Combining an Electrochemical Continuous Glucose Sensor With an Insulin Delivery Cannula: A Feasibility Study.

BACKGROUND: Combining a continuous glucose monitor with an insulin delivery cannula (CGM-IS) could benefit clinical outcomes. We evaluated the feasibility of a single-needle insertion electrochemical investigational CGM-IS (Pacific Diabetes Technologies, Portland, Oregon) in type 1 diabetes adults. METHODS: Following 48 hours run-in using a Medtronic 780G in manual mode with a commercial insulin set, 12 participants commenced insulin delivery using the CGM-IS. A standardized test meal was eaten on the mornings of days 1 and 4. Venous samples were collected every 10 minutes one hour prior to and 15 minutes post-meal for four hours. CGM-IS glucose measurements were post-processed with a single capillary blood calibration during warm-up and benchmarked against YSI. A Dexcom G6 sensor was worn post-consent to study end. RESULTS: Mean absolute relative difference (MARD) for the CGM-IS glucose measurements was 9.2% (484 paired data points). Consensus error grid revealed 88.6% within zone A and 100% in A + B. Mean (SD) % bias was -3.5 (11.7) %. There were 35 paired YSI readings <100 mg/dL cutoff and 449 ≥100 mg/dL with 81.4% within ±15 mg/dL or ±15%, and 89.9% within ±20 mg/dL or ±20%. Two cannula occlusions required discontinuation of insulin delivery: one at 70 hours post insertion and another during the day 4 meal test. Mean (SD) Dexcom glucose measurements during run-in and between meal tests was respectively 161.3 ± 27.3 mg/dL versus 158.0 ± 25.6 mg/dL; P = .39 and corresponding mean total daily insulin delivered by the pump was 58.0 ± 25.4 Units versus 57.1 ± 28.8 Units; P = .47. CONCLUSIONS: Insulin delivery and glucose sensing with the investigational CGM-IS was feasible. Longer duration studies are needed.

Improved Satisfaction While Maintaining Safety and High Time in Range (TIR) With a Medtronic Investigational Enhanced Advanced Hybrid Closed-Loop (e-AHCL) System.

OBJECTIVE: To determine feasibility and compare acceptance of an investigational Medtronic enhanced advanced hybrid closed-loop (e-AHCL) system in adults with type 1 diabetes with earlier iterations. RESEARCH DESIGN AND METHODS: This nonrandomized three-stage (12 weeks each) exploratory study compared e-AHCL (Bluetooth-enabled MiniMed 780G insulin pump with automatic data upload [780G] incorporating an updated algorithm; calibration-free all-in-one disposable sensor; 7-day infusion set) preceded by a run-in (non-Bluetooth 780G [670G V4.0 insulin pump] requiring manual data upload; Guardian Sensor 3 [GS3] requiring calibration; 3-day infusion set), stage 1 (780G; GS3; 3-day infusion set), and stage 2 (780G; calibration-free Guardian Sensor 4; 3-day infusion set). Treatment satisfaction was assessed by Diabetes Technology Questionnaire (DTQ)-current (primary outcome) and other validated treatment satisfaction tools with glucose outcomes by continuous glucose monitoring metrics. RESULTS: Twenty-one of 22 (11 women) participants (baseline HbA1c 6.7%/50 mmol/mol) completed the study. DTQ-current scores favored e-AHCL (123.1 [17.8]) versus run-in (101.6 [24.2]) and versus stage 1 (110.6 [20.8]) (both P < 0.001) but did not differ from stage 2 (119.4 [16.0]; P = 0.271). Diabetes Medication System Rating Questionnaire short-form scores for "Convenience and Efficacy" favored e-AHCL over run-in and all stages. Percent time in range 70-180 mg/dL was greater with e-AHCL versus run-in and stage 2 (+2.9% and +3.6%, respectively; both P < 0.001). Percent times of <70 mg/dL for e-AHCL were significantly lower than run-in, stage 1, and stage 2 (-0.9%, -0.6%, and -0.5%, respectively; all P < 0.01). CONCLUSIONS: e-AHCL was feasible. User satisfaction increased compared with earlier Medtronic HCL iterations without compromising glucose control.

Hierarchical End Points in Prior Heart Failure Trials and the HEART-FID Trial.

BACKGROUND: Clinical trials in heart failure (HF) traditionally use time-to-event analyses focusing on death and hospitalization for HF. These time-to-first event analyses may have more limited abilities to assess the probability of benefiting from a therapy, especially if that benefit manifests as improved functional status rather than reduced risk of death or HF hospitalization. Hierarchical end points including clinical outcomes and patient status measures allow for ranked evaluation of outcomes in 1 metric assessing whether patients randomized to intervention or control are more likely to derive an overall benefit while also allowing more patients to contribute to the primary outcome. METHODS: We review the rationale for using hierarchical end points in HF trials, provide examples of HF trials that used this type of end point, and discuss its use in the HEART-FID trial (Randomized Placebo-Controlled Trial of Ferric Carboxymaltose as Treatment for Heart Failure With Iron Deficiency), the largest HF trial to date implementing a hierarchical end point analysis for the primary outcome. RESULTS: Using a hierarchical end point as the primary outcome allows for the inclusion of different types of outcomes in 1 ranked end point, making it possible to more holistically assess the potential utility of a new therapy on patient well-being and outcomes. CONCLUSIONS: Hierarchical end points assess the potential utility of a new therapy on patient well-being and outcome more holistically than time-to-first event analysis. Trials that would not have been feasible due to decreasing rates of death and hospitalization in the HF population can use hierarchical end points to successfully power studies to identify promising HF therapies. The HEART-FID trial used hierarchical end points to better determine the role of intravenous ferric carboxymaltose in patients with HF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037931.

Genomic, transcriptomic, and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti-cancer metabolites.

Plants accumulate a vast array of secondary metabolites, which constitute a natural resource for pharmaceuticals. Oldenlandia corymbosa belongs to the Rubiaceae family, and has been used in traditional medicine to treat different diseases, including cancer. However, the active metabolites of the plant, their biosynthetic pathway and mode of action in cancer are unknown. To fill these gaps, we exposed this plant to eight different stress conditions and combined different omics data capturing gene expression, metabolic profiles, and anti-cancer activity. Our results show that O. corymbosa extracts are active against breast cancer cell lines and that ursolic acid is responsible for this activity. Moreover, we assembled a high-quality genome and uncovered two genes involved in the biosynthesis of ursolic acid. Finally, we also revealed that ursolic acid causes mitotic catastrophe in cancer cells and identified three high-confidence protein binding targets by Cellular Thermal Shift Assay (CETSA) and reverse docking. Altogether, these results constitute a valuable resource to further characterize the biosynthesis of active metabolites in the Oldenlandia group, while the mode of action of ursolic acid will allow us to further develop this valuable compound.

Delayed diagnosis of tuberculosis: risk factors and effect on mortality among older adults in Hong Kong.

OBJECTIVE: To assess the risk factors and effects of delayed diagnosis on tuberculosis (TB) mortality in Hong Kong. METHODS: All consecutive patients with TB notified in 2010 were tracked through their clinical records for treatment outcome until 2012. All TB cases notified or confirmed after death were identified for a mortality survey on the timing and causes of death. RESULTS: Of 5092 TB cases notified, 1061 (20.9%) died within 2 years of notification; 211 (4.1%) patients died before notification, 683 (13.4%) died within the first year, and 167 (3.3%) died within the second year after notification. Among the 211 cases with TB notified after death, only 30 were certified to have died from TB. However, 52 (24.6%) died from unspecified pneumonia/sepsis possibly related to pulmonary TB. If these cases are counted, the total TB-related deaths increases from 191 to 243. In 82 (33.7%) of these, TB was notified after death. Over 60% of cases in which TB diagnosed after death involved patients aged ≥80 years and a similar proportion had an advance care directive against resuscitation or investigation. Independent factors for TB notified after death included female sex, living in an old age home, drug abuse, malignancy other than lung cancer, sputum TB smear negative, sputum TB culture positive, and chest X-ray not done. CONCLUSIONS: High mortality was observed among patients with TB aged ≥80 years. Increased vigilance is warranted to avoid delayed diagnosis and reduce the transmission risk, especially among elderly patients with co-morbidities living in old age homes.

Development of a Low-Cost and Effective Trapping Device for Apple Maggot Fly (Diptera: Tephritidae) Monitoring and Control in Mexican Commercial Hawthorn Groves.

Few efforts have been made in Mexico to monitor Rhagoletis pomonella (Walsh) (Diptera: Tephritidae) in commercial hawthorn (Crataegus spp.) crops. Therefore, the main objectives of this study were to evaluate infestation levels of R. pomonella in feral and commercial Mexican hawthorn and to assess the efficacy of different trap-lure combinations to monitor the pest. Wild hawthorn was more infested than commercially grown hawthorn at the sample site. No differences among four commercial baits (Biolure, ammonium carbonate, CeraTrap, and Captor + borax) were detected when used in combination with a yellow sticky gel (SG) adherent trap under field conditions. However, liquid lures elicited a slightly higher, although not statistically different, capture. Cage experiments in the laboratory revealed that flies tended to land more often on the upper and middle than lower-bottom part of polyethylene (PET) bottle traps with color circles. Among red, orange, green, and yellow circles attached to a bottle trap, only yellow circles improved fly captures compared with a colorless trap. A PET bottle trap with a red circle over a yellow background captured more flies than a similar trap with yellow circles. An SG adherent yellow panel trap baited with ammonium carbonate was superior to the improved PET bottle trap (red over a yellow background) baited with different liquid proteins, but a higher proportion of females and no differences in fly detection were measured in PET traps baited with protein lures. These trials open the door for future research into development of a conventional nonadherent trap to monitor or control R. pomonella.

Surfactant utilization and short-term outcomes in an era of non-invasive respiratory support in Canadian neonatal intensive care units.

OBJECTIVE: Increased use of non-invasive respiratory support (NRS) in the delivery room management of preterm neonates has resulted in delayed surfactant treatment, yet the short-term effects of this change are unknown. The aim of this study was to comparatively evaluate the use of surfactant and the short-term outcomes prior to and after the implementation of early routine use of NRS. STUDY DESIGN: Eligible infants of <29 weeks gestational age (GA) admitted to a Canadian tertiary neonatal center during two time periods (2005 to 2008 and 2010 to 2013) were included in this retrospective cohort study. Timing of surfactant (prophylactic vs therapeutic) and short-term outcomes were compared between the two groups. Univariate and multivariate regression analysis was performed to determine the adjusted odds ratio (AOR) along with 95% confidence interval (CI) of receiving exogenous surfactant and developing bronchopulmonary dysplasia (BPD) using the later cohort as the reference group. Subgroup analyses were also performed for infants <26 and 26 to 286/7 weeks GA, respectively. RESULTS: A total of 3980 and 5137 infants were included in the first and second time periods, respectively. There was no significant difference in overall surfactant utilization between the two time periods (AOR 1.00, 95% CI 0.89, 1.13). However, between 2005 and 2008, a lower proportion of neonates received therapeutic surfactant compared with the later cohort (47.1% vs 56.9%, P<0.01) but were more likely to receive prophylactic surfactant (52.9% vs 43.1%, P<0.01). BPD overall was significantly higher in the earlier cohort (AOR 1.19, 95% CI 1.07, 1.33), particularly among the <26 weeks gestation subgroup (AOR 1.34, 95% CI 1.08, 1.66). CONCLUSION: Early routine use of NRS did not impact overall surfactant utilization rate, although therapeutic surfactant administration rates were higher with a concomitant decrease in BPD rates.

Computer simulation of energy use, greenhouse gas emissions, and costs for alternative methods of processing fluid milk.

Computer simulation is a useful tool for benchmarking electrical and fuel energy consumption and water use in a fluid milk plant. In this study, a computer simulation model of the fluid milk process based on high temperature, short time (HTST) pasteurization was extended to include models for processes for shelf-stable milk and extended shelf-life milk that may help prevent the loss or waste of milk that leads to increases in the greenhouse gas (GHG) emissions for fluid milk. The models were for UHT processing, crossflow microfiltration (MF) without HTST pasteurization, crossflow MF followed by HTST pasteurization (MF/HTST), crossflow MF/HTST with partial homogenization, and pulsed electric field (PEF) processing, and were incorporated into the existing model for the fluid milk process. Simulation trials were conducted assuming a production rate for the plants of 113.6 million liters of milk per year to produce only whole milk (3.25%) and 40% cream. Results showed that GHG emissions in the form of process-related CO2 emissions, defined as CO2 equivalents (e)/kg of raw milk processed (RMP), and specific energy consumptions (SEC) for electricity and natural gas use for the HTST process alone were 37.6g of CO2e/kg of RMP, 0.14 MJ/kg of RMP, and 0.13 MJ/kg of RMP, respectively. Emissions of CO2 and SEC for electricity and natural gas use were highest for the PEF process, with values of 99.1g of CO2e/kg of RMP, 0.44 MJ/kg of RMP, and 0.10 MJ/kg of RMP, respectively, and lowest for the UHT process at 31.4 g of CO2e/kg of RMP, 0.10 MJ/kg of RMP, and 0.17 MJ/kg of RMP. Estimated unit production costs associated with the various processes were lowest for the HTST process and MF/HTST with partial homogenization at $0.507/L and highest for the UHT process at $0.60/L. The increase in shelf life associated with the UHT and MF processes may eliminate some of the supply chain product and consumer losses and waste of milk and compensate for the small increases in GHG emissions or total SEC noted for these processes compared with HTST pasteurization alone. The water use calculated for the HTST and PEF processes were both 0.245 kg of water/kg of RMP. The highest water use was associated with the MF/HTST process, which required 0.333 kg of water/kg of RMP, with the additional water required for membrane cleaning. The simulation model is a benchmarking framework for current plant operations and a tool for evaluating the costs of process upgrades and new technologies that improve energy efficiency and water savings.

Coagulase-negative staphylococcus sepsis in preterm infants and long-term neurodevelopmental outcome.

OBJECTIVE: The objective of this study was to examine the impact of Coagulase-negative staphylococcus (CoNS) sepsis in preterm infants on the neurodevelopmental outcomes at 30 to 42 months corrected age (CA). STUDY DESIGN: This is a retrospective cohort study. All preterm infants born at <29 weeks gestational age between 1995 and 2008 and had a neurodevelopmetnal assessment at 30 to 42 months CA were eligible. The neurodevelopmetnal outcomes of infants exposed to CoNS sepsis were compared with infants unexposed to any type of neonatal sepsis. RESULT: A total of 105 eligible infants who were exposed to CoNS sepsis were compared with 227 infants with no neonatal sepsis. In univariate analysis, infants with CoNS sepsis were more likely to have total major disability (odds ratio (OR)=1.9; 95% CI: 1.07 to 3.38) and cognitive delay (OR=2.53; 1.26 to 5.14).There was no significant difference in the incidence of cerebral palsy, blindness and deafness between the two groups. After correcting for potential confounders, CoNS sepsis was associated with increased risk of cognitive delay (adjusted odds ratio (aOR)= 2.23; 95% CI 1.01 to 4.9), but not with the total major disability (aOR=1.14; 95% CI: 0.55 to 2.34). CONCLUSION: Our study suggests that CoNS sepsis in preterm infants might be associated with increased risk for cognitive delay at 36 months CA.

Niche differentiation and colonization of a novel environment by an asexual parasitic wasp.

How do asexual taxa become adapted to a diversity of environments, and how do they persist despite changing environmental conditions? These questions are linked by their mutual focus on the relationship between genetic variation, which is often limited in asexuals, and the ability to respond to environmental variation. Asexual taxa originating from a single ancestor present a unique opportunity to assess rates of phenotypic and genetic change when access to new genetic variation is limited to mutation. Diachasma muliebre is an asexual Hymenopteran wasp that is geographically and genetically isolated from all sexual relatives. D. muliebre attack larvae of the western cherry fruit fly (Rhagoletis indifferens), which in turn feed inside bitter cherry fruit (Prunus emarginata) in August and September. R. indifferens has recently colonized a new host plant with an earlier fruiting phenology (June/July), domesticated sweet cherries (P. avium), and D. muliebre has followed its host into this temporally earlier niche. We tested three hypotheses: 1) that all D. muliebre lineages originate from a single asexual ancestor; 2) that different D. muliebre lineages (as defined by unique mtDNA haplotypes) have differentiated on their ancestral host in an important life-history trait, eclosion timing; and 3) that early-eclosing lineages have preferentially colonized the new sweet cherry niche. We find that mitochondrial COI and microsatellite data provide strong support for a single ancestral origin for all lineages. Furthermore, COI sequencing revealed five mitochondrial haplotypes among D. muliebre, and individual wasps possessing one distinctive mitochondrial haplotype (haplotype II) eclosed as reproductive adults significantly earlier than wasps with all other haplotypes. In addition, this early-eclosing lineage of D. muliebre is one of two lineages that have colonized the P. avium habitat, consistent with the preferential colonization hypothesis. These data suggest that D. muliebre has evolved adaptive phenotypic variation despite limited genetic variation, and that this variation has subsequently allowed an expansion of some wasps into a novel habitat. The D. muliebre system may allow for in-depth study of adaptation and long-term persistence of asexual taxa.

Computer simulation of energy use, greenhouse gas emissions, and process economics of the fluid milk process.

Energy-savings measures have been implemented in fluid milk plants to lower energy costs and the energy-related carbon dioxide (CO2) emissions. Although these measures have resulted in reductions in steam, electricity, compressed air, and refrigeration use of up to 30%, a benchmarking framework is necessary to examine the implementation of process-specific measures that would lower energy use, costs, and CO2 emissions even further. In this study, using information provided by the dairy industry and equipment vendors, a customizable model of the fluid milk process was developed for use in process design software to benchmark the electrical and fuel energy consumption and CO2 emissions of current processes. It may also be used to test the feasibility of new processing concepts to lower energy and CO2 emissions with calculation of new capital and operating costs. The accuracy of the model in predicting total energy usage of the entire fluid milk process and the pasteurization step was validated using available literature and industry energy data. Computer simulation of small (40.0 million L/yr), medium (113.6 million L/yr), and large (227.1 million L/yr) processing plants predicted the carbon footprint of milk, defined as grams of CO2 equivalents (CO2e) per kilogram of packaged milk, to within 5% of the value of 96 g of CO 2e/kg of packaged milk obtained in an industry-conducted life cycle assessment and also showed, in agreement with the same study, that plant size had no effect on the carbon footprint of milk but that larger plants were more cost effective in producing milk. Analysis of the pasteurization step showed that increasing the percentage regeneration of the pasteurizer from 90 to 96% would lower its thermal energy use by almost 60% and that implementation of partial homogenization would lower electrical energy use and CO2e emissions of homogenization by 82 and 5.4%, respectively. It was also demonstrated that implementation of steps to lower non-process-related electrical energy in the plant would be more effective in lowering energy use and CO2e emissions than fuel-related energy reductions. The model also predicts process-related water usage, but this portion of the model was not validated due to a lack of data. The simulator model can serve as a benchmarking framework for current plant operations and a tool to test cost-effective process upgrades or evaluate new technologies that improve the energy efficiency and lower the carbon footprint of milk processing plants.

A field test for host fruit odour discrimination and avoidance behaviour for Rhagoletis pomonella flies in the western United States.

Prezygotic isolation due to habitat choice is important to many models of speciation-with-gene-flow. Habitat choice is usually thought to occur through positive preferences of organisms for particular environments. However, avoidance of non-natal environments may also play a role in choice and have repercussions for post-zygotic isolation that preference does not. The recent host shift of Rhagoletis pomonella (Diptera: Tephritidae) from downy hawthorn, Crataegus mollis, to introduced apple, Malus domestica, in the eastern United States is a model for speciation-with-gene-flow. However, the fly is also present in the western United States where it was likely introduced via infested apples ≤ 60 years ago. R. pomonella now attacks two additional hawthorns in the west, the native C. douglasii (black hawthorn) and the introduced C. monogyna (English ornamental hawthorn). Flight tunnel tests have shown that western apple-, C. douglasii- and C. monogyna-origin flies all positively orient to fruit volatile blends of their respective natal hosts in flight tunnel assays. Here, we show that these laboratory differences translate to nature through field-trapping studies of flies in the state of Washington. Moreover, western R. pomonella display both positive orientation to their respective natal fruit volatiles and avoidance behaviour (negative orientation) to non-natal volatiles. Our results are consistent with the existence of behaviourally differentiated host races of R. pomonella in the west. In addition, the rapid evolution of avoidance behaviour appears to be a general phenomenon for R. pomonella during host shifts, as the eastern apple and downy hawthorn host races also are antagonized by non-natal fruit volatiles.

Recurrent and founder mutations in the Netherlands: the cardiac phenotype of DES founder mutations p.S13F and p.N342D.

BACKGROUND: Desmin-related myopathy (DRM) is an autosomally inherited skeletal and cardiac myopathy, mainly caused by dominant mutations in the desmin gene (DES). We describe new families carrying the p.S13F or p.N342D DES mutations, the cardiac phenotype of all carriers, and the founder effects. METHODS: We collected the clinical details of all carriers of p.S13F or p.N342D. The founder effects were studied using genealogy and haplotype analysis. RESULTS: We identified three new index patients carrying the p.S13F mutation and two new families carrying the p.N342D mutation. In total, we summarised the clinical details of 39 p.S13F carriers (eight index patients) and of 21 p.N342D carriers (three index patients). The cardiac phenotype of p.S13F carriers is fully penetrant and severe, characterised by cardiac conduction disease and cardiomyopathy, often with right ventricular involvement. Although muscle weakness is a prominent and presenting symptom in p.N342D carriers, their cardiac phenotype is similar to that of p.S13F carriers. The founder effects of p.S13F and p.N342D were demonstrated by genealogy and haplotype analysis. CONCLUSION: DRM may occur as an apparently isolated cardiological disorder. The cardiac phenotypes of the DES founder mutations p.S13F and p.N342D are characterised by cardiac conduction disease and cardiomyopathy, often with right ventricular involvement.

Medium effects on the direct cis-trans photoisomerization of 1,4-diphenyl-1,3-butadiene in solution.

Quantum yields for the photoisomerization of trans,trans-1,4-diphenyl-1,3-butadiene (tt-DPB), determined in benzene, cyclohexane, methylcyclohexane, hexane, and perfluorohexane, confirm the low values reported earlier for benzene and cyclohexane and reveal even lower values in the last two solvents. In contrast to trans-stilbene (t-St), fluorescence and torsional relaxation leading to photoisomerization do not account exclusively for S(1)tt-DPB decay. Competing radiationless singlet excited-state decay pathways exist in tt-DPB, which do not lead to photoisomerization and may not involve large-amplitude torsional motions. Our results invalidate analyses of tt-DPB fluorescence quantum yields and lifetimes that assign all radiationless decay to the isomerization channel. Gas-phase chromatography analysis of tt-DPB photoisomerization in hexane shows the reaction to be concentration-independent and reveals, for the first time, a significant, two-bond photoisomerization pathway, φ(tt→tc) = 0.092 and φ(tt→cc) = 0.020. The dominant one-bond-twist (OBT) process is accompanied by a bicycle pedal (BP) process that accounts for almost 20% of tt-DPB photoisomerization. The OBT tt-DPB photoisomerization quantum yield is largest in benzene (Bz) and smallest in perfluorohexane (PFH). Contrary to expectations, reduction in medium friction in PFH is accompanied by a decrease in φ(tt→tc). The 1(1)B(u)/2(1)A(g) order and energy gap appear to control the contribution of torsional relaxation to radiationless decay. Lowering the 1(1)B(u) energy as in Bz favors photoisomerization. Reversal of the 1(1)B(u)/2(1)A(g) order in PFH is accompanied by short τ(f) and small φ(f) and φ(tt→tc) values that suggest the presence of competing 2(1)A(g) → 1(1)Ag relaxation paths that are unproductive with respect to photoisomerization. We conclude that the Birks extension to diphenylpolyenes of the Orlandi-Siebrand cis-trans photoisomerization mechanism is not valid. Photoisomerization appears to occur in the 1(I)B(u) state, and we argue that this applies to t-St as well.

Management and prevention of spontaneous pneumothorax using pleurodesis in Hong Kong.

BACKGROUND: The practice of pleurodesis for the management and prevention of spontaneous pneumothorax (SP) is uncertain. DESIGN: A retrospective multicentre analysis of patients admitted to 12 hospitals in Hong Kong with SP in 2004 and who subsequently underwent pleurodesis for the same episode. RESULTS: Pleurodesis was performed in 394 episodes. Initial medical chemical pleurodesis was performed for 258 (65.5%) patients ('initial medical group'), while 136 (34.5%) underwent initial surgical pleurodesis ('initial surgical group'). Secondary spontaneous pneumothorax (SSP; 237 episodes, 60.2%) was the most common indication for pleurodesis; it was also performed after a first episode of primary spontaneous pneumothorax (PSP) in 22 episodes (5.6%). Tetracycline derivatives (172 episodes, 66.7%) were the most popular sclerosing agents in the initial medical group. Those in the initial medical group were older and were more likely to be males, have SSP, chronic obstructive pulmonary disease and a history of past pleurodesis (P < 0.05) compared to the initial surgical group. Compared to the tetracycline group, more patients who initially received talc slurry had the procedure performed by surgeons, had larger (≥2 cm) pneumothorax or required suction during initial drainage (P < 0.05). CONCLUSIONS: Despite the availability of international guidelines, there is considerable variation in pleurodesis for SP.

Minocycline and talc slurry pleurodesis for patients with secondary spontaneous pneumothorax.

SETTING: Few studies have evaluated the sclerosing efficacy of minocycline, and none have specifically compared its sclerosing efficacy and safety profiles with talc slurry in secondary spontaneous pneumothorax (SSP). DESIGN: A retrospective analysis was conducted in patients with SSP who underwent chemical pleurodesis from January to December 2004 with minocycline or talc slurry in 12 public hospitals of Hong Kong. RESULT: There were 121 episodes of minocycline pleurodesis and 64 episodes of talc slurry pleurodesis. Immediate procedural failure were similar in the minocycline and talc slurry groups (21.5% vs. 28.1%, P = 0.31). Presence of interstitial lung disease, ≥ 2 previous episodes of pneumothorax, requiring mechanical ventilation during pleurodesis and persistent air leak before pleurodesis were independently associated with procedural failure. Pain was experienced in respectively 44.6% and 37.5% of the minocycline and the talc slurry groups. Pain was more common in patients receiving high doses of talc (≥ 5 g; P = 0.03). Respiratory distress was found in respectively 1.7% and 1.6% of the minocycline and talc slurry groups. CONCLUSION: Minocycline and talc slurry had comparable sclerosing efficacy in SSP, with immediate success rates of >70%. Pain was the most common adverse effect and respiratory distress was uncommon. Both appeared to be effective and safe for chemical pleurodesis in SSP.

Antiplatelet therapy in percutaneous coronary intervention: recent advances in oral antiplatelet agents.

PURPOSE OF REVIEW: Dual antiplatelet therapy with aspirin and clopidogrel, in conjunction with heparin, is the most common antithrombotic strategy in percutaneous coronary intervention (PCI) used to reduce peri-procedural ischaemic complications. However, there remains significant inter-individual variability in post-treatment platelet inhibition with this current established therapy. This review focuses on recent developments in oral antiplatelet agents used in PCI, which promise to overcome, at least in part, current shortfalls. RECENT FINDINGS: Genetic polymorphisms and medication interactions involving CYP3A4 or CYP2C19, patient compliance and higher platelet reactivity in certain subgroups, such as those with diabetes, are important factors contributing to inter-individual variability in post-treatment platelet inhibition. Higher clopidogrel doses have been associated with improved clinical outcomes, especially in those presenting with acute coronary syndrome. Newer agents, namely prasugrel and ticagrelor, have been shown to have greater potency and superior clinical outcomes. However, this comes with a price of increased bleeding complications. SUMMARY: Whereas more potent antiplatelet therapies are associated with improved outcome, balancing the risk of bleeding and peri-procedural ischaemic complications remains a key aspect to consider when choosing among the ever-increasing number of agents available. The role of intravenous glycoprotein IIb/IIIa (GPIIb/IIIa) needs to be re-examined in the current context of such potent oral antiplatelet agents. Further research will hopefully help to determine the preferred antithrombotic strategy in patients undergoing PCI.

Relationship between oxygen saturation and the mode of oxygen delivery used in newborn resuscitation.

OBJECTIVE: To compare the rate of increase in oxygen saturation in babies receiving supplemental oxygen during resuscitation with those transitioning in room air. STUDY DESIGN: Prospective observational study. Infants were resuscitated with supplemental oxygen and continuous recording of preductal oxygen saturation was started immediately after birth. Oxygen saturation measurements from healthy newborns transitioned in room air were used for comparison. RESULT: A total of 186 infants were included--70 received supplemental oxygen and 116 were transitioned in room air. Compared with healthy infants transitioned in room air, infants receiving 100% oxygen by positive-pressure ventilation (PPV) did not differ significantly in the rate of increase in oxygen saturation (1.5% per minute, P=0.26), whereas infants receiving 100% free-flow oxygen had a significantly slower rate of increase in oxygen saturation (1.2% per minute, P=0.04). CONCLUSION: Babies receiving 100% oxygen by free flow had a slower increase in oxygen saturation compared with healthy infants transitioned in room air, whereas those receiving 100% oxygen by PPV had a similar increase in oxygen saturation compared with healthy infants transitioned in room air.

Correction of dystrophia myotonica type 1 pre-mRNA transcripts by artificial trans-splicing.

Dystrophia myotonica type 1 (DM1), the most common muscular dystrophy in adults, results from expansion of a CTG repeat in the 3'-untranslated region of the dystrophia myotonica protein kinase gene (DMPK). Correction of the mutant DMPK transcript is a potential therapeutic strategy in DM1. We investigated the efficacy of artificial trans-splicing molecules (ATMs) to target and correct DMPK transcripts. ATMs designed to target intron 14 of DMPK pre-mRNA transcripts were tested for their ability to trans-splice the transcripts of a DMPK mini-gene construct and the endogenous DMPK transcripts of human myosarcoma cells (CCL-136). On agarose gel electrophoresis analysis, six of eight ATMs showed trans-splicing efficacy when applied to DMPK mini-gene construct transcripts, of which three were able to trans-splice endogenous DMPK pre-mRNA transcripts in myosarcoma cells, with trans-splicing efficiency ranging from 1.81 to 7.41%. These findings confirm that artificial trans-splicing can repair DMPK pre-mRNA and provide proof-of-principle evidence for this approach as potential therapeutic strategy for DM1.