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PubMed2026

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↗
PubMed2025

Intraspecific divergence within Microcystis aeruginosa mediates the dynamics of freshwater harmful algal blooms under climate warming scenarios.

Intraspecific biodiversity can have ecosystem-level consequences and may affect the accuracy of ecological forecasting. For example, rare genetic variants may have traits that prove beneficial under future environmental conditions. The cyanobacterium responsible for most freshwater harmful algal blooms worldwide, Microcystis aeruginosa, occurs in at least three types. While the dominant type occurs in eutrophic environments and is adapted to thrive in nutrient-rich conditions, two additional types have recently been discovered that inhabit oligotrophic and eutrophic environments and have genomic adaptations for survival under nutrient limitation. Here, we show that these oligotrophic types are widespread throughout the Eastern USA. By pairing an experimental warming study with gene expression analyses, we found that the eutrophic type may be most susceptible to climate warming. In comparison, oligotrophic types maintained their growth better and persisted longer under warming. As a mechanistic explanation for these patterns, we found that oligotrophic types responded to warming by widespread elevated expression of heat shock protein genes. Reduction of nutrient loading has been a historically effective mitigation strategy for controlling harmful algal blooms. Our results suggest that climate warming may benefit oligotrophic types of M. aeruginosa, potentially reducing the effectiveness of such mitigation efforts. In-depth study of intraspecific variation may therefore improve forecasting for understanding future whole ecosystem dynamics.

Microcystis↗
PubMed1976

[Changes in the serum activity of lysosomal enzymes in rats after the use of propoxur (Baygon) insecticide. 2. The dynamics of beta-N-acetylglucosaminidase].

The influence of 1/50 and 1/10 LD50 of the monomethylcarbamate insecticide Propoxur (Baygon) on the lysosome enzyme beta-N-acetylglucose-aminidase serum activity is studied in white rats upon daily administration per os, over a period of 2, 4, 8, 15, 30, 60 and 90 days. A statistically significant increase of the enzyme activity is recorded at 15 days after introduction of 1/50 LD50, and at 15 and 30 days after 1/10 LD50 administration, followed by a reduction of the activity and returning to normal values. In all likelihood, the harmful effect of Propoxur on the lysosome and cellular membrane decreases after the 15th day because of activation of the microsome enzymes which, in turn, speed up the process of rendering innocuous the insecticide administered.

Acetylglucosaminidase↗
PubMed1979

Effect on paroxysmal re-entrant supraventricular tachycardia of a drug affecting calcium transport (Ro 11-1781).

The effect of Ro 11-1781, a drug that affects calcium transport, in 10 patients with paroxysmal supraventricular tachycardia (PSVT), was studied by intracardiac recording and stimulation. The re-entry circuit involved an accessory pathway that conducted only in the ventriculo-atrial direction in 5 patients, and was confined to the A-V node in 5 cases. Prior to administration of Ro 11-1781 tachycardia could be initiated in all patients. An intravenous bolus of 2 mg/kg during PSVT terminated the tachycardia in all cases by blockade in the A-V node. Ro 11-1781 lengthened the A-V nodal conduction time as well as the functional and effective refractory period of the A-V node. The effective refractory period of the "fast" pathway was variably changed. After Ro 11-1781 the tachycardia zone was abolished in 3 cases, reduced in 3, increased in 3 and was converted to an echo zone in 1. The ability to sustain the PSVT was lost in one subject. The heart rate during PSVT was slowed following Ro 11-1781. Ro 11-1781 appears to be useful for the termination of PSVT, but its ability to prevent PSVT varies. Beneficial effects include abolition or narrowing of the tachycardia zone, loss of the ability to sustain PSVT and a reduction in heart rate during PSVT. The widening of the tachycardia zone may be harmful.

Adult↗
PubMed1978

Treatment of obesity: cost-benefit assessment of behavioral therapy, placebo, and two anorectic drugs.

Mazindol, diethylpropion, and a placebo were compared with behavioral therapy for effectiveness in producing weight reduction in an outpatient obesity clinic. Each method was also compared in cost and harmful side effects. The patients were recruited from the middle and lower socioeconomic groups. Of the 120 patients beginning treatment, only 33 completed the entire 14-week study. There was no statistically significant difference in the weight loss among the treatment groups. The program of behavioral therapy was administered by a dietitian who as experienced in the techniques of behavior modification; the drug treatment groups were seen by physicians. We conclude that behavioral therapy may be the treatment of choice in an outpatient obese population since it requires little physician time, is less expensive, and avoids the side effects of anorectic drugs.

Appetite Depressants↗
PubMed1976

Deleterious effects of copulation in Drosophila females as a function of growth temperature of both sexes.

In Drosophila females, copulation always results in a reduction of longevity but the gravity of the phenomenon varies according to growth temperature. The harmful effect of adult males, or aggressiveness, is maximum when growth took place at a middle temperature. Female sensitivity, on the other hand, is at a maximum when larvae were reared at exteme, low or high, temperatures.

Aggression↗
PubMed1977

Hypertension in the elderly.

The available data indicate that classical hypertension, defined here as a diastolic blood pressure greater than or equal to 95 mm Hg, is a widely prevalent and as important a risk factor for the cardiovascular diseases in those aged 65 and over as it is in those under 65. The limited available data also indicate that pure systolic hypertension, defined here as a systolic blood pressure exceeding 160 mm Hg with a diastolic pressure under 95 mm Hg, also very common at age 65 and over, is also related to excess cardiovascular morbidity and mortality in the elderly. However, it is not clear whether this latter relationship is indicative of cause and effect, or merely reflects the fact that in the elderly pure systolic hypertension is a sign of extensive sclerosis of large arteries. The results of Veterans Administration studies on antihypertensive therapy indicate that the elderly patient with classical hypertension is amenable to effective treatment, and that the benefits of such treatment significantly outweigh the risks. Great care is needed in the use of drugs for the management of hypertension in elderly patients, especially to minimize risk of hypotensive episodes and their possible harmful consequences; but with judicious and careful therapy, hypertension of this type can be controlled with reduction in excess risk of morbidity and mortality, at least for those with average diastolic pressures greater than or equal to 105 mm Hg. The lack of data on the benefits of treatment for those with pure systolic hypertension precludes any recommendations in regard to pharmacologic treatment of this condition.

Adult↗
PubMed1976

[Behaviour of the lung as an organ of absorption and reaction when air-borne contaminants are inhaled (author's transl)].

The pulmonary resorption of air pollutants constitute a significant factor for the whole body burden of men, as can be shown for lead, SO2 and CO. Particle size as well as water and lipid solubility of the noxious agents are important variables for the extent of the interaction with the pulmonary surface. Main objects for the inhalative pollutants are the bronchioli terminales and the respiratory epithel. The electronmicroscopic investigations point out a specific irritability of these structures as far as lead, oxydants and fibers are concerned. Comparatively low concentrations of the agents produce, in chronic exposure, changes in the caliber of the small airways and widening of the ductus alveolares and the alveoli. In addition to the reduction of the inner lungsurface one observes a thickening of the diffusion barrier in loco through some harmful substances. A number of pollutants influence a primary cytotoxic effect on alveolar macrophages. Thereby the bacterial infection resistance of the lung is reduced; moreover the phagozytes play an important part for the detoxification of carcinogenic carbohydrates. Hence the lung functions as a resorptionorgan, as a protectionorgan and as an object of damage for various air pollutants.

Absorption↗
PubMed1977

Benzo[a]yrenedione/benzo[a]pyrenediol oxidation-reduction couples and the generation of reactive reduced molecular oxygen.

The ability of the isomeric quinone metabolites of benzo[a]pyrene, benzo[a]pyrene-6,12-dione, benzo[a]pyrene-1,6-dione, and benzo[a]pyrene-3,6-dione to undergo reversible, univalent oxidation-reduction cycles involving the corresponding benzo[a]pyrenediols and intermediate semiquinone radicals has been characterized. Under anaerobic conditions, all three benzo[a]pyrenediones are easily reduced to benzo[a]pyrenediols, even by mild biological agents such as NAD(P)H, cysteamine, and glutathione. The benzo[a]pyrenediols, in turn, are very rapidly autoxidized to the benzo[a]pyrenediones when exposed to air. Substantial amounts of hydrogen peroxide are produced during these autoxidations, and other reactive reduced oxygen species, such as the superoxide and hydroxyl radicals, are probably formed transiently as well. The benzo[a]pyrenediol-benzo[a]pyrenedione interconversions proceed by one-electron steps; the corresponsing semiquinone radicals can be monitored by electron spin resonance spectroscopy as inter mediates during these reactions carried out at high pH. Benzo[a]pyrenediones induce DNA strand scission when incubated with bacteriophage T7 DNA. This damage is modified by conditions which indicate that reduced oxygen species propagate the free-radical reactions responsible for the strand scission. Benzo[a]pyrenediones are electron-acceptor substrates for NADH dehydrogenase from Clostridium kluyveri. Catalytic amounds of these benzo[a]pyrene metabolites, together with this respiratory enzyme function as cyclic oxidation-reduction couples which link NADH and molecular oxygen in the continuous production of hydrogen peroxide. These data, together with preliminary results with cells in culture, indicate that benzo[a]pyrenediones are potentially harmful metabolites of benzo[a]pyrene, acting by processes which lead to their regeneration rather than depletion; nucleic acid and call damage is probably produced by the reactive reduced oxygen species resulting from such regenerative oxidation-reduction cycles.

Benzopyrenes↗
PubMed1975

Influence of changes in arterial PCO2 on cerebral blood flow and cerebral energy state during hypothermia in the rat.

In order to study the relationship between arterial PCO2 and cerebral blood flow (CBF) in hypothermia, the body temperature of artifically ventilated rats was decreased to 22 degreesC, and changes in CBF were evaluated from arteriovenous differences in oxygen content (AVDO2) at PaCO2 values of 15, 30, 40 and 60 mm Hg. The results were compared to those obtained at normal body temperature (37 degrees C) over the PaCO2 range 15-60 mm Hg. Separate experiments were performed to evaluate CBF and CMRO2 at 22 degrees C and a PaCO2 of 15 mm Hg, using an inert gas technique for CBF. The tissue contents of phosphocreatine, ATP, ADP, AMP and lactate were measured in hypothermic animals at PaCO2 values of 15, 30 and 60 mm Hg. The results showed that changes in CBF were of the same relative magnitude in hypothermia and normothermia when PaCO2 was increased from about 35 to about 60 mm Hg. However, with a decrease in PaCO2 the reduction in CBF was much more pronounced in hypothermia, and at PaCO2 15 Mm Hg CBF was less then 20% of the value measured in normothermic and normocapnic animals. The results of the metabolite measurements gave no evidence of tissue hypoxia in spite of the pronounced reduction in CBF. Although the results demonstrate that the brain of a hypothermic animal is protected against the harmful effects of a lowered CBF, it may not warrant recommending hyperventilation in clinical cases of hypothermia, especially not in patients with arteriosclerosis or cerebrovascular diseases.

Adenosine Diphosphate↗
PubMed1979

Behavioral treatment of caffeinism: reducing excessive coffee drinking.

Excessive coffee drinking can have deleterious effects because of the large amounts of caffeine that are ingested. Caffeine is thought to be addicting, and prolonged and excessive use can lead to caffeinism, a condition that has serious behavioral and physiological side effects. The present study developed and evaluated a treatment program to reduce excessive daily coffee drinking to moderate and presumably safer levels. Three habitual coffee drinkers received individualized changing criterion programs that systematically and gradually reduced their daily caffeine intake. The coffee drinkers were required to self-monitor and plot their daily intake of caffeine. They received monetary prizes for not exceeding the treatment phase criteria and forfeited a portion of their pretreatment deposit when they did. Their coffee drinking decreased from almost nine cups per day (over 1100 mg of caffeine) during baseline to less than three cups per day (less than 343 mg) at the end of treatment or a reduction of 69%. The treatment effect was maintained during a 10-month follow-up, averaging a 67% reduction from baseline. The program appears to be a reasonable method of reducing and then maintaining daily caffeine intake at less harmful levels.

Behavior Therapy↗
PubMed1978

Intravenous and oral practolol in the acute stages of myocardial infarction.

The influence of routine administration of the beta adrenoceptor blocking drug practolol on the outcome of acute myocardial infarction has been studied in 94 patients. The study was restricted to patients under the age of 70 experiencing their first myocardial infarction and in whom there was no contraindication to beta blockade. In the treated group an initial dose intravenous practolol 15 mg was followed by five oral doses of practolol 200 mg at 12 h intervals. A significant reduction in heart rate and systolic blood pressure was apparent in the treated group within 2 h. No difference was detectable in the course of the acute stage of the illness between treated and control patients, apart from a significant reduction in the incidence of atrial fibrillation among those receiving practolol. Patients with inferior infarctions showed a tendency to develop potentially harmful bradycardia and hypotension on receiving practolol which lead to withdrawal of the drug in many cases. At regular review over 7 mth no detectable difference emerged between the treated and control groups in the incidence of cardiac failure, death or reinfarction.

Acute Disease↗
PubMed1979

Outcome of pregnancy in women using different methods of contraception.

During the years 1968-74, 17,032 women were recruited to the Oxford Family Planning Association prospective study of the effects of different methods of contraception. The present analysis, which concerns 5700 pregnancies experienced by the participants in the investigation, adds to the evidence that ex-users of oral contraceptives and intrauterine devices suffer no delecterious effects on the outcome of pregnancy in terms of miscarriage, ectopic gestation, stillbirth, congenital malformation, alteration in the sex ratio or reduction in birth weight. Accidental pregnancies in women taking oral contraceptives were few in the present study (66 in all), but it seems likely that harmful effects of exposure of the fetus to the pill in utero, if any, occur infrequently. Women experiencing an accidental pregnancy with an intrauterine device in situ are at a markedly increased risk of miscarriage and ectopic gestation and are more likely to give birth to an underweight infant than other women.

Abnormalities, Drug-Induced↗
PubMed1978

Ten-year experience with DDAVP in treatment of diabetes insipidus.

Thirty patients with central diabetes insipidus were treated with 1-deamino-9-D-arginine vasopressin (DDAVP) during the period of 3--10 years. DDAVP was applicated in 1--3 intranasal doses daily. The dosage varied between 7--42 microgram/24 h. The diuresis before the treatment ranged between 28,000--7,600 ml/24 h (mean 13,883 ml/24 h) and was decreased by DDAVP below 2000 ml/24 h in 21 patients (70%) and to 2000--4000 ml/24 h in 8 patients (26.6%). In a single case it was not possible to reduce the diuresis from 20,000 ml below 8,000 ml/24 h. Favourable properties of DDAVP: absence of reduction of potency, lack of important side-effects and prolonged action were not lost even in the course of the long term treatment. No harmful effects of DDAVP were noted. Blood count as well as renal function tests were not affected by the treatment. All the patients preferred DDAVP to their previous therapy.

Adult↗
PubMed1976

An ammonia-oxidizing bacterium, Nitrosovibrio tenuis nov. gen. nov. sp.

An ammonia-oxidizing, autotroph growing, slender, curved rod was isolated from the soil of Hawaii. It is well distinguishable from any other nitrifying bacteria thus far described by their morphology. The cells are 1.1-3.0 mum long and 0.3-0.4 mum wide. They are motile by means of 1-4 subpolar to lateral flagella. In contrast to most of the ammonia-oxidizing bacteria the isolated vibrio is void of an extensive cytomembrane system. To categorize this not yet described species we propose to create the new genus Nitrosovibrio and to classify the isolated strain as Nitrosovibrio tenuis.

Ammonia↗
PubMed1976

Is mild preeclampsia (EPH gestosis) harmful to the baby?

Mild preeclampsia, as defined by a rise in blood pressure to 140/90 mm Hg or more in the third trimester of pregnancy, does not affect the baby either in terms of increased perinatal mortality or a reduction in birth weight. Higher maternal weight gains are associated with greater birth weight of the babies in primigravidae, provided that proteinuria does not occur. Reduction of water retention by diuretic treatment does not lower the incidence of preeclampsia, does reduce the weight of the baby.

Birth Weight↗
PubMedDate not supplied

[Pulmonary complications of acute myocardial infarct. Therapeutic orientation].

The heart and the lung make up an inseparable anatomic and functional unit. The changes in one affect the other and vice versa. In acute myocardial infarction a heart failure syndrome develops. This syndrome is characterized by passive pulmonary congestion, which leads to hypoxemia. This hypoxemia indicate the functional disturbance of the lung, and the hemodinamic evolution of the disease. Arterial gases determination is the best way to assess the sickness progression. A certain paralelism exists among the central venous saturation, cardiac insufficiency and the degree of pulmonary disfunction. Such a procedure is not very appreciable and does not substitute the direct analysis of the arterial PO2. The pulmonary complications in the myocardial infarction shock are directly responsable of death in 50% of the patients. To heart failure and shock, hipperfusion and hypoxia are added. Many vessels close due to the decrease in the pulmonary flow. This brings about the release of substances that are toxic to the vessel causing an inflammatory vascular reaction. The decrease in the flow harms the lung cell and for this reason atelectasia or alveolar colapse occur; besides inducing the formation of shunts. Under these conditions the lung compliance decreases. The areas that are badly ventilated and hypoperfused can easily become infected and pneumonitis and abscesses cause even more harm to the tissue. The decrease in the speed of circulation and hematologic changes of shock, induce a diseminated intravascular coagulation. What was stated before leads to an important reduction of the lung as a depurating organ and makes the shock irreversible. As far as therapy is concerned in the prevention of vascular colaps and the improvement of the oxemia, oxygen is very useful when there is a venous congestion (clinically, X rays, and oxemia). When the concentration of O2 is lower than 50% in the cases with slight cardiac failure; do not use oxygen in higher concentrations unless the hypoxia is associated to acute pulmonary edema and shock. Mechanic ventilators, and intermitent possitive pressure are recommended even though they have a posenous effect on the cardiac output. Always keep the air ways permeable: changing position, breathing exercises, humidifications, aspiration of secretions, intubation, or traqueostomy depending upon the various cases.

Acute Disease↗