Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer.

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4+/CD8a+ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

[Design and application of heating device and temperature control system for dialysis fluid bag in continuous renal replacement therapy].

In the process of continuous renal replacement therapy (CRRT), various factors such as the temperature of replacement fluid, the flow of fluid and the circulation of blood in cardiopulmonary bypass, lead to the temperature of the blood injected back into the body is often lower than normal. It leads to the decrease of body temperature and the occurrence of hypothermia, which can be life-threatening in severe cases. In clinical practice, medical staff mostly reduces the occurrence of hypothermia in patients with CRRT by means of the heating device of the machine, the heating of the liquid temperature box for cardiopulmonary bypass, and the application of heating blankets, but the effect is not ideal. Therefore, medical staff of the department of critical care medicine of the Second Affiliated Hospital of Anhui Medical University designed a heating device and temperature control system for CRRT dialysis fluid bag, and obtained the National Invention Patent of China (ZL 2021 1 0334906.7). The device includes a heating and thermal insulation device and a temperature control system, wherein the heating and thermal insulation device is composed of the body of the heating dialysis fluid bag and the temperature control structure, which solves the problems of safe and efficient liquid heating and thermal insulation during the CRRT process. The temperature control system can display the dynamic state of the patient's body temperature, adjust the temperature of the dialysis fluid bag in time, and monitor the temperature of the blood transfusion in real time through the cooperation of the five modules of data collection, data handle, data analysis, regulation and display. This design is applied to CRRT, which can achieve precise control of body temperature of critically ill patients, and has certain clinical significance.

Light-triggered on-site rapid formation of antibacterial hydrogel dressings for accelerated healing of infected wounds.

An optimal wound dressing can seal variously shaped wounds and provide a complete barrier to resist bacterial invasion; more importantly, the dressing can be stretched or compressed when the wounds are subjected to external forces and quickly return to its original state after the forces are withdrawn. Here, we designed dressings with light-triggered on-site rapid formation of antibacterial hydrogel for the accelerated healing of infected wounds. The pro-hydrogel, composed of acrylamide (AM) and dopamine-hyaluronic acid-ε-poly-l-lysine (DA-HA-EPL), was filled into the Vibrio vulnificus-infected wound. A 405-nm blue light was exerted on the wound to rapidly photopolymerize AM to its polymer, i.e., polyacrylamide (PAM). A hydrogel network of PAM/DA-HA-EPL immediately formed on site within several seconds to insulate the wound. PAM/DA-HA-EPL possessed adhesion performance to adapt to changes in wound morphologies due to external forces. Moreover, it presented high antibacterial ability due to the presence of EPL, in vitro biocompatibility and the ability to promote cell migration. Vibrio vulnificus-infected wounds were established on full-thickness mouse skin, and the hydrogel dressing exhibited high healing efficiency in terms of skin tissue regeneration, collagen deposition, and angiogenesis. PAM/DA-HA-EPL is a promising hydrogel dressing for the accelerated healing of infected wounds.

DDPG-Based Throughput Optimization with AoI Constraint in Ambient Backscatter-Assisted Overlay CRN.

The combination of ambient backscatter (AB) communications (ABCs) and RF-powered cognitive radio networks (CRNs) deals with challenges of both energy supply and spectrum shortage, and improves the network performances. With the expansion of wireless networks, many applications raise requirements for both high-throughput and timely data. Driven by these facts, we study the long-term throughput optimization of the secondary network in the AB-assisted overlay CRN (ABO-CRN), ABCs, and CRNs with the age of information (AoI) constraint, which is a novel metric for measuring the freshness of data received by receivers. Due to the dynamic environment, complete knowledge of the environment could not be obtained. Then, the deep deterministic policy gradient (DDPG), a deep reinforcement learning (DRL) method that addresses decision issues in both continuous and discrete spaces, is deployed to address the throughput optimization. We consider the impacts of time and energy allocation on the reward when the AoI constraint can not be satisfied, and develop the corresponding reward functions. Furthermore, we analyze the impacts of the minimum throughput requirement and maximum allowable AoI on the throughput and AoI of the secondary networks in the ABO-CRN, ABCs, and CRNs. We compare the throughput optimization scheme under the AoI constraint with two baseline schemes (i.e., throughput-optimal (T-O) and AoI-optimal (A-O) baseline schemes), and the simulation results show that the throughput of the ABO-CRN is close to the optimal throughput of the T-O baseline scheme, and the AoI of the ABO-CRN is close to the optimal AoI of the A-O baseline scheme.

Theoretical investigation on the fluorescence properties and ESIPT mechanism of the Al3+ ion sensor 1-((2-hydroxynaphthalen-1-yl)methylene)urea(OCN).

A new action mechanism for the fluorescent detection on the Al3+ ion of the sensitive 1-((2-hydroxynaphthalen-1-yl)methylene)urea(OCN) is theoretically studied. The extensive theoretical calculations on the OCN and the isomer structure OCN-T are performed. The emission and absorption spectra consistent with the experiment value. The absorption spectra peaks (362 nm and 326 nm) of OCN and OCN-T molecules are attributed to the experimentally observed absorption spectra at 356 nm and 314 nm, respectively. The calculated fluorescence value of the OCN-AL structure is 460 nm, while the OCN-T-AL structure has no fluorescence. These results better explain that OCN and its isomers OCN-T are involved in the absorption, and the detection spectrum signal is emitted from the OCN-AL complex. The OCN and OCN-T molecules are obvious hydrogen bonding systems. The excited state intramolecular proton transfer photochemical behaviors and detecting Al3+ ion photophysical changes were explained for the first time at the molecular level. As driving force of excited state intramolecular proton transfer (ESIPT) reaction, the bond parameters and vibrational frequencies of intramolecular hydrogen bond were analyzed by optimizing structures and calculating infrared spectra, analysis of frontier molecular orbitals. To further elucidate the proton transfer reactive paths, the scanned the potential energy curves (PECs) of OCN and OCN-T chemosensor in different electronic states are plotted. This work proposes a reasonable explanation for the detection mechanism of the OCN sensor.

The sensing mechanism of a flavone-based ESIPT fluorescent chemodosimeter for selective recognition towards fluoride: a theoretical.

The sensing mechanism of 3-hydroxyflavone-based (3-HF) fluorescent chemodosimeter 3-triisopropylsilylflavone (3-TPSF) for detecting fluoride (F-) has been theoretically investigated. The calculated Laplacian bond order confirms that the Si-O bond of 3-TPSF is the reaction site of F-. The free energy barrier of 18.33 kcal mol-1 indicates that F-triggered desilylation reaction can occur and then form the anionic state of 3-HF (3-HF-) with a fluorescence peak at 545 nm. 3-HF- captures H+ of the mixed aqueous medium to be transformed into 3-HF with an intramolecular hydrogen bond (O1-H⋯O2). The energy barrier of 1.86 kcal mol-1 in the S1 state obtained from the constructed potential energy curves confirms that the excited state intramolecular proton transfer (ESIPT) in 3-HF occurs to form a tautomer structure, which produces a long-wavelength emission of 549 nm. The fluorescence emitted from both 3-HF- and 3-HF agrees with the experimental value of 530 nm appearing after adding F-. Charge transfer analyses indicate that the extent of intramolecular charge transfer in 3-HF- is more intense than that of 3-TPSF, which induces a large Stokes shift of 180 nm. Therefore, the sensing mechanism is attributed to the combination of a large charge transfer feature and ESIPT that are caused by desilylation reaction. The significant fluorescence change makes 3-TPSF a chemodosimeter for detecting F-.

Sufentanil alleviates cerebral ischemia-reperfusion injury by inhibiting inflammation and protecting the blood-brain barrier in rats.

Stroke is a brain system disease with a high fatality rate and disability rate. About 80% of strokes are ischemic strokes. Cerebral ischemia-reperfusion injury (CIRI) caused by ischemic stroke seriously affects the prognosis of stroke patients. The purpose of this study is to investigate the effect of sufentanil (SUF) on CIRI model rats. We used middle cerebral artery occlusion (MCAO) to make the CIRI model in rats and monitored region cerebral blood flow (rCBF) to ensure that blood flow was blocked and recanalized. We used ELISA and RT-PCR to detect the expression of inflammatory factors in rat serum and brain tissue. In addition, we detected the expression of metalloproteinase (MMP) 2, MMP9 and collagen IV in brain tissues and performed Evans blue (EB) assay to determine the permeability of the blood-brain barrier (BBB). Finally, we clarified the apoptosis of brain tissue through the TUNEL staining and the detection of caspase3, Bcl2 and Bax. Various concentrations of SUF, especially 5, 10 and 25 µg/kg of SUF, all alleviated the infarct size, neurological function and brain edema of MCAO rats. SUF pretreatment also effectively reduced the expression of inflammatory cytokines in MCAO rats, including interleukin (IL)-1ß, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α. In addition, SUF also inhibited MMP2 and MMP9 and promoted the expression of collagen IV, indicating that SUF attenuated the destruction of the BBB. SUF also inhibited caspase3 and Bax rats and promoted Bcl2 in MCAO rats, thus inhibiting cell apoptosis. SUF pretreatment effectively improved the neurological function and cerebral infarction of MCAO rats, inhibited excessive inflammation in rats, protected the BBB, and inhibited cell apoptosis in brain tissue.

The mechanisms of a bifunctional fluorescent probe for detecting fluoride and sulfite based on excited-state intramolecular proton transfer and intramolecular charge transfer.

The mechanisms of 2-(Benzo[d]thiazol-2-yl)phenol-based bifunctional probe (HBT-FS) for detecting fluoride (F-) and sulfite (SO3 2-) based on excited-state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) have been theoretically studied. Laplacian bond order of HBT-FS indicates that the F- ion cleaves the Si-O bond and then forms Compound 2 possessing a six-membered ring with a hydrogen bond. Potential energy curves and dynamic simulations confirm that ESIPT in Compound 2 occurs along with this hydrogen bond and forms a keto structure with an emission at 623 nm, which agrees with the observed experimental value (634 nm) after adding F-. Therefore, the fluorescence red-shift (from 498 to 634 nm) of HBT-FS observed in experiment after adding F- is caused by ESIPT. The SO3 2- ion is added to the C5 site of HBT-FS, which is confirmed by orbital-weighted dual descriptor, and then forms Compound 3 with fluorescence located at 404 nm. The experimentally measured fluorescence at 371 nm after adding SO3 2- is assigned to Compound 3. Charge transfer analyses indicate that the ICT extent of Compound 3 is relatively weak compared with that of HBT-FS because of the destruction of the conjugated structure by the addition reaction of SO3 2-, which induces the blue-shift of the fluorescence of HBT-FS from 498 to 371 nm. The different fluorescence responses make HBT-FS a fluorescent probe to discriminatorily detect F- and SO3 2-.

Efficacy and safety of traditional Chinese medicine decoction combined with chemotherapy in the treatment of advanced colorectal cancer: A protocol of a systematic review and meta-analysis.

BACKGROUND: Colorectal cancer has become a major chronic and difficult disease endangering human health. After thousands of years of precipitation, traditional Chinese medicine in China is now also being applied in clinical treatment, with its unique advantages in the treatment of cancer. However, the efficacy of traditional Chinese medicine in the treatment of advanced colorectal cancer still cannot reach consensus in the world. Therefore, the aim of this study was to provide a scheme to evaluate the efficacy and safety of traditional Chinese medicine decoction in the treatment of advanced colorectal cancer, thus providing clinical decision-making. METHODS AND ANALYSIS: The systematic review and meta-analysis will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The following 8databases will be searched: China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Wan Fang Data, the Chinese Science and Technology Periodical Database (VIP), PubMed, Cochrane Library, Embase, and Web of Science. Relevant data will be performed by Revman 5.3 software provided (Cochrane Collaboration) and Stata 14.0 statistical software. RESULTS: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. INPLASY REGISTRATION NUMBER: INPLASY202080102.

Theoretical study on the sensing mechanism of a fluorescence chemosensor for the cyanide anion.

The sensing mechanism of the ratiometric fluorescence chemosensor 2-((6-(diethylamino)quinolin-2-yl)methylene)malononitrile (3A) for the cyanide anion (CN-) has been investigated theoretically. The calculated results show that the small reaction barrier (8.58 kcal/mol) of 3A implies a rapid response speed to CN-, and that the large interaction energy (25.75 kcal/mol) between 3A and CN- indicates a high selectivity to CN-. The results of condensed dual descriptor calculation confirm that CN- attacks the C2 site of 3A rather than other sites. The nucleophilic addition reaction of CN- breaks the original conjugation structure of 3A and results in the redistribution of the charge. The frontier molecular orbitals (MOs) and the Hirshfeld population analysis demonstrate that the long-rang electronic transition between the diethylamino moiety and the dicyanovinyl group in 3A is cut off after the addition of CN- and a local electronic transition between the quinoline and diethylamino moiety is formed. These changes lead to a blue shift (63 nm) of the fluorescence emission in the nucleophilic addition product (P) compare to 3A.

Theoretical study on excited-state intramolecular proton transfer process of cyanide group substituted 2-(2-hydroxyphenyl)benzothiazole.

In this work, the influence of cyanide group substituted on the excited-state intramolecular proton transfer of 2-(2-hydroxyphenyl)benzothiazole (HBT) has been theoretical studied. It is found that the intramolecular hydrogen bonds of HBT and its cyanide substituted derivatives are significantly strengthened in the first excited (S1) state, while this strengthening tends to decrease with the substitution of cyano group. The natural population analysis (NPA) is performed to interpret this phenomenon and the calculated results show that the introduction of cyano groups induces intramolecular charge transfer, leading to the decrease of electrostatic interaction of intramolecular hydrogen bond in the S1 state compared to isolated HBT. Therefore, proton transfer of HBT and its derivatives become difficult with the introduction of cyano groups, which is consistent with the calculated potential barriers (1.95, 2.71 and 2.81 kcal/mol respectively) of the three molecules in the S1 state. This work interprets the hindrance of cyanide group on the proton transfer of HBT and its derivatives in the S1 state, which will bring new insight into the study of analogous molecular system.

TDDFT study on excited state intramolecular proton transfer mechanism in 2-amino-3-(2'-benzazolyl)-quinolines.

The intramolecular proton transfer reaction of the 2-amino-3-(2'-benzoxazolyl)-quinoline (ABO) and 2-amino-3-(2'-benzothiazolyl)-quinoline (ABT) molecules in both S0 and S1 states at B3LYP/6-311++G(d,p) level in ethanol solvent have been studied to reveal the deactivation mechanism of the tautomers of the two molecules from the S1 state to the S0 state. The results show that the tautomers of ABO and ABT molecules may return to the S0 state by emitting fluorescence. In addition, the bond lengths, angles and infrared spectra are analyzed to confirm the hydrogen bonds strengthened upon photoexcitation, which can facilitate the proton transfer process. The frontier molecular orbitals (MOs) and natural bond orbital (NBO) are also calculated to indicate the intramolecular charge transfer which can be used to explore the tendency of ESIPT reaction. The potential energy surfaces of the ABO and ABT molecules in the S0 and S1 states have been constructed. According to the energy potential barrier of 9.12kcal/mol for ABO molecule and 5.96kcal/mol for ABT molecule, it can be indicated that the proton transfer may occur in the S1 state.

Enhancing siRNA-based cancer therapy using a new pH-responsive activatable cell-penetrating peptide-modified liposomal system.

As a potent therapeutic agent, small interfering RNA (siRNA) has been exploited to silence critical genes involved in tumor initiation and progression. However, development of a desirable delivery system is required to overcome the unfavorable properties of siRNA such as its high degradability, molecular size, and negative charge to help increase its accumulation in tumor tissues and promote efficient cellular uptake and endosomal/lysosomal escape of the nucleic acids. In this study, we developed a new activatable cell-penetrating peptide (ACPP) that is responsive to an acidic tumor microenvironment, which was then used to modify the surfaces of siRNA-loaded liposomes. The ACPP is composed of a cell-penetrating peptide (CPP), an acid-labile linker (hydrazone), and a polyanionic domain, including glutamic acid and histidine. In the systemic circulation (pH 7.4), the surface polycationic moieties of the CPP (polyarginine) are "shielded" by the intramolecular electrostatic interaction of the inhibitory domain. When exposed to a lower pH, a common property of solid tumors, the ACPP undergoes acid-catalyzed breakage at the hydrazone site, and the consequent protonation of histidine residues promotes detachment of the inhibitory peptide. Subsequently, the unshielded CPP would facilitate the cellular membrane penetration and efficient endosomal/lysosomal evasion of liposomal siRNA. A series of investigations demonstrated that once exposed to an acidic pH, the ACPP-modified liposomes showed elevated cellular uptake, downregulated expression of polo-like kinase 1, and augmented cell apoptosis. In addition, favorable siRNA avoidance of the endosome/lysosome was observed in both MCF-7 and A549 cells, followed by effective cytoplasmic release. In view of its acid sensitivity and therapeutic potency, this newly developed pH-responsive and ACPP-mediated liposome system represents a potential platform for siRNA-based cancer treatment.

Interventions for treating ankle fractures in children.

BACKGROUND: Ankle fractures, which usually occur after a twisting incident, are a diverse collection of injuries with different levels of complexity and severity. They have an incidence of 1 in 1000 a year in children. Treatment generally involves splints and casts for minor fractures and surgical fixation with screws, plates and pins followed by immobilisation for more serious fractures. OBJECTIVES: To assess the effects (benefits and harms) of different interventions for treating ankle fractures in children. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (22 September 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 8), MEDLINE (1946 to September Week 2 2015), MEDLINE In-Process & Other Non-Indexed Citations (21 September 2015), EMBASE (1980 to 2015 Week 38), CINAHL (1937 to 22 September 2015), trial registers (17 February 2015), conference proceedings and reference lists of articles. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials evaluating interventions for treating ankle fractures in children. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full articles for inclusion, assessed risk of bias and collected data. We undertook no meta-analysis. MAIN RESULTS: We included three randomised controlled trials reporting results for 189 children, all of whom had a clinical diagnosis of a "low risk" ankle fracture. These were predominantly classified as undisplaced Salter-Harris type I fractures of the distal fibula. All three trials compared non-surgical management options. The three trials were at high risk of bias, primarily relating to the impracticality of blinding participants and treating clinicians to the allocated interventions.Two trials compared the Aircast Air-Stirrup ankle brace versus a rigid cast, which was a removable fibreglass posterior splint in one trial (trial A) and a below-knee fibreglass walking cast in the other trial (trial B). In trial A, both devices were removed at around two weeks. In trial B, removal of the brace was optional after five days, while the walking cast was removed after three weeks. There was low-quality evidence of clinically important differences in function scores at four weeks in favour of the brace groups of both trials. Function was measured using the Activities Scale for Kids-performance (ASKp; score range 0 to 100, higher scores mean better function) in trial A and using a modified version of the ASKp score (range 0 to 100%, higher percentages mean better function) in trial B. The results for trial A (40 participants) were median 91.9 in the brace group versus 84.2 in the splint group. The results for trial B (104 participants) were 91.3% versus 85.3%; mean difference (MD) 6.00% favouring brace (95% confidence interval (CI) 1.38% to 10.62%). Trial B indicated that 5% amounted to a clinically relevant difference in the modified ASKp score. Neither trial reported on unacceptable anatomy or related outcomes or long-term follow-up. There was very low-quality evidence relating to adverse events, none of which were serious. Trial A found twice as many children with pressure-related complications in the brace group (10 of 20 versus 5 of 20). In contrast, trial B found four times as many children in the cast group had adverse outcomes assessed in terms of an unscheduled visit to a healthcare provider (4 of 54 versus 16 of 50). Both trials linked some of the adverse events in the brace group with the failure to wear a protective sock. There was very low-quality evidence indicating an earlier return to pre-injury activity in the brace groups in both trials. Trial B provided low-quality evidence that children much prefer five days or more wearing an ankle brace than three weeks immobilised in a walking ankle cast. There was moderate-quality evidence of a lack of difference between the two groups in pain at four weeks.The third trial compared the Tubigrip bandage plus crutches and advice versus a plaster of Paris walking cast for two weeks and reported results at four weeks' follow-up for 45 children with an inversion injury of the ankle. The trial found very low-quality evidence of little difference in pain and function between the two groups, measured using a non-validated pain and function score at four weeks. The trial did not report on adverse effects. There was very low-quality evidence of an earlier return to normal activities, averaging six days, in children treated with Tubigrip (mean 14.17 days for Tubigrip versus 20.19 days for cast; MD -6.02 days, 95% CI -8.92 to -3.12 days).Recent evidence from magnetic resonance imaging studies of the main category of injury evaluated in these three trials suggests that most of the injuries in these trials were sprains or bone bruises rather than fractures of the distal fibular growth plate. AUTHORS' CONCLUSIONS: There is low-quality evidence of a quicker recovery of self reported function at four weeks in children with clinically diagnosed low-risk ankle fractures who are treated with an ankle brace compared with those treated with a rigid cast, especially a non-removable walking cast. There is otherwise a lack of evidence from randomised controlled trials to inform clinical practice for children with ankle fractures. Research to identify and address priority questions on the treatment of these common fractures is needed.

FOXP3 autoantibody as a potential early prognostic serum biomarker in patients with cervical cancer.

BACKGROUND: Overexpression of tumor-associated antigens has been reported in many types of cancer and may trigger secretion of their autoantibodies. The present work was designed to test whether circulating antibody to FOXP3 protein-derived antigens was altered in early cervical cancer and cervical benign tumors. METHODS: A total of 141 patients with cervical cancer, 133 patients with cervical benign tumors and 148 healthy age-matched volunteers were recruited. The level of circulating anti-FOXP3 IgG antibody was tested using an enzyme-linked immunosorbent assay developed in-house with linear peptide antigens derived from FOXP3 protein. The linear peptide antigens were designed according to the computational prediction of HLA-II epitopes. RESULTS: Student's t test showed that anti-FOXP3 IgG in the malignant tumor group and the benign tumor group was significantly higher than in the control group (t = 6.127, p < 0.001; t = 2.704, p = 0.007). In addition, patients with stage I cervical cancer (t = 2.968, p = 0.003) had a significantly higher level of FOXP3 autoantibodies than patients with benign tumors. The sensitivity against >90 % specificity was 20.6 % with an interassay deviation of 11.7 % in the cervical cancer group. Based on a cut-off value determined by the 98th percentile of the control group IgG levels, the anti-FOXP3 IgG positivity was 2.1 % in patients with cervical cancer compared to 2.0 % in the health controls (chi-squared = 0.004, p = 0.952, OR = 1.051, 95 % CI 0.209-5.295). CONCLUSION: The circulating autoantibody to FOXP3 reflecting the continuous development of the cervical lesion, may be a potential biomarker with early prognostic values for cervical cancer.

Relative effectiveness of robot-assisted and standard laparoscopic prostatectomy as alternatives to open radical prostatectomy for treatment of localised prostate cancer: a systematic review and mixed treatment comparison meta-analysis.

OBJECTIVE: To compare the effectiveness of robot-assisted and standard laparoscopic prostatectomy. METHODS: A care pathway was described. We performed a systematic literature review based on a search of Medline, Medline in Process, Embase, Biosis, Science Citation Index, Cochrane Controlled Trials Register, Current Controlled Trials, Clinical Trials, WHO International Clinical Trials Registry and NIH Reporter, the Health Technology Assessment databases, the Database of Abstracts of Reviews of Effects, and relevant conference abstracts up to 31st October 2010). Additionally, reference lists were scanned, an expert panel consulted, and websites of manufacturers, professional organisations, and regulatory bodies were checked. We selected randomised controlled trials (RCTs) and non-randomised comparative studies, published after 1st January 1995, including men with localised prostate cancer undergoing robot-assisted or laparoscopic prostatectomy compared with the other procedure or with open prostatectomy. Studies where at least 90% of included men had clinical tumour stages T1 to T2 and which reported at least one of our specified outcomes were eligible for inclusion. A mixed-treatment comparison meta-analysis was performed to generate comparative statistics on specified outcomes. RESULTS: We included data from 19 064 men across one RCT and 57 non-randomised comparative reports. Robotic prostatectomy had a lower risk of major intra-operative harms such as organ injury [0.4% robotic vs 2.9% laparoscopic], odds ratio ([OR] {95% credible interval [CrI]} 0.16 [0.03 to 0.76]), and a lower rate of surgical margins positive for cancer [17.6% robotic vs 23.6% laparoscopic], OR [95% CrI] 0.69 [0.51 to 0.96]). There was no evidence of a difference in the proportion of men with urinary incontinence at 12 months (OR [95% CrI] 0.55 [0.09 to 2.84]). There were insufficient data on sexual dysfunction. Surgeon learning rates for the procedures did not differ, although data were limited. CONCLUSIONS: Men undergoing robotic prostatectomy appear to have reduced surgical morbidity, and a lower risk of a positive surgical margin, which may reduce rates of cancer recurrence and the need for further treatment, but considerable uncertainty surrounds these results. We found no evidence that men undergoing robotic prostatectomy are disadvantaged in terms of early outcomes. We were unable to determine longer-term relative effectiveness.

The associations between personality, diet and body mass index in older people.

OBJECTIVE: Personality traits are related to numerous health outcomes and health-related behaviors. To date, however, little is known about how personality traits are associated with dietary behavior, an important aspect of lifestyle in the current "toxic food environment." The present study investigated the associations of between Five-Factor Model personality traits, dietary patterns, and body mass index (BMI). METHODS: The sample consisted of 1,091 members of Lothian Birth Cohort 1936 tested at age 70 years. Dietary patterns were measured using a detailed and validated food frequency questionnaire (FFQ). Principal components analysis of the FFQ items identified four dietary dimensions, which were named 'Mediterranean style diet,' 'health aware diet,' 'convenience diet,' and 'sweet foods'. Personality traits were measured with NEO Five-Factor Inventory. The effects of childhood intelligence, education, and sex were controlled. RESULTS: Endorsing the Mediterranean style diet dimension was associated with high Openness and Extraversion, and low Neuroticism. High scores on the health aware diet dimension were associated with high Agreeableness and Conscientiousness. Endorsing the convenience diet dimension was associated with low Openness and high Neuroticism. Preference for sweet foods was associated with low Openness. High BMI was associated with high scores on the convenience diet dimension and low Conscientiousness. CONCLUSIONS: Personality traits, especially Openness, are associated with dietary patterns in older age. The pattern of findings may indicate that, in older people, dietary habits may be less related to how controlled they are and more related to their levels of openness and emotional and social adjustment. Policy implications are discussed.

Eltrombopag for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of eltrombopag (GlaxoSmithKline) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with chronic immune or idiopathic thrombocytopenic purpura (ITP), as part of the their Single Technology Appraisal (STA) process. The Aberdeen Technology Assessment Review (TAR) Group, commissioned to act as the evidence review group (ERG), critically reviewed and supplemented the submitted evidence. This paper describes the company submission, the ERG review and NICE's subsequent decisions. The ERG critically appraised the clinical and cost-effectiveness evidence submitted by the manufacturer, independently searched for relevant literature, conducted a critical appraisal of the submitted economic models and explored the impact of altering some of the key model assumptions as well as combining relevant sensitivity analyses. Three trials were used to inform the safety and efficacy aspects of this submission; however, one high-quality randomized controlled trial (RAISE study) was the principal source of evidence and was used to inform the economic model. Eltrombopag had greater odds of achieving the primary outcome of a platelet count between 50 × 10^9/L and 400 × 10^9/L during the 6-month treatment period than placebo (odds ratio [OR] 8.2, 99% CI 3.6, 18.7). In the eltrombopag group, 50/83 (60%) of non-splenectomized patients and 18/49 (37%) of splenectomized patients achieved this outcome. The median duration of response was 10.9 weeks for eltrombopag (splenectomized 6 and non-splenectomized 13.4) compared with 0 for placebo. Eltrombopag patients required less rescue medication and had lower odds of bleeding events for both the splenectomized and the non-splenectomized patients. For a watch-and-rescue strategy of care, the comparator was placebo and the ERG found that substantial reductions in the cost of eltrombopag are needed before the incremental cost per QALY is less than £30,000. There was significant uncertainty, with the incremental cost-effectiveness ratio (ICER) reported varying from £33,561 to £103,500 per QALY (splenectomized) and £39,657 to £150,245 per QALY (non-splenectomized). All costs are presented in £, year 2008 values, as this was the costing year for the manufacturer's model. Other than bleeding, no adverse events were modelled. In relation to the long-term treatment model, the ERG questioned the robustness of the use of non-randomized non-comparative data. The base-case results restricting the time horizon to 2 years and prescribing eltrombopag as second-line treatment post-rituximab were found to be favourable towards eltrombopag. As rituximab is not a licensed treatment for ITP, the ERG were concerned that its inclusion may not be reflective of clinical practice. None of the treatment sequences resulted in an ICER approaching the recommended threshold of £30,000 per QALY gained. Eltrombopag appears to be a safe treatment for ITP (although long-term follow-up studies are awaited) and has short-term efficacy. However, NICE found based on the evidence submitted and reviewed that there was no robust evidence on the long-term efficacy or cost effectiveness of eltrombopag and a lack of direct evidence for eltrombopag tested against other relevant comparators.

Depressive symptoms and diet: their effects on prospective inflammation levels in the elderly.

It has been reported that a Mediterranean-type diet in old age is protective against inflammation in Italians with depressive symptoms. In the present study, we explore this hypothesis in a non-Mediterranean, elderly sample, and further disentangle whether it is a Mediterranean diet per se or a healthy diet, in general, that confers this protective effect. The sample is a cohort of people born in 1936, who were assessed on diet and depressive symptoms at age 70. Inflammatory markers, C-reactive protein, fibrinogen and albumin, were collected at ages 70 and 73, while Interleukin-6 transferrin and ferritin were measured at the second time-point only. Controlling for confounding factors (e.g., CVD risk factors, medication) no interaction effect of depressive symptoms and Mediterranean diet was observed on inflammation. However, a main effect of Mediterranean diet on change in C-reactive protein was significant (ß=-0.10, p=0.03), and so too was an effect of the 'Health Aware' diet on ferritin (ß=-0.12, p=0.02). An interaction between depressive symptoms and a Health Aware diet on transferrin levels showed that there was an association between increased depressive symptoms and inflammation in those following a Health Aware diet. Our results indicate that there are advantages of a Mediterranean diet over a Health Aware diet with respect to the progression of inflammation in old age and that depressive symptoms compound inflammatory burden only for specific biomarkers and under specific dietary conditions unrelated to the Mediterranean diet.