bluuebunny/crossref_metadata_2025 huggingface dataset:
Approach to clinical care in humanitarian contexts
Authors: Venugopal Raghu
Published: January 2019

This chapter on the approach to clinical care in humanitarian contexts outlines the fundamentals of providing care in humanitarian settings, including overall guidance on clinical care, key aspects of patient triage, and approaches for paediatrics. It providers important overarching considerations for readers, recognizing the realities and challenges in providing care in the field.
Mass casualty triage
Authors: Giannou Christos , Turnbull Jennifer
Published: January 2019

This chapter on mass casualty triage outlines the fundamentals of providing care in humanitarian settings, including overall guidance to clinical care, key aspects of patient triage, including the rationing of care based on priority for treatment, and approaches for paediatrics. It clarifies the differences between medical triage and mass casualty triage, describes the process of balancing needs with the resources available, recognizing situations where large numbers of patients overwhelm resources, and discusses triage models and organization, triage teams, and triage algorithms.
Patient with unintentional weight loss
Authors: Maskalyk James
Published: January 2019

This chapter outlines the reality in many humanitarian settings, where low resources and limitations in human resources, diagnostics, and infrastructure make the controlled diagnostic process more challenging, supporting a more symptomatic approach to diagnosis and management. This chapter outlines the key principles of syndromic case management, including essential components of clinical assessment, development of differential diagnoses, and flow charts for management for the most commonly encountered conditions and most important causative agents. The management principles contained in this chapter are adapted for humanitarian settings and provide opportunities for capacity building when highly trained local human resources may be scarce.
Diarrhoea and vomiting
Authors: Moons Peter , Buard Vincent , Venugopal Raghu
Published: January 2019

This chapter outlines the reality in many humanitarian settings, where low resources and limitations in human resources, diagnostics, and infrastructure make the controlled diagnostic process more challenging, supporting a more symptomatic approach to diagnosis and management. This chapter outlines the key principles of syndromic case management, including essential components of clinical assessment, development of differential diagnoses, and flow charts for management for the most commonly encountered conditions and most important causative agents. The management principles contained in this chapter are adapted for humanitarian settings and provide opportunities for capacity building when highly trained local human resources may be scarce.
Tuberculosis and HIV in humanitarian contexts
Authors: Saranchuk Peter
Published: January 2019

This chapter outlines the fundamentals of tuberculosis (TB) and human immunodeficiency virus (HIV) as seen in humanitarian settings, including disease assessments, approach to diagnosis, treatment, and monitoring. It outlines the epidemiological background and interconnectivity of the two infections, the high burden of both diseases in many humanitarian settings, and the advantages of addressing TB and HIV in a coordinated manner. It provides detailed clinical management guidance including diagnosis, clinical management options, opportunistic infections, treatment monitoring, and prevention.
Venomous animal bites and stings and marine poisoning
Authors: Warrell David A.
Published: January 2019

This chapter provides the reader with essential information on venomous animals, and the risk they may pose in many humanitarian settings, especially in rural, remote, and tropical settings. Humanitarian providers will have the responsibility of preventing and treating venomous bites and stings both in the local community as well as among their team members, and this chapter provides the necessary information to help guide planning, decision-making, and management.
Response to epidemic disease
Authors: Pegg AnneMarie
Published: January 2019

This chapter describes the explosive impact epidemic diseases can have in the humanitarian setting, and outlines four principal diseases with epidemic potential in humanitarian settings (cholera, dysentery, measles, and meningitis). It covers the fundamental precipitants of infectious disease spread in humanitarian settings, including displacement, disruption of the local health services, and overcrowding, and the important principles to prevent spread, such as advance planning, hygiene measures, surveillance, and response.
Cardiac conditions
Authors: Kassam Saleem
Published: January 2019

This chapter outlines the spectrum of cardiac conditions seen in humanitarian and low-resource settings, including acute and chronic conditions, and presentations not commonly seen in more developed settings. The chapter offers providers guidance for the recognition and management of the most common cardiovascular conditions found in humanitarian settings, including infectious, degenerative, and congenital conditions.
Chronic non-communicable diseases
Authors: Boulle Philippa , Aloudat Tammam
Published: January 2019

With approximately 80% of non-communicable disease (NCD) mortality occurring in low- and middle-income countries, and a prevalence expected to continue trending upwards, this chapter lays out the essential information on the burden of NCDs and their importance in humanitarian settings. It outlines the general principles of NCDs, including their widespread prevalence and contribution to preventable morbidity and premature mortality. It provides specific guidance for the clinical recognition and care of the main NCDs (cancer, chronic respiratory diseases, diabetes, thyroid disease, haemoglobinopathies, and renal disease), including management guidance which recognize the realities and often limited resources in the field.
Palliative care
Authors: O’Neill Joseph
Published: January 2019

This chapter covers a fundamentally important and often overlooked area of medicine, and outlines how even in humanitarian crises palliative care principles should be applied to relieve suffering for those with life-threatening illness. As not all humanitarian situations allow comprehensive textbook palliative care services for all patients, this chapter provides the underlying principles of palliation, implementation in low-resource environments, and key management components to allow adoption in varying contexts.
Wound care and minor surgical procedures
Authors: Beveridge Massey
Published: January 2019

This chapter provides essential management guidance for medical providers in low-resource environments when surgical services are not readily available. ‘Wound care and minor surgical procedures’ serves as a refresher for the management of minor surgical conditions commonly encountered, such as active external bleeding, chest tube insertion, abscess drainage, and emergency cricothyroidotomy, which can adequately be dealt with by the medical provider.
Orthopaedics and limb injuries
Authors: Rowley David
Published: January 2019

This chapter provides essential management guidance for medical providers in low-resource environments when surgical services are not readily available. ‘Orthopaedics and limb injuries’ provides information on the simple techniques that can be applied by any doctor in the management of bone and joint trauma and infection.
Medical waste management
Authors: Van den Noortgate Joos , Van den Bergh Rafael , Maes Peter
Published: January 2019

This chapter on medical waste management outlines the principles of waste management as essential determinants of health, quality of life, and dignity. It describes the principles of healthcare waste management and based on extensive implementation experience, offers a pragmatic adaptation of approaches most suitable for low-income countries.
A New Psychopharmacology Nomenclature
Authors: Ghaemi S. Nassir
Published: January 2019

An innovative textbook of psychopharmacology would fail if it continued to use false and outdated terminology for drug classes. All these terms began as clinical shorthand in the 1960s for possible clinical effects of an exciting new crop of medications, most of whose mechanisms were unknown. The uneducated guesses of that era have been reified into phrases that patients and clinicians use as if they are true. This chapter provides a new classification system for psychotropic drugs, based on biological mechanisms, that is considered more accurate scientifically and more neutral clinically than the current system based on purported clinical indications. Terms like “antipsychotic” and “antidepressant” are misleading clinically and invalid scientifically, since those agents often are more or less effective than those names imply. A mechanism-based classification is neutral, allowing clinical decisions to be based on clinical research data, not the linguistic implications of drug class terminology.
Maintenance Treatment Designs
Authors: Ghaemi S. Nassir
Published: January 2019

Proof of the long-term efficacy with medications is based on maintenance clinical trial designs. Such maintenance studies in psychiatry tend to be “enriched” for the preselection of acute treatment responders. In short, drug responders are preselected, and then they are studied for drug response. The approach taken is tautologous, and it does not test drug efficacy validly. The reasons for this judgment are provided. If this critique is valid, then most psychotropic drugs have not been proven to be effective long-term based on scientifically valid data. This conclusion holds especially for antidepressants in “major depressive disorder” and for antipsychotics in bipolar illness.
Monoamine Agonists (“Antidepressants”), Including Dopamine Agonists (“Stimulants”)
Authors: Ghaemi S. Nassir
Published: January 2019

The drug class of monoamine agonists includes agents called antidepressants and stimulants. Monoamine agonists are the most widely used class of psychotropic drugs. There are three major monoamines, and thus three main types of monoamine agonists. We consider each in turn: the serotonin reuptake inhibitors (SRIs), norepinephrine reuptake inhibitors (NRIs), and dopaminergic agents. We also discuss the dopamine agonists—bupropion (Wellbutrin) and amphetamines (“stimulants”), as well as other new monoamine agonists. The clinical pharmacology of specific agents within each class, including their efficacy and side effects, is explored. Specific phenomena surveyed include SRI tolerance, sexual dysfunction, drug interactions, serotonin withdrawal syndrome, and suicide and akathisia.
Other Agents (Glutamate Antagonists, Antihistamines, Melatonin Agonists, and Others)
Authors: Ghaemi S. Nassir
Published: January 2019

A final drug class of other agents includes glutamate antagonists, antihistamines, and melatonin agonists. These agents have a range of clinical uses, but most are used symptomatically to produce sedation or reduce anxiety or for other symptoms. The clinical pharmacology of specific agents within each class, including their efficacy and side effects, is explored. Specific phenomena surveyed include the inefficacy of novel anticonvulsants for mood: clinicians and researchers have been excited about novel anticonvulsants, most of which have either anti-glutamate or pro-GABA effects. None have proven effective for affective illness or for any important psychiatric use, except perhaps for some mild anxiolytic effects for the GABAergic agents. The purported benefits of ketamine are also investigated.
Drug Class Summaries and Dosing Guidelines
Authors: Ghaemi S. Nassir
Published: January 2019

A “mood stabilizer” is a drug that prevents mania and depressive episodes in bipolar disorder. The four drugs that have reasonable evidence that they can do this are lithium, Depakote, carbamazepine, and Lamictal. Second generation antipsychotics are not mood stabilizers, despite the FDA maintenance indications that many have received, because of the invalidity of the enriched, randomized, discontinuation maintenance design. Thus, all patients with bipolar illness should receive one of those four mood stabilizers, and dopamine blockers should be used as adjuncts, but not by themselves. In this chapter, a summary is given of the major drug classes, and the agents within those classes. Specific dosing guidelines are provided for most agents. Main clinical side effects and drug interactions are reviewed.
Beyond Symptoms
Authors: Ghaemi S. Nassir
Published: January 2019

The four classic diagnostic validators of psychiatry are appraised: symptoms, course, genetics, and treatment response/biological markers. Of these, course of illness is seen as the most important and the most neglected. The non-specificity of treatment response and the inadequacy of symptoms is emphasized. If symptoms are not the primary target for drug treatment, as the Hippocratic tradition teaches, then diagnosis becomes extremely important for the practice of clinical psychopharmacology. The role of genetics is important, but it is limited to highly genetic diseases. Related to DSM-5 and its predecessors, the application of these diagnostic validators demonstrates that most DSM diagnoses are not valid.
Schizophrenia and Schizoaffective Conditions
Authors: Ghaemi S. Nassir
Published: January 2019

The diagnosis and treatment of schizophrenia has a long history, with interesting diagnostic aspects, and slow but consistent work on treatment. In this chapter, diagnostic aspects of schizophrenia and schizoaffective illness are examined first, followed by further discussion of treatment with modern dopamine blockers. Despite an extensive research database, it is unfortunately true that most treatments for schizophrenia are symptomatic and modest in effect. They are important, but they have not had extensive benefit in modifying the disease or altering the course of the illness, unlike the larger benefits seen with lithium and mood stabilizers in bipolar illness. The extent to which the dopamine blockers are helpful in schizophrenia, and not, requires careful discussion. Harm with dopamine blocker medications is found in available neuroimaging data on the brain. More benefit is found in schizoaffective presentations than in classic schizophrenia.
Carcinogenicity of Psychotropic Drugs
Authors: Ghaemi S. Nassir
Published: January 2019

The use of psychotropic medications has dramatically increased over the past two decades, especially with serotonin reuptake inhibitors and amphetamines. The majority of U.S. prescriptions for psychotropic drugs happen at the primary care level, usually for anxiety and depressive symptoms and their physical correlates. Given the extensive use of these agents, carcinogenic risk should be carefully weighed when prescribing long-term drug therapies. Some psychotropic drugs have some evidence of carcinogenicity based on animal (preclinical) studies. Other agents do not have such evidence. Whether such risk extends into long-term human use is unclear. The animal data are summarized here and available human data also are investigated.
Children
Authors: Ghaemi S. Nassir
Published: January 2019

In this chapter, other aspects of psychopharmacological treatment of children are considered, specifically for diagnoses or symptoms of depression, manic states, anxiety, and behavioral problems, as well as autism and OCD. The occurrence of psychiatric symptoms in children does not reflect static disease entities, usually, but rather either diseases in process, which become evident in their final state in adulthood, or other social and cultural factors, such as abuse, trauma, and neglect. Attention deficit disorder (ADD) is not a disease in itself, usually, but rather a mistaken diagnosis when distractibility or impulsivity is caused by mood illnesses or anxiety states. Long-term randomized data with amphetamines indicate no greater functional benefit than with psychosocial interventions for ADD. Notable harms exist, including stunted height and possible neurotoxicity.
Ethnic and Racial Groups
Authors: Ghaemi S. Nassir
Published: January 2019

In specific ethnic and racial groups, there may be differences in response to psychotropic medications, partly based on pharmacogenetic differences, but also due to cultural variations in the experience of psychiatric symptoms. These differences should be taken into account when extrapolating from research conducted mostly in the United States and Europe. Most research on psychotropic medications has been conducted in Western industrialized countries, mostly on Caucasians. It is reasonable to ask about the relevance of this research to other ethnic and racial groups. In Western countries, specifically, African-Americans, Hispanics, and Asians have been the most studied of these. There is limited research in Africa and the Middle East on the effects of psychotropic medications. In this chapter, available research will be reviewed with a focus on its relevance for clinical treatment as well as on diagnostic aspects.
Polypharmacy
Authors: Ghaemi S. Nassir
Published: January 2019

“Polypharmacy” means the prescription of multiple medications at once. Sometimes this is justified, sometimes not. Some clinicians prefer the term “co-therapy” or something of that ilk to justify the practice. In this chapter, the term “polypharmacy” is retained and evidence for harms as well as benefits are examined. Polypharmacy reflects the observation that psychotropic agents often are given in combination with other agents. The clinical research evidence for such combinations tends to be small. The practice of polypharmacy historically reflects treatment in the setting of limited scientific evidence for benefit of the treatments given. The medical tradition of Oliver Wendell Holmes and William Osler argues against polypharmacy and for therapeutic conservatism when scientific evidence for treatment efficacy is limited or absent.
Treatment versus Enhancement
Authors: Ghaemi S. Nassir
Published: January 2019

The concept of “treatment” is based on a “biomedical” model of disease. In this model, illness represents a breakdown of the physical constituents of the body, leading to a functional loss of a capacity to perform typical activities of the organism. The proponent of the “enhancement” approach to the therapy of depression comes at the problem from other disease models. Any of the alternative non-biomedical models imply the conclusion that therapeutic interventions in depression should seek to enhance the functioning of the individual, rather than simply to permit redress of loss of functioning. Therefore, besides using psychotropic drugs for treatment of symptoms, many patients and clinicians seek psychotropic drugs to enhance normally variable psychological traits. This enhancement approach to practice appears to be most active in relation to the use of amphetamines to heighten attention, energy, and libido, as well as to lose weight. The use of psychotropic agents for such nonmedical uses raises some ethical questions, as well as contradicting the Hippocratic tradition of focusing medication treatment on diseases.
The “Med Check”
Authors: Ghaemi S. Nassir
Published: January 2019

A major myth in contemporary psychiatry, repeated by psychiatry residency directors and their residents, is the cliché “ ‘Psychopharm’ is easy; psychotherapy is hard.” The truth is that learning psychopharmacology is as hard as learning psychotherapy—perhaps harder, because it entails not only knowledge about medications, but knowledge and skill about diagnosis, about interviewing, and about relating to the patient. The follow-up psychopharmacology visits occur after the initial diagnostic interview. Often pejoratively called “med checks,” such visits tend to consist of brief symptom assessments, followed by pill adjustments for symptoms. Pill-for-symptom treatment is poor psychopharmacology, and therefore an inappropriate focus. Instead, follow-up visits need to be long enough to allow for attention to the interpersonal relationship, such as transference. Again, the use of psychotherapeutic methods is helpful. Such an approach will enhance adherence, the lack of which is a major aspect of treatment failure.
Clinical Cases
Authors: Ghaemi S. Nassir
Published: January 2019

Seventeen case reports are provided applying the principles described in this volume, including the following triad of principles: 1. Treat diseases, not symptoms. 2. Do not use DSM-based diagnoses. 3. Focus on the course of the illness, not just its symptoms, when you are making diagnoses. In addition, specific pharmacological aspects of medications as used in practice are explored in the context of specific cases—mood illnesses; PTSD; personality states; purported ADD; seasonality in affective illness; stopping antidepressants for “depression”; first depression in a young adult; pre-adolescent depression versus bipolar illness; when benzodiazepines are preferable to SRIs for anxiety; hyperthymia misdiagnosed as treatment-resistant depression; premenstrual mood dysphoric disorder; low-dose divalproex for misdiagnosed narcissistic personality disorder; suicidality and antidepressants in borderline personality—and more.
Reflections on the Art of Psychopharmacology
Authors: Ghaemi S. Nassir
Published: January 2019

A number of aphorisms are provided by thinkers and clinicians that relate to the practice of psychopharmacology.
Towards the best kidney failure prediction tool: a systematic review and selection aid
Authors: Ramspek Chava L , de Jong Ype , Dekker Friedo W , van Diepen Merel
Published: January 2019

Background

Prediction tools that identify chronic kidney disease (CKD) patients at a high risk of developing kidney failure have the potential for great clinical value, but limited uptake. The aim of the current study is to systematically review all available models predicting kidney failure in CKD patients, organize empirical evidence on their validity and ultimately provide guidance in the interpretation and uptake of these tools.

Methods

PubMed and EMBASE were searched for relevant articles. Titles, abstracts and full-text articles were sequentially screened for inclusion by two independent researchers. Data on study design, model development and performance were extracted. The risk of bias and clinical usefulness were assessed and combined in order to provide recommendations on which models to use.

Results

Of 2183 screened studies, a total of 42 studies were included in the current review. Most studies showed high discriminatory capacity and the included predictors had large overlap. Overall, the risk of bias was high. Slightly less than half the studies (48%) presented enough detail for the use of their prediction tool in practice and few models were externally validated.

Conclusions

The current systematic review may be used as a tool to select the most appropriate and robust prognostic model for various settings. Although some models showed great potential, many lacked clinical relevance due to being developed in a prevalent patient population with a wide range of disease severity. Future research efforts should focus on external validation and impact assessment in clinically relevant patient populations.
A 4-Day Incubation Period of Plasmodium falciparum Infection in a Nonimmune Patient in Ghana: A Case Report
Authors: Orish Verner , Afutu Leslie , Ayodele Oladapo , Likaj Lorena , Marinkovic Aleksandra , Sanyaolu Adekunle
Published: January 2019

Plasmodium falciparum can cause severe infection and has the shortest incubation period compared with all the other Plasmodium species. Incubation periods of 9–14 days for the immune and 6–14 days for the nonimmune have been reported for P. falciparum. However, an incubation period of less than 5 days has not been reported, as of yet. This report presents a case of a 23-year-old nonimmune female who presented with signs and symptoms 4 days after being bitten by mosquitoes while visiting Ghana. The patient was successfully treated with a 1-day course of parenteral artesunate, followed by a 3-day course of oral artemisinin combination therapy.
Sweden’s Parliamentary Democracy at 100
Authors: Lindvall Johannes , Bäck Hanna , Dahlström Carl , Naurin Elin , Teorell Jan
Published: January 2019

This article assesses how Swedish parliamentary democracy works today, almost one hundred years into its history. Our main research question is whether the transformation of the Swedish party system since the 1980s—and especially since 2010, when the populist-radical-right Sweden Democrats entered parliament—has altered the way parliamentary democracy works. We provide new evidence on Sweden’s changing party system, the formation and duration of cabinets, decision-making in parliament and the relationship between what parties say in election campaigns and what they do in government. Our main conclusion is that at least by the election of 2018, surprisingly little had changed. Cabinets have formed quickly, and once formed, they have survived until the next election. The bills governments have sent to parliament have usually passed, often getting the support of one or more opposition parties. Governing parties have managed to implement approximately 80 per cent of the promises they have made in their election manifestos. That said, the relationship between the executive and the legislature was contested in the 2010–2014 and 2014–2018 parliaments, and after the election of 2018, it took a very long time to form a new government. The concluding section discusses what the future might hold.
Are Less Developed Countries More Exposed to Multinational Tax Avoidance? Method and Evidence from Micro-Data
Authors: Johannesen Niels , Tørsløv Thomas , Wier Ludvig
Published: January 2019

This paper uses a global dataset with information about 210,000 corporations in 142 countries to investigate whether tax avoidance by multinational firms is more prevalent in less-developed countries. The paper proposes a novel approach to studying cross-border profit shifting, which has relatively low data requirements and is therefore particularly well-suited for the context of developing countries. The results consistently show that the sensitivity of reported profits to profit-shifting incentives is negatively related to the level of economic and institutional development. This may explain why many developing countries opt for low corporate tax rates in spite of urgent revenue needs and severe constraints on the use of other tax bases.
Alcohol Drinking in Chinese Methadone-maintained Clients: A Self-medication for Depression and Anxiety?
Authors: Zhong Bao-Liang , Xu Yan-Min , Xie Wu-Xiang , Lu Jin , Yu Wen-Bo , Yan Jun
Published: January 2019

Objectives:

Unhealthy alcohol use is associated with negative health outcomes in clients attending methadone maintenance therapy (MMT) programs. However, debates exist regarding the methadone dose of drinkers, and little is known about the health outcomes of drinkers with other types of alcohol use. This study examined the drinking pattern and its association with methadone dose, and depressive and anxiety symptoms in Chinese clients undergoing MMT.

Methods:

A secondary data analysis was conducted with data from a large-scale cross-sectional survey of 549 clients of 3 MMT clinics in Wuhan, China. Depression, anxiety, and alcohol dependence were measured with Zung Self-rating Depression Scale, Zung Self-rating Anxiety Scale, and Alcohol Dependence Scale, respectively. Drinking pattern was assessed using 3 indicators: weekly amount of alcohol consumed, weekly frequency of alcohol consumed, and severity of alcohol dependence.

Results:

The prevalence of current drinking, hazardous drinking, regular drinking, and alcohol abuse/dependence was 29.0%, 10.4%, 14.2%, and 8.7%, respectively. In adjustment analyses, relative to nondrinkers, drinkers had significantly lower weight-based methadone dose (β = −0.136, P = 0.008); hazardous drinkers, irregular drinkers, and drinkers without alcohol abuse/dependence had less severe depression (β = −3.67, P = 0.004; β = −2.37, P = 0.034; β = −3.20, P = 0.001) and anxiety (β = −4.90, P < 0.001; β = −3.24, P = 0.006; β = −4.52, P < 0.001), but drinkers with alcohol abuse/dependence had more severe depression (β = 5.55, P < 0.001) and anxiety (β = 4.31, P = 0.005).

Conclusion:

In Chinese MMT clinics, drinkers may use alcohol to compensate for inadequate MMT and self-medicate negative emotions. Compared with nondrinkers, the severities of depression and anxiety were lower among drinkers without alcohol abuse/dependence, but higher among those with alcohol abuse/dependence.
Cardiac Remodeling and Reversible Pulmonary Hypertension During Pneumonitis in Rats after 13-Gy Partial-Body Irradiation with Minimal Bone Marrow Sparing: Effect of Lisinopril
Authors: Jacobs Elizabeth R. , Narayanan Jayashree , Fish Brian L. , Gao Feng , Harmann Leanne M. , Bergom Carmen , Gasperetti Tracy , Strande Jennifer L. , Medhora Meetha
Published: January 2019

Total-body irradiation causes acute and delayed toxicity to hematopoietic, pulmonary, cardiac, gastrointestinal, renal, and other organ systems. Angiotensin-converting enzyme inhibitors mitigate many of the delayed injuries to these systems. The purpose of this study was to define echocardiographic features in rats at two times after irradiation, the first before lethal radiation pneumonitis (50 d) and the second after recovery from pneumonitis but before lethal radiation nephropathy (100 d), and to determine the actions of the angiotensin-converting enzyme inhibitor lisinopril. Four groups of female WAG/RijCmcr rats at 11–12 wk of age were studied: nonirradiated, nonirradiated plus lisinopril, 13-Gy partial-body irradiation sparing one hind leg (leg-out partial-body irradiation), and 13-Gy leg-out partial-body irradiation plus lisinopril. Lisinopril was started 7 d after radiation. Echocardiograms were obtained at 50 and 100 d, and cardiac histology was assessed after 100 d. Irradiation without lisinopril demonstrated echocardiographic transient pulmonary hypertension by 50 d which was largely resolved by 100 d in survivors. Irradiated rats given lisinopril showed no increase in pulmonary artery pressures at 50 d but exhibited left ventricular remodeling. By 100 d these rats showed some signs of pulmonary hypertension. Lisinopril alone had no impact on echocardiographic end points at either time point in nonirradiated rats. Mild increases in mast cells and fibrosis in the heart were observed after 100 d following 13-Gy leg-out partial-body irradiation. These data demonstrate irradiation-induced pulmonary hypertension which was reversed in survivors of pneumonitis. Lisinopril modified cardiovascular remodeling to enhance survival in this model from 41% to 86% (p = 0.0013).
Delayed Effects of Acute Radiation Exposure (Deare) in Juvenile and Old Rats: Mitigation by Lisinopril
Authors: Medhora Meetha , Gao Feng , Gasperetti Tracy , Narayanan Jayashree , Khan Abdul Hye , Jacobs Elizabeth R. , Fish Brian L.
Published: January 2019

Our goal is to develop lisinopril as a mitigator of delayed effects of acute radiation exposure in the National Institute of Allergy and Infectious Diseases program for radiation countermeasures. Published studies demonstrated mitigation of delayed effects of acute radiation exposure by lisinopril in adult rats. However, juvenile or old rats beyond their reproductive lifespans have never been tested. Since no preclinical models of delayed effects of acute radiation exposure were available in these special populations, appropriate rat models were developed to test lisinopril after irradiation. Juvenile (42-d-old, prepubertal) female and male WAG/RijCmcr (Wistar) rats were given 13-Gy partial-body irradiation with only part of one hind limb shielded. Lethality from lung injury between 39–58 d and radiation nephropathy between 106–114 d were recorded. All irradiated-only juvenile rats were morbid from delayed effects of acute radiation exposure by 114 d, while lisinopril (24 mg m−2 d−1) started 7 d after irradiation and continued improved survival to 88% (p = 0.0015, n ≥ 8/group). Old rats (>483-d-old, reproductively senescent) were irradiated with 13-Gy partial-body irradiation keeping part of one leg shielded and additionally shielding the head in some animals. Irradiated old females developed lethal nephropathy, and all became morbid by 170 d after irradiation, though no rats displayed lethal radiation pneumonitis. Similar results were observed for irradiated geriatric males, though 33% of rats remained alive at 180 d after irradiation. Lisinopril mitigated radiation nephropathy in old rats of both sexes. Finally, comparison of delayed effects of acute radiation exposure between irradiated juvenile, adult, and old rats showed younger rats were more sensitive to delayed effects of acute radiation exposure with earlier manifestation of injuries to some organs.
Radiation Nephropathy in a Nonhuman Primate Model of Partial-Body Irradiation With Minimal Bone Marrow Sparing—Part 2: Histopathology, Mediators, and Mechanisms
Authors: Parker George A. , Cohen Eric P. , Li Na , Takayama Kyle , Farese Ann M. , MacVittie Thomas J.
Published: January 2019

Male rhesus macaques were subjected to partial-body irradiation at 10, 11, or 12 Gy with 5% bone marrow protection. Animals were euthanized when dictated by prospectively determined clinical parameters or at approximately 180 d following irradiation. Histological sections of kidney were stained with hematoxylin and eosin as well as a battery of histochemical and immunohistochemical stains. Histopathological alterations were centered on glomerular changes and fibrosis of glomeruli and the interstitial compartment. These changes were first noted in animals necropsied approximately 100 d postirradiation and continued in animals necropsied through the observation period. Glomerular changes included congestion, thrombosis, erythrocyte degeneration, capillary tuft dilation, fibrin deposition, altered quantity and dispersion pattern of von Willebrand factor, increased mesangial matrix, and mesangial deposits of material that stained positively with periodic acid-Schiff staining. Areas of interstitial and glomerular fibrosis, as demonstrated by Masson’s trichrome staining, were topographically associated with increased immunohistochemical staining for connective tissue growth factor, alpha smooth muscle actin, and collagen 1, but there was little staining for transforming growth factor beta. Fibrotic glomeruli had reduced microvascularity as demonstrated by reduced CD31 immunohistochemical staining. Vascular congestion was commonly noted in the region of the corticomedullary junction, and proteinaceous casts were commonly noted in cortical and medullary tubules. Longitudinal analysis of histopathological alterations provided evidence defining the latency, severity, and progression of delayed radiation-induced kidney injury.
Targeted Metabolomics Reveals Metabolomic Signatures Correlating Gastrointestinal Tissue to Plasma in a Mouse Total-body Irradiation Model
Authors: Jones Jace W. , Clifford Zachary , Li Fei , Tudor Gregory L. , Farese Ann M. , Booth Catherine , MacVittie Thomas J. , Kane Maureen A.
Published: January 2019

High-throughput, targeted metabolomics was used to identify early time-point small intestine and plasma metabolite markers of gastrointestinal acute radiation syndrome. The small intestine metabolite markers were cross correlated to plasma metabolites in order to identify minimally invasive circulating markers. The radiation exposure covered lethal and sublethal gastrointestinal acute radiation syndrome. The small intestine and plasma metabolite profiles were generated at 1 and 3 d postexposure following total-body irradiation. The small intestine and plasma metabolite profiles for mice receiving radiation at day 1 and 3 postexposure were significantly different from sham-irradiated mice. There were 14 metabolite markers identified at day 1 and 18 metabolite markers at day 3 that were small-intestine-specific plasma markers of gastrointestinal acute radiation syndrome. A number of the identified metabolites at day 1 were amino acids. Dysregulation of amino acid metabolism at 24 h post-total-body irradiation provides potential insight into the initial inflammatory response during gastrointestinal acute radiation syndrome.
Radiation Nephropathy in a Nonhuman Primate Model of Partial-body Irradiation with Minimal Bone Marrow Sparing—Part 1: Acute and Chronic Kidney Injury and the Influence of Neupogen
Authors: Cohen Eric P. , Hankey Kim G. , Farese Ann M. , Parker George A. , Jones Jace W. , Kane Maureen A. , Bennett Alexander , MacVittie Thomas J.
Published: January 2019

Acute and chronic kidney injury may occur after accidental prompt radiation exposures. We have modeled their occurrence in a nonhuman primate model. Subjects who are exposed to more than 5-Gy prompt irradiation are apt to show blood cell cytopenias and be treated with granulocyte colony-stimulating factors such as Neupogen® or Neulasta® to mitigate the hematologic injury of the acute radiation syndrome. Neupogen or Neulasta are now approved by the US Food and Drug Administration for this indication. This will significantly increase the number of survivors of acute radiation exposures who will be at risk for delayed effects of radiation exposure, which includes acute and chronic kidney injury. The primary objectives of the present two companion manuscripts were to assess natural history of delayed radiation-induced renal injury in a nonhuman primate model of acute, high-dose, partial-body irradiation with 5% bone marrow sparing to include the clinical and histopathological evidence and the effect of Neupogen administration on morbidity and mortality. In this study, 88 nonhuman primates underwent 10- or 11-Gy partial-body irradiation with 5% bone marrow sparing, of which 36 were treated with Neupogen within 1, 3, or 5 d postirradiation. All animals were followed up to 180 d after irradiation. Renal function and histology end points showed early acute and later chronic kidney injury. These end points were not affected by use of Neupogen. We conclude that use of Neupogen to mitigate against the hematopoietic acute radiation syndrome has no impact on acute or chronic kidney injury.
Switching to paliperidone extended release in patients with schizophrenia dissatisfied with previous olanzapine treatment
Authors: Si Tian Mei , Cai Shang Li , Zhuo Jian Min , Zhang Li Li
Published: January 2019

Objective:

This post hoc analysis of an open-label, single-arm, multicenter study was designed to assess the efficacy, safety, and tolerability of paliperidone extended release (ER) in Chinese patients with non-acute schizophrenia, after switching from olanzapine.

Methods:

Patients with schizophrenia who were dissatisfied with prior olanzapine treatment switched to flexible paliperidone ER (3–12 mg/day) based on clinical judgment. Change from baseline to week 12 in Positive and Negative Syndrome Scale (PANSS) total scores (primary endpoint), PANSS subscale scores, response rate, Clinical Global Impression-Severity (CGI-S) score, personal and social performance (PSP) scores, patient satisfaction with treatment score, change in sleep quality, level of daytime sleepiness and safety were evaluated.

Results:

Out of 118 enrolled patients, 95 (81%) completed the study. Mean duration of study was 76.9 (23.85) days. The primary endpoint, mean (SD) PANSS total score changed significantly from baseline to endpoint (−19.6 [18.71], P <.0001). Secondary endpoints including PANSS subscale score, PSP, patient satisfaction and daytime drowsiness also significantly improved (P <.001). Most commonly reported (≥1%) treatment-emergent adverse events were akathisia (n = 14 [12%]) and insomnia (n = 9 [8%]).

Conclusions:

Switching to flexible-dosed paliperidone ER in patients dissatisfied with prior olanzapine treatment achieved good efficacy and tolerability consistently over 12 weeks.
Etiology analysis of nonspecific chronic cough in children of 5 years and younger
Authors: Chen Xin , Peng Wan-Sheng , Wang Lei
Published: January 2019

This study aims to analyze the etiology of nonspecific chronic cough in children of 5 years and younger, in order to improve the diagnostic and treatment levels of pediatricians for nonspecific chronic cough in young children.

The clinical data of 85 cases of children of 5 years old and below, who suffered from nonspecific chronic cough between the period of January 2015 and August 2016 were retrospectively analyzed.

The etiology distribution of 85 cases of children with nonspecific chronic cough were as follows: 27 cases had cough variant asthma (31.8%), 32 cases had upper airway cough syndrome (37.6%), 16 cases had cough after infection (18.8%), 3 cases had gastroesophageal reflux cough (3.5%), 2 cases had allergic cough (2.4%), and 5 cases had unknown causes of cough (5.9%).

The main composition ratio of the etiology of chronic cough in children of 5 years old and below is as follows (in sequence): upper airway cough syndrome, cough variant asthma, and post infection cough.
Global gene expression analysis of cell-free RNA in amniotic fluid from women destined to develop preeclampsia
Authors: Jung Yong Wook , Shim Jung In , Shim So Hyun , Shin Yun-jeong , Shim Sung Han , Chang Sung Woon , Cha Dong Hyun
Published: January 2019

Preeclampsia (PE) is a disorder specific to pregnancy characterized by new-onset hypertension and proteinuria after 20 weeks of gestation. There is no definite treatment for PE except delivery of the placenta. The purpose of this study was to elucidate the biological pathways involved in the development of PE and to discover a novel biomarker for PE by performing global gene expression analysis of amniotic fluid cell-free RNA.

The participants were recruited from the Department of Obstetrics and Gynecology of CHA Gangnam Medical Center (Seoul, Korea) between March 2014 and February 2015. Eight samples were collected from 8 subjects at second trimester who were later diagnosed with PE. From the amniotic fluid samples, cell-free RNA extraction was performed and gene expression was analyzed using the GeneChip PrimeView Array. Transcriptome data previously analyzed by our group from 9 euploid mid-trimester amniotic fluid samples were used as the control for comparative analysis. Functional analysis of the probe sets was performed using the online Database for Annotation, Visualization, and Integrated Discovery (DAVID) toolkit 6.7.

We identified 1841 differentially expressed genes (DEGs) between the PE group and the control. Of these, 1557 genes were upregulated in the PE group, while 284 genes were upregulated in the control. The functional annotation of DEGs identified specific enriched functions such as “transport,” “signal transduction,” and “stress response.” Functional annotation clustering with enriched genes in the PE group revealed that translation-related genes, cell–cell adhesion genes, and immune-related genes were enriched. KEGG pathway analysis showed that several biological pathways, including the ribosome pathway and various immune pathways, were dysregulated. Several genes, including RPS29, IGF-2, and UBC, were significantly upregulated in PE, up to tenfold.

This study provides the first genome-wide expression analysis of amniotic fluid cell-free RNA in PE. The results showed that gene expression involving the ribosome pathway and immunologic pathways are dysregulated in PE. Our results will aid in understanding the underlying pathogenesis of PE.
Colorectal follicular lymphoma
Authors: Wang Mei-Lian , Chang Jiang , Huang Hua , Fu Wen , Niu Yi-chun , Lu Ming-Liang , Shrestha Shikha
Published: January 2019

Rationale:

Considering the low incidence of colorectal follicular lymphoma (FL) and its clinical features in endoscopic views, only a few studies have described the pathological diagnosis and treatment of this disease. This study aimed to reveal the overall process of clinical diagnosis and treatment of colorectal FL by conducting a case review.

Patient concerns:

A 27-year-old female presented to our department because of “severe bloody stool” lasting for more than 1 month. Her primary symptom was melena. Colonoscopy revealed widespread flat polyps with various immunophenotypes (CD10+, BCL2+, BCL6+, cyclin D1-, CD5-) in the colorectal area.

Diagnosis:

In accordance with manifestations on positron emission tomography–computed tomography (PET/CT), the patient was diagnosed with stage IV colorectal FL.

Interventions:

PET/CT reexamination after 2 courses of rituximab, cyclophosphamide, liposomal doxorubicin, vincristine sulfate, and hydroprednisone (R-CHOP) regimen and 3 courses of R-CHOP plus etoposide regimen for chemotherapy indicated a significant reduction in tumor burden. Subsequently, rituximab was administered alone in 2 treatment courses.

Outcomes:

Lesions on PET/CT disappeared after reexamination. No recurrence was observed within the 12-month follow-up period.

Lessons:

Colorectal FL is a rare disease with an inert clinical course and is common in the ileocecal area. Endoscopic views show multiple polyps. Interventional treatment is usually provided after observation of clinical symptoms or during disease progression. The disease has a relatively good prognosis.
Brain metastasis from ovarian clear cell carcinoma
Authors: Liu Ping , Liu Wei , Feng Yuhua , Xiao Xiangyu , Zhong Meizuo
Published: January 2019

Rationale:

Epithelial ovarian carcinoma (EOC) is the most common type of ovarian carcinoma, and the leading cause of female genital tract cancer-related deaths. However, brain metastasis (BM) of EOC is rare, with an incidence of only 1% to 2%. Ovarian clear cell carcinoma (OCCC), accounting for 5% to 25% of all EOC cases, has a poor prognosis compared with other epithelial cell type carcinomas.

Patient concerns:

We retrospectively analyzed the clinical data of a 62-year-old female, who was hospitalized with the main complaint of BM detection for 1 month. She was first diagnosed with ovarian cancer in 2004, and underwent a left oophorectomy. Three years later, the cancer metastasized to the other side, and she underwent a right oophorectomy, followed by 7 courses of platinum-based chemotherapy. She received regular follow-up, and tumor markers and pelvic imaging did not show any signs of progression until July 2012.

Diagnosis:

Combining the clinical manifestations with the results of radiological and pathological examinations, the findings were consistent with a diagnosis of BM from OCCC.

Interventions:

She received more than 20 courses of chemotherapy since July 2012. The BM was detected in 2016, and she underwent an intracranial lesion resection.

Outcomes:

Unfortunately, the patient went into a coma after the surgery, and passed away 1 month later.

Lessons:

For early detection of BM in long-term ovarian cancer, emphasis should be placed on the patient's neurological symptoms and signs as well as serum tumor marker changes. The combination of surgery, radiology, and chemotherapy may achieve long overall survival.