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Pharmacy benefit management (PBM) companies are the middlemen of the pharmaceutical industry, designing plans for sponsors and insurers and pushing the products of manufacturers. Their unique position can often create conflicts of interest, which has been the basis of much litigation. This article reviews the structure of the PBM industry and analyzes concerns arising from its handling of prescription drug pricing, manufacturer rebates and discounts, and mail order pharmacies. After surveying several legislative proposals, it concludes with a comprehensive outline for legislation to eliminate underhanded dealing in the industry and lower the cost of prescription drugs.
We report a fatal case of coxsackievirus B4 chronic infection in a 30-year-old woman with a diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disorder controlled by rituximab monotherapy for 3 years. Initially presenting as self-limited meningitis, the infection remained silent for 8 months before the sudden onset of fulminant myocarditis. Analysis of the complete genome showed that the same virus was responsible for both episodes.
In 1994, South Africa emerged as a leader in tobacco taxation among middle-income countries. From 1994 to 2009, sharp excise-tax increases, complemented by progressive tobacco-control legislation, led to major declines in smoking and significant revenue gains. However, since 2010, many of these gains have been reversed. The entry of small, locally based tobacco companies disrupted a previously stable market and contributed to a surge in illicit trade. Institutional failures, exacerbated by the tobacco industry's underhanded tactics, at the South African Revenue Service between 2014 and 2018, and the industry's conduct during the 20-week tobacco sales ban in 2020, further entrenched the illicit market. Since 2020, more than half of all cigarettes sold in South Africa are illicit, severely undermining tobacco taxation and other tobacco-control attempts. This paper offers a historical perspective on tobacco taxation in South Africa, to highlight lessons for other countries. It demonstrates that while well-designed tax policy can yield major health and revenue benefits, sustained success requires vigilance. An excise tax approach that targets tax incidence (ie, total taxes as a percentage of the retail price) must account for industry pricing strategies and allow for timely policy adjustments. Long-term effectiveness also hinges on strong enforcement, transparent supply chain regulation and safeguarding policy processes from industry influence. Across all aspects of tax policy, South Africa's experience underscores the need for governments to remain alert to an industry that will exploit any weakness for profit. Complacency can swiftly undo years of progress.
Cholangiocarcinoma (CCA) is a malignant biliary system tumor and the second most common primary hepatic neoplasm, following hepatocellular carcinoma. CCA still has an extremely high unfavorable prognosis, regardless of type and location, and complete surgical resection remains the only curative therapeutic option; however, due to the underhanded onset and rapid progression of CCA, most patients present with advanced stages at first diagnosis, with only 30 to 60% of CCA patients eligible for surgery. Recent innovations in medical imaging combined with the use of radiomics and artificial intelligence (AI) can lead to improvements in the early detection, characterization, and pre-treatment staging of these tumors, guiding clinicians to make personalized therapeutic strategies. The aim of this review is to provide an overview of how radiological features of CCA can be analyzed through radiomics and with the help of AI for many different purposes, such as differential diagnosis, the prediction of lymph node metastasis, the defining of prognostic groups, and the prediction of early recurrence. The combination of radiomics with AI has immense potential. Still, its effectiveness in practice is yet to be validated by prospective multicentric studies that would allow for the development of standardized radiomics models.
Unique compared with recent and prehistoric Homo sapiens, Neandertal humeri are characterised by a pronounced right-dominant bilateral strength asymmetry and an anteroposteriorly strengthened diaphyseal shape. Remodeling in response to asymmetric forces imposed during regular underhanded spear thrusting is the most influential explanatory hypothesis. The core tenet of the "Spear Thrusting Hypothesis", that underhand thrusting requires greater muscle activity on the right side of the body compared to the left, remains untested. It is unclear whether alternative subsistence behaviours, such as hide processing, might better explain this morphology. To test this, electromyography was used to measure muscle activity at the primary movers of the humerus (pectoralis major (PM), anterior (AD) and posterior deltoid (PD)) during three distinct spear-thrusting tasks and four separate scraping tasks. Contrary to predictions, maximum muscle activity (MAX) and total muscle activity (TOT) were significantly higher (all values, p<.05) at the left (non-dominant) AD, PD and PM compared to the right side of the body during spear thrusting tasks. Thus, the muscle activity required during underhanded spearing tasks does not lend itself to explaining the pronounced right dominant strength asymmetry found in Neandertal humeri. In contrast, during the performance of all three unimanual scraping tasks, right side MAX and TOT were significantly greater at the AD (all values, p<.01) and PM (all values, p<.02) compared to the left. The consistency of the results provides evidence that scraping activities, such as hide preparation, may be a key behaviour in determining the unusual pattern of Neandertal arm morphology. Overall, these results yield important insight into the Neandertal behavioural repertoire that aided survival throughout Pleistocene Eurasia.
To explore and quantify the physical and functional effects of stabilizing the torso with electrical stimulation of the paralyzed hip and trunk musculature after motor complete tetraplegia. Single-subject case study with repeated measures and concurrent controls. Academic outpatient rehabilitation center. Forty-four-year-old man with C4 American Spinal Injury Association grade A tetraplegia 20 years postspinal cord injury. A surgically implanted multichannel pulse generator and intramuscular stimulating electrodes to activate lumbar erector spinae, quadratus lumborum, and gluteus maximus muscles bilaterally. Outcomes assessed with and without stimulation included (1) spinal alignment and pelvic orientation, (2) pulmonary function and ventilatory volumes, (3) forward bimanual reaching distance, (4) seated stability and resistance to externally applied disturbances, (5) maximal force and speed of rowing-like movements, and the ability to (6) independently return to an erect seated position from full forward or lateral flexion and (7) roll in bed without assistance. Stimulation improved spinal convexity and kyphosis by 26 degrees and 21 degrees , reduced posterior pelvic tilt by 11 degrees , increased forced expiratory volume and vital capacity by 10% and 22%, and improved forward reach by more than 7cm. Average resistance to sagittal disturbances increased by more than 40% (P<.002), and mean force exerted during underhanded pulling more than doubled (P=.014) with stimulation. Restoration of upright sitting in both sagittal and coronal planes and bed turning was made possible through appropriately timed activation of the hip and trunk muscles. A neuroprosthesis for controlling the paralyzed torso can positively impact spinal alignment, seated posture, pulmonary function, trunk stability, and reach. Stimulation of hip and trunk muscles can improve performance of activities of daily living as well as enable independent wheelchair and bed mobility.
Because of a militant movement spearheaded by women in 1992, the sale and consumption of almost all types of potable alcohol is a criminal offense in Andhra Pradesh state in India. Previously, the government had supported a Varuna Vahini (Flood of Liquor) policy which saw the aggressive marketing of the alcoholic beverage "arrack" in rural areas. This policy resulted in revenue from the excise duty on liquor amounting to more than 10% of the state's annual budget in 1991-92. Political parties were also funded by underhanded financial contributions from the liquor industry. While the wisdom of a government-imposed prohibition is still being questioned, the political impact of the women's struggle is plain. The struggle began as individual groups of women tried to keep arrack out of their villages. The women joined forces because of their common experience of the destruction of their lives by arrack and because the government-financed literacy campaign was run by nongovernmental organizations who included in the literacy primers stories about women suffering at the hands of alcoholic husbands. The women were not opposed to alcohol itself but to the new packaging of the cheap beverage which made it readily available in remote locations where people had to trek miles for water. The women were furious that their husbands were spending all of their wages on the drink and were tired of being harassed by drunken husbands. The women focused on arrack suppliers and traders rather than on consumers, so they received the passive support of many men. The women restricted their activities to their own villages and enjoyed the support of the nongovernmental organizations, although the struggle was led by local women themselves. Now the struggle has passed from poor, rural women to middle class, urban women and men who espouse Gandhian ideals and demand total prohibition. Whether or not the women in the villages will be able to deal with the consequences of state-wide total prohibition, they have managed to shake the foundations of political power.
Skilled actions exhibit adjustment in calibration to bring about their goals. The sought-after calibrations change as a function of the environmental situation that stages the actions. In these experiments participants sat on one side of a rotating carousel and threw beanbags underhanded at a target fixed on the opposite side. Logically, aimed throwing in this situation involves adjustment to fit changes in limb dynamics (originating from Coriolis forces) and changes in perceived projectile kinematics (originating from the tangential velocity of thrower and target). We studied whether such adjustment involved one or multiple components of recalibration. An initial experiment showed that exposure to rotation while throwing beanbags produced a robust recalibration in the direction of underhanded throws as manifest in throwing at stationary targets from a stationary position. Following some initial decay this recalibration persisted and approached an asymptote. Subsequent experiments suggested two independent components of recalibration. One is based on limb dynamics and accounts for the initial decay. The other is based on the perceived projectile kinematics and accounts for the stable change in throwing direction. These results raised the question of how multiple components of recalibration of an action are related. We propose that movement components are independent and calibrated separately at different levels in the organization of an action.
Sepsis is a life-threating organ dysfunction caused by a dysregulated host response to infection. This study proposed a new tool, i.e. modified qSOFA, for the early prognostic assessment of septic patients. All cases of sepsis/septic shock consecutively observed in 2 years (January 2017-December 2018), at St. Anna University Hospital of Ferrara, Italy, were included. Each patient was evaluated with qSOFA and a modified qSOFA (MqSOFA), i.e. adding a SpO2/FiO2 ratio to qSOFA. Logistic regression and survival analyses were applied to compare the two scores. A total number of 1137 consecutive cases of sepsis and septic shock were considered. Among them 136 were excluded for incomplete report of vital parameters. A total number of 668 patients (66.7%) were discharged, whereas 333 (33.3%) died because of sepsis-related complications. Data analysis showed that MqSOFA (AUC 0.805, 95% C.I. 0.776-0.833) had a greater ability to detect in-hospital mortality than qSOFA (AUC 0.712, 95% C.I. 0.678-0.746) (p < 0.001). Eighty-five patients (8.5%) were reclassified as high-risk (qSOFA< 2 and MqSOFA≥ 2) resulting in an improvement of sensitivity with a minor reduction in specificity. A significant difference of in-hospital mortality was observed between low-risk and reclassified high-risk (p < 0.001) and low-risk vs. high-risk groups (p < 0.001). We demonstrated that MqSOFA provided a better predictive score than qSOFA regarding patient's outcome. Since sepsis is an underhanded and time-dependent disease, physicians may rely upon the herein proposed simple score, i.e. MqSOFA, to establish patients' severity and outcome.
Chronic pain has been traditionally defined by pain duration, but this approach has limited empirical support and does not account for chronic pain multidimensionality. Defining chronic pain solely by duration is based on the view that acute pain signals potential tissue damage, whereas chronic pain results from central sensitization in which pain is sustained after nociceptive inputs have diminished. Chronic urological pain is a prevalent condition, which can represent a major challenge to health care providers due to its complex aetiology and poor response to therapy. In most cases, clear signs of on-going tissue trauma, inflammation or infection are not present. Despite this, more underhanded pathophysiological mechanisms, affecting the urinary system or other pelvic organ systems (musculoskeletal, neurologic, urologic, gynaecologic) and some psychological aspects may be present. In this article, some pathophysiological aspects of visceral pain are discussed; the definition of 'chronic pain', the mechanism of action of drugs used in the treatment of pain and the rationale for association therapy are also reviewed.
Bribery is a complicated, multi-dimensional issue. Upon first glance, most westerners would immediately condemn it as an underhanded, unfair means of gaining an advantage in a competitive or legal situation, and so it is in virtually every case in the westernized world. However, the issue becomes much more complicated in the international context, particularly in developing nations, where giving and accepting bribes is often normal and expected. This paper serves to inform ethical decision-making in situations where the "right choice" is unclear with regards to bribery, primarily for individuals performing aid work in foreign countries with corrupt officials and police officers. In such contexts, a simple offering of food, money, or a small trinket may make the difference between a person being able to accomplish meaningful, life-changing work for the local populace or having that work significantly slowed at best and being thrown out of the country, robbed, or imprisoned in worse cases. The larger scale bribery issues in international business and the laws pertaining to them are also discussed.
The aim of the present study was to examine whether movement contingent sensory effects could be used to prime and facilitate motor performance on a ball-tossing task. The ball-tossing task was performed across two consecutive days, and consisted of an acquisition phase and a test phase. During the acquisition phase, participants (N = 30) practiced an underhanded ball tossing task to a near and far target (N = 360 total, n = 180 each distance). Tosses that landed near the target immediately produced an auditory feedback tone upon landing, with unique tones for both the near and far target. In the test phase, the auditory tones preceded the toss and served as imperative stimuli for the tossing task. The test phase consisted of three tossing conditions (corresponding, non-corresponding, and control) in which the participants responded to the tones by tossing the ball to either the corresponding or non-corresponding target associated with the tones during learning. Findings indicated that both accuracy and consistency of ball tossing improved when the toss was preceded by the corresponding auditory feedback associated with the successful execution of the action during learning. The present study extends previous research by showing that complex actions consisting of multiple degrees of freedom can be primed via movement contingent sensory effects. Furthermore, this study demonstrates that movement-effect priming can impact distal measures of motor performance (e.g., accuracy of tossing), as opposed to the features of movement production (e.g., response selection, initiation, and execution).
The aim of this study was to evaluate the prevalence of antiphospholipid antibodies (aPLs) in infertile women undergoing in vitro fertilization (IVF). From January 2012 to December 2017, 520 consecutive clinical records of infertile women undergoing IVF were evaluated. Among them, 100 consecutive clinical records of patients with positive autoantibodies were selected. In 100/520 (19.23%) women, positive auto-antibodies were detected: 35/520 (6.73%) fulfilled classification criteria for a systemic disease. Positive aPLs were observed in 43 women (8.27%): 17/520 (3.27%) fulfilled diagnostic criteria for PAPS/APS, whereas patients with positive aPLs, who fulfilled diagnostic criteria for a systemic autoimmune disease other than APS were 18/520 (3.46%). LA and aCL were the main aPLs detected 53.49% and 44.19% respectively, whereas aB2GPI were found in 25.58%. we suggest that women with infertility may represent a subpopulation of patients with underhanded systemic autoimmune syndromes in which the main symptoms represented are obstetrical complications. We, therefore, recommend evaluating aPLs in all patients undergoing IVF with the aim of recognizing women at a higher risk of miscarriage or pregnancy morbidity.
Logically, and by most common standards, academics would be pleased to be cited, considering it a form of recognition of their intellect. In return, especially those with high citation counts, such as Clarivate Analytics' Highly Cited Researchers, can benefit through peer recognition, rewards, funding, securing a better position, or expanding a collaborative network. Despite known and untold benefits, one issue has not been discussed: the right to refuse to be cited or the right to refuse a citation. Academics might not want to be cited by papers published in truly predatory journals, papers with false authors, or sting papers with falsified elements that employ underhanded ethical tactics. Currently, academics generally have the freedom to select where they publish their findings and choose studies they cite, so it is highly probable that requests to remove citations or refuse citations might never become formal publishing policy. Nonetheless, this academic discussion is worth having as valid and invalid literature increasingly gets mixed through citations, and as the grey zone between predatory/non-predatory and scholarly/unscholarly becomes increasingly difficult to distinguish.
A textual analysis of post-World War II social psychology methodology manuals and handbook chapters on "methods" indicates that the introduction of the experimental method was enforced and gradually strengthened through the use of scientific rhetoric and the minimization of alternative research strategies. As a consequence, by the 1960s experimentation had become such an established identifying feature of psychological social psychology that the acceptability of ideas in the field came to depend largely on the ability of authors to couch them in the language of the experiment. Text writers continually shored up the defenses of scientific legitimacy and denigrated all other types of argument. We explore three sources of tension or strains evident as contradictions in these texts: (1) between a rational experimenter's carefully following prescribed, logic-generated scientific practices and the investigator's artfully or intuitively designing research; (2) between social psychologists' missionary activities of proselytizing the experiment as the primary research method and social psychologists' apologies and insecurities expressed about using experiments; and (3) between the treatment of participants as docile and submissive versus portraying them as underhanded and damaging to the outcome of the research. In addition, we briefly reexamine the strain (4) between sober scientific experimentation and a playful "fun and games" approach to experimentation (Lubek & Stam, 1995).
Objective: Investigate the current situation of lung cancer cough diagnosis and treatment and the awareness of related issues among Chinese medical providers. Methods: Doctors, nurses, pharmacists from the oncology department, respiratory department, or general department were investigated using an electronic questionnaire from January 29 to March 29, 2021. There were 25 questions about lung cancer in the questionnaire. The questionnaire was including the most common accompanying symptoms in patients with lung cancer, the incidence of lung cancer-related cough, the assessment of the proportion of central antitussive drugs, and the commonly used central antitussives. Results: Questionnaires from 2 424 medical providers were collected from 402 hospitals in 21 provincial administrative units. Cough was the most common symptom in lung cancer. Most physicians believed that the incidence of lung cancer-related cough was 51%~75%, while the proportion of patients satisfied with the treatment was only 11%~20%. The evaluation of lung cancer-related cough was seriously insufficient. The leading cause of lung cancer-related cough was tumors. And the main problem was the inadequate antitussive effect of drugs in lung cancer-related cough management. The proportion of central antitussive medication usage in the secondary and tertiary hospitals was 93.9% and 92.0%, significantly higher than 75.0% in Primary hospitals (χ²=8.390, P=0.015). The proportion of the physicians who underhanded that codeine is at risk of addiction was 76.6% and 72.0% in the secondary and tertiary hospitals, which were significantly higher than 53.9% in Primary hospitals (χ²=9.240, P=0.010). In different occupations, the proportions of doctors and pharmacists who knew the risk of addicting to codeine were 73.0% and 82.6%, which were significantly higher than the 66.4% of nurses (χ²=21.200, P<0.001). The Chinese medical providers were lack of training about the basic knowledge of using central antitussive medication. Conclusions: The proportion of patients who were satisfied with the effect of cough treatment is low. The medical staff did not have enough awareness of this. There was an urgent need to develop a consensus and standardize lung cancer cough diagnosis and treatment in China. 目的： 了解我国肺癌相关性咳嗽诊疗现状及医务人员对相关问题的认知情况。 方法： 2021年1月29日至3月29日，以电子问卷形式，对全国肿瘤科、呼吸科、全科等肺癌相关咳嗽诊疗科室的医师、护士和药师进行调研。除基本信息外，收集共计25个肺癌相关问题，包括肺癌患者最常见伴随症状、肺癌相关性咳嗽发生率及评估、中枢镇咳用药比例、常用中枢镇咳药等。 结果： 收集到全国21个省级行政单位、402家医院、2 424名医护人员的调查问卷。咳嗽是肺癌患者最常见的伴随症状，多数医师认为肺癌相关性咳嗽发生率为51%~75%，而对咳嗽治疗效果表示满意的患者比例仅为11%~20%。肺癌相关性咳嗽的评估严重不足，肿瘤相关因素是引起肺癌相关性咳嗽的主要原因。药物镇咳作用不够理想是目前肺癌相关性咳嗽管理的最主要问题。二、三级医院使用中枢镇咳药物比例分别为93.9%和92.0%，显著高于一级医院的75.0%，差异有统计学意义（χ²=8.390，P=0.015）。二、三级医院了解可待因存在成瘾风险的人员比例分别为76.6%、72.0%，显著高于一级医院的53.9%，差异有统计学意义（χ²=9.240，P=0.010）。不同职业中，了解可待因存在成瘾风险的医师和药师比例分别为73.0%、82.6%，显著高于护士的66.4%，差异有统计学意义（χ²=21.200，P<0.001）。关于中枢镇咳药物基本认知方面，医务工作者培训严重不足。 结论： 对咳嗽治疗效果表示满意的患者比例较低，医务人员对此认知不足，应尽快形成我国的肺癌相关性咳嗽诊疗共识和规范。.