insurance for THA ($17,148 versus $31,260, P < .001) and TKA ($16,723 versus $33,593, P < .001). Additionally, differences were seen in surplus amounts between Medicare Advantage and Private Commercial insurance for THA ($3,504 versus $7,128, P < .001) and TKA ($5,581 versus $10,477, P < .001). Deficits were higher in Private Commercial patients undergoing TKA (15.2 versus 6%, P = .001). CONCLUSION: The lower average surplus associated with Medicare Advantage plans may lead to financial strain on provider groups who care for these patients and face additional overhead costs.

Routine Use of Bladder Scans After Primary Total Joint Arthroplasty is Not Necessary: Results of a Protocol Change.

BACKGROUND: Postoperative urinary retention is a common concern after total joint arthroplasty (TJA) and can cause discomfort, incontinence and, if left untreated, myogenic changes to the bladder. However, overdiagnosis of postoperative urinary retention by bladder scans may lead to unnecessary interventions and delayed discharges. The purpose of this study was to compare the safety of two bladder management protocols following TJA. METHODS: From January 3, 2022 to April 29, 2022, 519 consecutive patients operated on by thirteen surgeons underwent routine postoperative bladder scanning (standard protocol). From February 28, 2022 to April 29, 2022, a new protocol was introduced by three surgeons in 209 consecutive patients using a specific algorithm (selective protocol) so that only symptomatic patients had bladder scans. The primary outcome of interest was catheterization rate. Chi-square and Students t-tests were used for analyses. There were 37.7% of patients in the selective group who received scans. RESULTS: Times to catheterization, readmissions, emergency department visits, and straight catheterization rates (15.0 versus 14.8% P = .999) were similar. More scans in the selective group resulted in intervention (39.2 versus 15.0%, P < .001). Prevoid volumes were higher in the selective protocol (608 versus 448 mL, P < .001). Postvoid volumes were similar (233 versus 223 mL, P = .497). There was one readmission for a urinary tract infection in the standard group and no urinary-related readmissions in the selective group. CONCLUSION: The selective protocol had a higher rate of same day discharge, fewer bladder scans, and did not lead to increased rates of urinary-related complications. These findings suggest that selective bladder scanning for symptomatic patients can be safely instituted for TJA patients.

Comparing Risk Assessment Between Payers and Providers: Inconsistent Agreement in Medical Comorbidity Records for Patients Undergoing Total Joint Arthroplasty.

BACKGROUND: The proper risk adjustment for total hip arthroplasty (THA) and total knee arthroplasty (TKA) relies on an accurate assessment of comorbidity profiles by both the payer and the institution. The purpose of this study was to determine how strongly comorbidities tracked by our institution agreed with the same comorbidities reported by payers in patients undergoing THA and TKA. METHODS: All patients of a single payer undergoing primary THA and TKA at a single institution between January 5, 2021 and March 31, 2022 were included (n = 876). There were 8 commonly collected medical comorbidities obtained from institutional medical records and matched with patient records reported by the payer. Fleiss Kappa tests were used to determine agreement of payer data with institutional records. There were 4 medical risk calculations collected from our institutional records and compared with an insurance member risk score reported by the payer. RESULTS: Comorbidities reported by the institution differed significantly from those reported by payers, with Kappa varying between 0.139 and 0.791 for THA, and 0.062 and 0.768 for TKA. Diabetes was the only condition to demonstrate strong agreement for both procedures (THA; k = 0.791, TKA; k = 0.768). The insurance member risk score demonstrates the closest association with total cost and surplus for THA regardless of insurance type and for TKA procedures paid for with private commercial insurance. CONCLUSION: There is a lack of agreement between medical comorbidities within payer and institutional records for both THA and TKA. These differences may put institutions at a disadvantage within value-based care models and when optimizing patients perioperatively.

Mortality and Complications Following Early Conversion Arthroplasty for Failed Hip Fracture Surgery.

BACKGROUND: Hip fracture in older patients leads to high morbidity and mortality. Patients who are treated surgically but fail acutely face a more complex operation with conversion total hip arthroplasty (THA). This study investigated mortalities and complications in patients who experienced failure within one year following hip fracture surgery requiring conversion THA. METHODS: Patients aged 60 years or more undergoing conversion THA within one year following intertrochanteric or femoral neck fracture were identified and propensity-matched to patients sustaining hip fractures treated surgically but not requiring conversion within the first year. Patients who had two-year follow-up (91 conversions; 247 comparisons) were analyzed for 6-month, 12-month, and 24-month mortalities, 90-day readmissions, surgical complications, and medical complications. RESULTS: Nonunion and screw cutout were the most common indications for conversion THA. Mortalities were similar between groups at 6 months (7.7% conversion versus 6.1% nonconversion, P = .774), 12 months (11% conversion versus 12% nonconversion, P = .999), and 24 months (14% conversion versus 22% nonconversion, P = .163). Survivorships were similar between groups for the entire cohort and by fracture type. Conversion THA had a higher rate of 90-day readmissions (14% versus 3.2%, P = .001), and medical complications (17% versus 6.1%, P = .006). Inpatient and 90-day orthopaedic complications were similar. CONCLUSION: Conversion THA for failed hip fracture surgery had comparable mortality rates to hip fracture surgery, with higher rates of perioperative medical complications and readmissions. Conversion THA following hip fracture represents a potential "second hit" that both surgeons and patients should be aware of with initial decision-making.

VipariNama: RNA viral vectors to rapidly elucidate the relationship between gene expression and phenotype.

Synthetic transcription factors have great promise as tools to help elucidate relationships between gene expression and phenotype by allowing tunable alterations of gene expression without genomic alterations of the loci being studied. However, the years-long timescales, high cost, and technical skill associated with plant transformation have limited their use. In this work, we developed a technology called VipariNama (ViN) in which vectors based on the tobacco rattle virus are used to rapidly deploy Cas9-based synthetic transcription factors and reprogram gene expression in planta. We demonstrate that ViN vectors can implement activation or repression of multiple genes systemically and persistently over several weeks in Nicotiana benthamiana, Arabidopsis (Arabidopsis thaliana), and tomato (Solanum lycopersicum). By exploring strategies including RNA scaffolding, viral vector ensembles, and viral engineering, we describe how the flexibility and efficacy of regulation can be improved. We also show how this transcriptional reprogramming can create predictable changes to metabolic phenotypes, such as gibberellin biosynthesis in N. benthamiana and anthocyanin accumulation in Arabidopsis, as well as developmental phenotypes, such as plant size in N. benthamiana, Arabidopsis, and tomato. These results demonstrate how ViN vector-based reprogramming of different aspects of gibberellin signaling can be used to engineer plant size in a range of plant species in a matter of weeks. In summary, ViN accelerates the timeline for generating phenotypes from over a year to just a few weeks, providing an attractive alternative to transgenesis for synthetic transcription factor-enabled hypothesis testing and crop engineering.

Analysis of Costs Associated With Increased Length of Stay After Total Joint Arthroplasty at a Single Private Practice.

INTRODUCTION: As the demand for total hip arthroplasty (THA) and total knee arthroplasty (TKA) increases, so does the financial burden of these services. Despite efforts to optimize spending and bundled care payments, THA and TKA costs still need to be assessed. Our study explores the relationship between perioperative costs and length of stay (LOS) for THA and TKA. METHODS: A total of 614 patients undergoing THA or TKA at a single private practice with LOS from zero to 3 days were identified. All patients were insured by private or Medicare Advantage insurance from a single provider. Primary outcomes included total costs and their relationship with LOS, classified into surgeon reimbursement, facility costs, and anesthesia costs. Secondary outcomes included readmission rates and discharge disposition. Analyses involved Student t-test, analysis of variance, and chi-square tests. RESULTS: Longer LOS was associated with increased total, facility, and anesthesia costs. Costs for THA patients were stable except for reduced surgeon reimbursement with longer LOS. Patients undergoing TKA experienced an increase in facility costs with longer LOS. Total facility and anesthesia costs increased with LOS for Medicare Advantage patients, but surgeon reimbursement remained stable. Privately insured patients experienced higher total and facility costs but stable surgeon reimbursement and anesthesia costs regardless of LOS. CONCLUSION: Our study shows an increase in total cost with longer LOS, especially pronounced in privately insured patients. A notable reduction was observed in the surgeon reimbursement for Medicare Advantage patients with extended LOS. These findings underscore the need for efficient surgical practices and postoperative care strategies to optimize hospital stays and control costs.

The Effect of Cemented Implants Placed During Initial TKA on Surgical Time and Expenses in Revision TKA.

INTRODUCTION: Revision total knee arthroplasty (rTKA) is a complex procedure that often requires the removal of previous implants. There is little information evaluating the difference between removing cemented or noncemented knee prostheses in revision surgeries. The purpose of this study was to determine whether removing cemented or noncemented implants would affect surgical time and expenses incurred during revision procedures. METHODS: This retrospective cohort study used a single-institution database to identify 300 patients who underwent femoral and tibial implant rTKA from 2016 to 2022 because of mechanical complications (infection cases excluded). Radiographs and surgical reports were used to confirm whether the fixation technique was cemented (N = 243) or noncemented (N = 57). The primary outcomes were surgical time and surgery costs. Secondary outcomes included readmission rates, revision implants used, stem usage, and insurance type. RESULTS: The average surgical time was 121 minutes for noncemented and 128 minutes for cemented procedures (P = 0.118). The 90-day readmission rates for each group were similar at 7.00% for the cemented cohort and 8.77% for the noncemented cohort (P = 0.643). For patients with Medicare Advantage, the respective surgery costs were $1,966 for noncemented and $1,968 for cemented TKA (P = 0.988). For patients with commercial insurance, the respective surgery costs were $4,854 for noncemented and $5,660 for cemented TKA (P = 0.330). CONCLUSION: Primary knee fixation type, cemented or noncemented, did not appear to influence the surgical duration or surgical costs of both-implant revision knee surgery indicated for mechanical complications.

D-type cyclins regulate DNA mismatch repair in the G1 and S phases of the cell cycle, maintaining genome stability.

The large majority of oxidative DNA lesions occurring in the G1 phase of the cell cycle are repaired by base excision repair (BER) rather than mismatch repair (MMR) to avoid long resections that can lead to genomic instability and cell death. However, the molecular mechanisms dictating pathway choice between MMR and BER have remained unknown. Here, we show that, during G1, D-type cyclins are recruited to sites of oxidative DNA damage in a PCNA- and p21-dependent manner. D-type cyclins shield p21 from its two ubiquitin ligases CRL1SKP2 and CRL4CDT2 in a CDK4/6-independent manner. In turn, p21 competes through its PCNA-interacting protein degron with MMR components for their binding to PCNA. This inhibits MMR while not affecting BER. At the G1/S transition, the CRL4AMBRA1-dependent degradation of D-type cyclins renders p21 susceptible to proteolysis. These timely degradation events allow the proper binding of MMR proteins to PCNA, enabling the repair of DNA replication errors. Persistent expression of cyclin D1 during S-phase increases the mutational burden and promotes microsatellite instability. Thus, the expression of D-type cyclins inhibits MMR in G1, whereas their degradation is necessary for proper MMR function in S.

Induction of Bdnf from promoter I following electroconvulsive seizures contributes to structural plasticity in neurons of the piriform cortex.

BACKGROUND: Electroconvulsive therapy (ECT) efficacy is hypothesized to depend on induction of molecular and cellular events that trigger neuronal plasticity. Investigating how electroconvulsive seizures (ECS) impact plasticity in animal models can help inform our understanding of basic mechanisms by which ECT relieves symptoms of depression. ECS-induced plasticity is associated with differential expression of unique isoforms encoding the neurotrophin, brain-derived neurotrophic factor (BDNF). HYPOTHESIS: We hypothesized that cells expressing the Bdnf exon 1-containing isoform are important for ECS-induced structural plasticity in the piriform cortex, a highly epileptogenic region that is responsive to ECS. METHODS: We selectively labeled Bdnf exon 1-expressing neurons in mouse piriform cortex using Cre recombinase dependent on GFP technology (CRE-DOG). We then quantified changes in dendrite morphology and density of Bdnf exon 1-expressing neurons. RESULTS: Loss of promoter I-derived BDNF caused changes in spine density and morphology in Bdnf exon 1-expressing neurons following ECS. CONCLUSIONS: Promoter I-derived Bdnf is required for ECS-induced dendritic structural plasticity in Bdnf exon 1-expressing neurons.

Electroconvulsive seizures influence dendritic spine morphology and BDNF expression in a neuroendocrine model of depression.

BACKGROUND: Electroconvulsive therapy (ECT) is a rapid and effective treatment for major depressive disorder. Chronic stress-induced depression causes dendrite atrophy and deficiencies in brain-derived neurotrophic factor (BDNF), which are reversed by anti-depressant drugs. Electroconvulsive seizures (ECS), an animal model of ECT, robustly increase BDNF expression and stimulate dendritic outgrowth. OBJECTIVE: The present study aims to understand cellular and molecular plasticity mechanisms contributing to the efficacy of ECS following chronic stress-induced depression. METHODS: We quantify Bdnf transcript levels and dendritic spine density and morphology on cortical pyramidal neurons in mice exposed to vehicle or corticosterone and receiving either Sham or ECS treatment. RESULTS: ECS rescues corticosterone-induced defects in spine morphology and elevates Bdnf exon 1 and exon 4-containing transcripts in cortex. CONCLUSIONS: Dendritic spine remodeling and induction of activity-induced BDNF in the cortex represent important cellular and molecular plasticity mechanisms underlying the efficacy of ECS for treatment of chronic stress-induced depression.

BDNF-TrkB signaling in oxytocin neurons contributes to maternal behavior.

Brain-derived neurotrophic factor (Bdnf) transcription is controlled by several promoters, which drive expression of multiple transcripts encoding an identical protein. We previously reported that BDNF derived from promoters I and II is highly expressed in hypothalamus and is critical for regulating aggression in male mice. Here we report that BDNF loss from these promoters causes reduced sexual receptivity and impaired maternal care in female mice, which is concomitant with decreased oxytocin (Oxt) expression during development. We identify a novel link between BDNF signaling, oxytocin, and maternal behavior by demonstrating that ablation of TrkB selectively in OXT neurons partially recapitulates maternal care impairments observed in BDNF-deficient females. Using translating ribosome affinity purification and RNA-sequencing we define a molecular profile for OXT neurons and delineate how BDNF signaling impacts gene pathways critical for structural and functional plasticity. Our findings highlight BDNF as a modulator of sexually-dimorphic hypothalamic circuits that govern female-typical behaviors.

Bdnf mRNA splice variants differentially impact CA1 and CA3 dendrite complexity and spine morphology in the hippocampus.

Brain-derived neurotrophic factor (BDNF) is an activity-dependent neurotrophin critical for neuronal plasticity in the hippocampus. BDNF is encoded by multiple transcripts with alternative 5' untranslated regions (5'UTRS) that display activity-induced targeting to distinct subcellular compartments. While individual Bdnf 5'UTR transcripts influence dendrite morphology in cultured hippocampal neurons, it is unknown whether Bdnf splice variants impact dendrite arborization in functional classes of neurons in the intact hippocampus. Moreover, the contribution of Bdnf 5'UTR splice variants to dendritic spine density and shape has not been explored. We analyzed the structure of CA1 and CA3 dendrite arbors in transgenic mice lacking BDNF production from exon (Ex) 1, 2, 4, or 6 splice variants (Bdnf-e1, -e2, -e4, and -e6-/- mice) and found that loss of BDNF from individual Bdnf mRNA variants differentially impacts the complexity of apical and basal arbors in vivo. Consistent with the subcellular localization studies, Bdnf Ex2 and Ex6 transcripts significantly contributed to dendrite morphology in both CA1 and CA3 neurons. While Bdnf-e2-/- mice showed increased branching proximal to the soma in CA1 and CA3 apical arbors, Bdnf-e6-/- mice showed decreased apical and basal dendrite complexity. Analysis of spine morphology on Bdnf-e6-/- CA1 dendrites revealed changes in the percentage of differently sized spines on apical, but not basal, branches. These results provide further evidence that Bdnf splice variants generate a spatial code that mediates the local actions of BDNF in distinct dendritic compartments on structural and functional plasticity.

Evaluation of DNA aptamers directed to thrombin as potential thrombus imaging agents.

Two DNA aptamers directed against two separate exosites on human alpha-thrombin were evaluated for thrombus-imaging potential. Aptamer ODN 1 is directed to the thrombin substrate binding site (exosite 1). Our finding that ODN 1 competes with fibrin for binding to exosite 1 on thrombin suggests that ODN 1 will not be useful for thrombus imaging. Aptamer ODN 2 is directed against the thrombin heparin binding site (exosite 2). ODN 2 bound to model thrombi that were formed either by clotting purified fibrinogen with thrombin, or by recalcifying citrated plasma. As the thrombin content of thrombi was increased the rate of ODN 2 uptake into preformed thrombi increased, whereas the rate of release of ODN 2 out of preformed thrombi decreased. This in vitro data suggested that ODN 2 might be useful for thrombus imaging because it can bind to exosite 2 on fibrin-bound thrombin. However, in a rabbit jugular vein model using thrombus supplemented with human thrombin, ODN 2 uptake was equal to the ovalbumin control, and did not reflect thrombin content. While the in vitro results with ODN 2 were consistent with thrombus imaging, the rapid clearance of ODN 2 from circulation, combined with slow mass transfer in the clot, seem to work against in vivo thrombin-dependent imaging or washout analysis.

The Internet as a vehicle to communicate health information during a public health emergency: a survey analysis involving the anthrax scare of 2001.

BACKGROUND: The recent public health risks arising from bioterrorist threats and outbreaks of infectious diseases like SARS (Severe Acute Respiratory Syndrome) highlight the challenges of effectively communicating accurate health information to an alarmed public. OBJECTIVE: To evaluate use of the Internet in accessing information related to the anthrax scare in the United States in late 2001, and to strategize about the most effective use of this technology as a communication vehicle during times of public health crises. METHODS: A paper-based survey to assess how individuals obtained health information relating to bioterrorism and anthrax during late 2001. We surveyed 500 randomly selected patients from two ambulatory primary care clinics affiliated with the Brigham and Women's Hospital in Boston, Massachusetts. RESULTS: The response rate was 42%. While traditional media provided the primary source of information on anthrax and bioterrorism, 21% (95% CI, 15%-27%) of respondents reported searching the Internet for this information during late 2001. Respondents reported trusting information from physicians the most, and information from health websites slightly more than information from any traditional media source. Over half of those searching the Internet reported changing their behavior as a result of information found online. CONCLUSIONS: Many people already look to the Internet for information during a public health crisis, and information found online can positively influence behavioral responses to such crises. However, the potential of the Internet to convey accurate health information and advice has not yet been realized. In order to enhance the effectiveness of public-health communication, physician practices could use this technology to pro-actively e-mail their patients validated information. Still, unless Internet access becomes more broadly available, its benefits will not accrue to disadvantaged populations.

Opportunities to enhance patient and physician e-mail contact.

The purpose of our study was to evaluate how e-mail is currently used between physicians and patients in an integrated delivery system, and to identify developments that might promote increased use of this form of communication. A paper-based survey questionnaire was administered to 94 primary care physicians. We evaluated the role e-mail currently plays in a physician's typical work day, physician views on the impact of e-mail on phone use and the barriers to increasing the use of e-mail with patients. 76% of physicians surveyed responded. All respondents currently use e-mail. Close to 75% of physicians use e-mail with their patients, but the vast majority do so with only 1-5% of those patients. 50% of physicians believe that up to 25% of their patients would send e-mail to them if given the option, with an additional 37% believing that between 25% and 50% of patients would value this option. The main reported barriers to physician-patient e-mail related to workload, security and payment. Our survey findings indicate that with adequate pre-screening, triage, and reimbursement mechanisms physicians would be open to substantially increasing e-mail communication with patients.

Incorporation of 8-histaminyl-deoxyadenosine [8-(2-(4-imidazolyl)ethylamino)-2'-deoxyriboadenosine] into oligodeoxyribonucleotides by solid phase phosphoramidite coupling.

The 3'phosphoramidite of 8-histaminyl deoxyadenosine has been prepared and successfully incorporated into a short oligodeoxyribonucleotide. The synthetic methodology leading to this preparation is given and the implications for developing new DNAzymes as well as probing unusual nucleic acid structures are discussed.

The nonsaphenous vein of the popliteal fossa: prevalence, patterns of reflux, hemodynamic quantification, and clinical significance.

BACKGROUND: A large tortuous vein coursing over the posterior aspect of the knee and the upper calf may give rise to a constellation of varicose veins unrelated to the great (GSV) or small (SSV) saphenous veins. Designated the popliteal fossa vein (PFV), it perforates the deep popliteal fascia and empties into the deep system. We examined the prevalence, anatomic reflux patterns, hemodynamic role, and clinical significance of the PFV. METHODS: We examined 543 patients (818 limbs) with venous disease, aged 14 to 94 years (median, 55 years). The study consisted of group A, comprising limbs with a PFV, and group B, formed by the remaining limbs. The history, clinical examination, and venous duplex scan findings were analyzed retrospectively. Venous clinical severity and venous segmental disease scores of group A were compared with those of an equal number of CEAP-, sex-, and age-matched control limbs. In situ venous hemodynamics of the PFV obtained with duplex scan are reported. RESULTS: A PFV was found in 24 (2.93%) of 818 limbs (95% confidence interval [CI], 1.8%-4.1%); 24 (4.4%) of 543 subjects (95% CI, 2.7%-6.2%), 12 men and 12 women aged 23 to 82 years (median, 54 years) had a PFV. CEAP clinical classes in limbs with a PFV were as follows: C2, 15 limbs; C3, 5 limbs; C4, 2 limbs; C5, 1 limb; and C6, 1 limb. Proximal and distal (92%), superficial (100%), perforator (87.5%), and complex-pattern (41.7%) reflux occurred more often in group A (P < .01). Incompetence in the GSV (75%), posterior arch, and posteromedial and saphenous tributaries was also more frequent in group A (P < .05). SSV reflux in group A (29%) matched that in group B. The PFV terminated at the deep system (96% in the popliteal vein) above the SSV (median distance, 1.5 cm; 95% CI, 0.5-2 cm). The odds ratio for a PFV in limbs with prior SSV disconnection was 5.68. Deep reflux was evenly distributed in group A (41.7%) and group B (27%). The prevalence of incompetent perforators was 283% (95% CI, 194%-373%) in group A and 96% (95% CI, 95%-98%) in group B (P < .001). PFV tributaries were distributed at the popliteal area (100%); the posterior (87.5%), medial (62.5%), and lateral (37.5%) upper calf; and the posterior distal thigh (17%), often projecting to the posterior GSV arch (50%). The (median) peak velocity of reflux in the PFV was 82.6 cm/s, the mean velocity was 17.7 cm/s, the duration was 2.4 seconds, the volume flow was 231.5 mL/min, and the expelled volume was 9.3 mL. The median diameter of the PFV at the crossing of the fascia was 0.527 cm. Venous clinical severity (range, 2-17; median, 5.5) and venous segmental disease (range, 0.5-8; median, 2.75) scores in limbs with a PFV exceeded (P

Communicating health information to an alarmed public facing a threat such as a bioterrorist attack.

Considerable literature exists on the communication of risk to the public through channels such as television, radio, and newspapers. However, little has been written on the communication of risk through less traditional communication forms, such as the Internet. The purpose of this study was to investigate the role of the Internet as an additional source of health information to that provided by the traditional news media in managing the public's response to an emerging health risk such as a bioterrorist attack. Despite some of the Internet's advantages over traditional media, including the depth and speed in which information can be conveyed to different audiences, the Internet was underutilized during fall 2001, when it became important to convey information on the risks of anthrax. A number of developments are required if the health care system is to capitalize on the Internet's potential as a risk communication device. These developments include research into public Internet searching behavior and further development in the role of search engines and government agencies in organizing quality health information.