Prolonged Steroid Use Research Articles

Temporal artery biopsy harvesting length audit, patient satisfaction with post op management. A guide for clinical commissioning group planning

Introduction Giant cell or temporal arteritis (GCA) is a vasculitis mainly affecting patients over 50yrs. Diagnosis is facilitated by a temporal artery biopsy (TAB). Due to the increased risk loss of visual loss, patients are started on high dose steroids to reduce this risk. However, a timely diagnosis with the aid from a TAB can help steer the patient into a more medically directed pathway of an appropriate reduction or prolonged use of steroids. We used British Society of Rheumatology (BSR) guidelines to audit our harvest length (recommend > 20 mm) and a telephone questionnaire to follow up patients.

PROFILE OF PATIENTS OF GLAUCOMA IN JAMMU PROVINCE (A HOSPITAL BASED STUDY)

Background: Glaucoma comprises group of disorder which cause damage to the ganglion cells and optic nerve fibers resulting in permanent loss of vision. Glaucoma is a silent killer of vision, the only treatable factor is IOP which can be lowered by medical means, laser treatment or surgery.
 Objectives: The objective of the study was to see profile of patients of glaucoma in jammu province.
 Material and method: The present prospective study involved 200 patients was conducted in the out-patient department of ophthalmology at tertiary care hospital of North India. After meeting inclusion & exclusion crieteria the patients underwent detailed clinical history, general examination, complete ophthalmological examination including dilated fundus examination, intra ocular pressure measurement, gonioscopy etc was done to diagnose different types of glaucoma.
 Results: Maximum number of patients i.e.128 were seen in age group of ≥50yrs followed by 60 in 41-50 yrs. Males i.e. 127 outnumbered females in present study. Total of 139 were from rural area. Maximum patients complain of diminution of vision ie 180 followed by pain in 135. Vision of 6/24-6/18 i.e. 59 (R/E) & 57 (L/E) followed by PL to <6/60 in 48(R/E) & 47(L/E) patients whereas PL absent was seen in 12 patients. Gonioscopically angle was open in 172(R/E) & 174(L/E) patients. Total of 102 patients had POAG.
 Conclusion: From present study we may conclude that glaucoma problem was more common in elderly age group and in males. It can lead to loss of vision among patient who suffer extreme optic nerve damage without realizing it. Therefore, for everybody above the age of 40years, it is mandatory to have IOP checked once a year especially if there is any risk factor for glaucoma like diabetes mellitus, myopia, family history of glaucoma, prolonged use of topical steroids etc.
 Keywords: Glaucoma, Gonioscopy, Intraocular Pressure(IOP), Visual acuity.

771 No Increase in Odds for Infection or Malignancy When Treating to Disease Severity in Elderly IBD Patients

INTRODUCTION: The prevalence of inflammatory bowel disease (IBD) in the elderly population is increasing. Current studies suggest that the use of immunosuppressive therapies in this population leads to a higher risk of complications, particularly an increase in infections. However, many studies show prolonged steroid use and ongoing active inflammation in elderly patients, suggesting undertreatment of their IBD. The aims of this study were to assess for an increase in infections or malignancy among an elderly Veteran population of IBD patients with treatment based on disease severity and disease activity. METHODS: After obtaining IRB approval, we performed a retrospective chart review of all VA IBD patients seen in the outpatient Gastroenterology Clinics at the Hunter Holmes McGuire VA Medical Center from January 1, 1999 through March 27, 2019. Data collected included demographic data, details of the IBD history, medication use, and any history of infection or malignancy after IBD diagnosis. Breslow-Day test was used to determine the Odds Ratios between elderly (diagnosed at 60 years or older) and non-elderly cohorts for each outcome based on medication use. RESULTS: 153 Veterans with IBD were included: 126 (82.4%) male, 80 (52.3%) had UC, and 132 (86.3%) diagnosed <60 years of age (Table 1). At enrollment, most non-elderly subjects were treated with 5-ASAs (49%) then biologics (44%) compared to 62% of elderly subjects on 5-ASA and 38% on biologics. At one year of follow-up, there was no difference in the odds of developing infection or malignancy for elderly compared to non-elderly IBD patients with any IBD therapy (Table 2). CONCLUSION: In this single-center retrospective study, we found no increase in infections or malignancy in elderly IBD patients regardless of IBD therapy. Our elderly cohort is small, so our study may have been underpowered, however data collection is ongoing.

3081 Four Severe Adverse Events Within One Week in a Patient With Ulcerative Colitis in the Setting of Prolonged High-Dose Steroid Use

INTRODUCTION: Prolonged high-dose steroids are known to predispose patients to opportunistic infections and bowel perforation. Here we present a unique case with Inflammatory Bowel Disease (IBD) who within 6 weeks developed four high-dose prednisone-related complications, including clostridium difficile (C. Diff) and cytomegalovirus (CMV) colitis, herpes simplex virus esophagitis and lastly colonic perforation. This case highlights the challenges of steroid refractory ulcerative colitis and the importance of alternative medications like biologics when patients don't have an adequate response to intravenous steroids in order to prevent iatrogenic immunosuppression-related adverse events. CASE DESCRIPTION/METHODS: A 73-year-old male had a past medical history of pan-UC presented to his primary care provider with diarrhea; tests for infectious causes, including C. Diff and CMV, were negative and colonoscopy with biopsy specimens supported a diagnosis of severe UC. Patient was started on prednisone and mesalamine but presented to the ED 2 weeks later due to ongoing symptoms. C. Diff was again ruled out and he was discharge on same dose of prednisone and mesalamine. 2 weeks later he was hospitalized for worsening abdominal pain, diarrhea and weight loss. Stool testing for C. Diff was positive so he was switched to intravenous methylprednisolone and oral vancomycin. During this time he was also found to have biopsy proven CMV colitis and HSV esophagitis. Despite treating him with ganciclovir, the patient remained symptomatic; CT was obtained which revealed free air due to a sigmoid perforation. The patient underwent a total abdominal colectomy with ileostomy. His post-operative course was unremarkable is currently off all immunosuppressive therapy, h as an ileostomy and overall is doing well. DISCUSSION: UC refractory to high dose steroid treatment is evident within one week after initiation of treatment. At that time, a change in treatment needs to be made and biologics should be considered in patients not responding to steroids. Our patient initially had negative serum (CMV) and stool (C. Diff) tests which led to ongoing steroid use. CMV typically develops after four or more weeks of severe immunosuppression. Herpes can flare up in anybody who is deeply immunosuppressed and colonic perforation – if associated with high-dose steroids – typically occurs also after four or more weeks of treatment. Our case illustrates that high-dose steroids can cause many complications within a short duration in a single patient.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Achieving and Sustaining Remission while Reducing Organ Damage

Due to advances in treatment, antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is no longer a universally fatal condition; however, difficulties remain in managing its chronic relapsing-remitting course. Current standard of care1 aims to control the multi-system damaging vasculitis but exposes patients to the risk of severe treatment toxicities in the short and long-term, particularly from high-dose or prolonged steroid use. Moreover, a lack of knowledge around disease recognition in real-world clinical practice often impedes patient access to the required specialist care. In this article, three experts in the field of AAV, Prof Annette Bruchfeld, Prof Kirsten de Groot, and Prof David Jayne, offer their views on the current status of disease assessment and management. In a series of interviews conducted by the European Medical Journal in June and July 2019, the experts identified present challenges and future goals, and discussed the impact of remission and relapse on patients with AAV. In particular, they voiced their concerns over the clinical risks of therapy versus sustained disease control and suggested how improvements in healthcare services and communication could transform patient care.

Steroid Use Associated With Increased Odds of 30-Day Mortality in Surgical Patients With Metastatic Spinal Tumors in the Setting of Disseminated Disease.

Steroid administration is part of a standard treatment regimen in metastatic spinal cord compression, though the appropriate dose, duration, efficacy, and risks remain controversial. To analyze the risk of preoperative steroid use on 30-d mortality in surgical metastatic spinal tumors with dissemination disease using a large multicenter national database. Adult patients who underwent surgical treatment for metastatic spine tumors between 2005 and 2014 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. Demographic, preoperative risk factors, operative information, and postoperative events were extracted. Multivariate logistical regression modeling was used to investigate the association with preoperative steroid use with the outcome of interest, 30-d mortality. Other independent risk factors associated with 30-d mortality were also identified. Five hundred fifty-two patients underwent surgical treatment of spinal metastases with disseminated cancer present at time of surgery. Independent risk factors of 30-d mortality included prolonged steroid use (odds ratio [OR] 2.48, 95% confidence interval [CI]: 1.22-5.04, P=.012), dependent functional status (OR 2.91, 95% CI: 1.68-5.04, P<.001), history of bleeding disorder (OR 2.80, 95% CI: 1.16-6.74, P=.021), history of smoking (OR 2.26, 95% CI: 1.11-4.61, P=.024), preoperative transfusions (OR 2.91, 95% CI: 1.02-8.29, P=.049), and preoperative infection/sepsis (OR 2.67, 95% CI: 1.18-6.08, P=.02). Our model demonstrates very strong predictive capabilities, with an area under the receiver operating characteristic curve of 0.7447. Steroid use is associated with a significant increased risk of 30-d mortality in surgical metastatic spine tumor patients with disseminated disease. These findings warrant further investigation in controlled experimental environments.

Variables associated with 30-day postoperative complications in lower extremity free flap reconstruction identified in the ACS-NSQIP database.

Lower extremity free flaps are a common way to treat both traumatic and oncologic lower extremity wounds. These patients often suffer postoperative complications. We sought to use the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to identify variables associated with postoperative complications. Patients who had free flap procedure and a primary diagnosis code for lower extremity pathology were identified in the NSQIP database from 2006 to 2017. NSQIP includes data on preoperative, intraoperative, and postoperative variables, including information up to 30 postoperative days. Current procedural terminology (CPT) codes for free flaps and international classification of diseases (ICD) 9 and 10 codes for lower extremity pathology were used for our cohort. We examined overall and major complication rates. Major complications were defined as reoperation, readmission, organ space infection, or death. Univariate and multivariate analyses were used to identify associations with complications. Four hundred and eighty-three patients underwent lower extremity free flaps. Overall complication rate was 31.6% and major complication rate was 14.9%. Prolonged operative time (OR = 2.81, CI:1.76-4.48, p < .001), preoperative steroid use (OR = 3.04, CI:1.12-8.29, p = .030), and preoperative anemia (OR = 4.10, CI:2.00-8.41, p < .001) were independently associated with any complication. Diabetes (OR = 2.56, CI:1.24-5.29, p = .011) and prolonged operative time (OR = 3.75, CI:2.17-6.47, p < .001) were independently associated with major complications. In lower extremity flap reconstruction, associations with overall complications include prolonged operative time, steroid use, and anemia. Associations with major complications included diabetes and prolonged operative time. These associations can be used to guide interventions on patients identified to have greater risk of complications.

SAT-529 Practice Patterns in the Treatment of Male Osteoporosis

Introduction: Although osteoporosis in men is now recognized as a significant public health issue, it still remains undertreated. Despite guidelines recommending treatment for men at high risk for fracture, including those with osteopenia (T-score between -1.0 and -2.5) and a Fracture Risk Assessment Tool (FRAX) score ≥3% for a hip fracture or ≥ 20% for any fracture, little is known about physician practice patterns regarding osteoporosis treatment in men. Methods: We conducted a nationwide survey of physician members of the Endocrine Society, American Academy of Family Practice and American Geriatrics Society. We used the modified Dillman method of survey administration. Respondents were asked to identify scenarios for which they were likely to initiate treatment for osteoporosis in their male patients. We conducted a multivariable logistic regression analysis controlling for physician characteristics to identify correlates of treatment initiation for a man aged ≥50 years with a T score -1.7 and FRAX score 3.2% for a hip fracture. Results: Response rate was 63% (359/566). The majority of respondents reported that they often to almost always prescribe bisphosphonates for treatment of osteoporosis in men (75%). Overall, 76% of respondents reported that they would treat a male patient with a recent non-traumatic fracture and 71% stated that they would treat a male patient with prolonged use of steroids. While the majority of the respondents reported that they would treat a male patient aged ≥50 years with a T-score -2.8 (87%), only 37% reported they would treat a male patient aged ≥50 years with a T-score -1.7 and FRAX score 3.2% for hip fracture. In multivariable analysis, primary care physicians and geriatricians were less likely to initiate treatment in this latter scenario compared to endocrinologists (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.21-0.74; OR 0.31, 95% CI 0.17-0.59, respectively). Additionally, physicians with >20 years in practice were also less likely to initiate treatment for the same scenario (OR 0.36, 95% CI 0.19-0.70). Practice setting, male patient volume and whether physicians read guidelines were not significantly associated with treatment initiation in this scenario. Conclusions: We found that primary care physicians, geriatricians and physicians with >20 years in practice are less likely to treat men with osteopenia at a high risk for fractures based on their FRAX score. These findings emphasize that continued efforts are needed to mitigate undertreatment of osteoporosis in men and improve patient care.

Ulcerative Colitis: Shifting Sands.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with considerable disease burden. We review some current misconceptions about UC in adults with the aim of optimizing care for patients. Although UC and Crohn’s disease (CD) are considered discrete diseases, distinctions between them are not always clear-cut and phenotypes may change over time. Patient management should take into account disease manifestations, disease severity and extent, and response to prior treatments. Although disease extent often defines severity, distal UC is not always less disabling than extensive disease as patients can progress to more extensive disease. In addition, severe proctitis can give rise to severe and debilitating symptoms, with a substantial impact on health-related quality of life. UC carries an increased risk of colorectal cancer (CRC) compared with CD; however, more recent data indicate a similar risk of CRC in CD with colonic involvement as with UC. Corticosteroids are widely used to induce remission in UC, and prolonged use of steroids in patients with UC is common, but corticosteroid-free maintenance of remission is an important therapeutic goal. Although biologic therapies provide a valuable treatment option in UC, they are not clinically effective in all patients and are also associated with secondary loss of response.

Pathological fracture due to prolonged steroid use in a child with transverse myelitis

Abstract Introduction Transverse myelitis (TM), a rare inflammatory disease of the spinal cord, is treated with corticosteroids that could result in other complications. Case report We present the case of a 4-year-old boy with a closed left femoral fracture after he hit the floor. He was diagnosed with TM 1 year ago and was treated with oral methylprednisolone for 8 months. Discussion In children, the prolonged use of corticosteroid enhances the osteoclast activity but reduces the osteoblast activity; this imbalance bone turnover causes osteoporosis that increases the fracture risk, which depends on the corticosteroid dose and treatment duration. Of note, the risk of fracture might last for years. Conclusion The increased risk of fracture because of the prolonged use of corticosteroids might not impede the corticosteroid treatment if indicated. Hence, bone health status and nutritional monitoring must be performed at the beginning of treatment in children who need corticosteroid therapy with a cumulative dose >1 g/year.

Hypercortisolism Signature: A Florid Case of Iatrogenic Cushing's Syndrome Induced by Topical Steroid

Clinical Image Topical corticosteroids are the most common drugs used to treat acute and chronic inflammatory skin diseases. Topical corticosteroids are available in different preparations, concentrations, and potencies. Prolonged use of them may cause systemic adverse effects including Cushing’s syndrome and hypothalamic-pituitary-adrenal axis suppression. Development of the features of Cushing's syndrome depends on the dose, duration, and potency of the corticosteroids. Here we report a case of a 19-year-old young male who developed full blown iatrogenic Cushing’s syndrome after use of clobetasol propionate cream 0.05% for recurrent dermatophytic infections (Tinea corporis, et cruris, et fecei) for 2-3 years. Laboratory evaluation revealed, morning (8:00 AM) adrenocorticotropic hormone (ACTH): 3.2 pg/mL (N: 0-46 pg/mL); morning serum cortisol: <0.1 μg/dL (N: 5.0-25.0 μg/dL) suggestive of hypothalamic-pituitary-adrenal (HPA) axis suppression secondary to topical steroid use. Other routine laboratory parameters were within normal reference range. The clobetasol propionate cream was discontinued and supplemented with oral hydrocotisone till the HPA axis recovers. This case demonstrates that injudicious prolonged use of topical steroids can have disastrous consequences (Figure 1).

Risk factors for damage in childhood-onset systemic lupus erythematosus in Asians: a case control study

BackgroundAccumulated damage is an important prognostic factor in systemic lupus erythematous. However, the pattern of disease damage and its risk factors have not been well studied in childhood-onset systemic lupus erythematosus (cSLE) in Asia. The objectives are to evaluate the pattern of damage and to identify the risk factors for accumulated damage in an Asian group of cSLE.MethodsA retrospective chart review was conducted on a group of 59 patients with cSLE. Patient demographics and clinical variables were first collected at diagnosis. Over the course of their disease, clinical variables considered as risk factors for damage were also collected. Damage was measured using the Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index (SDI) for each patient at their last encounter. Based on their SDI scores, patients were then dichotomized to two groups: a group with presence of disease damage (SDI ≥1) and a group with absence of disease damage (SDI score = 0). Clinical variables including age at diagnosis, gender, ethnicity, disease duration, disease manifestations, laboratory values at diagnosis, disease activity at diagnosis and last encounter, major organ involvement, number of lupus flares, major infection, and intensity of immunosuppressive medications were compared between the two groups. Growth failure and estimated glomerular filtration rate (eGFR) were also analysed as secondary outcomes.ResultsAfter a median disease duration and follow up of 7.8 years, 39 patients (66.1%) had no disease damage while 20 patients (33.9%) had acquired disease damage. Disease damage most frequently occurred in the ocular (15.3%), neuropsychiatric (11.9%) and musculoskeletal (11.9%) domains. The most frequent forms of damage were cataracts (11.9%), and avascular necrosis (unilateral and bilateral combined 10.2%). After controlling for other variables, presence of neuropsychiatric manifestations remained the only statistically significant risk factor for damage. The rate of growth failure in our group of patients was 16%. Patients who experienced growth failure were significantly younger at disease diagnosis. The median age of diagnosis was 10 for those who experienced growth failure, whereas the median age of diagnosis was 13 for those who did not experience growth failure. Despite a high rate of renal involvement in the group (79.7%), renal damage was only seen in 3.2% of the patients. 91.5% of the studied group had normal eGFR of ≥90 ml/min/1.73m2 at their last follow up.ConclusionThis group of patients had a low rate of damage accrual, with one of the lowest rates in renal damage when compared to other cohorts reported. The presence of neuropsychiatric manifestations was identified as the most significant risk factor for disease damage, while the most frequent forms of damage were cataracts and avascular necrosis, which were both related to prolonged steroid use. Despite the limitations of this study, it highlights the need for larger prospective studies to understand the relationship between childhood-onset SLE and its resulting damage.

Wednesday, September 26, 2018 7:35 AM–9:00 AM ePosters: P22. Single-center, matched-pair comparative study of spine surgery in patients with solid organ transplantation: short- and long-term clinical outcomes

BACKGROUND CONTEXT Solid organ transplant is the mainstay of treatment for a wide variety of several end-stage organ diseases. The number of patients who will benefit from it is expected to increase due to improvement in distribution system for organs from donors, the discovery of novel immunosuppressive treatment/regimens, and better per- and post-operative management of these patients in general. Hence, an increasing number of these patients are becoming reasonable candidates for subsequent, elective surgeries such as spine surgery. Even though these patients are considered to be a high-risk group for surgery generally, clinical outcomes of spine surgery in patients with solid organ transplantation are not well-documented in the current literature partly due to its substantially rare incidence. Furthermore, prolonged use of steroids as well as immunosuppressant such as cyclosporine is associated with a decrease in bone mineral density. Thus, these outcome data might be of particular importance to consider surgical options for this high-risk cohort and inform them of specific risks and complications associated with spinal surgery after organ transplantation. PURPOSE Summarize clinical outcomes of spine surgery in solid organ recipients, such as readmission rate, infectious complications, and mortality, to facilitate clinical decision-making processes for this specific cohort. STUDY DESIGN/SETTING Retrospective, single-center, propensity-matched cohort. PATIENT SAMPLE Patients who underwent spine surgery at a single institution with previous history of solid organ transplantation were included and compared with a matched-cohort without solid organ transplantation. OUTCOME MEASURES Thirty-day readmission rate, 90-day medical complication rate, one-year infectious complication rate, one-year mortality, and functional outcomes such as ambulatory status, which was rated on a four-point scale (4, independently ambulatory; 3, requiring a cane; 2, requiring a walker; and 1, wheelchair bound). METHODS Single-center, retrospective data review from 2010 to 2016 yielded a total of 4,968 patients who underwent spine surgery. Amongst those, 28 patients had a previous history of solid organ transplantation. Patients from the database were propensity-matched for age, sex, body mass index (BMI), smoking status, diagnoses, procedures, co-morbidities other than diseases which had prompted organ transplantation at 1:2 ratio, which yielded 56 matched-patients. Clinical outcomes of (A) 28 patients with organ transplantation and (B) 56 matched-patients were compared and statistically analyzed. Intergroup comparison of binary variables was performed via Fisher's exact test. Intergroup comparison of continuous variables was achieved using unpaired t-tests. All reported p values are 2-sided and p values RESULTS Baseline characteristics including age, sex, BMI, smoking, diagnoses, procedures, and co-morbidities (ASA scale) were similar between the two groups with no statistically significant difference, which validated our matching methods. There were no statistically significant intergroup differences in operative data such as operative time, estimated blood loss, operated levels, and use of bone morphogenetic protein-2. In terms of functional outcomes, postoperative improvement in ambulatory status was comparable between the two groups (A) 16.7% vs. (B) 18.1%, p>.99). However, the organ-recipient group resulted in longer hospital stays (A) 7.2days vs. (B) 4.3days, p CONCLUSIONS Spinal surgery after solid organ transplantation resulted in substantially increased complication rates when compared with the matched-control group, while other variables such as baseline characteristics, operative data, and functional outcomes were similar between the two groups. Careful patient selection, meticulous perioperative care, and thorough informed consent of potential complications would be imperative when performing spine surgery on this cohort.

Distinctive Infectious Complications in Patients with Central Nervous System Lymphoma Undergoing Thiotepa, Busulfan, and Cyclophosphamide-conditioned Autologous Stem Cell Transplantation

We investigated the incidence of viral, fungal, bacterial, and parasitic infections observed in 57 patients with central nervous system lymphoma after thiotepa, busulfan, and cyclophosphamide-conditioned autologous stem cell transplantation (TBC-ASCT) and 79 patients with systemic non-Hodgkin lymphoma after traditional carmustine, etoposide, cytarabine, and melphalan–conditioned ASCT (BEAM-ASCT). Twenty of 57 (35%) TBC-ASCT patients had detectable viremia with human herpesvirus 6, cytomegalovirus, adenovirus, or BK virus, versus 9 of 79 (11%) BEAM-ASCT patients. Eight TBC-ASCT patients had clinically relevant viral infections (4 human herpesvirus 6, 2 cytomegalovirus, 1 adenovirus, 2 BK virus), versus 0 in the BEAM-ASCT group. Four TBC-ASCT patients suffered infections from either a fungal or parasitic pathogen versus 1 BEAM-ASCT patient. TBC was associated with greater risk of viral reactivation compared with BEAM, independent of other factors (hazard ratio, 4.42; 95% confidence interval, 1.9 to 11.3; P < .001). Prolonged lymphopenia and steroid use in the peri- and post-ASCT period did not explain these observed differences. The pathogenesis of these unusual infections in TBC-ASCT patients remains incompletely understood, and may involve more potent immune suppression with TBC conditioning. Clinicians should be aware of these differences in infection risk in TBC-ASCT patients, which more closely parallel those seen in allogenic hematopoietic cell transplantation recipients. New prophylactic approaches to help minimize these infections should be considered in this population.

Socioeconomics of Administering Rituximab for Nephrotic Syndrome.

Nephrotic syndrome is a type of intractable disease caused by a disorder in the kidneys, which produces swelling. Although some patients show rapid improvement and recover completely with conventional treatment, many others experience frequent recurrence (frequently relapsing nephrotic syndrome) while some remain dependent on the same high dose of steroids they were initially prescribed at the start of treatment (steroid-dependent nephrotic syndrome). In the latter cases, side effects of prolonged steroid use are a major issue. Some reports show that administering rituximab is effective in treating patients with steroid resistance. However, drugs like rituximab, directed at specific molecular targets, are generally expensive and therefore need to be evaluated from a health economics perspective before being approved for widespread use. The research team compared the number of relapses and total medical costs in the 24-month period before and the same period after patients took rituximab. We found that relapse decreased from a mean of 4.30 (±2.76) times to 0.27 (±0.52) times, and the total medical costs shrank from USD 2,923 to 1,280 per month (mainly the result of lower inpatient costs). The study also identified a correlation between lower urinary protein levels and a reduction in total medical costs. Rituximab, therefore, proved beneficial in both clinical and cost-effective terms. While rising healthcare costs are becoming a major social problem, we should expect that the development of new drugs with high cost performance will be encouraged from the vantage of socioeconomics.

Duchenne muscular dystrophy: overview and future challenges

Duchenne muscular dystrophy is a muscle disease caused by mutation in the gene that encodes the cytoskeletal protein dystrophin. It is inherited in an X-linked recessive fashion. A number of therapies are continuously being developed to slow down the progression of the disease and increase patients’ life expectancy. Steroid use in Duchenne muscular dystrophy is associated with a lower mortality rate (hazard ratio = 0.24; 95% CI = 0.07–0.91; p = 0.0351). Although recent studies have concluded that prolonged steroid use is associated with short stature and overweight, a meta-analysis of 12 studies has shown that steroids can increase strength, muscle function, and quality of life. Restoration of dystrophin gene expression is the basis of genetically engineered therapies. Potential therapies of this type include exon skipping, the use of recombinant adeno- associated virus which delivers mini-dystrophin, and surrogate gene transfer. In their development, the common challenges are associated with the size of gene product and the origin of dystrophin gene expression. Stem cells are promising for future therapy. Regardless of the challenges and controversies associated with stem cells, several clinical trials show an increase of muscle strength in patients who have received such therapies.

Urine reference intervals for human chorionic gonadotropin (hCG) isoforms by immunoextraction-tandem mass spectrometry to detect hCG use.

Human chorionic gonadotropin (hCG) stimulates testosterone production by the testicles and can normalize suppressed testosterone concentrations in males following prolonged anabolic steroid use. Because of the potential for abuse by males, hCG is on the World Anti-Doping Agency (WADA) list of prohibited substances. The majority of WADA-accredited laboratories measure urinary hCG using an automated immunoassay. Only immunoassays that recognize the intact alpha and beta heterodimer of hCG (intact hCG) should be used to measure urinary hCG for doping control purposes since intact hCG is the only biologically active molecule. WADA further requires that confirmation testing is performed using an intact hCG immunoassay that is different from the one used in the initial testing procedure or by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study we measured the concentration of intact hCG, free β-subunit (hCGβ) and β-subunit core fragment (hCGβcf) in 570, 275, and 256 male urine samples, respectively, by an immunoextraction LC-MS/MS method. Mean concentrations of intact hCG, hCGβ and hCGβcf were 0.04IU/L, 0.47pmol/L and 0.16pmol/L, respectively. The upper reference limits (97.5th percentile) for intact hCG, hCGβ and hCGβcf were 0.21IU/L, 0.40pmol/L, and 1.86pmol/L, respectively. Based on these data, we recommend a threshold of 1.0IU/L for intact hCG (false positive rate of <1 in 10 000) for detecting male athletes that dope with hCG.

Management of Inflammatory Bowel Disease in the Elderly Patient: Challenges and Opportunities.

The population of older patients with inflammatory bowel disease (IBD) continues to grow, partly reflecting the aging global population in general. The debilitating effects of IBD compound age-related decrements in health and functional capacity, and make the medical management of older patients with Crohn's disease and ulcerative colitis distinctly challenging to clinicians. Here, we review the recent literature describing the pharmacologic management of IBD in this population, with focus on the safety, tolerability, and efficacy of common treatment options, such as steroids, immunomodulators, tumor necrosis factor-α antagonists, and integrin antagonists; surgical interventions in older patients are also discussed. Few studies have systematically and prospectively evaluated the clinical challenges in the medical management of IBD in this patient population, leaving a limited evidence base to which clinicians can turn to for guidance. Treatment patterns may thus be suboptimal. For example, prolonged steroid use in the elderly was found to be common, causing significant morbidity from side effects in a particularly vulnerable population. Finally, within the context of a limited evidence base, we discuss common treatment scenarios to define the parameters within which physicians can individualize care for older patients with IBD. Overall, older patients with IBD are at higher risk of adverse events and less treatment responsiveness compared with younger patients, underscoring the need for future studies to fully characterize appropriate treatment courses for this population.

Dose finding study of the intratumoral administration of the oncolytic polio/rhinovirus recombinant (PVSRIPO) against WHO grade IV malignant glioma (MG).

e13533 Background: The live attenuated oral poliovirus vaccine was modified to contain a heterologous internal ribosomal entry site stemming from human rhinovirus type 2, creating PVSRIPO. PVSRIPO recognizes CD155, an oncofetal cell adhesion molecule and tumor antigen widely expressed ectopically in malignancy. We report results of the dose finding trial evaluating PVSRIPO delivered intratumorally by convection-enhanced delivery (CED). Methods: Eligible patients were adults with recurrent supratentorial WHO grade IV MG; solitary tumor 1-5.5cm in diameter; ≥4 weeks after chemotherapy, bevacizumab or study drug; adequate organ function; KPS≥70%; and positive anti-polio titer. The original two-step continual reassessment method dose escalation was amended to decrease to dose level(DL) -1 and DL -2 after observing prolonged steroid use in patients treated on higher DLs. Results: As of 2/01/2017, 52 pts were treated on study (1 each at DL1 and DL3, 7 at DL2, 2 at DL4, 4 at DL5, 24 at DL -1 and 13 at DL -2). Only one DLT was observed, a grade 4 intracranial hemorrhage at the time of catheter removal on DL5. Grade 3 or higher adverse events possibly, probably or definitely related to PVSRIPO include: lymphopenia (grade 3, n = 1), steroid myopathy (grade 3, n = 1), cerebral edema (grade 4, n = 1), headache (grade 3, n = 1), dystonia (grade 3, n = 1), pyramidal tract syndrome (grade 3, n = 6), seizure (grade 3, n = 1; grade 4, n = 1), delusions (grade 3, n = 1), hypertension (grade 3, n = 1), and thromboembolic events (grade 3, n = 2). At a median follow-up of 20.1 months, 20.8% of pts remain alive at 36-month post PVSRIPO infusion, compared to 4% of an historical control. Four pts remain alive more than 22 months post treatment without having received any additional intervention following PVSRIPO at 57.5+, 56.4+, 27.9+ and 23.2+ months. Conclusions: Infusion of PVSRIPO via CED is safe and encouraging efficacy results are observed. The dose finding study is now completed and we are initiating clinical trials evaluating combination of PVSRIPO with other therapies. Clinical trial information: NCT01491893.

Epidemiology and clinical characteristics of invasive mould infections: A multicenter, retrospective analysis in five Asian countries.

Formal, large-scale, multicenter studies of invasive mould infection (IMI) in Asia are rare. This 1-year, retrospective study was designed to assess the incidence and clinical determinants of IMI in centers in five countries (Thailand, Taiwan, Singapore, China, India). Patients treated in a single year (2012) were identified through discharge diagnoses, microbiology, and histopathology logs, and entered based on published definitions of IMI. A total of 155 cases were included (median age 54 years; 47.7% male). Of these, 47.7% had proven disease; the remainder had probable IMI. The most frequent host factors were prolonged steroid use (39.4%) and recent neutropenia (38.7%). Common underlying conditions included diabetes mellitus (DM; 30.9%), acute myeloid leukemia (19.4%), and rheumatologic conditions (11.6%). DM was more common in patients with no recent history of neutropenia or prolonged steroid use (P = .006). The lung was the most frequently involved site (78.7%), demonstrating a range of features on computed tomography (CT). Aspergillus was the most common mould cultured (71.6%), primarily A. fumigatus and A. flavus, although proportions varied in different centers. The most often used antifungal for empiric therapy was conventional amphotericin. Ninety-day mortality was 32.9%. This is the first multicenter Asian study of IMI not limited to specific patient groups or diagnostic methods. It suggests that DM and rheumatologic conditions be considered as risk factors for IMI and demonstrates that IMI should not be ruled out in patients whose chest features on CT do not fit the conventional criteria.