Blending Indigenous and western science: Quantifying cultural burning impacts in Karuk Aboriginal Territory.

The combined effects of Indigenous fire stewardship and lightning ignitions shaped historical fire regimes, landscape patterns, and available resources in many ecosystems globally. The resulting fire regimes created complex fire-vegetation dynamics that were further influenced by biophysical setting, disturbance history, and climate. While there is increasing recognition of Indigenous fire stewardship among western scientists and managers, the extent and purpose of cultural burning is generally absent from the landscape-fire modeling literature and our understanding of ecosystem processes and development. In collaboration with the Karuk Tribe Department of Natural Resources, we developed a transdisciplinary Monte Carlo simulation model of cultural ignition location, frequency, and timing to simulate spatially explicit cultural ignitions across a 264,399-ha landscape within Karuk Aboriginal Territory in northern California. Estimates of cultural ignition parameters were developed with Tribal members and knowledge holders using existing interviews, historical maps, ethnographies, recent ecological studies, contemporary maps, and generational knowledge. Spatial and temporal attributes of cultural burning were explicitly tied to the ecology of specific cultural resources, fuel receptivity, seasonal movement patterns, and spiritual practices. Prior to colonization, cultural burning practices were extensive across the study landscape with an estimated 6972 annual ignitions, averaging approximately 6.5 ignitions per Indigenous fire steward per year. The ignition characteristics we document align closely with data on historical fire regimes and vegetation but differ substantially from the location and timing of contemporary ignitions. This work demonstrates the importance of cultural burning for developing and maintaining the ecosystems present at the time of colonization and underscores the need to work collaboratively with Indigenous communities to restore ecocultural processes in these systems.

Too hot, too cold, or just right: Can wildfire restore dry forests of the interior Pacific Northwest?

As contemporary wildfire activity intensifies across the western United States, there is increasing recognition that a variety of forest management activities are necessary to restore ecosystem function and reduce wildfire hazard in dry forests. However, the pace and scale of current, active forest management is insufficient to address restoration needs. Managed wildfire and landscape-scale prescribed burns hold potential to achieve broad-scale goals but may not achieve desired outcomes where fire severity is too high or too low. To explore the potential for fire alone to restore dry forests, we developed a novel method to predict the range of fire severities most likely to restore historical forest basal area, density, and species composition in forests across eastern Oregon. First, we developed probabilistic tree mortality models for 24 species based on tree characteristics and remotely sensed fire severity from burned field plots. We applied these estimates to unburned stands in four national forests to predict post-fire conditions using multi-scale modeling in a Monte Carlo framework. We compared these results to historical reconstructions to identify fire severities with the highest restoration potential. Generally, we found basal area and density targets could be achieved by a relatively narrow range of moderate-severity fire (roughly 365-560 RdNBR). However, single fire events did not restore species composition in forests that were historically maintained by frequent, low-severity fire. Restorative fire severity ranges for stand basal area and density were strikingly similar for ponderosa pine (Pinus ponderosa) and dry mixed-conifer forests across a broad geographic range, in part due to relatively high fire tolerance of large grand (Abies grandis) and white fir (Abies concolor). Our results suggest historical forest conditions created by recurrent fire are not readily restored by single fires and landscapes have likely passed thresholds that preclude the effectiveness of managed wildfire alone as a restoration tool.

To burn or not to burn: An empirical assessment of the impacts of wildfires and prescribed fires on trace element concentrations in Western US streams.

The use of low-severity prescribed fires has been increasingly promoted to reduce the impacts from high-severity wildfires and maintain ecosystem resilience. However, the effects of prescribed fires on water quality have rarely been evaluated relative to the effects of wildfires. In this study, we assessed the effects of 54 wildfires and 11 prescribed fires on trace element (arsenic, selenium, and cadmium) concentrations of streams draining burned watersheds in the western US. To obtain results independent of the choice of method, we employed three independent analytical approaches to evaluate fire effects on water quality for the first three post-fire years. In general, we observed significant increases in trace element concentrations in streams burned by large, high-severity wildfires, despite substantial variability across sites. Comparatively, we did not observe increases in the spring mean concentration of arsenic, selenium, and cadmium in watersheds burned by prescribed fires. Our analysis indicated that the post-fire trace element response in streams was primarily influenced by burn area, burn severity, post-fire weather, surface lithology, watershed physiography, and land cover. This study's results demonstrate that prescribed burns could lessen the post-fire trace element loads in downstream waters if prescribed fires reduce subsequent high severity fires in the landscape.

High-Performance and Stable Semi-Transparent Perovskite Solar Cells through Composition Engineering.

Semi-transparent perovskite solar cells (ST-PeSCs) have tremendous potential as solar windows owing to their higher efficiency and visible transmittance. However, studies toward this application are still nascent, particularly in unraveling the interplay between how the perovskite composition impacts the achievable device performance and stability. Here, the role of A- and X-site modification in APbX3 perovskites is studied to understand their influence on these factors. Through detailed experimental and simulation work, it is found that a perovskite composition consisting of cesium (Cs) and formamidinium (FA) at the A-site delivers the best device performance over a range of band gaps, which are tuned by changes to the X-site anion. Using this optimized perovskite composition, power conversion efficiencies of 15.5% and 4.1% are achieved for ST-PeSCs with average visible transmittance values between 20.7% and 52.4%, respectively. Furthermore, the CsFA-based ST-PeSCs show excellent long-term stability under continuous illumination and heating. The stability of the precursor solutions across each of the studied compositions has also been considered, showing dramatic differences in the structural properties of the perovskites and their device performance for all mixed A-site compositions possessing the archetypal methyl ammonium species, while also confirming the superior stability of the CsFA precursor solutions.

Human ignitions on private lands drive USFS cross-boundary wildfire transmission and community impacts in the western US.

Wildfires in the western United States (US) are increasingly expensive, destructive, and deadly. Reducing wildfire losses is particularly challenging when fires frequently start on one land tenure and damage natural or developed assets on other ownerships. Managing wildfire risk in multijurisdictional landscapes has recently become a centerpiece of wildfire strategic planning, legislation, and risk research. However, important empirical knowledge gaps remain regarding cross-boundary fire activity in the western US. Here, we use lands administered by the US Forest Service as a study system to assess the causes, ignition locations, structure loss, and social and biophysical factors associated with cross-boundary fire activity over the past three decades. Results show that cross-boundary fires were primarily caused by humans on private lands. Cross-boundary ignitions, area burned, and structure losses were concentrated in California. Public lands managed by the US Forest Service were not the primary source of fires that destroyed the most structures. Cross-boundary fire activity peaked in moderately populated landscapes with dense road and jurisdictional boundary networks. Fire transmission is increasing, and evidence suggests it will continue to do so in the future. Effective cross-boundary fire risk management will require cross-scale risk co-governance. Focusing on minimizing damages to high-value assets may be more effective than excluding fire from multijurisdictional landscapes.

Severe fire weather and intensive forest management increase fire severity in a multi-ownership landscape.

Many studies have examined how fuels, topography, climate, and fire weather influence fire severity. Less is known about how different forest management practices influence fire severity in multi-owner landscapes, despite costly and controversial suppression of wildfires that do not acknowledge ownership boundaries. In 2013, the Douglas Complex burned over 19,000 ha of Oregon & California Railroad (O&C) lands in Southwestern Oregon, USA. O&C lands are composed of a checkerboard of private industrial and federal forestland (Bureau of Land Management, BLM) with contrasting management objectives, providing a unique experimental landscape to understand how different management practices influence wildfire severity. Leveraging Landsat based estimates of fire severity (Relative differenced Normalized Burn Ratio, RdNBR) and geospatial data on fire progression, weather, topography, pre-fire forest conditions, and land ownership, we asked (1) what is the relative importance of different variables driving fire severity, and (2) is intensive plantation forestry associated with higher fire severity? Using Random Forest ensemble machine learning, we found daily fire weather was the most important predictor of fire severity, followed by stand age and ownership, followed by topographic features. Estimates of pre-fire forest biomass were not an important predictor of fire severity. Adjusting for all other predictor variables in a general least squares model incorporating spatial autocorrelation, mean predicted RdNBR was higher on private industrial forests (RdNBR 521.85 ± 18.67 [mean ± SE]) vs. BLM forests (398.87 ± 18.23) with a much greater proportion of older forests. Our findings suggest intensive plantation forestry characterized by young forests and spatially homogenized fuels, rather than pre-fire biomass, were significant drivers of wildfire severity. This has implications for perceptions of wildfire risk, shared fire management responsibilities, and developing fire resilience for multiple objectives in multi-owner landscapes.

Silk provides a new avenue for third generation biosensors: Sensitive, selective and stable electrochemical detection of nitric oxide.

Using heme entrapped in recombinant silk films, we have produced 3rd generation biosensors, which allow direct electron transfer from the heme center to an electrode avoiding the need for electron mediators. Here, we demonstrate the use of these heme-silk films for the detection of nitric oxide (NO) at nanomolar levels in the presence and absence of oxygen. The sensor was prepared by drop-casting a silk solution on a glassy carbon electrode modified with multiwalled carbon nanotubes (MWCNT) followed by infusion with heme. The sensor was characterized by cyclic voltammetry and showed well defined and reversible Fe+/ Fe3+ redox couple activity, with NO detection by oxidation at potentials above +0.45V or reduction at potentials below - 0.7V. Evaluation of the effect of pH on the sensor response to NO reduction indicated a maximum response at pH 3. The sensor showed good linearity in the concentration range from 19 to 190nM (R2 = 0.99) with a detection limit of 2nM. The sensor had excellent selectivity towards NO with no or negligible interference from oxygen, nitrite, nitrate, dopamine and ascorbic acid and retained 86% of response after 2 months of operation and storage at room temperature.

Design of silk proteins with increased heme binding capacity and fabrication of silk-heme materials.

In our previous studies, heme was bound into honeybee silk to generate materials that could function as nitric oxide sensors or as recoverable heterogeneous biocatalysts. In this study, we sought to increase the heme-binding capacity of the silk protein by firstly redesigning the heme binding site to contain histidine as the coordinating residue and secondly, by adding multiple histidine residues within the core of the coiled coil core region of the modified silk protein. We used detergent and a protein denaturant to confirm the importance of the helical structure of the silk for heme coordination. Aqueous methanol treatment, which was used to stabilize the materials, transformed the low-spin, six-coordinate heme to a five-coordinate high-spin complex, thus providing a vacant site for ligand binding. The optimal aqueous methanol treatment time that simultaneously maintains the helical protein structure and stabilizes the silk material without substantial leaching of heme from the system was determined.

Aeromedical evacuation of patients with pneumocephalus: outcomes in 21 cases.

INTRODUCTION: Aeromedical evacuation of patients with posttraumatic and/or post-surgical pneumocephalus has often been regarded with great concern. The expansion of intracranial air with increasing altitude can theoretically result in tension pneumocephalus, with potentially fatal results. This concern is primarily based on extremely rare case reports and theoretical models rather than any significant clinical experience. We report the outcomes of a series of 21 patients with posttraumatic and/or post-craniotomy pneumocephalus who underwent long-range air evacuation from a combat theater in military aircraft. METHODS: The estimated volume for each patient was calculated with a simplified method, purposely intended to err toward overestimation, based on computerized tomography scans performed within 24 h prior to air travel. RESULTS: The volumes of pneumocephalus ranged from 0.6 to 42.7 ml, with mean volume of 9.3 ml and median volume of 4.2 ml. No patient sustained a temporary or permanent neurologic decline as a result of air transportation. Three patients with continuous monitoring of intracranial pressure (ICP) were not observed to have any sustained pressure elevations during flight. DISCUSSION: We conclude that pneumocephalus in the head-injured and/or craniotomy patient is not likely by itself to be an absolute contraindication to air evacuation. The mechanism causing pneumocephalus, its time course, progression, and the rate of altitude change are likely more important factors in determining its clinical significance. More clinical experience is required to better assess the safety of aeromedical evacuation of these patients, but this small series suggests that it is not as dangerous as previously thought.

Tigecycline: an evidence-based review of its antibacterial activity and effectiveness in complicated skin and soft tissue and intraabdominal infections.

INTRODUCTION: There is an urgent need for novel agents to manage serious bacterial infections, particularly those contracted in healthcare facilities. Tigecycline is a novel broad-spectrum glycylcycline with good activity against Gram-positive, many Gram-negative, anaerobic, and some atypical pathogens that has been developed to address this need. AIMS: To review the evidence for the use of tigecycline in serious and complicated skin and soft tissue and intraabdominal infections. EVIDENCE REVIEW: There is substantial evidence that tigecycline is as effective as vancomycin plus aztreonam in complicated skin and skin structure infections (SSSIs) and as effective as imipenem plus cilastatin in intraabdominal infections. Limited evidence shows effectiveness in patients with resistant Acinetobacter infection in an intensive care unit, and the possibility that the use of tigecycline may reduce length of hospital stay. The drug is well tolerated, with nausea and vomiting as the major adverse effects. OUTCOMES SUMMARY: The introduction of tigecycline should be beneficial at a time of increasing problems with bacterial resistance, and evidence to date has been sufficient for regulatory approval for complicated SSSIs and intraabdominal infections. Research into tigecycline's efficacy in other infectious diseases (notably pneumonia and bacteremia) is ongoing. Further good quality studies and ongoing surveillance for any emerging bacterial resistance will be needed to determine outcomes with tigecycline relative to other novel antibacterial agents, and to explore the economic implications of its adoption.

Oxaliplatin: in operable colorectal cancer.

Oxaliplatin is available in numerous countries for the treatment of metastatic colorectal cancer (in conjunction with fluoropyrimidine therapy). The activity of oxaliplatin in advanced disease has led to investigation of its potential in operable disease. The addition of oxaliplatin to adjuvant therapy with fluorouracil and folinic acid (FOLFOX4 regimen) is associated with a significantly greater disease-free survival at 3 years (78% vs 73%; p = 0.002), according to results of the MOSAIC (Multicenter International Study of Oxaliplatin/5FU/Leucovorin [folinic acid] in the Adjuvant Treatment of Colon Cancer) trial, a study in 2246 patients with stage II or III colon cancer. In addition, a 23% reduction in the risk of disease recurrence after surgery was seen with FOLFOX4 compared with fluorouracil/folinic acid in the MOSAIC trial. Results from several phase I/II studies suggest that the addition of oxaliplatin to preoperative radiochemotherapy may be of benefit in patients with locally advanced lower rectal cancer in terms of disease downstaging and sphincter preservation. Oxaliplatin was generally well tolerated in the MOSAIC trial and neuro- and myelotoxicity with FOLFOX4 were manageable.

Tinzaparin sodium: a review of its pharmacology and clinical use in the prophylaxis and treatment of thromboembolic disease.

Tinzaparin sodium (tinzaparin; innohep) is a low molecular weight heparin (LMWH) formed by the enzymatic degradation of porcine unfractionated heparin (UFH). In clinical trials, once-daily subcutaneous (SC) tinzaparin was effective and generally well tolerated in the prophylaxis and treatment of thromboembolic disease. SC tinzaparin 75 anti-Xa IU/kg/day showed similar thromboprophylactic efficacy to adjusted-dosage oral warfarin in patients undergoing total hip arthroplasty; in patients undergoing knee replacement, the incidence of deep vein thrombosis (DVT) was significantly lower with tinzaparin. The drug had similar efficacy to equivalent-dosage SC enoxaparin sodium in orthopaedic surgery. In patients undergoing general surgery, SC tinzaparin 3500 anti-Xa IU/day was of equivalent thromboprophylactic efficacy to SC UFH 5000IU twice daily. Encouraging preliminary results have been obtained with tinzaparin in the prevention of DVT in patients with complete motor paralysis. In the initial treatment of acute proximal DVT and pulmonary embolism, SC tinzaparin 175 anti-Xa IU/kg/day was at least as effective as adjusted-dosage intravenous (IV) UFH. In the outpatient treatment of venous thromboembolism, tinzaparin has demonstrated similar efficacy to dalteparin sodium (dalteparin) and warfarin. Tinzaparin was effective in preventing clotting in haemodialysis circuits; the anticoagulant efficacy of tinzaparin in patients undergoing haemodialysis was similar to that of SC dalteparin and similar to or less than (although in this case the tinzaparin dose was too low for sufficient anticoagulant efficacy) that of IV UFH. Advantages of tinzaparin over UFH and warfarin include ease of administration and lack of need for laboratory monitoring. Tinzaparin is more cost effective than UFH in the treatment of established thromboembolic disease, and home-based treatment with tinzaparin may offer greater cost benefits than hospital-based therapy. Tinzaparin is well tolerated, including in elderly patients and those with renal impairment receiving long-term treatment. Incidences of major bleeding complications were low and reports of heparin-induced thrombocytopenia were infrequent in clinical studies. In conclusion, tinzaparin is a valuable LMWH in the prophylaxis and management of thromboembolic disease.

Insulin glargine: an updated review of its use in the management of diabetes mellitus.

Insulin glargine is a human insulin analogue prepared by recombinant DNA technology. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant in relation to conventional human insulins, with no pronounced peak over 24 hours. This allows once-daily administration as basal therapy. Early randomised trials with insulin glargine generally showed greater reductions in fasting blood or plasma glucose levels and a reduced frequency of nocturnal hypoglycaemia relative to neutral protamine Hagedorn (NPH) insulin in patients with type 1 diabetes mellitus. In addition to this basal therapy, patients continued to use the regular mealtime insulin regimen to which they were accustomed. More recent data with insulin glargine have included evidence of improved glycaemic control, with improvements in satisfaction with treatment over NPH insulin. Furthermore, the time of day at which insulin glargine is injected has no clinically relevant effect on glycaemic control in these patients. There are also data from small, nonblind studies to suggest comparable glycaemic control with insulin glargine and continuous subcutaneous insulin infusion. Results from comparative studies and meta-analyses in individuals with type 2 diabetes show lower incidences of nocturnal hypoglycaemia with insulin glargine than with NPH insulin, with two studies showing a significantly greater improvement in glycosylated haemoglobin levels with insulin glargine than with NPH. Insulin glargine is well tolerated, and is not associated with greater immunogenicity or increases in bodyweight than NPH insulin. Long-term data show maintenance of glycaemic control with insulin glargine for up to 39 months in adults and children with type 1 and adults with type 2 diabetes. In conclusion, insulin glargine is an effective and well tolerated basal insulin therapy when given as a single daily subcutaneous injection to patients with diabetes, with benefits in terms of glycaemic control and reduced frequency of hypoglycaemia over regimens based on conventional basal insulins. Accumulating data and official recommendations show the suitability of insulin glargine for first-line use in selected patients with type 2 diabetes who require insulin treatment, as well as in patients with type 1 disease, and confirm its use in children and adolescents.

Insulin lispro: a pharmacoeconomic review of its use in diabetes mellitus.

UNLABELLED: Insulin lispro is a recombinant insulin analogue with transposed amino acids (proline and lysine) at positions 28 and 29 near the C-terminus of the B-chain. The most prominent practical advantage of insulin lispro over human soluble insulin lies in its very rapid onset of action. This property allows it to be injected immediately before meals and minimises the demands made on patients with type 1 diabetes mellitus, and those with type 2 disease who require insulin, by the ongoing need for careful meal planning and timing. Numerous clinical studies have shown significant improvements in postprandial glycaemic control, with some evidence of reduced rates of severe or nocturnal hypoglycaemia, relative to conventional human insulin in patients receiving lispro-based insulins. Quality-of-life studies show consistent preferences by patients for and increased treatment satisfaction with insulin lispro over human soluble insulin, particularly with variations of the Diabetes Treatment Satisfaction Questionnaire. Willingness of patients and taxpayers to pay additional costs for insulin lispro or a premixed lispro-based formulation over conventional human insulins, and cost benefits favouring formulary inclusion, have been shown in well designed studies carried out in Australia and Canada. Spanish data suggest cost effectiveness in terms of episodes of severe hypoglycaemia avoided, and preliminary German resource utilisation data indicate cost savings related to reduced hospitalisation and general practice costs, with insulin lispro relative to human soluble insulin. CONCLUSIONS: Insulin lispro and premixed formulations of lispro-based insulins offer quality-of-life improvements relative to conventional human insulins in patients with diabetes mellitus. Participants in well designed studies have expressed a preference for lispro-based insulins and have been shown to be willing to pay for the advantages they offer, and current cost-benefit data favour the inclusion of these insulins in formularies and their reimbursement by third party payers. Further research into the pharmacoeconomic implications of insulin lispro use in the long term is needed, particularly with respect to effects on indirect costs and those associated with complications of diabetes mellitus.

Esomeprazole: a review of its use in the management of acid-related disorders.

UNLABELLED: Esomeprazole (S-isomer of omeprazole), the first single optical isomer proton pump inhibitor, generally provides better acid control than current racemic proton pump inhibitors and has a favourable pharmacokinetic profile relative to omeprazole. In a large well designed 8-week trial in patients (n >5000) with erosive oesophagitis, esomeprazole recipients achieved significantly higher rates of endoscopically confirmed healed oesophagitis than those receiving lansoprazole. Respective healed oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were 92.6 and 88.8%. Overall, esomeprazole was also better than omeprazole, although these differences were not always statistically significance. Ninety-two to 94% of esomeprazole recipients (40mg once daily) achieved healed oesophagitis versus 84 to 90% of omeprazole recipients (20mg once daily). Esomeprazole was effective across all baseline grades of oesophagitis; notably, relative to lansoprazole, as baseline severity of disease increased, the difference in rates of healed oesophagitis also increased in favour of esomeprazole. Resolution of heartburn was also significantly better with esomeprazole 40mg than with these racemic proton pump inhibitors. Long-term (up to 12 months) therapy with esomeprazole effectively maintained healing in these patients. Once-daily esomeprazole 20 or 40mg for 4 weeks resolved symptoms in patients with symptomatic gastro-oesophageal reflux disease (GORD) without oesophagitis. Symptoms were effectively managed in the long-term with symptom-driven on-demand esomeprazole (20 or 40mg once daily). Eradicating Helicobacter pylori infection is considered pivotal to successfully managing duodenal ulcer disease. Seven days' treatment (twice-daily esomeprazole 20mg plus amoxicillin 1g and clarithromycin 500mg) eradicated H. pylori in >/=86% of patients (intention-to-treat), a rate that was similar to equivalent omeprazole-based regimens. Esomeprazole is generally well tolerated, both as monotherapy and in combination with antimicrobial agents, with a tolerability profile similar to that of other proton pump inhibitors. Few patients discontinued therapy because of treatment-emergent adverse events (<3% of patients), with very few (<1%) drug-related serious adverse events reported. CONCLUSIONS: Esomeprazole is an effective, well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis and overall, provided better efficacy than omeprazole. Notably, in a large (n >5000 patients) double-blind trial, esomeprazole 40mg provided significantly better efficacy than lansoprazole in terms of healing rates and resolution of symptoms. Long-term therapy with esomeprazole maintained healed oesophagitis in these patients. Esomeprazole also proved beneficial in patients with symptomatic GORD without oesophagitis. Thus, esomeprazole has emerged as an option for first-line therapy in the management of acid-related disorders.

Esomeprazole: a review of its use in the management of acid-related disorders in the US.

UNLABELLED: Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to be developed as a single optical isomer. It provides better acid control than current racemic proton pump inhibitors and has a favourable pharmacokinetic profile relative to omeprazole. In large well designed 8-week trials in patients with erosive oesophagitis, esomeprazole recipients achieved significantly higher rates of endoscopically confirmed healed oesophagitis than those receiving omeprazole or lansoprazole. Esomeprazole was effective across all baseline grades of oesophagitis; notably, relative to lansoprazole, as the baseline severity of disease increased, the difference in rates of healed oesophagitis also increased in favour of esomeprazole. In two trials, 94% of patients receiving esomeprazole 40mg once daily achieved healed oesophagitis versus 84 to 87% of omeprazole recipients (20mg once daily). In a study in >5000 patients, respective healed oesophagitis rates with once-daily esomeprazole 40mg or lansoprazole 30mg were 92.6 and 88.8%. Resolution of heartburn was also significantly better with esomeprazole than with these racemic proton pump inhibitors. Long-term (up to 12 months) therapy with esomeprazole effectively maintained healed oesophagitis in these patients. Esomeprazole 20 or 40mg once daily for 4 weeks proved effective in patients with symptomatic gastro-oesophageal reflux disease (GORD) without oesophagitis. Eradicating Helicobacter pylori infection is considered pivotal to successfully managing duodenal ulcer disease. Ten days' triple therapy (esomeprazole 40mg once daily, plus twice-daily amoxicillin 1g and clarithromycin 500mg) eradicated H. pylori in 77 to 78% of patients (intention-to-treat) with endoscopically confirmed duodenal ulcer disease. Esomeprazole is generally well tolerated, both as monotherapy and in combination with antimicrobial agents. The tolerability profile is similar to that of other proton pump inhibitors. Few patients discontinued therapy because of treatment-emergent adverse events (<3% of patients) and very few (<1%) drug-related serious adverse events were reported. CONCLUSIONS: Esomeprazole is an effective and well tolerated treatment for managing GORD and for eradicating H. pylori infection in patients with duodenal ulcer disease. In 8-week double-blind trials, esomeprazole effectively healed oesophagitis and resolved symptoms in patients with endoscopically confirmed erosive oesophagitis. Notably, in large (n >1900 patients) double-blind trials, esomeprazole provided significantly better efficacy than omeprazole or lansoprazole in terms of both healing rates and resolution of symptoms. Long-term therapy with esomeprazole effectively maintained healed oesophagitis in these patients. Esomeprazole was also effective in patients with symptomatic GORD. Thus, esomeprazole has emerged as an effective option for first-line therapy in the management of acid-related disorders.

Tamsulosin: a review of its pharmacology and therapeutic efficacy in the management of lower urinary tract symptoms.

UNLABELLED: Tamsulosin is a subtype-selective alpha(1A)- and alpha(1D )-adrenoceptor antagonist. alpha(1)-Receptors predominate in the prostate gland, prostatic capsule, prostatic urethra and bladder, and the relaxation of prostate and bladder smooth muscles is associated with improved maximal urine flow (Q(max)) and alleviation of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH). Tamsulosin 0.4 mg once daily in a modified-release formulation increased Q(max) and improved symptom scores relative to baseline to a greater extent than placebo in 12- and 13-week double-blind, randomised, multicentre, clinical trials in patients with LUTS, with statistical significance between treatments for Q(max) values in two of three published US and European studies. Tamsulosin is effective in patients with mild to severe LUTS associated with BPH, in patients with diabetes mellitus and in the elderly, and does not interfere with concomitant antihypertensive therapy. Pooled data based on patients receiving tamsulosin 0.4 or 0. 8mg once daily indicate maintenance of efficacy for up to 6 years. Tamsulosin 0.4 mg once daily was of similar efficacy to alfuzosin 2.5 mg three times daily, with less tendency to cause hypotensive effects, in a double-blind, randomised 12-week trial. Benefit of the drug has also been shown in patients with acute urinary retention or chronic abacterial prostatitis, those receiving high energy transurethral microwave thermotherapy, and in patients with prostate cancer with radiation-induced urethritis. Dizziness and abnormal ejaculation are stated to be the most common adverse events, with asthenia, postural hypotension and palpitations being seen less frequently (1 to 2% incidence), in patients receiving tamsulosin 0.4 mg once daily. Tamsulosin has not been associated with clinically significant changes in blood pressure in clinical trials. CONCLUSION: The alpha(1A)- and alpha(1D)-adrenoceptor antagonist tamsulosin, given at a dosage of 0.4 mg once daily in a modified-release formulation, is effective and well tolerated in the treatment of LUTS associated with BPH. Although the drug has been directly compared to date with one other agent only, data show overall that tamsulosin clearly offers advantages over other alpha(1)-adrenoceptor antagonists in terms of the need for a single daily dose only, and its low potential for hypotensive effects or interference with concomitant antihypertensive therapy. Dosage titration at the start of treatment is not necessary. Tamsulosin has a rapid onset of action and is effective in patients with moderate or severe symptoms. The drug is therefore a valuable therapeutic option, with both demonstrated and potential advantages over older nonselective agents, in the management of patients with LUTS associated with BPH.