Long-term Systemic Use Research Articles

Long-Term Systemic Use of Calcium Channel Blockers and Incidence of Primary Open-Angle Glaucoma

PurposeTo evaluate the association between the systemic use of calcium channel blockers (CCBs) and primary open-angle glaucoma (POAG) using a diverse nationwide dataset. DesignRetrospective cohort study Subjects213,424 individuals aged 40 years and older in the National Institutes of Health (NIH) All of Us dataset, notable for its demographic, geographic and medical diversity and inclusion of historically underrepresented populations. Patients with a diagnosis of POAG prior to use of any kind of anti-hypertensive medication were excluded. MethodsBivariate and multivariable regression analyses were performed to evaluate associations between CCB use and POAG. CCB use was further divided into exposure to dihydropyridine CCBs and non-dihydropyridine CCBs, and subgroup analyses were performed using Chi-square and Fisher’s tests. Main Outcome MeasuresDiagnosis of POAG ResultsWithin our cohort, 2,772 participants (1.3%) acquired a diagnosis of POAG, while 210,652 (98.7%) did not. Among patients who developed POAG, the mean age was 73.3 years, 52.5% were female, and 48.2% identified as White. Among POAG patients, 32.6% used one or more CCB, 28.2% used a dihydropyridine CCB, and 2.2% used a non-dihydropyridine CCB. In bivariate analysis, use of any CCBs was associated with an increased risk of POAG (OR: 1.29, 95% CI: 1.27-1.31, p<0.001). In multivariable analysis adjusting for age, gender, race, ethnicity, and comorbidities such as diabetes, hyperlipidemia, and hypertension, use of any CCBs remained associated with an increased risk of developing POAG (OR: 1.52, 95% CI: 1.33-1.74, p<0.001). When stratified by type of CCB, the use of dihydropyridine CCBs (OR: 1.31, 95% CI: 1.14-1.50, p<0.001) was associated with increased POAG risk. ConclusionsUse of dihydropyridine calcium channel blockers was associated with a significantly higher risk of developing POAG, both before and while adjusting for demographic factors and comorbid medical conditions.

Visual function loss in fungal sphenoid sinusitis: clinical characteristics and outcomes.

Potentially fatal fungal sphenoid sinusitis (FSS) causes visual damage. However, few studies have reported on its visual impairment and prognosis. Five hundred and eleven FSS patients with ocular complications treated at Beijing Tongren Hospital were recruited and clinical features and visual outcomes were determined. Thirty-two of the 511 patients (6%) had visual impairment, with 13 and 19 patients having invasive and noninvasive FSS, respectively. Eighteen patients (56.25%) had diabetes and 2 patient (6.25%) had long-term systemic use of antibiotics (n = 1) and corticosteroids (n = 1). All patients had visual impairment, which was more severe in invasive FSS than in noninvasive FSS. Bony wall defects and sclerosis were observed in 19 patients (59.38%), and 11 patients (34.38%) had microcalcification in their sphenoid sinusitis on computed tomography (CT). After a 5-year follow-up, three patients (9.38%) died. Patients with noninvasive FSS had a higher improvement rate in visual acuity than their counterparts. In the multivariate analysis, sphenoid sinus wall sclerosis on CT was associated with better visual prognosis. FSS can cause vision loss with persistent headaches, particularly in those with diabetes. CT showed the sphenoid sinus wall sclerosis, indicating a better visual prognosis in FSS with visual impairment.

Systemic Anticoagulation and Inpatient Outcomes of Pancreatic Cancer: Real-World Evidence from U.S. Nationwide Inpatient Sample.

Background: Pancreatic cancer can induce a hypercoagulable state which may lead to clinically apparent thrombosis. However, the effect of anticoagulants remains ambiguous. This study aimed to investigate the potential effect of long-term systemic anticoagulant usage on hospitalization outcomes of patients with pancreatic cancer. Methods: This retrospective study extracted all data from the U.S. Nationwide Inpatient Sample (NIS) database from 2005 to 2018. We included hospitalized adults ≥18 years old with a pancreatic cancer diagnosis identified by International Classification of Diseases ninth revision (ICD-9) and tenth revision (ICD-10) codes. We utilized diagnostic codes ICD9 V58.61 and ICD10 Z79.01, i.e., 'long-term use of anticoagulant', to identify individuals who were on a long-term systemic anticoagulant. The study cohort were then further grouped as being with or without long-term systemic use of an anticoagulant. Propensity score matching was performed to balance the characteristics of the two groups. The risks of life-threatening events, e.g., acute myocardial infarction (AMI), acute heart failure (AHF), sepsis, shock, and acute kidney injury (AKI), in-hospital death, and prolonged length of stay (LOS) in the hospital were compared between the groups by univariable and multivariable logistic regression analyses. Results: The study population consisted of 242,903 hospitalized patients with pancreas cancer, 6.5% (n = 15,719) of whom were on long-term systemic anticoagulants. A multivariable regression analysis showed that long-term systemic anticoagulant use was independently associated with lower odds of sepsis (aOR: 0.81, 95% CI: 0.76-0.85), shock (aOR: 0.59, 95% CI: 0.51-0.68), AKI (aOR: 0.86, 95% CI: 0.81-0.91), in-hospital mortality (aOR: 0.65, 95% CI: 0.60-0.70), and prolonged LOS (aOR: 0.84, 95% CI: 0.80-0.89). Conclusions: Long-term systemic anticoagulant use is associated with better clinical outcomes in terms of decreased risks of some life-threatening events, in-hospital death, and prolonged LOS among hospitalized patients with pancreatic cancer in the U.S.

Development and evaluation of a novel biodegradable implants with excellent inflammatory response suppression effect by hot-melt extrusion

PurposeDexamethasone (Dex) is a widely used drug for the treatment of inflammatory and autoimmune conditions, however, long-term systemic use of Dex is associated with serious adverse effects. The objective of the present study was to develop an implantable device to avoid side effects and realize a controlled release of Dex at the implant site. MethodsHydrophobic Dex was incorporated into biodegradable polyesters derived from PCL and Pluronic® L64 (PCL-Pluronic L64-PCL, PCLC) by hot-melt extrusion (HME) method to prepare Dex/PCLC implantable devices. Drug loading and encapsulation efficiency, a series of physicochemical properties, and in vivo features of the implants were studied. ResultsThe maximum value of the drug loading and encapsulation efficiency for the Dex/PCLC implants were up to 47% and 94%, respectively. Incorporation of Dex resulted in accelerated crystallization of PCLC, decreased the wettability, increased contact angles and viscosity, and accelerated Dex release rate and degradation rate from the implants in vivo. Moreover, Dex/PCLC implants showed excellent biocompatibility. Furthermore, the inflammatory response to the Dex/PCLC implants was less severe than that to the positive control group. ConclusionAll these results suggested that Dex/PCLC implants might be a safe and controlled local drug delivery system with excellent inflammatory response suppression effect.

Owner Perceptions of Long-Term Systemic Use of Subcutaneous Administration of Polysulfated Glycosaminoglycan.

Polysulfated glycosaminoglycan (PSGAG) is a slow-acting disease-modifying agent used to treat degenerative joint disease. Although labeled for intramuscular use, it is commonly given by owners via a subcutaneous (SC) route. There is little information on adverse events related to SC administration or what other therapies are used concurrently with PSGAG. We hypothesized that SC PSGAG is perceived by owners as having minimal adverse events and that it would most often be given with other therapies. Owners (n = 378) were surveyed about their perceptions regarding SC PSGAG prescribed to dogs at one veterinary rehabilitation clinic. Complete surveys were provided for 69 dogs (two owners had multiple dogs). Overall, 13/69 (18.8%) dogs had an adverse event reported during the use of PSGAG. Most events were considered minor (stomach upset, loose stool, pain at injection site, fear) and did not lead to discontinuation of PSGAG. One dog experienced a moderate adverse event (persistent gastrointestinal symptoms) and one a severe adverse event (thrombocytopenia, bruising), which resolved after discontinuing PSGAG. PSGAG is most commonly administered along with other medications and rehabilitation therapies. The present study demonstrates that SC administration of PSGAG is well tolerated in most of the dogs, with primarily mild, self-resolving adverse events.

Owner Perceptions of Long-Term Systemic Use of Subcutaneous Administration of Polysulfated Glycosaminoglycan.

Polysulfated glycosaminoglycan (PSGAG) is a slow-acting disease-modifying agent used to treat degenerative joint disease. Although labeled for intramuscular use, it is commonly given by owners via a subcutaneous (SC) route. There is little information on adverse events related to SC administration or what other therapies are used concurrently with PSGAG. We hypothesized that SC PSGAG is perceived by owners as having minimal adverse events and that it would most often be given with other therapies. Owners (n = 378) were surveyed about their perceptions regarding SC PSGAG prescribed to dogs at one veterinary rehabilitation clinic. Complete surveys were provided for 69 dogs (two owners had multiple dogs). Overall, 13/69 (18.8%) dogs had an adverse event reported during the use of PSGAG. Most events were considered minor (stomach upset, loose stool, pain at injection site, fear) and did not lead to discontinuation of PSGAG. One dog experienced a moderate adverse event (persistent gastrointestinal symptoms) and one a severe adverse event (thrombocytopenia, bruising), which resolved after discontinuing PSGAG. PSGAG is most commonly administered along with other medications and rehabilitation therapies. The present study demonstrates that SC administration of PSGAG is well tolerated in most of the dogs, with primarily mild, self-resolving adverse events.

A Cross-Session Dataset for Collaborative Brain-Computer Interfaces Based on Rapid Serial Visual Presentation.

Brain-computer interfaces (BCIs) based on rapid serial visual presentation (RSVP) have been widely used to categorize target and non-target images. However, it is still a challenge to detect single-trial event related potentials (ERPs) from electroencephalography (EEG) signals. Besides, the variability of EEG signal over time may cause difficulties of calibration in long-term system use. Recently, collaborative BCIs have been proposed to improve the overall BCI performance by fusing brain activities acquired from multiple subjects. For both individual and collaborative BCIs, feature extraction and classification algorithms that can be transferred across sessions can significantly facilitate system calibration. Although open datasets are highly efficient for developing algorithms, currently there is still a lack of datasets for a collaborative RSVP-based BCI. This paper presents a cross-session EEG dataset of a collaborative RSVP-based BCI system from 14 subjects, who were divided into seven groups. In collaborative BCI experiments, two subjects did the same target image detection tasks synchronously. All subjects participated in the same experiment twice with an average interval of ∼23 days. The results in data evaluation indicate that adequate signal processing algorithms can greatly enhance the cross-session BCI performance in both individual and collaborative conditions. Besides, compared with individual BCIs, the collaborative methods that fuse information from multiple subjects obtain significantly improved BCI performance. This dataset can be used for developing more efficient algorithms to enhance performance and practicality of a collaborative RSVP-based BCI system.

Dexamethasone Mechanism in Inflammatory Immune Mediated Disease and its Application in Treating 2019 Coronavirus Disease (COVID-19)

Since the very first medical use of dexamethasone (DEX) in 1958, this glucocorticoid (GC) has been widely used in various clinical applications. Compared to other GCs, DEX is highly potent and comes in multiple formulations for ease of local and systemic administrations. Recently, DEX has a new application for treating COVID-19 patients. DEX mainly inhibits expressions of inflammatory proteins and transcription factors necessarily for cell proliferation. DEX can both upregulate and downregulate expressions of the genes that facilitates anti- inflammatory effects and immunosuppression. Key proteins involved in DEX pathways are NF- B, AP-1, COX-2, and annexin A1. When used appropriately, DEX can minimize inflammatory pain and damage but it can also delay patient recovery by immunosuppression. Due to this duality, DEX should be used with caution for treatment considerations. Long-term systemic use could lead to debilitating adverse reactions and firm recommendations should be established in treating both acute and chronic disease with DEX.

Intra-articular leflunomide-loaded poly(ε-caprolactone) implants to treat synovitis in rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune pathology that manifests as chronic inflammatory arthropathy and synovitis. Treatment of rheumatoid arthritis is based on the administration of different types of drugs, including leflunomide, an antirheumatic drug. However, the long-term systemic use of leflunomide may be associated with adverse effects. Local therapy could be an efficient strategy to treat synovitis triggered by rheumatoid arthritis without inducing adverse effects. In this study, leflunomide-loaded poly(ε-caprolactone) implants (leflunomide PCL implants) were evaluated as local drug delivery systems capable of attenuating inflammation and angiogenesis, which represent events of synovitis. Leflunomide PCL implants were designed by hot molding technique; and they were characterized by FTIR and DSC. These analytical techniques demonstrated the chemical integrity and dispersion of drug into the polymeric chains. Then, a spectrophometric method was developed and validated to quantify the leflunomide incorporated into the PCL implants and released from them. Linearity was obtained by ordinary least squares regression method to estimate the linear regression equation. Residues were evaluated considering normality, independence and homoscedasticity. Precision was lower than 5 %, and accuracy ranged from 98 to 104.5 %. Quantitation limit was 2.0 μg mL-1. PCL implants provided controlled and sustained release of leflunomide for 30 consecutive days after inserting these systems in the subcutaneous tissue of mice. The main mechanisms of drug delivery were solubilization and diffusion from polymer. Then, a non-biocompatible sponge was inserted into the subcutaneous tissue of mice to function as a frame to develop the inflammatory and angiogenic processes. Leflunomide PCL implants were inserted in direct contact with the sponge. At 4, 7 and 10 days after-sponge implantation, the key components of inflammatory angiogenesis were measured to verify the regression of these events induced by drug. Leflunomide controlled released from polymeric implants downregulated the neutrophil and monocyte/macrophage infiltration due to the reduced expression of myeloperoxidase (MPO) and N-acetyl-β-d-glucosaminidase (NAG), respectively. As the influx of these pro-inflammatory cells was modulated by leflunomide, the production of nitric oxide (NO), a pro-inflammatory substance, reached low concentrations in the sponge. As a consequence of the modulation of inflammation at the pathological site, the angiogenic process was downregulated, since the hemoglobin levels in the sponge were drastically reduced. The accumulation of leflunomide in the pathological site did not induce nephrotoxicity or hepatototoxicity, as confirmed by histological analyses. Finally, intra-articular leflunomide PCL implants represent a potential therapeutic alternative to treat locally the synovitis triggered by rheumatoid arthritis without inducing systemic adverse effects.

The effectiveness of glucocorticoid hormones in the treatment of sensorineural disorders

Topicality: Effective treatment of acute sensorineural hearing loss is still relevant due to the fact that the number of diseases accompanied with impaired sound perceptions great, and the treatment outcome is often far from the desire done. Many researchers have noted the positive effect of systemic glucocorticoids in the treatment of acute hearing loss. Adverse effect sin case of long-term systemic use of hormones, such as insomnia, gastric ulcer, impaired glucose tolerance, arterial hypertension, etc., limitations or contraindications to their administration in patients with severe concomitant pathology, the existence of a hemato-perilymphatic barrier, which prevents penetration of glucocorticoids in to the inner environment of the ear, promote the wider use of intratympanic administration of hormones. The purpose of this study was to evaluate treatment effectiveness following intratympanic administration of glucocorticoid hormones in patients with acute sensorineural hearing loss and exudative otitis media. Materials and methods: Analysis was performed to compare treatment outcomes of 92 patients (the main group) with acute sensorineural hearing loss who were administered hormones intratympanically, with the treatment outcomes of 315 patients (the control group) receiving conventional therapy. Treatment outcomes of 23 patients with acute otitis media with effusion accompanied with combined hearing loss with a pronounced sensorineural component were analyzed. Results and discussion: As a result of the treatment, a statistically significant improvement in hearing was obtained in the main group compared to the control group. Of the 23 patients with otitis media with effusion who received the treatment, hearing has restored to the norm in 19 people, and the rest showed an improvement. Thus, intratympanic administration of glucocorticoids increases treatment effectiveness in patients with acute sensorineural hearing loss and helps to restore disturbed sound perception in the treatment of patients with otitis media with effusion.

A User-Centered Approach: Understanding Client and Caregiver Needs and Preferences in the Development of mHealth Apps for Self-Management.

BackgroundMany adolescents and young adults with chronic illness or disability often fail to develop the self-management skills necessary to independently handle medical and self-management routines. In light of these needs, we are developing iMHere 2.0 (Interactive Mobile Health and Rehabilitation), a mobile health (mHealth) system to support a self-management program.ObjectiveOur objective was to gather data from persons with brain and spinal cord anomalies (BSA) and their caregivers to better understand how mHealth would be most helpful in supporting them to proactively manage daily self-care routines and to access medical care as needed. The specific purpose was not only to gather feedback and to gain increased insight into the design of the new version of iMHere, but also to gather perspectives of new groups, namely adolescents as young as 12 years and their parents and/or caregivers.MethodsOur project employed focus group sessions and surveys to collect data from participants with BSA, as well as their caregivers. A total of six focus group sessions were conducted on four separate occasions until the data gathered reached saturation. The objectives of our focus group sessions were to better understand ways to develop mHealth systems to support self-management, to promote independence, to motivate long-term system use, and to prevent medical problems that lead to hospitalizations and emergency room visits for youth and young adults with BSA.ResultsA total of 16 youth and young adults with BSA and 11 caregivers participated in the sessions. Within and among our groups, the following five overarching themes emerged from the data: (1) make it easy, (2) engage, (3) educate and prepare, (4) motivate and support, and (5) personalize. Participants shared their perspectives and detailed information about mHealth apps that would be important for independence in self-care and self-management.ConclusionsOur findings suggest that most individuals keep their mobile phones with them at all times and typically use a mobile phone for social media, music, photos, and texting. Our qualitative analysis indicates that youth and young adults with BSA, as well as their caregivers, acknowledge the importance of being actively engaged in developing and using mHealth apps that monitor and manage their health care needs. Information gleaned from these focus group sessions and surveys have provided data to refine the iMHere 2.0 mHealth prototype platform that we have developed.

Preclinical Development and In Vivo Evaluation Of Next-Generation Compstatin Analogs With Improved Systemic Profiles: A Novel Option For The Treatment Of Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired orphan disease that is characterized by complement-mediated lysis of clonal populations of erythrocytes that lack glycosyl-phosphatidyl-inositol (GPI)-anchored complement regulators. Hemolysis and uncontrolled complement activation on affected platelets may contribute to the thrombophilia typical of PNH, which largely accounts for the morbidity and mortality of the disease. The introduction of the therapeutic antibody Eculizumab, which blocks activation of complement component C5, to the clinic has dramatically improved the treatment of PNH as it protects from hemolysis and possibly thromboembolisms; yet it also imposes high costs to the health care system. Moreover, while C5-targeted therapy efficiently impairs intravascular lysis of erythrocytes, it does not prevent their ongoing opsonization with activation fragments of complement component C3, thereby increasing the potential for extravascular lysis by immune cells. As a consequence, there is an unmet clinical need, and intervention at the level of C3 is expected to lead to a more comprehensive protection of PNH erythrocytes. Compstatin is a 13-residue disulfide-bridged peptide that selectively binds to human and primate forms of the central complement component C3 and its active fragment, thereby preventing the conversion of C3 to C3b which is essential for the functioning of all initiation, amplification, and terminal pathways of complement. Owing to their potent inhibitory activity of C3 activation, and due the comparatively low production costs of these peptidic drugs, compstatin analogs present an attractive option for the development of improved PNH therapeutics. Whereas early compstatin analogs are in clinical development for the local treatment of age-related macular degeneration, a long-term systemic use of compstatin for treating PNH places higher demands on this drug class. In this study, we therefore evaluated next-generation compstatin analogs with distinct pharmacokinetic properties concerning their efficacy and suitability for systemic administration. For this purpose, the lead analog Cp40 and a PEGylated derivative thereof were evaluated in complement activation assays, binding studies, and in a well-established ex vivo model of PNH using patient-derived erythrocytes. In addition, compstatin analogs were injected to non-human primates (cynomolgus monkeys) in order to determine administration strategies suitable for the treatment of PNH. Both Cp40 and its PEGylated derivatives prevented complement activation equally well, thereby indicating that N-terminal PEGylation does not substantially interfere with the activity of the peptide. Importantly, both compounds impaired deposition of C3 activation fragments on the surface of PNH erythrocytes as determined by FACS analysis and prevented their lysis with an IC50 of ∼4 µM. Pharmacokinetic profiling showed that PEGylation substantially improved the plasma half-life of Cp40 to more than 5 days whereas the non-PEGylated compound still exerted a value (t1/2 > 12 hours) that surpasses most peptide drugs. We therefore also evaluated repetitive subcutaneous injection of non-PEGylated Cp40 and could show that doses of 1 mg/kg every 12 hours were sufficient to maintain a therapeutic plasma level of compstatin in cynomolgus monkeys. Both strategies appear highly promising, and further evaluation of the in vivo efficacy and consideration of aspects such as production cost, treatment flexibility/control, and long-term plasma profiles will help determining the best route. Hence, our study provides critical evidence for the efficacy of compstatin analogs in the treatment of PNH, aiming to achieve a better control of all complement-mediated disease manifestations, reveals two suitable options for systemic administration of such peptidic complement inhibitors, and paves the way for a clinical application of this compound class in PNH. Disclosures:Ricklin:University of Pennsylvania: Patent application on Cp40, Patent application on Cp40 Patents & Royalties. Risitano:Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Lambris:Amyndas Pharmaceuticals: Equity Ownership; University of Pennsylvania: Patent application on Cp40 Patents & Royalties.

Implicación de los neuroesteroides en la conducta normal y patológica

The nervous system synthesises steroids (then called neurosteroids) de novo from cholesterol. These substances play a role in a number of functions related to the allosteric modulation of the main ionotropic receptors in the central nervous system (CNS). To describe the most important behavioural and cognitive processes in which neurosteroids are involved and which can open up new perspectives for research focused above all on their possible therapeutic use in pathologies affecting the CNS, such as the cognitive impairment associated to neurodegenerative diseases, addictions like alcoholism, anxiety disorders, and epilepsy and convulsive behaviour. We provide a brief outline of the concept of neurosteroids, their synthesis, how they act on receptors for neurotransmitters and their distribution throughout nerve tissue. We then offer an extensive, up-to-date, critical review of the main psychological processes that they are involved in. Neurosteroids offer an important therapeutic potential. In epileptiform behaviour, no tolerance is developed to the anticonvulsive effects of these substances with repeated administration, unlike the case of benzodiazepines, although the study of synthetic analogues and agents that step up the synthesis of neurosteroids in the CNS seems to be decisive owing to the limitation imposed by the long-term systemic use of hormones. In anxiety disorders, they offer several advantages that are comparable to the prototypical anxiolytic agents, that is, benzodiazepines, but also their chief side effects, such as sedation. In cognitive impairment, the enormous potential for cognitive enhancement in animal models is not reproduced in humans with dementia, although controlled clinical trials are needed to evaluate the benefits and risks of replacement therapy with steroids.

Effects of short‐term treatment with systemic prednisone on bone healing: an experimental study in rats

Long-term systemic use of corticosteroids causes osteoporosis and increased risk of fracture. However, the effect of short-term use of corticosteroids on bone healing is not well defined. The aim of the present study was to test the influence of short-term systemic corticosteroid therapy on bone healing. Standardized bone defects (2 mm diameter) were formed in the middle of the femur in 40 male rats. Rats were divided into two groups; control group (n = 20) and prednisone-treated group (n = 20). Subcutaneous injection of either sterile normal saline (control) or 0.020 mg kg(-1) dose of prednisone was administered just before surgery and thereafter daily for 3 days. Histopathological cross sections were taken 1, 2, 3 and 4 weeks after surgery. There was no statistically significant difference between the prednisone group and the control group. No inhibitory effects were seen following short-term corticosteroid treatment.

Hormone replacement therapy (HRT)--risks and benefits.

Despite 50 years of use, the first large randomized placebocontrolled clinical trials of postmenopausal hormone treatment and disease have only been reported in the last few years. These trials provided some surprising results, and raise questions about the short-term risk and long-term benefit of estrogen. Because clinical trials are the cornerstone of evidence-based medicine, this paper emphasizes clinical trial results whenever such are available. Clinical trials have shown that estrogen therapy is very effective treatment for vasomotor symptoms (hot flushes and night sweats), 1 which can begin several years before the last menstrual period when hormone levels are fluctuating. 2 Clinical trials have also shown that estrogen can reduce vaginal dryness and urethritis, and that topical estrogen is at least as effective as systemic estrogen. 3 The big questions about hormone therapy are not about short-term use for vasomotor symptoms or topical use for urogenital symptoms, but about long-term systemic use with its possible benefits, such as prevention of fractures, heart disease, colon cancer, or dementia, and risks, most notably breast and uterine cancer. 4

Studying long-term system use

Studying long-term system use

Death from Asthma in Children

We have recorded 29 cases of death from asthma in children who had visited the Department of Pediatrics of Doai Memorial Hospital between 1965 and 1987. These cases have been analyzed. They were 18 males and 11 females. The mean age at death was 12.4 years and we found that in later childhood and adolescence the age at death had been increasing since 1973. The duration from final attack to death was very short: less than 1 hour: 21% and less than 2 hours: 50%. About half of the cases could not reach the hospital. Ten cases died within one year after cessation of long-term systemic use of steroid. Severe attacks of asthma were particularly likely to occur during the reducing period or following cessation of these drugs. The importance of adequate and vigorous initial therapy in severe asthmatic attacks should be emphasized. The causes of death are as follows: asphyxia: 23 cases (one complicated by aspiration, one withdrawal syndrome of steroid, one subendocardial haemorrhage and two pneumothorax cases), anaphylactic shock to ACTH: 1 case, shock to stimulant: 1 case, following emergency operation: 1 case and unknown: 3 cases. Asthma death in children in Japan is reviewed.