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Oxidative stress in bacteria and protein damage by reactive oxygen species.

The advent of O2 in the atmosphere was among the first major pollution events occurred on earth. The reaction between ferrous iron, very abundant in the reductive early atmosphere, and oxygen results in the formation of harmful superoxide and hydroxyl radicals, which affect all macromolecules (DNA, lipids and proteins). Living organisms have to build up mechanisms to protect themselves against oxidative stress, with enzymes such as catalase and superoxide dismutase, small proteins like thioredoxin and glutaredoxin, and molecules such as glutathione. Bacterial genetic responses to oxidative stress are controlled by two major transcriptional regulators (OxyR and SoxRS). This paper reviews major key points in the generation of reactive oxygen species in bacteria, defense mechanisms and genetic responses to oxidative stress. Special attention is paid to the oxidative damage to proteins.

Adaptation, Physiological↗

Comparative Efficacy of Non-opioid Analgesic Drugs for Chronic Cancer Pain: A Bayesian Network Meta-analysis.

PURPOSE: While opioids remain the primary pharmacological intervention for cancer pain management, their clinical utility is frequently compromised by dose-limiting toxicities. This study aimed to determine the comparative efficacy, opioid-sparing potential, and clinical hierarchy of non-opioid adjuvant drug classes. The study was structured around the PICO framework to evaluate the pharmacological strategies currently utilized in multimodal clinical oncology. METHODS: A systematic search of electronic databases (PubMed, Embase, Cochrane) was conducted for randomized controlled trials (RCTs) published between 2000 and 2025. The primary outcome was global analgesic efficacy (standardized mean difference [SMD]), while secondary outcomes included the opioid-sparing effect, defined as the percentage reduction in morphine equivalent daily dose (MEDD) and the incidence of treatment-emergent adverse events (Harms). A Bayesian network meta-analysis (NMA) was performed to rank treatments using SUCRA values. The methodological quality was assessed using the Cochrane Risk of Bias (RoB 2.0) tool. RESULTS: Twenty-three RCTs (n = 1845) met the inclusion criteria. Nonsteroidal anti-inflammatory drugs (NSAIDs) (-1.10) and anticonvulsants (-1.06) demonstrated the most robust analgesic effects. The SUCRA ranking confirmed a clear hierarchy, with the combination of anticonvulsants and antidepressants showing the highest probability of efficacy. A significant opioid-sparing effect was observed for gabapentinoids and ketamine, facilitating MEDD reduction. While serious adverse events were rare, minor harms (somnolence, dizziness) were more frequent in the most effective classes. CONCLUSION: Our NMA provides a robust evidence base for a "Clinical Tier" system, ranking adjuvants by their balance of efficacy and safety. These findings support the early integration of Tier I agents (anticonvulsants and NSAIDs) to optimize pain control and reduce opioid-related toxicities in chronic cancer pain management.

Humans↗

Impact of the heroin 'drought' on patterns of drug use and drug-related harms.

Since late 2000, anecdotal reports from drug users and health professionals have suggested that there was a reduction in the supply of heroin in Adelaide in the first half of 2001, referred to as a heroin 'drought'. The aim of this paper was to critically review evidence for this, using data obtained from 100 injecting drug users surveyed for the 2001 Illicit Drug Reporting System (IDRS). This project is carried out annually in all Australian jurisdictions, and collects up-to-date information on the markets for heroin, methamphetamine, cocaine and cannabis. This paper also investigates the possible implications of this 'drought' on patterns of drug use and drug-related harms. The 2001 IDRS found consistent reports by users of an increase in the price of heroin, together with decreases in purity and availability. These factors resulted in a decrease in the frequency of self-reported heroin use among those surveyed in 2001, and a concomitant increase in the use of other drugs, in particular methamphetamine and morphine. The heroin 'drought' appears to have had a substantial impact on several indices of drug-related harm. There was a marked decrease in the number of opioid-related fatalities, and hospital data also showed reductions in heroin-related presentations. Treatment service data showed an increase in the number of admissions related to amphetamines. There is a need for health promotion and education on the adverse effects of methamphetamine use, and the development of improved treatment protocols for methamphetamine abuse and dependence.

Australia↗

Glutathione peroxidase mimics as novel antioxidants from vegetables.

Vegetables are generally recognized as rich sources of dietary antioxidants for inhibiting lipid peroxidation. Here we investigated lipid hydroperoxide (LOOH)-reducing activity of several vegetables to estimate their role on the prevention of lipid peroxidation in food and the digestive tract. By using HPLC analysis, we screened vegetables possessing the ability to convert 13-hydroperoxyoctadecadienoic acid (13-HPODE) to its reduced derivative, 13-hydroxyoctadecadienoic acid (13-HODE). Welsh onion (Allium fistulosum L.) was found to be highly active in the reduction of 13-HPODE among tested vegetables. There was no relationship between 13-HPODE reducing activity and GSH peroxidase (GPX) activity in the tested vegetables. 13-HPODE-reducing activity of welsh onion was enhanced by the addition of sulfhydryl compounds including glutathione (GSH). Neither GPX inhibitor nor heat treatment suppressed 13-HPODE-reducing activity effectively. These results suggest that welsh onion and other vegetables contain GPX mimics responsible for the reduction of LOOH. GPX mimics may be helpful in the attenuation of harmful effect of LOOH from food.

Antioxidants↗

Minimization of excess sludge production for biological wastewater treatment.

Excess sludge treatment and disposal currently represents a rising challenge for wastewater treatment plants (WWTPs) due to economic, environmental and regulation factors. There is therefore considerable impetus to explore and develop strategies and technologies for reducing excess sludge production in biological wastewater treatment processes. This paper reviews current strategies for reducing sludge production based on these mechanisms: lysis-cryptic growth, uncoupling metabolism, maintenance metabolism, and predation on bacteria. The strategies for sludge reduction should be evaluated and chosen for practical application using costs analysis and assessment of environmental impact. High costs still limit technologies of sludge ozonation-cryptic growth and membrane bioreactor from spreading application in full-scale WWTPs. Bioacclimation and harmful to environment are major bottlenecks for chemical uncoupler in practical application. Sludge reduction induced by oligochaetes may present a cost-effective way for WWTPs if unstable worm growth is solved. Employing any strategy for reducing sludge production may have an impact on microbial community in biological wastewater treatment processes. This impact may influence the sludge characteristics and the quality of effluent.

Animals↗

[Medical waste management: the law and its application].

Medical waste management in Croatia is regulated by three fundamental legal acts: Waste Act, Ordinance on Waste Types and Directive on Manipulation of Waste Generated in Health Care. The implementation of these acts and waste management in general are also supported by Transport of Hazardous Materials Act and Toxic Substances Act. Modern trends in waste management promote an integral approach also called "waste chain". This integral approach to medical waste management is based on hierarchical structuring of waste management structure from the point at which the waste is produced to its final disposal. Priority is always given to reducing the amount and the harmfulness of waste by replacing harmful materials with those that are not, but where this is not possible, waste management includes reduction by sorting and separating, pretreatment on site, safe transportation, final treatment and sanitary disposal. Methods of choice for the final treatment should be the least harmful for human health and environment. Integral medical waste management could greatly reduce quantities of medical waste and consequently financial strains. Even though Croatian regulations define and cover all steps in the waste management chain their implementation is one of the country's greatest issues. Improper practice is seen from waste production in healthcare institutions to the final disposal, and includes handling, sorting, use of containers, or treatment in incinerators. Information on quantities, type and flow of medical waste are inadequate, just as sanitary control. In addition, Croatia lacks locations for sanitary landfills. Croatia has signed international conventions on the supervision and control of transfrontier waste shipments. Within the CARDS project, Croatia has started to harmonise its laws with acquis communitaire related to waste management. Although waste management is one of the priorities defined within the National Environment Action Plan, Croatia still has not made a strategy for waste management.

Croatia↗

Thrombolysis compared with heparin for the initial treatment of pulmonary embolism: a meta-analysis of the randomized controlled trials.

BACKGROUND: Randomized trials and meta-analyses have reached conflicting conclusions about the role of thrombolytic therapy for the treatment of acute pulmonary embolism. METHODS AND RESULTS: We performed a meta-analysis of all randomized trials comparing thrombolytic therapy with heparin in patients with acute pulmonary embolism. Eleven trials, involving 748 patients, were included. Compared with heparin, thrombolytic therapy was associated with a nonsignificant reduction in recurrent pulmonary embolism or death (6.7% versus 9.6%; OR 0.67, 95% CI 0.40 to 1.12, P for heterogeneity=0.48), a nonsignificant increase in major bleeding (9.1% versus 6.1%; OR 1.42, 95% CI 0.81 to 2.46), and a significant increase in nonmajor bleeding (22.7% versus 10.0%; OR 2.63, 95% CI 1.53 to 4.54; number needed to harm=8). Thrombolytic therapy compared with heparin was associated with a significant reduction in recurrent pulmonary embolism or death in trials that also enrolled patients with major (hemodynamically unstable) pulmonary embolism (9.4% versus 19.0%; OR 0.45, 95% CI 0.22 to 0.92; number needed to treat=10) but not in trials that excluded these patients (5.3% versus 4.8%; OR 1.07, 95% CI 0.50 to 2.30), with significant heterogeneity between these 2 groups of trials (P=0.10). CONCLUSIONS: Currently available data provide no evidence for a benefit of thrombolytic therapy compared with heparin for the initial treatment of unselected patients with acute pulmonary embolism. A benefit is suggested in those at highest risk of recurrence or death. The number of patients enrolled in randomized trials to date is modest, and further evaluation of the efficacy and safety of thrombolytic therapy for the treatment of high-risk patients with acute pulmonary embolism appears warranted.

Acute Disease↗

Consecutive adenine sequences are potential targets in photosensitized DNA damage.

Based on direct spectroscopic measurements of hole transfer in DNA and quantification of the yield of DNA oxidative damage, consecutive adenine sequences were found to be a good launching site for photosensitizers to inject a hole in DNA, where the following rapid hole transfer between adenines causes a long-lived charge-separated state leading to DNA oxidative damage. According to the results, the essential requisites for an efficient and/or harmful photosensitizer are determined as follows: to be able to oxidize adenine to trigger hole transfer between adenines, and react rapidly with molecular oxygen following its reduction, avoiding charge recombination and making the reaction irreversible. These results will greatly help us to classify photosensitizers harmful to human health, and to design an improved photosensitizer for biochemical applications.

Adenine↗

Normothermic ischaemic cardiac arrest of the isolated perfused rat heart: effects of trifluoperazine and lysolecithin on mechanical and metabolic recovery.

To evaluate the hypothesis that maintenance of the integrity of myocardial membrane systems and prevention of Ca2+ influx into the cell are significant in the survival of ischaemic tissue, the effect of trifluoperazine and lysolecithin, were tested on the recovery of globally ischaemic rat hearts. Trifluoperazine increases membrane stabilization, inhibits calmodulin and binds to other Ca2+-dependent proteins. Lysolecithin, on the other hand, has a detergent action on myocardial cell membranes and facilitates Ca2+ ingress in ischaemic tissue. With trifluoperazine (2.45 microM), added before induction of ischaemia or during reperfusion only, hearts subjected to 40 min normothermic ischaemic cardiac arrest recovered mechanically. Untreated hearts failed after 20 min of ischaemia. The drug had no effect on tissue high energy phosphate levels or mitochondrial oxidative phosphorylation. Conversely, lysolecithin (2.5-10 microM) caused all hearts to fail after being subjected to 15 min ischaemia. Mechanical failure during reperfusion of such hearts was associated with a significant reduction in tissue ATP and CrP levels. Trifluoperazine counteracted the harmful effects of lysolecithin to a limited extent.

Adenosine Diphosphate↗

Impact of dietary sodium on cardiovascular disease morbidity and mortality.

Many public health agencies recommend universal restriction of dietary sodium to 100 mmol/L or less per day. This reflects the belief that because sodium restriction reduces blood pressure, it will therefore also reduce cardiovascular disease morbidity and mortality. Although large (100 mmol/L/24 h) reductions in sodium intake do produce a measurable decline in aggregate blood pressure, there is great heterogeneity in individual response, probably reflecting differing genetic, environmental, and behavioral characteristics. Moreover, sodium depletion has multiple other effects including activation of the renin-angiotensin system and the sympathetic nervous system, and increase in insulin resistance. Since the health effect will be the sum of these multiple good and bad effects of sodium reduction, outcome trials are needed to determine the benefit or harm of alteration in sodium intake. Unfortunately, no clinical trial has addressed the question of whether a lower sodium diet would improve or extend life. The best available data derives from six prospective cohort studies. In sum, the scant available observational data do not rule out the possibility of benefit for some and increased risk for others. Considerable experience--most recently the hormone replacement study--underscores the hazards of extrapolating clinical recommendations from observational data alone. In the absence of any evidence from randomized trials of morbidity and mortality outcomes, and in the face of inconsistent observational studies, a universal recommendation for sodium restriction is unwarranted and inconsistent with the principles of evidence-based medicine.

Blood Pressure↗

Liver blood flow and oxygen consumption during metabolic acidosis and alkalosis in the greyhound.

1. Hepatic arterial and portal venous blood flow and hepatic oxygen consumption were measured in two groups of greyhounds anaesthetized with pentobarbitone. Flows were measured with electromagnetic flowmeters. 2. In the first group the effects of metabolic acidosis produced by the infusion of a molar solution of lactic acid were studied. In the second group the effects of metabolic alkalosis produced by the infusion of a molar solution of sodium bicarbonate were studied. 3. In the acidotic group hepatic arterial blood flow decreased from 35.2 to 9.6 ml min-1 100 g-1 of liver whereas portal venous blood flow increased from 94.2 to 126.1 ml min-1 100g-1 of liver. Total liver blood flow was unchanged. Hepatic oxygen consumption increased, but not significantly, while hepatic venous oxygen content decreased significantly. Hepatic arterial resistance increased from 1.18 to 2.77 mmHg min-1 ml-1 while peripheral resistance was virtually unchanged. Portal venous pressure increased from 7.08 to 11.6 mmHg. 4. In the alkalotic group portal venous blood flow increased from 112 to 137 ml min-1 100 g-1 of liver. Hepatic arterial blood flow increased, but not significantly. Total liver blood flow increased from 151 to 185 ml min-1 100 mg-1 of liver. There were no significant changes in hepatic oxygen consumption. 5. It is concluded that metabolic acidosis reduces the supply of oxygen to the liver owing to the reduction in hepatic arterial blood flow and is therefore potentially harmful, whereas metabolic alkalosis probably has no biologically significant effect on liver blood flow.

Acidosis↗

Use of quality-adjusted life year weights with dose-response models for public health decisions: a case study of the risks and benefits of fish consumption.

Risks associated with toxicants in food are often controlled by exposure reduction. When exposure recommendations are developed for foods with both harmful and beneficial qualities, however, they must balance the associated risks and benefits to maximize public health. Although quantitative methods are commonly used to evaluate health risks, such methods have not been generally applied to evaluating the health benefits associated with environmental exposures. A quantitative method for risk-benefit analysis is presented that allows for consideration of diverse health endpoints that differ in their impact (i.e., duration and severity) using dose-response modeling weighted by quality-adjusted life years saved. To demonstrate the usefulness of this method, the risks and benefits of fish consumption are evaluated using a single health risk and health benefit endpoint. Benefits are defined as the decrease in myocardial infarction mortality resulting from fish consumption, and risks are defined as the increase in neurodevelopmental delay (i.e., talking) resulting from prenatal methylmercury exposure. Fish consumption rates are based on information from Washington State. Using the proposed framework, the net health impact of eating fish is estimated in either a whole population or a population consisting of women of childbearing age and their children. It is demonstrated that across a range of fish methylmercury concentrations (0-1 ppm) and intake levels (0-25 g/day), individuals would have to weight the neurodevelopmental effects 6 times more (in the whole population) or 250 times less (among women of child-bearing age and their children) than the myocardial infarction benefits in order to be ambivalent about whether or not to consume fish. These methods can be generalized to evaluate the merits of other public health and risk management programs that involve trade-offs between risks and benefits.

Adolescent↗

Effects of bleaching with carbamide peroxide gels on microhardness of restoration materials.

The objective of this in vitro study was to quantitatively assess the effects of bleaching with 10 and 15% carbamide peroxide (CP) on restoration materials by performing superficial microhardness analysis. Acrylic cylindrical containers (4 x 2 mm) were filled with the following restoration products: Charisma (Heraues Kulzer, Vila Santa Catarina, São Paulo, Brazil), Durafill VS (Heraeus Kulzer), Vitremer (3M, Sumaré, São Paulo, Brazil), Dyract (Dentsply, Petrópolis, Rio de Janeiro, Brazil), and Permite C (SDI, São Paulo, São Paulo, Brazil). Sixty samples were prepared of each restoration material. Twenty samples received bleaching treatment with 10% CP, 20 samples received bleaching treatment with 15% CP, and 20 samples were kept submerged in artificial saliva, which was replaced daily. The treatment consisted of immersion of the specimens in 1 cm3 of CP at 10 and 15% for 6 hours per day during 3 weeks, whereupon the test specimens were washed, dried, and kept immersed in artificial saliva for 18 hours. Then the test and control specimens were analyzed using a microhardness gauge. The Knoop Hardness Number (KHN) was taken for each test and control specimen at five different locations by applying a 25 g force for 20 seconds. The values obtained were transformed into KHNs and the mean was calculated. The data were submitted to statistical analysis by analysis of variance and Tukey test, p < .05. The means/standard deviations were as follows: Charisma: CP 10% 38.52/4.08, CP 15% 34.31/6.13, saliva 37.36/4.48; Durafill VS: CP 10% 18.65/1.65, CP 15% 19.38/2.23, saliva 18.27/1.43; Dyract AP: CP 10% 30.26/2.81, CP 15% 28.64/5.44, saliva 33.88/3.46; Vitremer: CP 10% 28.15/3.04, CP 15% 17.40/3.11, saliva 40.93/4.18; and Permite C: CP 10% 183.50/27.09, CP 15% 159.45/5.78, saliva 215.80/26.15. A decrease in microhardness was observed for the materials Dyract AP, Vitremer, and Permite C after treatment with CP at 10 and 15%, whereas no effect on either of the two composites (Charisma and Durafill) was verified. CLINICAL SIGNIFICANCE The application of the carbamide peroxide gels at 10 and 15% did not alter the microhardness of the composite resins Charisma and Durafill. In situ and clinical studies are necessary to enable one to conclude that the reduction in microhardness of the materials effectively results in clinical harm to the restorations.

Analysis of Variance↗

Use of specific indicators to detect warfarin-related adverse events.

PURPOSE: The use of specific indicators, or "triggers," to identify adverse drug events (ADEs) associated with warfarin therapy is described. SUMMARY: Automated triggers provided by laboratory and pharmacy data were used to identify potential ADEs associated with warfarin therapy among patients treated in the emergency room or admitted to six community hospitals between July 2002 and December 2003. The triggers consisted of an International Normalized Ratio (INR) of greater than 3.0 and pharmacy orders for vitamin K. Pharmacists reviewed the triggers monthly for clinical determination of ADEs during preintervention and postintervention periods. Interventions consisted of staff education and real-time adjustments in therapy. A 39% overall reduction in ADEs occurred between the preintervention and postintervention periods. Harmful ADEs declined by 70%. CONCLUSION: INRs of greater than 3.0 and vitamin K administration appeared to be reliable indicators of warfarin-associated ADEs, and detection with these indicators appeared to reduce ADEs when combined with appropriate interventions.

Aged↗

National screening policies in general practice: a case study of routine screening for partner abuse.

Internationally-recognised criteria for screening for a particular disorder require the following: availability of a clear diagnosis; a suitable validated screening test; acceptability of routine screening by patients and health providers; benefits of earlier detection and application of appropriate interventions to prevent the progression of a disorder, and hence reduction in incidence of morbidity and mortality; identification of possible harm from screening (false positives, false negatives, adverse effects of labelling, early diagnosis or unnecessary treatment of persons with true-positive test results with inconsequential disease) and weighing this against potential benefits; identification of possible sub-populations with the possibility of targeted screening of high-risk populations; good quality evidence of interventions effective in preventing or managing the disorder; and a cost-effectiveness assay. The New Zealand Ministry of Health have launched a best-practice guideline recommending all female general practice patients sixteen years and over be routinely screened for physical and sexual abuse by their partners. Inter-partner violence, especially against women by male partners and expartners, is a serious public health problem. However, review of existing research indicates that this guideline meets none of the criteria listed above. Considerable funding is invested in training health providers to implement this screening protocol, but, in the absence of effectiveness studies, cost-effectiveness cannot be assessed. Under current conditions, routine screening of adult women for partner abuse cannot be justified. However, GPs should be encouraged to learn about partner abuse and consider this possibility in patients presenting with physical injuries, psychological disturbance or social dysfunction, especially in high-risk patients. Research should be supported for the development and validation of effective, acceptable screening tools and randomised controlled trials of appropriate interventions. The desire to intervene for the public good should not dictate the implementation of a screening programme that disregards accepted screening criteria.

Adolescent↗

[Sexual behavior and contraceptive practices among university students].

The aim of this work was to study the knowledge, opinions and sexual behaviour of a sample of 464 students from the Universidad Austral de Chile. Results show that 78% of male and 41% of female students have had a sexual intercourse and that 78% of males and 72% of females with an active sexual life use contraceptive methods. The principal reasons to avoid the use of these methods are the irregularity of sexual intercourse and the reduction in pleasure. Most students think that these methods are harmful for their health but they should be used. The use of contraceptive methods increase with the frequency of sexual relations and university experience, but first year students use them more frequently than second year students. Most students know several contraceptive methods, but their knowledge about mechanisms of action is inadequate or distorted. Likewise, more than 50% think that it is possible to prevent pregnancy after a sexual intercourse. It is concluded that most sexually active students use contraceptive methods, but inappropriately. Stereotypes, myths and lack of information are influencing their sexual and contraceptive practices, showing incoherence between their knowledge and behavior. A possible explanation could be a scarce influence of high school and religion on their sexual formation.

Adolescent↗

Improving hospital productivity under PPS: managing cost reductions.

In this article, a number of tenets of faith concerning hospital productivity improvement are explored: cutting staff harms service quality; more staff buys more quality; reducing staff translates into reduced employee morale; and performance gains come only to those who work harder. Alternative mechanisms by which the organization may work smarter, rather than harder, are advanced. The use of efficient scheduling systems and work unit reorganization, especially when reinforced by an incentive pay plan, has led to significant scale cost reductions.

Diagnosis-Related Groups↗

Hyperbaric oxygenation for tumour sensitisation to radiotherapy.

BACKGROUND: Cancer is common and radiotherapy is one well-established treatment for some solid tumours. HBO may improve the ability of radiotherapy to kill hypoxic cancer cells, so the administration of radiotherapy while breathing HBO may result in a reduction in mortality and tumour recurrence. OBJECTIVES: To assess the benefits and harms of radiotherapy while breathing HBO. SEARCH STRATEGY: In November 2004 we searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library Issue 3), MEDLINE, EMBASE , CINAHL, DORCTHIM and reference lists of articles. Relevant journals were handsearched. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing the outcome of malignant tumours following radiation therapy while breathing HBO versus air (with or without sham therapy). DATA COLLECTION AND ANALYSIS: Three reviewers independently evaluated the quality of the relevant trials using the method of Schulz (Schulz 1995) and extracted the data from the included trials. MAIN RESULTS: Nineteen trials contributed to this review (2286 patients: 1103 allocated to HBO and 1153 control). With HBO, there was a reduction in mortality for head and neck cancers at both one year and five years after therapy (Relative risk (RR) 0.83, P = 0.03, number needed to treat (NNT) = 11 and RR 0.82, P = 0.03, NNT = 5 respectively), as well as improved local tumour control at three months (RR with HBOT 0.58, P = 0.006, NNT = 7). The effect of HBO varied with different fractionation schemes. Local tumour recurrence was less likely with HBO at one year (head and neck, RR 0.66, P < 0.0001, NNT = 5), two years (uterine cervix RR 0.60, P = 0.04, NNT = 5) and five years (head and neck (RR 0.77, P = 0.01). Any advantage is achieved at the cost of some adverse effects. There was a significant increase in the rate of both severe radiation tissue injury (RR 2.35, P < 0.0001, (number needed to harm (NNH) = 8) and the chance of seizures during therapy (RR 6.76, P = 0.03, NNH 22) with HBO. AUTHORS' CONCLUSIONS: There is some evidence that HBO improves local tumour control and mortality for cancers of the head and neck, and local tumour recurrence in cancers of the head and neck, and uterine cervix. These benefits may only occur with unusual fractionation schemes. HBO is associated with significant adverse effects including oxygen toxic seizures and severe tissue radiation injury. The methodological and reporting inadequacies of the primary studies included in this review demand a cautious interpretation. More research is needed for head and neck cancer, but is probably not justified for bladder cancer. There is little evidence available concerning malignancies at other anatomical sites on which to base a recommendation.

Combined Modality Therapy↗