Paul Andrew, the newly mounted innovative director of Salvatore Ferragamo, got here out swinging. “Men’s style nowadays, I assume it’s in a surely atrocious kingdom, pretty frankly,” he stated. “You move into any so-referred to as luxurious style house, and menswear is predominantly about hoodies and sweatpants and tank tops and T-shirts with logos all over them. There’s no difference between that and what the high-road brands are doing. I don’t actually find that luxurious.” Shots fired.
We have been within the Florence Chamber of Commerce constructing, which turned into mercifully air-conditioned—out of doors, oppressive Tuscan humidity had descended upon the whole day of Pitti Uomo. But the warmth, because it has been, became on: It becomes approximately seven hours from Andrew’s first menswear show as innovative director, and he becomes deliberating model Kiki Willems as she walked throughout the marble ground in a couple of white cutout ankle boots and an identical embroidered lace get dressed. (Andrew, who turned into promoted from head of women’s geared up-to-wear and shoes six months in the past, couldn’t withstand sprinkling some women’s seems into the display.) His imaginative and prescient of what real luxury is beginning right here.
Andrew didn’t say who these “luxurious” competitors are, but it’s clear who he’s talking about: the Guccis and Balenciaga of the world, whose sales have skyrocketed under designers who haven’t been afraid to pour jet fuel on their respective homes’ codes—which means, yes, they have designed some closely branded hoodies. “My approach to men’s fashion is very special,” Andrew stated, gesturing on the version board, wherein there’s now not a couple of jeans or sweats to be located many of the Talented Mr. Ripley-esque palettes. There’s a T-shirt—and it’s made of Napa leather. The faces on the board skew older than we’ve come to expect, too, Willems notwithstanding. Legendary art director Peter Saville (he of Joy Division’s cover art and worldwide fashion houses’ new logos) became set for his runway debut, as was Michi Berger-Sandhofer, a deputy chairman at Sotheby’s and buddy of Andrew’s.
Andrew’s mandate as innovative director isn’t simply to modernize the prevailing Ferragamo client—it’s to bring in a brand new technology. You know, the one that’s copping hoodies like there’s a cotton scarcity. But communicate is simply talk. So later that night, within the Piazza della Signoria (you realize, the square in Florence), Andrew virtually got here out swinging: The establishing appearance featured that Napa tee with a creamy pair of workwear-inspired belted cargo pants in a tailoring wool-cotton material. “Once you’ve worn the ones form of sport-stimulated clothes, it’s tough to go lower back to tailored, geared up garments, and I do not always see that coming returned in a robust manner,” Andrew had cited before the display (whilst wearing, I can also upload, beat-up black Carhartts).
Workwear, he says, is a way to attain that younger era—a strategy that felt even more promising while the ones pants emerged at the runway. They looked of a nice so that it will more than justify the unavoidably high charge tag—and, more importantly, with an handy slouch, they appeared absolutely cool. It’s now not definitely workwear, however it’s not what you think of while you assume “Ferragamo trouser,” either. Plus, the version was carrying considered one of a chain of shades paying homage to Oakley blades. The setting was a nod to Ferragamo’s Florentine history (it’s miles the first time—and final, apparently—a emblem has been able to maintain a display in the Piazza della Signoria), but the sun shades have been a sign that Andrew is asking ahead.
There changed into additionally a tanned leather vest this is all but destined for Dev Hynes’s cloth wardrobe, and a series of tight quick-sleeve ribbed knits you could consider seeing on a skater with a modeling settlement. Speaking of which, It-guy Evan Mock (the red-haired skater and version) became sitting within the the front row subsequent to Ferragamo fan Cole Sprouse, carrying the brand new Ferragamo knit tank. That the ones men will land up sporting these garments is already a small victory. In the beyond, Ferragamo’s menswear runway seems didn’t generally tend to make it to production. Another part of Andrew’s mandate, he says, is to “carry that fashion into the stores, in order that a greater style-ahead customer can come in and in reality discover matters” that they’re seeing on the runway, in magazines, and on licensed cool youngsters like Mock.
One piece that turned into drastically absent from Andrew’s Ferragamo runway? The iconic bit loafer. Andrew landed his authentic Ferragamo activity at the fulfillment of his award-prevailing eponymous shoes emblem, and he espouses a philosophy of “toe-to-head dressing.” At the display, the energy of the garments nearly obscured the reality that he’s completely overhauling Ferragamo’s men’s footwear program. There will nonetheless be your father’s favorite loafers, of course. But Andrew wanted to exhibit a emblem-new silhouette: a hybridized sneaker featuring a conventional bench-made top and a thick vulcanized trainer sole. Though Salvatore Ferragamo may not realize what to make of it, Andrew says the sneaker is a nod to the emblem founder’s appreciation of technology: “If you study the footwear he made inside the ’20s and ’30s now, you’d suppose they were from the ’60s and ’70s. He changed into ahead of the game with the aid of the use of latest generation from that point, however usually the best Italian craftsmanship and materials. So it’s got this excessive-tech, high-craft approach, which is honestly the philosophy right here these days.”
There are definitely folks who would really like to look Andrew juice Ferragamo income—which fell 14 percent in 2018—as quick as viable. Would he be able to accomplish that through adopting a high-street method? Maybe. But at the same time as Andrew isn’t looking to tear down Ferragamo’s Florentine walls, neither is he a designer entirely interested in his uncompromising imaginative and prescient, profits be damned. His work inside the womenswear branch, he says, has already brought about expanded income.
But possibly the riskiest circulate of his grand debut made Andrew’s priorities as creative director clear: Ferragamo’s iconic “Gancini” symbol became hard to spot. Those belts with the honking Ferragamo symbol? See ya. Andrew’s brief-term intention for menswear, he says, is to outline a clear aesthetic imaginative and prescient, so that when you see the collection—emblem or not—you understand that it’s Ferragamo. “That takes time,” he recognizes. “It doesn’t appear overnight.” With Tuesday night time’s display at Pitti Uomo, it’s game on.


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Background. The coronavirus pandemic (COVID-19) currently dominates all health problems. Adequate initial antimicrobial therapy of viral and bacterial pneumonia in patients with COVID-19 requires compliance with a number of features that are fundamentally important in the context of global growth of resistance of pathogenic flora to antimicrobial drugs.
Objective. To describe the features of antimicrobial therapy of viral and bacterial pneumonia in patients with COVID-19.
Materials and methods. Analysis of literature data on this issue.
Results and discussion. Severe coronavirus infection triggers an avalanche-like generalized inflammatory response with rapid vascular endothelial damage. Lungs is the main target organ of this aggression. A significant part of all endothelial cells of the body is concentrated in the lungs, so the cascade of multiorgan disorders begins with them. Liver, intestines, kidneys and muscles are the organs that suffer from extrapulmonary manifestations of COVID-19. SARS-CoV-2 сoronavirus also has neurotropism, so it is able to affect the nervous system, both central and peripheral. The pathogenesis, diagnosis and treatment of COVID-19 should be considered in terms of the approaches used in sepsis. This disease is characterized by the following laboratory changes: increased content of C-reactive protein, leukocytosis or leukopenia, lymphopenia, neutrophilia, increased activity of alanine and aspartate aminotransferases, creatine phosphokinase, lactate dehydrogenase, bilirubin and creatinine concentrations. However, sufficiently sensitive and specific markers for the diagnosis and prediction of COVID-19 are currently lacking. Until the results of the polymerase chain reaction for SARS-CoV-2 and, consequently, the confirmation of COVID-19, are absent, all patients with severe pneumonia and acute respiratory distress syndrome should be treated as patients with acute severe community-acquired pneumonia. Empirical combination antibiotic therapy should be started immediately. Patients over 60 years of age with pre-existing comorbidities need special attention. The spectrum of microbial flora in such patients includes Streptococcus pneumoniae, Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, gram-negative enterobacteria. This must be taken into account when choosing an antibiotic. In presence of intracellular pathogens, fluoroquinolones have an advantage over macrolides and tetracyclines. Due to the growing resistance of hospital flora to macrolides and the high risk of resistance to them in outpatient flora, the initial use of fluoroquinolones is one of the main trends in modern antibiotic therapy. The advantages of levofloxacin are the possibility of administration in short courses (750 mg once a day for 5 days), a wide activity spectrum, the ability to overcome the basic mechanisms of resistance, a good safety profile. Intravenous administration of levofloxacin is not inferior to the effectiveness of the combination of β-lactams and macrolides and can be completed by transferring the patient to oral treatment. For the treatment of patients at risk of Pseudomonas aeruginosa infection, combination therapy is prescribed – antipseudomonad cephalosporins of III-IV generation in combination with aminoglycosides, ciprofloxacin or levofloxacin. Alternatively, carbapenems are prescribed in combination with aminoglycosides (tobramycin – Braxon, “Yuria-Pharm”) or fluoroquinolones (levofloxacin – Leflocin, “Yuria-Pharm”). When methicillin-resistant Staphylococcus aureus is detected, the use of linezolid (Linelid, “Yuria-Pharm”) is advisable. Antibiotic therapy is often accompanied by fungal infections. In severe cases of the latter, as well as in pulmonary aspergillosis voriconazole (Vizealot, “Yuria-Pharm”) is prescribed.
Conclusions. 1. Severe coronavirus infection triggers an avalanche-like generalized inflammatory reaction with rapid damage to the vascular endothelium. 2. In the presence of intracellular pathogens, fluoroquinolones have an advantage over macrolides and tetracyclines. 3. The initial use of fluoroquinolones is one of the main trends in modern antibiotic therapy. 4. In the detection of methicillin-resistant Staphylococcus aureus, it is advisable to use linezolid. 5. In severe fungal infections and pulmonary aspergillosis, voriconazole is prescribed.
Background. Preeclampsia (PE) remains the leading cause of maternal and perinatal morbidity and mortality. As of today, there is no treatment for PE, and the childbirth is the only way to completely eliminate this condition. However, early childbirth is associated with a high risk of fetal morbidity and mortality.
Objective. To describe the role of endothelial dysfunction (ED) in the development of PE and the possibility of its correction; to evaluate the effectiveness of Tivortin (“Yuria-Pharm”) in the correction of uterine-fetal-placental dysfunction.
Materials and methods. Analysis of literature sources on this topic; own PLACENTA study. The study involved 535 women with mild PE at 26-29 weeks of gestation. Group I received standard therapy, group II – standard therapy in combination with Tivortin (4.2 g per day for 7-10 days).
Results and discussion. Until the fetus reaches viability, PE treatment is aimed at correcting hypertension, however, antihypertensive therapy does not have a beneficial effect on the condition of the kidneys and placental blood flow. Decreased blood flow in placenta leads to the syndrome of limited fetal development (SLFD) and multisystem ED. The development of PE is inextricably linked with the systemic damage to maternal endothelial cells and a further decrease in endothelium-dependent vasodilators, which promotes vasospasm and activates the coagulation cascade. PE is accompanied by the imbalance in the systems of prostacyclin and nitric oxide (NO), as well as thromboxane and endothelin. Superficial placentation with insufficient remodeling of the spiral arteries and impaired response to changes in blood flow is one of the main causes of PE. ED is the most studied pathogenetic mechanism of PE. NO has a potent vasodilating effect and is involved in inhibiting thromboxane formation, platelet aggregation and stimulating prostacyclin formation. NO-synthase of endothelial cells, the substrate of which is L-arginine, is the main enzyme of NO production. Disorders of vasodilation in pregnant women with PE can be eliminated by prescribing L-arginine. Literature data show that L-arginine is successfully used in the need to continue pregnancy, as well as to eliminate hypertension and correct SLFD. Canadian guidelines for the treatment of hypertensive complications of pregnancy state that L-arginine is able to improve uteroplacental blood flow. According to a study by J. Chen (2016), the inclusion of L-arginine contributes to both maternal and perinatal outcomes of pregnancy. The effect of L-arginine on fetal growth is mediated by promoting the production of creatine, skeletal muscle protein and growth hormone. L-arginine also promotes the synthesis of polyamines, which can stimulate the growth and development of placenta. Own studies have shown that the use of L-arginine (Tivortin, “Yuria-Pharm”) in the combined PE therapy had improved the growth rate of the fetus and its functional condition, which allowed to prolong pregnancy to the optimal term of childbirth, as well as improve the consequences of childbirth and adaptation of newborns in the early neonatal period. PE is not the only field of application of Tivortin: its intravenous administration in community-acquired pneumonia and pyelonephritis of pregnant women helps to quickly eliminate the pathological process. The results of the PLACENTA study found that Tivortin helped to improve uterine-fetal-placental blood flow and reduce the centralization of blood circulation. In the Tivortin group there was a smaller number of cesarean sections, a tendency to lower blood loss (by 19.5 %), a higher average score of newborns on the Apgar scale. Comparison of clinical and morphological changes showed that the administration of Tivortin in the late second and early third trimester of pregnancy reduces the likelihood of premature placental maturation by 2.1 %, halves the likelihood of placental necrosis, 10 times reduces the signs of hypoxia.
Conclusions. 1. ED, caused by a decrease in NO, is the main link in the PE pathogenesis. 2. In the human body NO is produced from L-arginine. 3. The use of L-arginine (Tivortin) improves uterine-fetal-placental blood flow, growth rate and functional status of the fetus, reduces fetal distress and allows to prolong pregnancy to the optimal term of childbirth.
S.P. Moskovko, O.V. Kyrychenko
Background. Each 6 seconds 1 person in the world dies of a stroke. The stages of stroke care are the following: case detection, emergency medical care, diagnosis, treatment in the hyperacute and acute period, early and subsequent rehabilitation. The main symptoms of stroke can be identified with the help of FAST system (face – facial asymmetry, arm – limb weakness, speech – blurred speech, time – time after the event).
Objective. To identify the main features of the management of stroke patients.
Materials and methods. Analysis of the guidelines and literature data.
Results and discussion. According to the recommendations of the American Heart Association for the emergency service, the time of processing of the call should be up to 90 seconds, the response time of the emergency service – 8 minutes, and the time spent at the place of care – up to 15 minutes. Upon admission to the hospital, the doctor of the stroke unit collects the anamnesis and takes a brief neurological examination, as well as determines the main physiological parameters. The nurse performs tests, the results of which come during thrombolysis. Then the patient undergoes a computed tomography, first aid is given and thrombolysis begins (still in the tomography apparatus). Time must be constantly documented. The median time should be 25 minutes. To organize the work of the stroke unit in the hyperacute and acute period of stroke it is necessary to create a local protocol – a document that lists the care procedures in a particular institution and describes the responsibility and coordination of individual units, time frames of each stage and basic medical services. It is also necessary to create a clinical roadmap for the patient, which includes a map of his moving, the content of procedures and their timer. Optimization of the stroke management is extremely important, as each 15 minutes of time saved leads to the 4 % reduction in mortality and to the 4 % increase in the likelihood of no adverse effects. In the first 3 hours it is especially important to monitor such parameters as body temperature, blood glucose, swallowing function (fever, sugar, swallowing – FESS) thoroughly. It is a significant problem, but for the most options of medical support the evidence base is insufficient, and therefore the doctor faces the choice to follow imperfect recommendations or to prescribe drugs according to the pathogenesis of cerebral ischemia. This choice has to be made in settings of severe time shortage, because the stroke kills 9,000 neurons every second. Stages of the ischemic cascade include ischemia, glutamate excitotoxicity, mitochondrial damage and dysfunction, oxidative and nitrosative stress, inflammation, and microcirculation disorders. Edaravone affects these stages, reducing the activity of oxygen radicals, the permeability of the blood-brain barrier, and the activity of secondary inflammation. This reduces the ischemic penumbra and the brain tissue necrosis area, which increases the likelihood of functional recovery. The study by M. Enomoto et al. (2019) showed that the use of edaravone and the endovascular reperfusion is a promising strategy for the treatment of ischemic stroke.
Conclusions. 1. To coordinate the work of the stroke unit in the hyperacute and acute period of stroke, it is necessary to create local protocols and the clinical roadmap. 2. During the first 3 hours it is especially important to monitor such parameters as body temperature, blood glucose, and swallowing function. 3. Edaravone affects the ischemic stroke, reducing the activity of oxygen radicals, the permeability of the blood-brain barrier, and the activity of secondary inflammation.
Background. Preventive check-ups reveal uterine fibroids for the first time in 1-5 % of women. In the presence of gynecological diseases this number is about 30-35 %. Pathomorphological examination of deceased women of different ages reveals fibroids in 77-85 % of them. The age of this diagnosis has become significantly younger, and it is important, because uterine fibroids are associated with problems with fertilization and pregnancy. Myomas are divided into types by localization (interstitial, intraligamentary, subserous, interstitial-subserous, submucosal, etc.).
Objective. To describe current trends in the treatment of uterine fibroids.
Materials and methods. Analysis of own experience in the treatment of fibroids and literature sources on this topic.
Results and discussion. Conservative myomectomy can be performed laparotomically, laparoscopically and hysteroscopically. It is often impossible to perform a traditional conservative myomectomy of large nodes of II-V grades without significant damage to the uterine wall, so as a result, conservative myomectomy turns into a hysterectomy. HiFu ablation is an another method of treating fibroids. This method is based on the influence of a high-power ultrasonic wave, which is generated by a radiating lens and passes through the patient’s body to the pathological focus. Degasated water acts as a conductor between the patient’s body and the lens. The goals of treatment are to preserve the uterus and to create the possibility of pregnancy. Before treatment, magnetic resonance imaging of the pelvic organs and assessment of the potential for malignancy must be performed. Criteria for the selection for ablation include the desire to preserve the uterus; established diagnosis of uterine fibroids, local adenomyosis; obvious symptoms of fibroids (abnormal uterine bleeding, dysmenorrhea, pain, secondary anemia); node size 1-15 cm (submucosal or intramural type of growth). The preservation of a woman’s fertility is a main indication for ablation. There are no alternative methods to HiFu ablation in terms of efficacy and safety, but if the nodes were too large or too numerous, conservative myomectomy is performed after significant tumor regression after two sessions of HiFu. The nodal bed and pelvic floor should be washed with decamethoxine solution during the operation. The required volume of solution is about 2 liters. The advantages of decamethoxine include the lack of absorption by the wound surface and a powerful bactericidal effect. If the walls of the uterus are thin and it is not possible to preserve their integrity during myomectomy, plastic surgery is performed with the introduction of high molecular weight hyaluronic acid to prevent the formation of adhesions and accelerate regenerative processes.
Conclusions. 1. Uterine fibroids are common tumors that in young women are accompanied by problems of fertilization and pregnancy. 2. It is often impossible to perform traditional conservative myomectomy of large nodes without significant damage to the uterine wall. 3. HiFu ablation is the modern method of treatment of fibroids. 4. Maintaining a woman’s fertility is a main indication for ablation.
Background. Arterial hypertension (AH) is a risk factor for stroke and myocardial infarction. In low-income countries, the prevalence of hypertension is 42 %. Hypertensive crisis (HC) is an acute increase in blood pressure – BP (systolic BP >200 mm Hg, diastolic BP >120 mm Hg), which is accompanied by the threat or progression of target organs damage and requires the immediate controlled reduction of BP.
Objective. To describe the emergency care for HC.
Materials and methods. Analysis of current recommendations and literature data.
Results and discussion. HC are classified into uncomplicated (uHC) and complicated (cHC). Perioperative hypertension can be considered a separate subtype of HC. Risk factors for HC include uncontrolled hypertension, refusal to take antihypertensive drugs, emotional stress, excessive fluid and salt intake, alcohol abuse, smoking, physical overload, meteopathic factors, obesity. uHC require BP lowering within 2-6 hours; drugs are administered orally; there is no need for hospitalization. cHC requires BP lowering within 30-120 minutes; drugs are administered intravenously; the patient must be hospitalized. After maintaining the target pressure <160/100 mm Hg within 2-3 hours the patient can be transitioned to the oral drug administration. Therapeutic armamentarium for HC includes nitroprusside, nicardipine, clevidipine, esmolol, labetalol, nitroglycerin, urapidil, and phenoldopam. Labetalol, nicardipine, clevedipine and phenoldopam are not available in Ukraine. The choice of drug should be based on the dominant linjury of the target organ. In case of uHC it is expedient to use nifedipine, captopril, metoprolol, propranolol, clonidine (all of them orally). It should be noted that the parenteral administration of antihypertensive drugs can be carried out only by specially trained personnel with monitoring of BP and hemodynamic parameters, as well as in the presence of conditions for resuscitation. Esmolol (Biblok, “Yuria-Pharm”) is indicated for HC with renal failure, dissection of the aorta or pulmonary edema. It is also advisable to use Biblok in perioperative hypertension. The peculiarities of the Biblok use include the need of infusion into a large diameter vein, usage of lineamats or infusomats, use for no more than 24 hours, and no abrupt termination of the infusion.
Conclusions. 1. HC is an acute increase in BP, which is accompanied by the development or progression of damage of target organs and requires immediate controlled reduction of BP. 2. Risk factors for HC include uncontrolled hypertension, refusal to take antihypertensive drugs, emotional stress, excessive fluid and salt intake, alcohol abuse, smoking, exercise, meteopathic factors, obesity. 3. Esmolol (Biblok) is indicated for HC with renal failure, aortic dissection or pulmonary edema, as well as perioperative hypertension.
M.M. Pylypenko, O.Yu. Khomenko
Background. The success of respiratory support depends on the effectiveness of improving gas exchange, reducing lung damage, and adaptation of the respirator. Reduction of lung damage has previously been reported in the context of ventilator-associated injury: barotrauma in case of high plateau pressure and driving pressure, volume trauma in case of large tidal volume, atelectasis trauma due to the cyclic collapse of lungs on exhalation and opening on inspiration.
Objective. To describe the features of lung damage during mechanical lung ventilation (MLV) and the possibility of its prevention.
Materials and methods. Analysis of literature sources on this topic.
Results and discussion. The main causes of “air hunger” breathing type and shortness of breath include hypoxia, acidosis, increased anatomical and functional dead space, psychomotor agitation and fear. Metabolic acidosis is compensated by hyperventilation and respiratory alkalosis, but it is treated by improving oxygenation. High-flow oxygenation helps to leach CO2 from the dead space. Psychomotor agitation and pain aggravate shortness of breath, so all components of these processes should be influenced by effective analgesia, providing the patient with a comfortable body position (especially obese people), ensuring the absence of hunger and thirst, creating conditions for night sleep and more. If all these measures are taken, but the patient’s agitation is maintained, sedation should be considered. Propofol and dexmedetomidine are increasingly used for short-term sedation. Approaches to sedation have been changing abroad in recent years. First, non-pharmacological methods are used and only then – pharmacological ones. First of all, it is recommended to achieve analgesia, and then – sedation. It is advisable to maintain moderate sedation (from 0 to -2 on the RASS scale) and avoid deep sedation (from -3 to -5 points on the RASS scale). Sedation should be stopped each morning for the wake-up test and the respirator quitting test. To improve the immediate consequences of treatment (duration of MLV and stay in the intensive care unit), it is advisable to minimize the use of benzodiazepines and prefer propofol or dexmedetomidine. The depth of sedation should be constantly monitored, however, even experienced physicians may not always be able to detect asynchrony and excessive sedation. Asynchrony is associated with the increased mortality and prolonged weaning. To assess the intensity of the patient’s respiratory effort, the index of rapid shallow breathing, the maximum vacuum in the airways and the pressure in 0.1 second after the start of the breathing attempt are used. If the latter exceeds 3.5 cm H2O, it indicates the excessive respiratory effort of the patient (Telias I. et al., 2020).
Conclusions. 1. The term “self-induced lung injury” has become widely used in the practice of anesthesiologists. 2. The need for respiratory support is determined primarily by the patient’s breathing efforts. 3. The ability to timely identify and respond to asynchrony helps to avoid self-induced lung damage.
Background. A doctor often has to answer the question whether it is sufficient to treat tuberculosis (TB) exclusively with the oral forms of anti-tuberculosis drugs (ATD). In general, the answer is yes, if the absorption of drugs and their delivery to the affected organs is not impaired. However, drug absorption is often impaired due to hypoalbuminemia, TB of the gastrointestinal tract or central nervous system, concomitant diseases of the digestive system, alcoholism, hyperthyroidism, diabetes, or in the elderly patients.
Objective. To evaluate the feasibility of using infusion forms of ATD.
Materials and methods. Review of current guidelines.
Results and discussion. The advantages of exclusively oral administration of ATD include convenience, low cost, the possibility of usage in an outpatient setting, whereas the main disadvantage is that it is not always possible to create the required concentration of ATD in blood plasma. In turn, the advantages of intravenous ATD include the creation of maximal concentrations in blood plasma and foci of infection, fewer side effects in the digestive system, patients’ awareness of the importance of treatment, whereas disadvantages are high cost and low adherence to treatment. The use of part of the ATD as a step therapy (course of intravenous infusions with subsequent transition to oral administration) allows to create the maximal concentration of active substances in blood plasma and affected organs at the beginning of treatment, to provide better cost/effectiveness ratio in comparison to previously listed regimens, and to increase the treatment adherence without compromising the quality of life of patients. The additional cost of intravenous ATD delivery devices is the main disadvantage. Criteria for the transition from the infusions to oral administration are the elimination of bacterial excretion, obtaining a stable positive dynamics of the clinical condition, elimination of the causes of the need for intravenous treatment (normalization of swallowing function, elimination of malabsorption). Indications for step therapy include the severe forms of TB, severe disorders of the central nervous system and gastrointestinal tract, the presence of severe comorbidities, pre- and postoperative periods, mental disorders, side effects of 3rd-4th degree in case of oral ATD intake. The duration of the infusion course is determined individually, but in average it is about 1-2 months. Such drugs as rifampicin, isoniazid, ethambutol, levofloxacin, moxifloxacin, linezolid, and carbapenems exist in the infusion form.
Conclusions. 1. Infusion of ATD as a part of step therapy can improve the quality of treatment of TB patients. 2. Criteria for the transition from infusions to oral administration are the elimination of bacterial excretion, obtaining a stable positive dynamics of the clinical condition, elimination of the causes of the need for intravenous treatment. 3. The duration of the infusion course is determined individually (in average – 1-2 months).
Background. Procedural sedation (PS) is a condition that allows patients to avoid discomfort when undergoing certain painful manipulations on the background of stable hemodynamics and respiration and maintaining the ability to respond adequately to verbal commands or tactile stimulation. PS is most often used in dentistry, maxillofacial surgery, endoscopy, ophthalmology, otorhinolaryngology.
Objective. Describe the main features of the PS.
Materials and methods. Analysis of literature data on this topic.
Results and discussion. Risk groups during PS include patients with cardiovascular decompensation, morbid obesity, obstructive sleep apnea, grade III-IV chronic renal failure, liver decompensation, as well as age over 70. The conditions for safe PS are as follows: all medical staff are trained to provide cardiorespiratory resuscitation; there is a constant quick access to resuscitation equipment; a routine pre-procedure assessment of the patient’s condition (especially the upper respiratory tract) was carried out; pre-procedure fasting was prescribed; careful monitoring of the patient’s condition is provided. The main scales for sedation assessment include Ramsay Sedation Scale, Sedation Agitation Scale, Motor Activity Assessment Scale, Vancouver Interactive and Calmness Scale, Richmond Agitation-Sedation Scale, Adaptation to Intensive Care Environment, Minnesota Sedation Assessment Tool. Midazolam, propofol, dexmedetomidine can be used for PS. Minimal sedation (anxiolysis) is a medical condition in which the patient responds normally to voice commands. Cognitive function and coordination in this condition may be impaired, however, cardiorespiratory function remains unchanged. Such sedation is prescribed in traumatology, maxillofacial surgery, urology, gynecology, plastic surgery. Moderate sedation is a medical suppression of consciousness in which the patient responds to voice commands accompanied by light tactile stimulation. Adequate respiration and functioning of the cardiovascular system is maintained. Diazepam/sibazone, midazolam, dexmedetomidine are prescribed for this purpose. The latter is recommended for fiber-optic intubation in a state of complete consciousness. The dangers of PS include passive aspiration and ventilation disorders, which leads to hypoxia and hypercapnia. Caution should be taken with propofol due to the possible development of respiratory depression and hemodynamics, pain in the vein during administration. Dexmedetomidine does not cause respiratory depression, however, this does not eliminate the need for monitoring.
Conclusions. 1. Adequate sedation during surgery is a logical component of the intervention if the regional methods of anesthesia are applicated. 2. Sedation outside the operating room will account for more and more of the use of anesthetics. 3. There is a need for clear regulation of PS. 4. When choosing a drug one should take into account the purpose of its administration, curability of complications, comfort and safety of the patient.
Background. Infusion therapy (IT) is one of the main methods of drug therapy optimization. The essence of IT is to correct homeostasis disorders in order to detoxify, to restore the disrupted microcirculation and tissue perfusion, to eliminate the disorders of rheological and coagulation blood properties, to eliminate metabolic disorders, to improve drug delivery to the pathological focus, to restore circulating blood volume, to normalize fluid and electrolyte and acid-base balance.
Objective. To describe modern IT.
Materials and methods. Analysis of the literature sources on this topic.
Results and discussion. Requirements for modern plasma substitutes include safety, sufficient and long-lasting volemic effect, rapid renal excretion, lack of accumulation and effect on the coagulation system, maximum similarity to blood plasma, and availability. There are several classes of plasma substitutes, and each of them has its own indications. For example, crystalloids are prescribed for dehydration, and colloids – for hypovolemia. The infusion volume is calculated based on the physiological needs of the organism, taking into account pathological fluid loss (fever, shortness of breath, postoperative wound drainage, vomiting, polyuria). Endogenous intoxication (EI) – a pathological condition that occurs as a result of exposure to toxic substances of exogenous or endogenous nature, which cause dysfunction and the development of extreme conditions – is an important field of IT application. EI can accompany chronic heart failure, peripheral vessels atherosclerosis, autoimmune and allergic diseases. Toxins have a direct (direct destruction of proteins and lipids, blocking of synthetic and oxidative processes in the cell) and indirect (microcirculation system and vascular tone disorders, changes of blood rheological properties) adverse effects. Clinical manifestations of EI include fever, malaise, and the dysfunction of various internal organs. As EI depletes the natural mechanisms of detoxification, worsens the clinical course of the disease, reduces drug sensitivity, suppresses immunity, it is an indication to detoxification via infusion. The tasks of the latter are to improve tissue perfusion, to provide hemodilution with a decrease in the toxins’ concentration, to stimulate diuresis, to eliminate acidosis, and to maintain the functional state of hepatocytes. For this purpose, solutions of polyatomic alcohols (Reosorbilact, Xylate, “Yuria-Pharm”) can be used. Reosorbilact increases the circulating blood volume, improves microcirculation and rheological blood properties, increases tissue perfusion, promotes “wash-out” of toxins, corrects acidosis and fluid and electrolyte balance, normalizes hepatocyte function, improving the own detoxification mechanisms. In case of microcirculation disturbances, it is reasonable to use the combined IT with the inclusion of Reosorbilact, Latren and Tivortin (“Yuria-Pharm”). Latren increases the elasticity of erythrocytes, reduces the aggregation of erythrocytes and platelets, normalizes the electrolyte composition of blood plasma, and Tivortin acts as a substrate for the formation of nitric oxide – the main signaling molecule of the endothelium. In addition to EI, IT usage is often prescribed for diabetic ketoacidosis. In such cases, it is advisable to use Xylate (“Yuria-Pharm”), which has antiketogenic properties, improves hemodynamics, corrects acidosis, and does not increase blood glucose levels. Xylate is recommended to be used only after preliminary rehydration with the help of isotonic saline solutions.
Conclusions. 1. IT is an important method of treating a number of diseases. 2. EI accompanies not only diseases that involve intoxication syndrome, but also almost all internal diseases. 3. Reosorbilact and Xylate are the optimal solutions for detoxification. 4. It is reasonable to use combined IT, for example, the combination of Reosorbilact with Latren and Tivortin.
Background. Infusion therapy (IT) has a number of features that both doctors and nurses need to know. IT can be performed via a needle, a peripheral intravenous catheter (PIC), and an implanted system for long-term infusions (ISLI).
Objective. To describe the features of short-term and long-term IT.
Materials and methods. Analysis of literature sources on this topic.
Results and discussion. First of all, every healthcare worker should remember that the patient should be identified before any manipulation and then the procedure may start. IT via the needle has a number of disadvantages: complications due to the frequent punctures and prolonged stay of needle in the vein; limited possibility of long-term IT; increased risk of needle injuries among medical staff. The advantages of PIC above needle include the lower risk of infection, better safety, the possibility of rapid administration of drugs in various combinations, easy use of IT and parenteral nutrition, and the ability to monitor central venous pressure. PIC are classified by the presence of an additional injection port, by the material from which they are made, by the shape of the needle tip sharpening, by the visibility on X-ray and size. Venoport Plus (“Yuria-Pharm”) is an elastic teflon catheter with a low coefficient of surface friction, X-ray contrast strips and the possibility of a long stay in a vein (up to 72 hours). The advantages of the Venoport Plus PIC are the adaptive shape of the cap, the optimal inclination angle and SMART SLOT – a hole near the tip of the needle, which allows you to visualize the blood between the catheter and the needle without waiting for it to appear in the indicator chamber. The most suitable for the PIC placement veins are located on the outside of the hand and on the inner surface of the forearm. It is recommended to use the ulnar vein only for laboratory blood sampling and emergency medical care. When choosing PIC one should take into account the vein diameter, necessary speed of infusion, potential time of stay of a catheter in a vein, and features of the infused solution. After installing PIC, it is advisable to use special transparent aseptic bandages. Bandage replacement is performed as needed; daily replacement is not required. After PIC installation and after infusion, PIC should be washed with 0.9 % NaCl, heparin (1:100 dilution), or Soda-Bufer solution (“Yuria-Pharm”). If the catheter is not used, washing should be performed once a day. ISLI Yu-Port (“Yuria-Pharm”) provides long-term venous access and can be used if the patient needs multiple administrations of drugs during a long course of therapy.
Conclusions. 1. IT can be conducted via a needle, PIC, or ISLI. 2. The advantages of PIC over the needle injection are lower risk of infection, better safety, the possibility of rapid administration of drugs in various combinations, facilitated use of IT and parenteral nutrition, and the ability to monitor central venous pressure. 3. PIC Venoport Plus (“Yuria-Pharm”) is an elastic teflon catheter with an adaptive shape of the cap and the optimal angle. 4. When choosing PIC one should take into account the vein diameter, the required speed of infusion, the potential time of stay of a catheter in a vein, and the features of the infused solution. 5. ISLI Yu-Port provides long-term venous access and can be used if necessary for the multiple administrations of drugs during a long course of therapy.

domain: literature


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domain: food


In the food production industry, there are strict health and safety regulations in place to ensure that consumers receive a product that is of superior quality. The ramifications of not meeting these government and industry standards can be hugely detrimental to a food producer. If poor-quality food makes it to market, this can cause illness to the consumer, resulting in legal consquences for the manufacturer. On the other hand, food that does not pass quality standards can result in wasted materials, higher manufacturing costs, and ultimately a loss in revenue.
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WE tv has picked-up a new docu-series, “Love Inc.,” about an unconventional Chicago family running an acclaimed matchmaking service. “Love Inc.” chronicles the ups and downs of the proprietors of LuvBizChicago, a family business run by head matchmakers Lisa and her ex-husband Jim, along with their adult children and Jim’s former mistress. The show follows the so-called hilariously combative family while they help real people find true love in the Windy City.
WE tv has ordered 6 episodes of “Love Inc.” which is expected to premiere next year. “Love Inc.” is co-executive produced by Patti Stanger for Patti Stanger Productions with Rob Lee for Bayonne Entertainment along with SallyAnn Salsano, the founder and president of 495 Productions, the company behind the record breaking hits “Jersey Shore” and “The Real.” Stanger will also appear in the series.

domain: artistic


text:
Judge says former Carmel doctor is a threat
Judge refuses to reduce bail for Carl Bergstrom
The former Carmel physician whose forcible rape conviction was overturned last year was back in a Salinas courtroom Thursday.
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The judge refused to lower the bail, saying Bergstrom posed a danger to the community and violated the terms of his release when he was previously granted bail.
Bergstrom will be back in court on March 22nd for pre-trial and trial setting.

domain: news


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domain: chemistry


Tottenham Hotspur played Liverpool at the Premier League of England on November 6. The match kicked off 16:30 UTC. Liverpool won 1-2.
Mohamed Salah scored the first goal on the 11th minute of the game followed by a goal from Harry Kane. Salah later scored 1 more. 1-2 is the final score.
Tottenham Hotspur (also known as Spurs, Tottenham, Tottenham Hotspur FC or Totthenham) and Liverpool (commonly referred to as LFC or Liverpool FC) meet again 9 months after the Premier League match which ended in a draw 1-1. Tottenham Hotspur are having a solid run at the moment winning their matches against Marseille and Bournemouth extending their unbeaten streak to 3 matches, however, one part of Tottenham Hotspur has trailed behind in terms of reliability—defence: they have been conceding goals for 5 consecutive matches now.
Liverpool are approaching the match in a good mood as well after claiming a 2-0 win in Group stage Group A against Napoli.
ScoreBat is covering Tottenham Hotspur vs Liverpool in real time, providing the live stream and live score of the match, team line-ups, full match stats, live match commentary and official video highlights. We cover all matches of England Premier League in real time and provide live streaming whenever possible.
You can watch Tottenham Hotspur vs Liverpool live stream here on ScoreBat when an official broadcast is available. We will provide only official live stream strictly from the official channels of the league or the teams whenever it is available. Live streaming will begin when the match is about to kick off.
We aggregate all official videos from official websites and Youtube channels of Liverpool and Tottenham Hotspur as well as the channels of the leagues that they compete in. So, whenever there is an official live broadcast of Tottenham Hotspur - Liverpool match available that isn't behind a paywall - you will be able to watch it on ScoreBat.
We only provide live streaming when we can find an official stream by the league or one of the teams. If you are unable to watch the live broadcast on this page it probably means that there are no official streamings available yet.
We are updating team formations and line-ups for Tottenham Hotspur - Liverpool in real time.
Tottenham Hotspur kicked off the game with Hugo Lloris, Ben Davies, Clement Lenglet, Eric Dier, Ryan Sessegnon who got substituted by Dejan Kulusevski on the 68th minute, Pierre-Emile Hojbjerg, Yves Bissouma who got substituted by Lucas Moura on the 89th minute, Rodrigo Bentancur, Emerson who got substituted by Matthew Doherty on the 68th minute, Ivan Perisic and Harry Kane as starters, with Fraser Forster, Matthew Doherty, Davinson Sanchez, Japhet Tanganga, Bryan Gil, Dejan Kulusevski, Lucas Moura, Pape Matar Sarr and Oliver Skipp on the bench.
Liverpool's starting eleven were Alisson, Andrew Robertson, Virgil van Dijk, Ibrahima Konate, Trent Alexander-Arnold, Fabinho, Thiago Alcantara, Harvey Elliott who got substituted by Jordan Henderson on the 74th minute, Roberto Firmino who got substituted by Curtis Jones on the 74th minute, Darwin Nunez who got substituted by Joseph Gomez on the 87th minute and Mohamed Salah who got substituted by Alex Oxlade-Chamberlain on the 90th minute, with Caoimhin Kelleher, Stefan Bajcetic Maquieira, Joseph Gomez, Calvin Ramsay, Kostas Tsimikas, Fabio Carvalho, Jordan Henderson, Curtis Jones and Alex Oxlade-Chamberlain on the bench.
Explore stats from Tottenham Hotspur vs Liverpool on ScoreBat - we are updating the numbers on this page every second of the game.
Tottenham Hotspur and Liverpool have met 5 times since January 2020. 2 matches ended in a draw while Liverpool have won 3 times. The most recent match between them took place on May 7, 2022 at the Premier League of England which ended in a draw - 1-1. Tottenham Hotspur have scored 5 goals in these 5 head-to-head matches in total while Liverpool have scored 9. So, overall, Liverpool have a better head-to-head record against Tottenham Hotspur in their recent history.
Tottenham Hotspur have won 11 of their 21 matches in Premier League, drawing 3 and having 7 defeats this season. They have scored 40 goals - 1.90 per match, conceding 31 - 1.48 per match. Liverpool have won 8 of their 19 matches in Premier League, drawing 5 and having 6 defeats this season. They have scored 34 goals - 1.79 per match, conceding 25 - 1.32 per match.
Tottenham Hotspur are on a winning streak - they have won Marseille and Bournemouth in their previous 2 matches while Liverpool have won Napoli in their previous match. Overall, Tottenham Hotspur have won 11 of their last 20 matches, losing 5 and drawing 4, while Liverpool have won 10 of their last 20 matches, losing 6 and drawing 4.
Tottenham Hotspur have won 3 times (1-2 against Marseille on 1st of November, 2-3 against Bournemouth on 29th of October and 2-0 against Everton on 15th of October), lost twice (1-2 against Newcastle United on 23rd of October and 2-0 against Manchester United on 19th of October) and drew once (1-1 against Sporting on 26th of October) in their most recent 6 matches.
Liverpool have won 4 times (2-0 against Napoli on 1st of November, 0-3 against Ajax on 26th of October, 1-0 against West Ham United on 19th of October and 1-0 against Manchester City on 16th of October) and lost twice (1-2 against Leeds on 29th of October and 1-0 against Nottingham Forest on 22nd of October) in their most recent 6 matches.
As always, England Premier League's live standings are availble and updated in real time. Tottenham Hotspur are the 5th in the table with 36 points after 21 matches, while Liverpool are the 9th with 29 points in 19 matches.
We are adding goal videos and full video highlights of the match between Tottenham Hotspur and Liverpool in real time. You can watch the goals by Mohamed Salah and Harry Kane as the videos of the goals are added usually minutes after the actual event if there are any official videos available. Full video highlights of Tottenham Hotspur - Liverpool are being added as they become available on the official social media channels of the league or the teams.


text:
QALYs: The Basics
This article is corrected by:
- Errata: Erratum Volume 13, Issue 8, 1065, Article first published online: 3 April 2009
Milton C. Weinstein, Department of Health Policy and Management, Harvard School of Public Health, 718 Huntington Avenue, Boston, MA 02115, USA. E-mail: firstname.lastname@example.org
The aim of this article is to review the concept of the quality-adjusted life-year (QALY), a widely used measure of health improvement that is used to guide health-care resource allocation decisions. The QALY was originally developed as a measure of health effectiveness for cost-effectiveness analysis, a method intended to aid decision-makers charged with allocating scarce resources across competing health-care programs [1–3]. We refer to this original concept of the QALY, as defined in the early literature, as the “conventional” QALY, recognizing that alternative conceptual models have been proposed, including but not limited to so-called “equity-weighted” QALYs. The US Panel on Cost-Effectiveness in Health and Medicine  and the National Institute of Health and Clinical Excellence (NICE) in Britain have both endorsed the conventional QALY for their “reference case,” i.e., a standardized methodological approach to promote comparability in cost-effectiveness analyses of different health-care interventions.
In using QALYs, we assume that a major objective of decision-makers is to maximize health or health improvement across the population subject to resource constraints. The use of QALYs further assumes that health or health improvement can be measured or valued based on amounts of time spent in various health states. The conventional QALY is therefore a valuation of health benefit. We note, however, that decision-makers may also have other objectives such as equity, fairness, and political goals, all of which currently must be handled outside the conventional Special Issue  addresses some of these variations on the conventional QALY. The QALY was not initially developed to aid individual patient decision-making, although its use has sometimes been extended into clinical decision analyses for this purpose.
The core concept of the conventional QALY is grounded in decision science and expected utility theory. The basic construct is that individuals move through health states over time and that each health state has a value attached to it. Health, which is what we are seeking to maximize, is defined as the value-weighted time—life-years weighted by their quality—accumulated over the relevant time horizon to yield QALYs. Health states must be valued on a scale where the value of being dead must be 0, because the absence of life is considered to be worth 0 QALYs. By convention, the upper end of the scale is defined as perfect health, with a value of 1. To permit aggregation of QALY changes, the value scale should have interval scale properties such that, for example, a gain from 0.2 to 0.4 is equally valuable as a gain from 0.6 to 0.8. States worse than dead can exist and they would have a negative value and subtract from the number of QALYs. These conditions, along with an assumption of risk neutrality over life-years, are sufficient to ensure that the QALY is a useful representation of health state preferences.
What Is Value?
In the conventional concept of QALYs, a health state that is more desirable is more valuable. Value is equated with preference or desirability. A critical question is: desirable to whom?
One possibility is to define the desirability of a health state based on how an individual would value being in that health state herself or himself. This measurement of individual preferences is commonly accomplished by preference surveys in which standard gambles, time trade-offs, or visual analog scales are used to assess preferences for specified health states. A key issue, to which we will return, is whether the relevant values for resource allocation decision-making are those of people who are currently experiencing the health state of interest, or those of people on whose behalf the decisions are being made and who may or may not be in the health state at the time they assess its value. An alternative to assessing preferences for health states directly is to assess preferences for a small set of health domains, or attributes, and then to construct a multiattribute utility as a summary measure that reflects preferences both within and across health domains.
As noted in passing previously, the desirability of a health state can also be conceptualized in terms of people's preferences about the health of the community (i.e., mainly the health of others, but possibly including themselves as a member) and not about their own health. Valuation of community health directly, instead of aggregating up from preferences about individual health, permits the decision-maker to incorporate objectives other than health maximization. We return to this issue later, and it is also discussed in the next article in this Special Issue . Preferences about health states in the community are sometimes measured using person trade-offs, although standard gambles, time trade-offs, and rating scales could be applied to this task as well as to individual health state preferences.
An important aspect of conventional QALYs—regardless of the preference measure or the perspective used in assessing health state values—is that the approach values health states and not changes in health states. Special Issue  (Nord et al. this issue) considers alternatives to the conventional QALY that value changes in, rather than absolute levels of, health as the valued outcome.
How Are QALYs Used?
Who are the decision-makers and what are they asking? Some of the broad categories of the uses of QALYs in health decisions are represented by the columns in Table 1, and we discuss these first. Next, we turn to the various attributes of the procedures used to define and construct the QALY measure, represented by the rows of Table 1. First, what is being valued? Second, whom should we ask, and whose preferences should matter: people currently experiencing the health state, or others? Third, what should be asked—what valuation technique should be used, and how should it be administered? Fourth, how are the health outcomes that are the object of the preference assessments defined? Are they health states (the conventional approach), paths of health states over time, or changes in health states, either at a point in time or over time? We take up these aspects of QALYs sequentially. The last two rows of Table 1, to which we will return in discussing each aspect of QALYs, summarize some of the additional assumptions needed to invoke the QALY as a reasonable measure of health or health improvement, and some additional considerations that are left out of the QALY.
Table 1. Matrix characterizing uses and definitions of QALYs
|Value concept: whose health outcome and whose preferences||Individual's health: ex ante desirability as seen by the individual||Individuals' health: experienced utility, then aggregated||Individuals' health: ex ante desirability as seen by each individual, then aggregated||Community health: the health of others,* as seen by each individual, then aggregated|
|Whom to ask:||The individual, informed by patients/disabled people†||Those affected by the activity; e.g., patients/disabled people, those “prevented” from a disease, etc.||Representative sample of population||Representative sample of population|
|Valuation technique:||SG,‡ TTO,§ RS||SG,‡ TTO,§ RS, or MAU instrument||SG,‡ TTO,§ RS, or MAU instrument||PTO, or transformation of MAU values|
|Health outcomes:||Complete health profiles over time∥||Health states and durations||Complete health profiles over time∥||Health states and durations||Health states and durations (conventional QALY application)||Health states and durations|
|Additional assumptions needed:||None, if SG used||Risk neutrality on longevity, additivity across time||Aggregation across individuals||Risk neutrality on longevity, additivity across time, aggregation across individuals||Risk neutrality on longevity, additivity across time, aggregation across individuals||Risk neutrality on longevity, additivity across time, aggregation across individuals|
|Additional considerations needed:|| || ||Equity of actual outcomes||Equity of actual outcomes||Equity of potential outcomes||Equity/fairness built in to some extent?|
What Is the Question?
We have arbitrarily divided the universe of questions for which QALYs, broadly defined, may provide part of the answer into three categories, as reflected in the three major columns in Table 1. The first category (in the right-hand column) comprises societal resource allocation questions—that is, priority setting across proposed programs and program changes. As stated above, this has been the primary focus of the conventional QALY. The second category (left-hand column) encompasses personal decisions that individuals make to affect their own health, including clinical decisions and decisions about the choice of health insurance coverage. A third category of QALY use, which we call societal audit or programmatic audit (middle column), is to evaluate ongoing activities or programs in terms of the health of a population. For this purpose, one needs a description of the health of the population, either at a point in time or changes over time.
The last two rows of Table 1, to which we will return in discussing each aspect of QALYs, summarize some of the additional assumptions that support the QALY as a reasonable measure of health or health improvement, and some additional considerations that are left out of the QALY.
What Is Being Valued?
For personal clinical or insurance decisions, the decision-maker is an individual (or household unit) who is concerned about the desirability of each of the possible health states. We often approach these decisions analytically by using decision trees or various kinds of optimization models in which the decision-maker seeks to optimize expected utility. Because the perspective is that of the individual decision-maker, the relevant utilities are those of the individual, as viewed at the time of the decision. Hence, if the possible outcomes of the decision include health states that the individual has never experienced, the relevant preferences are those of the individual ex ante the decision and ex ante any experience in the health state. Of course, a prudent decision-maker would seek to become well informed about those possible health states, including possibly asking people who have experienced them to convey how they feel about them.
For purposes of programmatic or societal audit, we are usually interested in valuing the current health of the affected population members from their own perspective. A variant approach might be to take into account not only the desirability of the current health states but also the desirability of the future health prospects of the members of the population, including life expectancy and anticipated health prognoses. A rationale for the latter approach to societal audit might be that if the population has a high prevalence of risk factors for future mortality and morbidity, their health would be considered less desirable than a population with similar current health but a better prognosis.
Whereas individual clinical or insurance decisions are governed by individual ex ante preferences, and programmatic or societal audits are accomplished by measuring individual ex post preferences, societal resource allocation decisions can be guided by measures of value either from the perspective of individuals (ex ante or ex post) or from the perspective of the community. For individuals, this amounts to measuring the desirability of health states to individuals—as in the case of individual clinical decisions—and then aggregating across individuals. This individual-based approach to measuring value is consistent with the principle of consumer sovereignty, the keystone of welfare economics, and this has been the approach most commonly applied in constructing conventional QALYs. Individual health preferences are measured through techniques such as the standard gamble, time trade-off, and visual analog scale. The preferences in conventional QALYs are usually ex ante, although they could also be based on the values expressed by individuals who find themselves in the health states ex post .
For societal resource allocation decisions, the value of a health outcome can also be elicited in terms of how individuals feel about the health of others or of the community as a whole, and then aggregated. The desirability of health states or health state changes to others can incorporate concerns for fairness as seen by each individual. For example, an individual might attach higher value to health changes for people who start out in poor health compared to people who start out in good health.
Whom Do We Ask?
From a societal point of view, we can either ask for people's preferences or values about their own health or about the health of others. To determine how people value their own possible health states, one would survey a representative sample of the affected population—which includes patients or disabled people as they occur in the population—and elicit preferences about a range of health states. People who have not experienced particular health states should ideally be informed by knowledge of what patients and disabled people tell them about what it is like to be in those states. Although one might draw a contrast between this ex ante approach and an ex post approach that limits the relevant preferences to people who are currently experiencing the health states of interest , there is not a complete dichotomy. Individuals do have opportunities to become informed about the adaptations that people go through when they experience the various possible health states that the individuals are being asked to value.
A different answer to the question of whom to ask for preferences to inform societal resource allocation decisions is to elicit preferences regarding the health of the community at large, rather than individual preferences for people's own health. When valuing the health of others, we would still tend to go to a representative sample of the population, which includes patients and disabled people as they occur and who are also informed by what they know about the views that patients or disabled people attach to their own health.
For programmatic or societal audit, we would go to the members of the population of interest, and for personal clinical decisions, we would go to the individual patient as the decision-maker. In the context of individual decisions, it is clearly the individual's own preferences that we are interested in, with the proviso that these preferences are informed by knowledge of people who are in the health states that they may have not yet experienced but may possibly experience.
What Do We Ask?
The standard gamble is the method of choice for personal clinical or insurance decisions, based on the principles of expected utility maximization from decision theory. Nevertheless, the time trade-off and possibly rating scales are also used to value health states because of concern that the standard gamble may be subject to cognitive biases in elicitation .
For the societal individualistic approach, preferences for QALYs are obtained by using the standard gamble, time trade-off, or rating scale, or by using multi-attribute instruments that apply these methods to obtain preferences within and across selected domains of health. For valuing the health of communities or others, the person trade-off offers an additional option. The person trade-off could also be used at the individualistic level, but it tends to be more naturally used in evaluating the health of communities.
How Do We Ask These Value Questions?
The standard gamble is based on well-defined, widely accepted axioms of consistency of preferences under uncertainty such as transitivity, independence, and continuity. The standard gamble stands alone among these measures by having been shown to have interval scale properties with respect to preferences, such that a change from 0.2 to 0.4 is equally valued as a change from 0.6 to 0.8 . The time trade-off tends to be approximately equivalent to the standard gamble, as demonstrated by several empirical studies. It has a unique conceptual relationship to QALYs because it is explicitly a trade-off of time with an impaired health state relative to healthy time—quality-adjusted time. The time-trade-off is theoretically equivalent to the standard gamble under the conditions in which QALYs are appropriate as a utility, which include risk neutrality with respect to longevity. Rating scales (including visual analog scales) are generally considered theoretically inferior to standard gambles or time trade-offs because of the scaling biases they entail and the fact that it involves a rating task rather than a choice task. Nevertheless, they are not subject to cognitive biases in elicitation that may be induced by the use of probabilities in the standard gamble elicitation task , nor are they affected by temporal discounting as in the time trade-off elicitation task .
Examples of multiattribute utility instruments include the EuroQOL 5-item scale (EQ-5D), The 7-item Health Utilities Index 2 scale, the 8-item Health Utilities Index 3 scale, the 6-item SF-6D scale based on the SF-36, the 4-item Quality of Well-Being scale, the 15-item 15D scale, and the 5-item Assessment of Quality of Life scale. In this approach, the health states that are valued comprise a matrix of combinations of health domains, or attributes, which are associated with the particular instrument. For example, the 243 health states in the EQ-5D are defined by selecting one of the three levels of health within each of the five health domains. Patients classify themselves into one of the cells in these matrices. Each cell comes with a score that has been previously obtained by a survey of members of the community. This is the method of choice in most contemporary cost-effectiveness studies. It was the approach recommended by the Panel on Cost-Effectiveness in Health and Medicine , and it is preferred by NICE. The problem is that different instruments give different results, partly due to the preference elicitation methods, partly due to choice of health attributes, and partly due to the manner in which interactions across the individual health attributes are modeled. Moreover, the value scores may be population-specific (by country or by sociodemographic characteristics of the respondents), although less so empirically than one might suspect.
The person trade-off is one example of another approach, which we might label as population equivalence methods. Here, individuals act as surrogate decision-makers and make hypothetical choices about competing programs, as if they were benevolent dictators. For example, the person trade-off might ask respondents to choose between helping X patients with condition A to improve to A′, versus helping Y patients with condition B improve to B′. The paradigm for a person trade-off involves asking representative members of the community to compare the desirability of giving numbers of patients' different health improvements. In one variation of this approach, one of X or Y is fixed and the other is adjusted until the respondent is indifferent between the two choices. At this point, the ratio of X to Y reflects the relative value of the improvement from B to B′ compared to the improvement from A to A′. Note that the respondent to the person trade-off is making judgments about the value of health outcomes for others. Another feature is that the person trade-off allows the respondent to incorporate some aspects of equity or fairness, in that the value of a health improvement can depend on the baseline level of health (A or B in the example); specifically, it is possible to attach a greater value to health improvement for people who start off in a worse health state than others.
How Are the Health Outcomes Defined?
In the conventional QALY approach, health outcomes are defined in terms of health states, and each state is valued at a particular point in time. Health state utilities are then summed over time to yield the number of QALYs, with discounting applied if the QALYs are being used in a cost-effectiveness analysis. By making the assumption that the value of being in a health state depends neither on the length of time spent in the health state, nor on the sequence of health states preceding or following it, the time dimension is taken out of the utility assessment process. A critical assumption in this regard is that QALY values, once obtained, are additive over time, possibly weighted by time preference if discounting is applied.
A more general approach, which relaxes the assumption that the value of a health state does not depend on the states that precede or follow it, nor on the length of time spent in it, (i.e., intertemporal utility independence), would be to assign value to sequences of health states over time, sometimes called health profiles . Valuation of health profiles is more general than valuing health states and then summing up, and is therefore theoretically superior because it does not involve the assumption of additivity of values over time. The practical problem with valuing health profiles is that, because outcomes are specified as complete lifetime paths of health states, there are potentially a very large number of them. In the context of a Markov model, a patient-level simulation, or even a clinical trial with multiple follow-up times, the task of valuing all possible paths or profiles is virtually intractable . If there are N possible health states and T time periods, the health profile approach requires NT valuations.
A third approach, covered in more detail by Nord et al. in this Special Issue , values neither absolute health states nor health profiles but focuses on changes in health states. Instead of valuing health state X and a preferred health state Y separately, value is attached directly to the improvement from X to Y. The person trade-off, in particular, invites the respondent to focus on both the origin and destination health states and, if desired, to attach greater value to health improvements from less desirable origin states. One essential difference between this approach and traditional QALYs is that when coupled with the person trade-off, this method for eliciting preferences for changes in health focuses on the health of a community, of which the respondent may (or may not) perceive himself to be a member.
A similar limitation also applies to this approach as for the health profile approach: the number of utility elicitations required can be very large. If there are N possible health states, the approach that values changes requires N × (N − 1) valuations—not as large as the number of possible health profiles but still larger than the number of possible health states. For example, if a range of health states as rich as is provided by the EQ-5D (243 health states) is desired, there would be 243 × 242 = 58,806 possible changes in health states to consider. Another problem with this approach is that the pathway for change from one health state to another can affect the valuation of that change: the value of improving from X to Y and then from Y to Z could be different from the value of a direct improvement from X to Z. In fact, if the valuations of changes are always independent of the pathway, then the approach is equivalent to valuing the health states themselves.
QALYs from First Principles
To conclude this article, and to serve as a springboard for the other articles in this Special Issue, we identify nine assumptions that underlie the conventional QALY approach as used in societal resource allocation decisions (Table 2).
Table 2. Underlying assumptions of the conventional QALY approach
|1. A resource-allocation decision must be made.|
|2. The outcomes of the alternatives can be specified in terms of health states, changes, and durations.|
|3. Resources are limited, and each alternative has resource implications (costs).|
|4. A major objective of the decision-maker is to maximize health of the population, subject to resource constraints.|
|5. Health is defined as value-weighted time (QALYs) over the relevant time horizon.|
|6. Value is measured in terms of preference (desirability).|
|7. Each individual is risk neutral with respect to longevity and has utility that is additive across time.|
|8. Value scores (preferences) measured across individuals can be aggregated and used for the group|
|9. QALYs can be aggregated across individuals; i.e., a QALY is a QALY regardless of who gains/loses it|
First, a resource allocation decision has to be made.
Second, the health-related consequences of the alternatives can be specified in terms of health states, changes in health states, and durations of health states over time. All nonhealth consequences are either measured as economic costs and included in the numerator of the cost-effectiveness ratio, or are omitted from quantitative consideration as part of the cost-effectiveness analysis.
Third, resources are limited, and each alternative has an impact on the resources available, i.e., an opportunity cost.
Fourth, a major objective of the decision-maker is to maximize the health of the population subject to resource constraints.
Fifth, health is defined as value-weighted time, over the relevant time horizon.
Sixth, value is measured in terms of preference or desirability.
These six premises do not restrict the method used to specify or value the health outcomes used in QALYs. Next, we turn to some more restrictive (and controversial) assumptions that relate specifically to the conventional QALY concept.
Seventh, each individual is risk neutral with respect to longevity and has utility that is additive over time. Risk neutrality is needed to justify the calculation of quality-adjusted life expectancy, that is, the average value of the possible numbers of QALYs, each weighted by its probability of occurring. Additivity over time, discussed previously, is the assumption that allows us to focus on valuing health states at points in time, without regard to their duration or sequence. These are very strong assumptions about preference that undoubtedly simplify reality, but they are necessary in order for QALYs to represent an individual's utility function for health over time. To say that the empirical evidence is mixed as to whether those assumptions provide a serviceable approximation to reality is probably generous for QALYs. For the most part, the evidence is that most people are probably risk averse with respect to their own longevity (although as societal agents, they may be less so), and there is substantial evidence that additivity over time may or may not hold. For example, there is evidence that people can live with a health problem for a short time, but that its perceived impact on health is more severe the longer they have it. This phenomenon has been called “maximum endurable time”. On the other hand, there is also evidence that people can adapt to adverse health conditions. Either of these behaviors would violate the assumption of additivity of utility or disutility over time, albeit in opposite ways.
Eighth, the value scores or preferences measured across individuals can be aggregated and used for the group. Finally, the QALYs calculated using the aggregated preference weights can themselves be aggregated across individuals.
Other Issues Surrounding QALYs: Discounting and Equity Weighting
QALYs as the valued outcome for purposes of societal resource allocation decision-making in health, as in other areas of policy, should reflect positive time preference or discounting. Discounting of both costs and QALYs, and at the same rate, is now the conventional assumption and is recommended by both the US Panel and by NICE. Despite the convergence of views in these two countries, there remain some controversies around discounting. In some countries, such as The Netherlands, the prevailing view is that costs should be discounted at a higher rate than QALYs. There is also the position that QALY should not be discounted at all if risk neutrality holds. The argument for discounting QALYs is driven largely by the opportunity cost argument, as espoused by the US Panel , and yet, a key assumption is that people as individuals are risk neutral and that QALYs are valued equally over time. This continues to be a dilemma that remains to be fully resolved.
Issues of equity and fairness are not incorporated quantitatively into the conventional QALY approach, beyond the basic assumption that each QALY across individuals gets equal weight. This does not mean that these issues are not important, but it does mean that they should be weighed by the decision-maker as additional considerations alongside aggregate QALY gains. Aggregate health gains, measured by conventional QALYs, are one of many inputs to the processes of individual clinical decision-making, societal or programmatic audit, or resource allocation. The other considerations, including equity and fairness, need to be considered separately in the conventional QALY approach. Examples of these aspects include age of the target population, the baseline health status of the target population, and, perhaps, the principle that there is more value in raising the minimum health in the population than in increasing average health by further improving the health of more healthy people. Political considerations may also compete with aggregate health improvement for a decision-maker's priority at the population level. There may be a felt need to give more priority to orphan diseases, to curing identifiable patients compared to preventing statistical disease, or to caring for the very youngest and oldest segments of the population because they are regarded as most vulnerable.
QALYs have made an important contribution to decision-making within the health field. Within the qualifications noted above, the conventional QALY remains a powerful conceptual tool that we believe can lead to improved decision-making. QALYs help to make choices, but there are many other dimensions to decision-making within the health-care arena, dimensions not covered by the conventional QALY. Nevertheless, the conventional QALYs are not intended to incorporate all concerns of decision-makers . Given the assumptions and the difficulties posed in measurement, it is important to maintain caution in the use of the QALY. It is nonetheless our view that the conventional QALY retains an important role in health-care decision-making.
We gratefully acknowledge the contributions to the content of this article gained through discussions with Norman Daniels, Mark Kamlet, and Erik Nord as members of the working group on theoretical foundations of QALYs.
Source of financial support: Funding for the ISPOR “Building a Pragmatic Road: Moving the QALY Forward” Consensus Development Workshop was made possible in part by grant 1R13 HS016841-01 from the Agency for Healthcare Research and Quality. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the US government. Funding for this Value in Health Special Issue, “Moving the QALY Forward: Building a Pragmatic Road” was made possible in part by Contract No. HHSN261200800148P from the National Cancer Institute.
Milton Weinstein, George Torrance, and Alistair McGuire have no conflicts to declare.