Application of Staged Negative Pressure Wound Therapy and Flap Surgery for Infection Control After Patellar Internal Fixation Surgery.

The anatomic position of the patella is superficial, making it vulnerable to injuries. Treatment of patella infection after internal fixation surgery remains a big challenge due to minimal soft tissue coverage and vital tissue exposure. Forty-two patients aged 10 to 59 years were admitted to the institution's burn unit between January 2010 and December 2019. Each presented with infection after patellar fracture surgery. Twenty-seven infections were superficial, whereas 15 were deep with pyogenous arthritis of the knee. Negative pressure wound therapy (NPWT) was applied after radical debridement to remove necrotic subcutaneous tissues and internal fixation devices. In addition, cases with septic arthritis were irrigated continuously with normal saline. After 5 to 10 days of NPWT treatment and irrigation, wound infection was well controlled. Afterward, 42 wounds were resurfaced with pedicled flaps, the 42 patients received 17 reverse-flow anterolateral thigh (ALT) perforator flap, 12 medial sural artery perforator flaps, 7 gastrocnemius musculocutaneous flaps, as well as 6 saphenous artery flaps. Thirty-seven flaps survived uneventfully. However, 3 flaps developed venous congestion in the distal end. Two flaps developed tip necrosis. All patients were followed up between 3 and 48 months. Infection beneath the flap occurred in 3 patients and healed after an additional debridement surgery. The staged NPWT and flap surgery strategy focus on thorough debridement and immediate internal fixation devices removal, effective fracture fixation, efficient NPWT application, targeted administration of antibiotics, and adequate soft tissue coverage. This study established that the procedure was effective in infection control after patellar internal fixation surgery.

Extended Paraumbilical Perforator Flap Pedicled With the Inferior Epigastric Artery for Coverage of Type III Circumferential Electrical Burns of the Wrist.

Type III electrical burns on the wrist are characterized by circumferential wounds, three dimensional with sandwich-like necrosis, and progressive blood circulation disturbances. Limb salvage is challenging, and success in meeting this challenge depends on vascular reconstruction and wound coverage. This article is intended for the following purposes: to investigate the principles of wound debridement, the management of involved blood vessels, and the clinical effects of the extended paraumbilical perforator flap pedicled with the inferior epigastric artery for coverage of type III circumferential electrical burns of the wrist. A total of 13 male patients (age, 20 to 43 years; average, 29 years) were enrolled in the study. After early escharotomy, debridement, and vascular reconstruction, all wounds were repaired with the extended paraumbilical perforator flap pedicled with the inferior epigastric artery. Flap survival was achieved in all 13 patients. Subcutaneous liquefaction necrosis and infection beneath the flap occurred in three patients. Radial or ulnar artery reconstruction via the great saphenous vein (GSV) graft was performed in 12 cases. All patients had a mean follow-up of 6 to 36 months, and the flaps demonstrated satisfactory flexibility and texture. Hand function was preserved in eight patients, and no patients developed abdominal hernia. Thorough debridement, early vascular reestablishment, and wound coverage are essential for the overall limb salvage effort for type III circumferential electrical burns of the wrist. The extended paraumbilical perforator flap may provide a new and appropriate option for the primary repair of extensive soft tissue defects.

Association of Coffee and Tea Intake with Bone Mineral Density and Hip Fracture: A Meta-Analysis.

Background and Objectives: Osteoporosis is characterized by low bone mass and high bone fragility. Findings regarding the association of coffee and tea intake with osteoporosis have been inconsistent. We conducted this meta-analysis to investigate whether coffee and tea intake is associated with low bone mineral density (BMD) and high hip fracture risk. Materials and Methods: PubMed, MEDLINE, and Embase were searched for relevant studies published before 2022. Studies on the effects of coffee/tea intake on hip fracture/BMD were included in our meta-analysis, whereas those focusing on specific disease groups and those with no relevant coffee/tea intake data were excluded. We assessed mean difference (MD; for BMD) and pooled hazard ratio (HR; for hip fracture) values with 95% confidence interval (CI) values. The cohort was divided into high- and low-intake groups considering the thresholds of 1 and 2 cups/day for tea and coffee, respectively. Results: Our meta-analysis included 20 studies comprising 508,312 individuals. The pooled MD was 0.020 for coffee (95% CI, -0.003 to 0.044) and 0.039 for tea (95% CI, -0.012 to 0.09), whereas the pooled HR was 1.008 for coffee (95% CI, 0.760 to 1.337) and 0.93 for tea (95% CI, 0.84 to 1.03). Conclusions: Our meta-analysis results suggest that daily coffee or tea consumption is not associated with BMD or hip fracture risk.

A review of the totality of evidence supporting the development and approval of a pegfilgrastim biosimilar (LA-EP2006).

OBJECTIVE: The totality-of-evidence approach requires that similarity between a proposed biosimilar and a reference biologic is demonstrated across a range of analytical, preclinical, and clinical parameters to establish biosimilarity. We describe the totality of evidence for Sandoz biosimilar pegfilgrastim (LA-EP2006 [marketed as Ziextenzo]) that supported its regulatory approval in Europe and the United States. METHODS: Analytical similarity to the reference biologic [marketed by Amgen as Neulasta] was first investigated with regard to physiochemical quality attributes such as primary structure, pegylation, higher-order structures, variants and impurities, molecular size variants, and formulation (protein content, pH, excipients, etc.). In vitro biological activity studies were performed to examine the primary mechanism of action of pegfilgrastim. Bioequivalence (clinical pharmacokinetics [PK] and pharmacodynamics [PD]) of Sandoz biosimilar pegfilgrastim to the reference biologic was studied in healthy volunteers; efficacy, safety, and immunogenicity were assessed during confirmatory clinical efficacy studies in patients undergoing treatment for breast cancer. RESULTS: No meaningful or relevant differences were identified between Sandoz biosimilar pegfilgrastim and the reference biologic during analytical testing. Similar receptor binding and induction of cellular proliferation in vitro confirmed no functional differences between the biologics. Clinical studies in healthy adult participants demonstrated PK/PD biosimilarity and a similar safety profile between biosimilar and reference pegfilgrastim. Clinical studies in a sensitive patient population also demonstrated similar efficacy, safety, and immunogenicity between Sandoz biosimilar pegfilgrastim and the reference biologic. CONCLUSIONS: The totality of evidence confirms that Sandoz biosimilar pegfilgrastim matches the reference biologic and will therefore provide equivalent efficacy and safety in all eligible indications.

Treatment of Pasteurella multocida infection with dressings containing honey and antibacterials: a case report.

Infections secondary to Pasteurella multocida frequently occur in patients who have been exposed to domestic pets. Human infections caused by Pasteurella multocida vary in severity, and clinical features include localised cellulitis, osteomyelitis, systemic bacteraemia, meningitis and pneumonia. No vaccine has been developed against Pasteurella multocida; it is treated with antibacterial agents and, in most cases, surgical intervention. This article discusses the authors' experience in treating a woman with severe cellulitis and osteomyelitis on her hand caused by Pasteurella multocida. She refused surgical intervention and was successfully treated with honey-containing dressings and antibiotics after failure to heal following conservative treatment using conventional wound dressings combined with antibiotics.

Distribution and drug resistance of pathogens in burn patients in China from 2006 to 2019.

BACKGROUND: In this study, recent trends in the distribution and drug resistance of pathogenic bacteria isolated from patients treated at a burn ward between 2006 and 2019 were investigated. AIM: To develop more effective clinical strategies and techniques for the prevention and treatment of bacterial infections in burn patients. METHODS: Clinical samples with positive bacteria were collected from patients at the burn ward in Beijing Jishuitan Hospital in China between January 2006 and December 2019. The samples were retrospectively analyzed, the distribution of pathogenic bacteria was determined, and the trends and changes in bacterial drug resistance during different period were assessed. Drug resistance in several main pathogenic bacteria from 2006 to 2011 and from 2012 to 2019 was comparatively summarized and analyzed. RESULTS: Samples from 17119 patients were collected and analyzed from 2006 to 2019. Surprisingly, a total of 7960 strains of different pathogenic bacteria were isolated at this hospital. Among these bacteria, 87.98% (7003/7960) of the strains were isolated from burn wounds, and only 1.34% (107/7960) were isolated from the blood of patients. In addition, 49.70% (3956/7960) were identified as Gram-positive bacteria, 48.13% (3831/7960) were Gram-negative bacteria, and the remaining 2.17% (173/7960) were classified as fungi or other pathogens. Importantly, Staphylococcus aureus (21.68%), Pseudomonas aeruginosa (14.23%), and Staphylococcus epidermidis (9.61%) were the top three pathogens most frequently isolated from patients. CONCLUSION: In patients treated at the burn ward in this hospital from 2006 to 2019, Staphylococcus aureus and Pseudomonas aeruginosa were the predominant clinical pathogens responsible for bacterial infections. The circumstantial detection and detailed monitoring of the intensity and growth of different pathogenic bacteria in clinical patients as well as tests of drug sensitivity during burn recovery are particularly important to provide guidelines for the application of antibiotics and other related drugs. Careful collection and correct, standard culture of bacterial specimens are also crucial to improve the efficiency of bacterial infection detection. Effective monitoring and timely clinical treatment in patients may help reduce the possibility and rate of infection as well as alleviate the effects of drug resistance among patients in burn centers.

Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study.

BACKGROUND: Alpelisib, a PI3Kα-selective inhibitor and degrader, plus fulvestrant showed efficacy in hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer in SOLAR-1; limited data are available in the post-cyclin-dependent kinase 4/6 inhibitor setting. BYLieve aimed to assess alpelisib plus endocrine therapy in this setting in three cohorts defined by immediate previous treatment; here, we report results from cohort A. METHODS: This ongoing, phase 2, multicentre, open-label, non-comparative study enrolled patients with hormone receptor-positive, HER2-negative, advanced breast cancer with tumour PIK3CA mutation, following progression on or after previous therapy, including CDK4/6 inhibitors, from 114 study locations (cancer centres, medical centres, university hospitals, and hospitals) in 18 countries worldwide. Participants aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 2 or less, with no more than two previous anticancer treatments and no more than one previous chemotherapy regimen, were enrolled in three cohorts. In cohort A, patients must have had progression on or after a CDK4/6 inhibitor plus an aromatase inhibitor as the immediate previous treatment. Patients received oral alpelisib 300 mg/day (continuously) plus fulvestrant 500 mg intramuscularly on day 1 of each 28-day cycle and on day 15 of cycle 1. The primary endpoint was the proportion of patients alive without disease progression at 6 months per local assessment using Response Evaluation Criteria in Solid Tumors, version 1.1, in patients with a centrally confirmed PIK3CA mutation. This trial is registered with ClinicalTrials.gov, NCT03056755. FINDINGS: Between Aug 14, 2017, and Dec 17, 2019 (data cutoff), 127 patients with at least 6 months' follow-up were enrolled into cohort A. 121 patients had a centrally confirmed PIK3CA mutation. At data cutoff, median follow-up was 11·7 months (IQR 8·5-15·9). 61 (50·4%; 95% CI 41·2-59·6) of 121 patients were alive without disease progression at 6 months. The most frequent grade 3 or worse adverse events were hyperglycaemia (36 [28%] of 127 patients), rash (12 [9%]), and rash maculopapular (12 [9%]). Serious adverse events occurred in 33 (26%) of 127 patients. No treatment-related deaths were reported. INTERPRETATION: BYLieve showed activity of alpelisib plus fulvestrant with manageable toxicity in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, after progression on a CDK4/6 inhibitor plus an aromatase inhibitor. FUNDING: Novartis Pharmaceuticals.

Efficacy of fractional carbon dioxide laser therapy for burn scars: a meta-analysis.

BACKGROUND: The present study evaluates the effectiveness of fractional carbon dioxide (CO2) laser for the treatment of burn scars. METHOD: Literature search was conducted in electronic databases and studies were selected by following pre-determined eligibility criteria. Random effect meta-analyses were performed to achieve the effect size of the changes (mean difference (MD) between post-treatment and pretreatment values) in selected scar assessment scale scores and other important outcome measures. RESULTS: 14 studies were included. Treatment of burn scars with fractional CO2 laser significantly improved Vancouver Scar Scale (MD -3.01 [95% confidence interval (CI) -3.79, -2.22]; p ˂ .00001), Patient and Observer Scar Assessment Scale (POSAS)- Patient (MD -14.38 [95% CI -17.62, -11.13]; p ˂ .00001, POSAS - Observer (MD -8.81 [9% CI -11.60, -6.02]; p ˂ .00001 and Scar Assessment Scale (MD 1.64 [95% CI 0.49, 2.78]; p = .005) scores especially with regards to pigmentation, vascularity, pliability, and height of scar. Pain and pruritis also improved with this treatment. Scar thickness measured with ultrasonography decreased non-significantly (MD -0.48 [95% CI -1.04, 0.09]; p = .1) whereas cutometer measures, R0 (scar firmness) and R2 (scar elasticity) did not change meaningfully. CONCLUSION: Fractional CO2 laser therapy is a valuable tool for the treatment of burn scars which has potential for reducing scar severity.

Free Flow-through Anterolateral Thigh Flaps for Wrist High-tension Electrical Burns: A Retrospective Case Series.

OBJECTIVE: The objective of this report was to demonstrate the clinical application of free flow-through anterolateral thigh flaps for the treatment of high-tension electrical wrist burns. METHODS: We collected the data of 8 patients with high-tension electrical wrist burns admitted to Beijing Jishuitan Hospital from January 2014 to December 2018. The clinical and pathological data were extracted from electronic hospital medical records. We obtained follow-up information through clinic visits. RESULTS: The injury sites for all 8 patients were the wrists, specifically 5 right and 3 left wrists, all of which were on the flexor side. Five patients had ulnar artery embolism necrosis and patency, with injury to the radial artery. Two patients had ulnar and radial arterial embolization and necrosis. The last patient had ulnar arterial embolization and necrosis with a normal radial artery. After debridement, the wound area ranged from 12 cm × 9 cm to 25 cm × 16 cm. The diagnoses for the eight patients were type II to type III high-tension electrical wrist burns. Free flow-through anterolateral thigh flaps (combined with great saphenous vein transplantation if necessary) were used to repair the wounds. The prognosis for all patients was good after six months to one year of follow-up. CONCLUSION: Treating wrist types II and III high-tension electrical burns is still challenging in clinical practice. The use of free flow-through anterolateral thigh flaps (combined with great saphenous vein transplantation if necessary) to repair the wound and to restore the blood supply for the hand at the same time is a good choice for treating severe wrist electrical burns.

Application of a pre-filled tissue expander for preventing soft tissue incarceration during tibial distraction osteogenesis.

BACKGROUND: Bone transport and distraction osteogenesis has been widely used to treat bone defects after traumatic surgery, but, skin and soft tissue incarceration can be as high as 27.6%. AIM: To investigate the efficacy of inserting a tissue expander to prevent soft tissue incarceration. METHODS: Between January 2016 and December 2018, 12 patients underwent implantation of a tissue expander in the subcutaneous layer in the vicinity of a tibial defect to maintain the soft tissue in position. A certain amount of normal saline was injected into the tissue expander during surgery and was then gradually extracted to shrink the expander during the course of transport distraction osteogenesis. The tissue expander was removed when the two ends of the tibial defect were close enough. RESULTS: In all 12 patients, the expanders remained intact in the subcutaneous layer of the bone defect area during the course of transport distraction osteogenesis. When bone transport was adequate, the expander was removed and the bone transport process was completed. During the whole process, there was no incarceration of skin and soft tissue in the bone defect area. Complications occurred in one patient, who experienced poor wound healing. CONCLUSION: The pre-filled expander technique can effectively avoid soft tissue incarceration. The authors' primary success with this method indicates that it may be a valuable tool in the management of incarcerated soft tissue.

Survival and Versatility of the Flow-Through Lateral-Thigh Free Flap in Severe Electrical Injuries to the Wrist.

BACKGROUND: The hand and wrist are most often in contact with electrical currents and thus most vulnerable to severe electrical burns. The treatment of such severe injury via surgical intervention remains a big challenge because of the vast tissue necrosis and the segmental vascular injury. The flow-through lateral-thigh free flap has been used effectively to resurface these defects and to reconstruct segmental vascular defects. METHODS: Between January 2014 and June 2017, 11 male patients aged 19 to 53 years were admitted to the burn unit of our institution. Each presented with severe electrical burns to the wrist with long segmental vascular injury, and 2 cases suffered from electrical burn on both wrists. After radical debridement, the soft-tissue and segmental artery defects were rebuilt through the application of flow-through lateral-thigh free flap for 1 of the ulnar or radial artery injury (7/12). Ulnar artery defects were rebuilt through the application of flow-through lateral-thigh free flap, and radial artery revascularization was done using a greater saphenous vein graft for both ulnar and radial artery injuries (5/12). Vascular condition was closely monitored throughout the treatment period. RESULTS: Forearm amputation was performed in 1 case as a result of distal immediate necrosis postinjury. Successful limb salvage was achieved in the other 12 wrists. Infection beneath the flap occurred in 3 cases but resolved after debridement. Over the course of the 3- to 12-month follow-up period, the free flaps maintained good texture and sharpness, distal circulation of affected limb became well established, and the appearances of the donor sites were acceptable. CONCLUSIONS: High-voltage electrical burns of the wrist are highly destructive, and sophisticated management of damage requires concomitant vascular reconstruction and soft-tissue coverage. The flow-through anterolateral-thigh flap is an optimal solution for this problem. Emphasis must be placed on the affected blood vessel throughout the treatment period.

Combined Assessment of Serum Alpha-Synuclein and Rab35 is a Better Biomarker for Parkinson's Disease.

BACKGROUND AND PURPOSE: It is essential to develop a reliable predictive serum biomarker for Parkinson's disease (PD). The accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. The purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. METHODS: Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. RESULTS: The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutoff age than in the group above the cutoff age. CONCLUSIONS: Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.

Protective effects of tiopronin against oxidative stress in severely burned patients.

OBJECTIVE: Tiopronin is an antioxidant. This study investigated the protective effect of tiopronin on oxidative stress in patients with severe burns. METHOD: Patients aged between 16 and 65 years old with >30% body surface area burns admitted to our burn unit from July 2011 to September 2016 were randomly divided into 3 groups: group A treated with tiopronin (15 mg/kg. 24 hrs), group B with vitamin C (792 mg/kg. 24 hrs), the other group with standard treatment (group C). All 3 groups also received standard treatment. Blood superoxide dismutase (SOD), malondialdehyde (MDA), and the biochemical indexes of liver, kidney, and heart were determined before treatment and 24 and 48 hrs after treatment. Samples from 8 normal healthy adult volunteers were also measured. The resuscitation fluid volume requirement for the first 24 hrs was calculated for 3 groups. RESULTS: The serum levels of MDA and the biochemical indexes in severely burned patients were higher than those in healthy volunteers (P<0.01). The serum SOD level of burn patients was lower (P<0.01). After treatment, the levels of SOD increased, the levels of MDA decreased, and the biochemical indexes of heart, liver, and kidney improved; these changes were more obvious in group A and group B compared to group C (P<0.05), and these changes were more obvious in group A compared to group B (P<0.05) at 48 hrs after treatment. There is less resuscitation fluid volume requirement to maintain adequate stable hemodynamic and urine output in the first 24 hrs in group A and group B compared to group C (P<0.05). CONCLUSION: Treatment with tiopronin could exert protective effects against burn-induced oxidative tissue damage and multiple-organ dysfunction, and also could reduce the volume of required fluid resuscitation in severely burned patients.

A Successful Limb Salvage of an Electrical Burned Patient With Extensive Soft Tissue and Femoral Bone Necrosis.

Severe electrical injury presents a formidable therapeutic challenge for surgeons because of the requirement for complex soft tissue and bony reconstruction to restore functionality of the injured area. The authors report on the limb salvage procedure for a patient with extensive soft tissue and femoral bone necrosis from a high-voltage electrical burn. The right thigh and knee were burned, resulting in large areas of muscle necrosis and a long segment of distal femur exposure and necrosis. Complete debridement of the area resulted in a 20 × 35 cm soft tissue defect and an 18-cm long distal femoral bone defect. The wound was repaired through latissimus dorsi muscle transplantation and bony reconstruction using the sequential Ilizarov osteogenesis method. The injured limb was retained, and the functional recovery of the patient's leg was satisfactory. This experience indicates that the combination of flap transplantation and the Ilizarov osteogenesis method are good options for the treatment of large soft tissue and huge segmental bony defects.

Extracorporeal Circulation During Lung Transplantation Procedures: A Meta-Analysis.

Extracorporeal circulation (ECC) is an invaluable tool in lung transplantation (lutx). More than the past years, an increasing number of centers changed their standard for intraoperative ECC from cardiopulmonary bypass (CPB) to extracorporeal membrane oxygenation (ECMO) - with differing results. This meta-analysis reviews the existing evidence. An online literature research on Medline, Embase, and PubMed has been performed. Two persons independently judged the papers using the ACROBAT-NRSI tool of the Cochrane collaboration. Meta-analyses and meta-regressions were used to determine whether veno-arterial ECMO (VA-ECMO) resulted in better outcomes compared with CPB. Six papers - all observational studies without randomization - were included in the analysis. All were considered to have serious bias caused by heparinization as co-intervention. Forest plots showed a beneficial trend of ECMO regarding blood transfusions (packed red blood cells (RBCs) with an average mean difference of -0.46 units [95% CI = -3.72, 2.80], fresh-frozen plasma with an average mean difference of -0.65 units [95% CI = -1.56, 0.25], platelets with an average mean difference of -1.72 units [95% CI = -3.67, 0.23]). Duration of ventilator support with an average mean difference of -2.86 days [95% CI = -11.43, 5.71] and intensive care unit (ICU) length of stay with an average mean difference of -4.79 days [95% CI = -8.17, -1.41] were shorter in ECMO patients. Extracorporeal membrane oxygenation treatment tended to be superior regarding 3 month mortality (odds ratio = 0.46, 95% CI = 0.21-1.02) and 1 year mortality (odds ratio = 0.65, 95% CI = 0.37-1.13). However, only the ICU length of stay reached statistical significance. Meta-regression analyses showed that heterogeneity across studies (sex, year of ECMO implementation, and underlying disease) influenced differences. These data indicate a benefit of the intraoperative use of ECMO as compared with CPB during lung transplant procedures regarding short-term outcome (ICU stay). There was no statistically significant effect regarding blood transfusion needs or long-term outcome. The superiority of ECMO in lutx patients remains to be determined in larger multi-center randomized trials.

Graphical Presentation of Patient-Treatment Interaction Elucidated by Continuous Biomarkers. Current Practice and Scope for Improvement.

BACKGROUND: Biomarkers providing evidence for patient-treatment interaction are key in the development and practice of personalized medicine. Knowledge that a patient with a specific feature - as demonstrated through a biomarker - would have an advantage under a given treatment vs. a competing treatment can aid immensely in medical decision-making. Statistical strategies to establish evidence of continuous biomarkers are complex and their formal results are thus not easy to communicate. Good graphical representations would help to translate such findings for use in the clinical community. Although general guidelines on how to present figures in clinical reports are available, there remains little guidance for figures elucidating the role of continuous biomarkers in patient-treatment interaction (CBPTI). OBJECTIVES: To combat the current lack of comprehensive reviews or adequate guides on graphical presentation within this topic, our study proposes presentation principles for CBPTI plots. In order to understand current practice, we review the development of CBPTI methodology and how CBPTI plots are currently used in clinical research. METHODS: The quality of a CBPTI plot is determined by how well the presentation provides key information for clinical decision-making. Several criteria for a good CBPTI plot are proposed, including general principles of visual display, use of units presenting absolute outcome measures, appropriate quantification of statistical uncertainty, correct display of benchmarks, and informative content for answering clinical questions especially on the quantitative advantage for an individual patient with regard to a specific treatment. We examined the development of CBPTI methodology from the years 2000 - 2014, and reviewed how CBPTI plots were currently used in clinical research in six major clinical journals from 2013 - 2014 using the principle of theoretical saturation. Each CBPTI plot found was assessed for appropriateness of its presentation and clinical utility. RESULTS: In our review, a total of seven methodological papers and five clinical reports used CBPTI plots which we categorized into four types: those that distinguish the outcome effect for each treatment group; those that show the outcome differences between treatment groups (by either partitioning all individuals into subpopulations or modelling the functional form of the interaction); those that evaluate the proportion of population impact of the biomarker; and those that show the classification accuracy of the biomarker. The current practice of utilizing CBPTI plots in clinical reports suffers from methodological shortcomings: the lack of presentation of statistical uncertainty, the outcome measure scaled by relative unit instead of absolute unit, incorrect use of benchmarks, and being non-informative in answering clinical questions. CONCLUSIONS: There is considerable scope for improvement in the graphical representation of CBPTI in clinical reports. The current challenge is to develop instruments for high-quality graphical plots which not only convey quantitative concepts to readers with limited statistical knowledge, but also facilitate medical decision-making.

Constructing an ROC Curve to Assess a Treatment-Predictive Continuous Biomarker.

This paper presents the idea of an ROC curve, which quantifies the discriminatory potential of a continuous biomarker for treatment selection when the outcome is continuous. The analysis assumes data from a randomized parallel group design. We use non-parametric density estimators to construct an ROC curve based on the probabilities that a (non-)responder, defined by better (worse) response to treatment as opposed to control, in the treatment group has a biomarker value above a value c. Our non-parametric approach comes close to the true AUC in a simulation study based on a normal distribution. Application to a real data set shows that despite a significant interaction term in a proportional hazards model, a biomarker may not be helpful for treatment decisions. Our proof-of-principle study opens the door to further developments and generalizations.

[Effect of echinacoside on replication and antigen expression of hepatitis B virus].

To verify the effect of echinacoside on replication and antigen expression of hepatitis B virus (HBV) by using HBV-transfected HepG2. 2. 15 cells as the in vitro model. The ELISA method was used to determine HBeAg and HBsAg levels in cellular supernatants. The effect of echinacoside on HBV replication was studied by using HBV transgenic mice as the in vivo model. First of all, the HBV DNA level in hepatic tissues was quantified with PCR method. Meanwhile, the serum transaminase levels and hepatic pathological changes were also evaluated. Subsequently, HBV transgenic mice were divided into five groups: the control group, the lamivudine group (50 mg · kg(-1)) and echinacoside high, medium and low dose group (50, 25 and 12.5 mg · kg(-1)). The mice were orally administered with drugs once per day for 30 days. At the 31st day, the mice serum was separated to measure HBsAg, HBeAg and HBV DNA. Additionally, the liver HBV DNA level and histopathological change were detected. The results indicated that echinacoside at 50 and 100 mg · L(-1) suppressed significantly HBsAg and HBeAg expressions on the sixth day, with the maximum inhibition ratios of 42.68% and 46.29%; And echinacoside at 100 mg · L(-1) also showed an inhibitory effect on HBV DNA. Besides, echinacoside at 50 mg · kg(-1) inhibited significantly HBsAg and HBeAg expressions of HBV transgenic mice, with the inhibition ratios of 42.82% and 29.12%, and reduced markedly the serum HBV DNA level in HBV transgenic mice. In conclusion, the study suggested that echinacoside has a strong effect against HBV replication and antigen expression.

Effects of Co-Worker and Supervisor Support on Job Stress and Presenteeism in an Aging Workforce: A Structural Equation Modelling Approach.

We examined the effects of co-worker and supervisor support on job stress and presenteeism in an aging workforce. Structural equation modelling was used to evaluate data from the 2010 wave of the Health and Retirement Survey in the United States (n = 1649). The level of presenteeism was low and the level of job stress was moderate among aging US workers. SEM revealed that co-worker support and supervisor support were strongly correlated (ß = 0.67; p < 0.001). Job stress had a significant direct positive effect on presenteeism (ß = 0.30; p < 0.001). Co-worker support had a significant direct negative effect on job stress (ß = -0.10; p < 0.001) and presenteeism (ß = -0.11; p < 0.001). Supervisor support had a significant direct negative effect on job stress (ß = -0.40; p < 0.001) but not presenteeism. The findings suggest that presenteeism is reduced by increased respect and concern for employee stress at the workplace, by necessary support at work from colleagues and employers, and by the presence of comfortable interpersonal relationships among colleagues and between employers and employees.

Dynamic correlation between induction of the expression of heme oxygenase-1 and hepatitis B viral replication.

Heme oxygenase­1 (HO­1) possesses significant potential as a drug target for hepatitis B, which may be transferable to patient therapy. The aim of the present study was to clarify the dynamic correlation between the hepatitis B virus (HBV) and HO­1. The levels of HBV replication and expression of HO­1 were investigated in HepG2.2.15 hepatoma cells following exposure to 5­50 µM hemin for 1­6 days. The mRNA expression levels of HO­1 were then detected using reverse transcription­quantitative polymerase chain reaction (RT­qPCR). HBV replication levels were determined by enzyme­immunoassay and a PCR­fluorescence quantitation assay. The results of the present study demonstrated that the mRNA expression levels of HO­1 increased in a dose­dependent manner in the HepG2.2.15 cells, following exposure to 5­50 µM hemin. The mRNA expression levels of HO­1 reached a peak following exposure of the cells to hemin for three days, subsequently the expression of HO­1 decreased. Following exposure to hemin at an optimal concentration of 50 µM for 1­6 days, the levels of the hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the cells were significantly reduced. This marked reduction in the expression of HBsAg and HBeAg reached its peak on the first day, following which the inhibition weakened as the duration of exposure increased. In addition, the inhibition of HBV DNA replication increased with the a longer duration of exposure. Furthermore, HBV DNA levels were significantly decreased following exposure to hemin for 3­6 days. In conclusion, the present study demonstrated that induced expression of HO­1 interfered with HBV replication in a dose and time­dependent manner, implying that a reduction of the HBV viral load may contribute to upregulation in the expression of HO­1.