EP20 Long term safety and efficacy of denosumab and zoledronate

Abstract Background Denosumab and zoledronate are increasingly prescribed for primary and secondary osteoporosis long-term management. Methods A retrospective audit was conducted at Basildon Hospital during 2012-2019 using the NICE guidelines standards to evaluate the long term safety and efficacy of denosumab and zoledronate. Number of patients was 84, diagnosed with osteoporosis or osteopenia, 34 of them received 10 or more denosumab injections and 50 patients planned to receive 5 zoledronate infusions (9 patients received 5 and 38 patients received 4). Results Forty percent of the patients were at their 8th decade followed by 28.57% and 21.42 % at their 9th and 7th decades respectively. More than 90% were Caucasian females. Primary prevention was in 39.28% and secondary prevention in 60.71%. The commonest sites of fracture were the wrist and vertebrae at 34.37% for each; followed by the neck of femur and humerous at 12.5% for each. Denosumab was the 1st, 2nd, 3rd or 4th line of treatment in 9.52%, 13.09%, 16.66% and 1.19% respectively; whereas zoledronate was the 1st, 2nd or 3rd line of treatment in 13.09%, 40.47% and 5.95% respectively. The commonest reason for choosing denosumab as the first line was chronic kidney disease, whereas the reason for choosing it as the 2nd or 3rd line was inefficacy of bisphosphonate in 69% or gastrointestinal side effects in 14%. Zoledronate was chosen in all cases because of intolerability to oral bisphosphonate or gastrointestinal side effects. Repeat DXA scan was performed after the 5th, 10th denosumab injections and the 3rd zoledronate infusions. After the 5th Denosumab, DXA scan showed improvement or stability in 100% and 85.29% at the spine and hip respectively whilst deterioration was seen in 14.7% at the hip. After the 10th denosumab, the rate of improvement or stability at the spine was reduced to 88.23% and decline was seen in 2.94%. At the hip area, 73.52% continued to show improvement or stability, whilst 17.66 % showed deterioration. After the 3rd zoledronate, 98% and 88% showed improvement or stability at the spine and hip respectively whilst deterioration seen in 2% and 12% at the spine and hip respectively. One patient on zoledronate experienced dental issues after the 4th injection and stopped treatment. There were no jaw osteonecrosis, no new fractures and no significant side effects with either denosumab or zoledronate. Ninety percent of patients who completed 10 denosumab injections were planned to continue for another 5 injections. Conclusion After the period of 3-5 years, denosumab and zoledronate were well tolerated and BMD was either stable or improved at both spinal and hip sites. There were few cases of deterioration mainly at the hip area with both zoledronate and denosumab. Future researches are needed to stratify guidelines on discontinuation of denosumab. Disclosures Z. Alkutobi None. D. Laila None. M. Tariq None. A. Nandagudi None.

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Randomized Trial of Erythromycin and Azithromycin for Treatment of Chlamydial Infection in Pregnancy

Infectious Diseases in Obstetrics and Gynecology ◽

10.1155/s1064744995000718 ◽

1995 ◽

Vol 3 (6) ◽

pp. 241-244 ◽

Cited By ~ 9

Author(s):

Marc F. Rosenn ◽

George A. Macones ◽

Neil S. Silverman

Keyword(s):

Side Effects ◽

Screening Tests ◽

Number Of Patients ◽

Significant Difference ◽

Gastrointestinal Side Effects ◽

The Cost ◽

Cure Rates ◽

To Receive ◽

In Pregnancy

Objective:The purpose of this study was to compare erythromycin and azithromycin in the treatment of chlamydial cervicitis during pregnancy with regard to efficacy, side effects, and compliance.Methods:In a prospective manner, 48 pregnant patients with cervical chlamydial infections diagnosed by routine screening tests were randomly assigned to receive either erythromycin, 500 mg q.i.d. for 7 days (N = 24), or azithromycin, 1 g as a one-time dose (N = 24). All sexual partners were given prescriptions for doxycycline, 100 mg b.i.d. for 7 days. The treatment efficacy was assessed by follow-up chlamydia testing 3 weeks after the therapy was completed. The side effects, intolerance to therapy, and overall compliance were evaluated by means of a standardized posttreatment questionnaire.Results:There was no significant difference in cure rates noted between the erythromycin group and the azithromycin group (77% vs. 91%, respectively;P= 0.24). Gastrointestinal side effects were reported more frequently among patients treated with erythromycin compared with patients treated with azithromycin (45% vs. 17%, respectively;P= 0.004). The patients who received erythromycin reported intolerance to therapy secondary to side effects more frequently than patients who received azithromycin (23% vs. 4%, respectively;P= 0.07). Furthermore, the patients in the azithromycin group were more likely to complete their course of therapy as prescribed than the patients in the erythromycin group (100% vs. 61%, respectively;P= 0.002).Conclusions:Azithromycin is efficacious and well tolerated for the treatment of chlamydial cervicitis in pregnancy. Erythromycin, though efficacious, is poorly tolerated, as demonstrated by the number of patients reporting significant side effects during the course of therapy. Since the cost of azithromycin is comparable to that of generic erythromycin, the present study supports the use of azithromycin as an alternative to erythromycin for the treatment of chlamydial cervicitis in pregnancy.

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Gastroprotection during long-term NSAID use – what we know after 120 years of observations?

Medycyna Faktów ◽

10.24292/01.mf.0221.1 ◽

2021 ◽

Vol 14 (2) ◽

pp. 132-137

Author(s):

Michał Lipiński

Keyword(s):

Side Effects ◽

Risk Stratification ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Broad Spectrum ◽

Nsaid Therapy ◽

Gastrointestinal Complications ◽

Gastrointestinal Side Effects ◽

Inflammatory Drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed classes of medications. The broad spectrum of side effects following long-term NSAID therapy includes mainly, but not only, gastrointestinal complications. Risk stratification of the gastrointestinal complications events is an important element of planning NSAIDs therapy, which allows to determine the indications for the use of proton pump inhibitors. This article presents the criteria for assessment and the method of adequate prevention of gastrointestinal side effects in patients receiving long-term NSAID therapy.

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Prospective evaluation of multitarget treatment of pediatric patients with helical intensity-modulated radiotherapy

Strahlentherapie und Onkologie ◽

10.1007/s00066-020-01670-4 ◽

2020 ◽

Vol 196 (12) ◽

pp. 1103-1115

Author(s):

Maria-Elena A. Salfelder ◽

Kerstin A. Kessel ◽

Uwe Thiel ◽

Stefan Burdach ◽

Severin Kampfer ◽

...

Keyword(s):

Survival Rate ◽

Side Effects ◽

Survival Rates ◽

Young Patients ◽

Intensity Modulated Radiotherapy ◽

High Survival ◽

Single Target ◽

Number Of Patients ◽

Grade 3

Abstract Background and purpose Radiotherapy (RT) is persistently gaining significance in the treatment of pediatric tumors. However, individual features of a growing body and multifocal stages complicate this approach. Tomotherapy offers advantages in the treatment of anatomically complex tumors with low risks of side effects. Here we report on toxicity incidence and outcome of tomotherapy with a focus on multitarget RT (mtRT). Materials and methods From 2008 to 2017, 38 children diagnosed with sarcoma were treated with tomotherapy. The median age was 15 years (6–19 years). Toxicity was graded according to the Common Terminology Criteria for Adverse Events v.4.03 and classified into symptoms during RT, acutely (0–6 months) and late (>6 months) after RT, and long-term sideeffects (>24 months). Results The main histologies were Ewing sarcoma (n = 23 [61%]) and alveolar rhabdomyosarcoma (n = 5 [13%]). RT was performed with a median total dose of 54 Gy (40.5–66.0 Gy) and a single dose of 2 Gy (1.80–2.27 Gy). Twenty patients (53%) received mtRT. Median follow-up was 29.7 months (95% confidence interval 15.3–48.2 months) with a 5-year survival of 55.2% (±9.5%). The 5‑year survival rate of patients with mtRT (n = 20) was 37.1 ± 13.2%, while patients who received single-target RT (n = 18) had a 5-year survival rate of 75 ± 10.8%. Severe toxicities (grade 3 and 4) emerged in 14 patients (70%) with mtRT and 7 patients (39%) with single-target RT. Two non-hematological grade 4 toxicities occurred during RT: one mucositis and one radiodermatitis. After mtRT 5 patients had grade 3 toxicities acute and after single-target RT 4 patients. One patient had acute non-hematological grade 4 toxicities (gastritis, pericarditis, and pericardial effusion) after mtRT. Severe late effects of RT occurred in 2 patients after mtRT and in none of the single-target RT patients. No severe long-term side effects appeared. Conclusion Our results showed acceptable levels of acute and late toxicities, considering the highly advanced diseases and multimodal treatment. Hence, tomotherapy is a feasible treatment method for young patients with anatomically complex tumors or multiple targets. Especially mtRT is a promising and innovative treatment approach for pediatric sarcomas, delivering unexpectedly high survival rates for patients with multifocal Ewing sarcomas in this study, whereby the limited number of patients should invariably be considered in the interpretation.

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Platinum-based chemotherapy: gastrointestinal immunomodulation and enteric nervous system toxicity

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00212.2014 ◽

2015 ◽

Vol 308 (4) ◽

pp. G223-G232 ◽

Cited By ~ 38

Author(s):

Vanesa Stojanovska ◽

Samy Sakkal ◽

Kulmira Nurgali

Keyword(s):

Nervous System ◽

Side Effects ◽

Enteric Nervous System ◽

Chemotherapeutic Agents ◽

Gut Dysfunction ◽

Bidirectional Communication ◽

Platinum Based Chemotherapy ◽

Gastrointestinal Side Effects ◽

Chemotherapeutic Treatment

The efficacy of chemotherapeutic treatment of colorectal cancer is challenged by severe gastrointestinal side effects, which include nausea, vomiting, constipation, and diarrhea. These symptoms can persist long after the treatment has been ceased. An emerging concept is the ability of platinum-based drugs to stimulate immunity, which is in contrast to conventional chemotherapeutic agents that are immunosuppressive. Here, we review the immunomodulatory aspects of platinum-based anticancer chemotherapeutics and their impact on gastrointestinal innervation. Given the bidirectional communication between the enteric nervous system and gastrointestinal immune system; exploring the consequences of platinum-induced immunogenicity will facilitate better understanding of gut dysfunction caused by chemotherapeutic agents. We propose that the development of future successful chemotherapeutics should rely on targeting the mechanisms underlying long-term gastrointestinal side effects.

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N-Acetylcysteine’s Attenuation of Fatigue After Repeated Bouts of Intermittent Exercise: Practical Implications for Tournament Situations

International Journal of Sport Nutrition and Exercise Metabolism ◽

10.1123/ijsnem.21.6.451 ◽

2011 ◽

Vol 21 (6) ◽

pp. 451-461 ◽

Cited By ~ 53

Author(s):

James N. Cobley ◽

Chris McGlory ◽

James P. Morton ◽

Graeme L. Close

Keyword(s):

Side Effects ◽

Muscle Fatigue ◽

Intermittent Exercise ◽

Adaptive Responses ◽

Short Term ◽

Treatment Dose ◽

Gastrointestinal Side Effects ◽

Matched Design ◽

Over Time

Production of reactive oxygen species (ROS) during muscle contractions is associated with muscle fatigue and damage in the short term and adaptive responses in the long term. When adaptation is inconsequential acute antioxidant supplementation may be able to attenuate muscle fatigue and damage to enhance performance. This study aimed to determine the effects of acute oral N-acetylcysteine (NAC) supplementation on Yo-Yo Intermittent Recovery Test Level 1 (YIRT-L1) performance after repeated bouts of damaging intermittent exercise. In a pair-matched design, 12 recreationally trained men engaged in 6 d of either NAC (n = 6) or placebo (n = 6) supplementation. After a treatment-loading day, participants completed 3 testing sessions, on alternating days, consisting of a preexercise isokinetic dynamometry (IKD) test, a damaging intermittent-exercise protocol, YIRT-L1, and a postexercise IKD test. Another IKD test was completed on the 2 intervening d. NAC treatment resulted in a significant preservation of YIRT-L1 performance (p ≤ .0005). IKD performance significantly deteriorated over time at all contraction speeds, and this deterioration was not influenced by treatment group. Plasma creatine kinase values increased significantly over time (p = .002) and were significantly greater in the NAC group than in the placebo group (p = .029). NAC induced mild gastrointestinal side effects. NAC supplementation may be a useful strategy to enhance performance during short-term competitive situations when adaption is inconsequential. Titration studies to elucidate a treatment dose that enhances performance without inducing side effects are now required.

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Kezdeti tapasztalataink spinalis muscularis atrophiában szenvedő gyermekek intravénás génterápiájával

Orvosi Hetilap ◽

10.1556/650.2020.31890 ◽

2020 ◽

Vol 161 (42) ◽

pp. 1806-1816

Author(s):

Borbála Mikos ◽

Anita Gergely ◽

Réka Balázsfi ◽

Edina Bányász ◽

Beáta Gyömörei ◽

...

Keyword(s):

Side Effects ◽

Troponin I ◽

Muscular Atrophy ◽

Safety Data ◽

Clinical Results ◽

Genetic Diagnostics ◽

Number Of Patients ◽

Movement Performance ◽

Term Basis

Összefoglaló. A veleszületett gerincvelői izomsorvadás ritka, progresszív neurodegeneratív betegség, a gyermekkori halál egyik legjelentősebb genetikai oka. Az orvostudomány lehetőségei a XXI. század előtt a progresszió megfékezésére, a szövődmények késleltetésére és ellátására korlátozódtak. A legsúlyosabb génhibában szenvedő gyermekeket általában kétéves kor előtt elveszítettük. A genetikai diagnosztika fejlődése lehetővé teszi a korai diagnózist, a súlyosság és a progresszió előrejelzését. A 2018-ban hazánkban engedélyezett intrathecalis nuszinerszennel a nagy betegszámon alapuló klinikai eredmények meggyőzőek. A 2019-től elérhető új, intravénás génpótló terápiával (onaszemnogén abeparvovek) kapcsolatos tapasztalatok még kisebb betegszámon alapulnak. Hazánkban öt betegnél került sor az alkalmazására a Bethesda Gyermekkórházban, szigorú szakmai kritériumok és előkészületek alapján. Közülük annak a három gyermeknek a kezeléséről számolunk be dolgozatunkban, akiknél már rendelkezünk utánkövetési tapasztalatokkal. Vizsgálatunk szerint a készítmény elősegíti a mozgásteljesítmény javulását. A mellékhatások elsősorban reverzibilis májenzim-emelkedésben, thrombocytopeniában, granulocytopeniában és a szívizom-nekroenzim emelkedésében nyilvánultak meg. Ezért fontosnak tartjuk a betegek szoros és tartós követését, a mellékhatások korai észlelése és elhárítása érdekében. Orv Hetil. 2020; 161(42): 1806–1816. Summary. Congenital spinal muscular atrophy is a rare, progressive neurodegenerative disease, one of the major genetic causes of childhood death. The possibilities of medicine to curb its progression and to delay and treat the disease’s complications were limited before the 21st century. Therefore, children with the most severe genetic defects were usually lost before their second birthday. Advances in genetic diagnostics allow for early diagnosis, prediction of severity and expected progression. Using intrathecal nusinersen (available in Hungary since 2018), clinical results based on a large number of patients are convincing. Experience with the new intravenous gene therapy (onasemnogene abeparvovec) available from 2019 is still based on a less number of patients. It was used in Hungary in Bethesda Hospital in five children based on strict professional criteria and preparations. Our paper summarizes the most important efficacy and safety data of the first three consecutive patients. According to our experiences, the product helps to improve movement performance. Side effects are mainly reversible elevations of liver enzymes and serum troponin-I levels, thrombocytopenia and granulocytopenia. Therefore, we found that it is important to monitor patients closely on a long-term basis in order to detect and eliminate side effects early. Orv Hetil. 2020; 161(42): 1806–1816.

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Long-term follow-up of the use of maintenance antibiotic therapy for chronic antibiotic-dependent pouchitis

Frontline Gastroenterology ◽

10.1136/flgastro-2017-100913 ◽

2018 ◽

Vol 9 (2) ◽

pp. 154-158 ◽

Cited By ~ 9

Author(s):

Jonathan P Segal ◽

Stephanie X Poo ◽

Simon D McLaughlin ◽

Omar D Faiz ◽

Susan K Clark ◽

...

Keyword(s):

Side Effects ◽

Antibiotic Therapy ◽

Antibiotic Use ◽

Safety And Efficacy ◽

Pouch Failure ◽

Patient Reported ◽

Long Term Follow Up ◽

Term Maintenance

ObjectiveRestorative proctolectomy is considered the procedure of choice in patients with ulcerative colitis who have failed medical therapy. Chronic pouchitis occurs in 10%–15% of patients, which often require long-term antibiotics to alleviate symptoms. Safety and efficacy of long-term maintenance antibiotics for chronic pouchitis has yet to be established. We aimed to assess the long-term safety and efficacy of maintenance antibiotic therapy for chronic pouchitis.DesignThis was an observational study. We followed up patients who were diagnosed with chronic antibiotic-dependent pouchitis.SettingData were collected from our single specialist pouch centre.PatientsPatients with chronic antibiotic-dependent pouchitis who had been maintained on antibiotics continuously for at least 1 year with a least one follow-up visit.Main outcome measureDevelopment of pouch failure defined by the need for an ileostomy, patient-reported side effects of antibiotics and development of antibiotic resistance found on stool coliform testing.ResultsLong-term use of antibiotics achieve remission in 21% of patients over a median follow-up of 102 (range 9–125). Pouch failure in association with chronic pouchitis after a median follow-up of 8.5 years occurred in 18%. Side effects of long-term antibiotic use occurred in 28% of patients, with resistance to antibiotics from at least one stool sample occurring in 78% patients.ConclusionsAlthough the use of antibiotics in chronic pouchitis may be justified, the use of long-term antibiotics must be weighed against potential complications associated with pouchitis and antibiotics.

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Acupuncture as a complementary therapy for cancer care: acceptability and preferences of patients and informal caregivers

10.21203/rs.3.rs-38589/v1 ◽

2020 ◽

Author(s):

Tessa Lefebvre ◽

Laura Tack ◽

Virginie Blieck ◽

Lieselot Cool ◽

Hans Pottel ◽

...

Keyword(s):

Side Effects ◽

Cancer Patients ◽

Cancer Care ◽

Informal Caregivers ◽

Participation Rate ◽

Complementary Therapy ◽

Care Clinic ◽

Supportive Cancer Care ◽

Number Of Patients ◽

To Receive

Abstract Background: Acupuncture provides a possible complementary therapy which can be used alongside or following cancer treatment to relieve side-effects for cancer patients and survivors, such as pain and depression. Equally, it can provide relief from symptoms such as anxiety and sleep disturbance, which are recognised as significant issues among caregivers of those with cancer. The aim of this study was to explore the acceptability and preferences of cancer patients, disease survivors and their informal caregivers in relation to acupuncture.Methods: A questionnaire was developed to explore acceptability and preferences of cancer patients, disease survivors and their caregivers in relation to acupuncture, including motivations to use acupuncture, preferred symptoms to be addressed, and practical issues (location; cost).Results: A participation rate of 94.5% was obtained, with 116 participating patients and survivors, and 54 caregivers. Acceptability of acupuncture was around 1/3 for patients (34.5%; 40/116) and almost half for informal caregivers (48.0%; 26/54). In terms of preferences, the day care clinic was the favoured location for patients (52.5%; 21/40) to undergo acupuncture, while there was no specific preference on location observed for caregivers. A large number of patients indicated they would be willing to pay to receive the complementary therapy (60%; 24/40). Symptoms of fatigue, feeling listless, and pain were most often identified as complaints patients and survivors would use acupuncture for (60.0%, 57.5%, and 47.5% respectively). For informal caregivers, 48.0% (26/54) expressed an interest in using acupuncture for their pain, stress and sleeping difficulties.Conclusions: This study indicates that many cancer patients, disease survivors and informal caregivers would accept acupuncture as a complementary therapy. They could further identify many symptoms they felt this therapy could relieve. This openness to acupuncture, and expressed preferences provide the foundations for this complementary therapy to be incorporated into holistic and supportive cancer care, both for patients and those supporting them.

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Immunization against Natural Helicobacter pylori Infection in Nonhuman Primates

Infection and Immunity ◽

10.1128/iai.66.9.4340-4346.1998 ◽

1998 ◽

Vol 66 (9) ◽

pp. 4340-4346 ◽

Cited By ~ 54

Author(s):

Andre Dubois ◽

Cynthia K. Lee ◽

Nancy Fiala ◽

Harry Kleanthous ◽

Patrick T. Mehlman ◽

...

Keyword(s):

Escherichia Coli ◽

Helicobacter Pylori ◽

Side Effects ◽

Nonhuman Primates ◽

Safety And Efficacy ◽

Antral Gastritis ◽

Breeding Groups ◽

H Pylori ◽

To Receive ◽

Monkey Colony

ABSTRACT Helicobacter pylori infection is widespread in some breeding groups of a rhesus monkey colony (71% H. pyloripositive by 1 year), and the rate of seroconversion is also high. As a result, these groups can be used to test the safety and efficacy of an anti-H. pylori vaccine. Nine-month-old female animals were randomized to receive either 8 mg of recombinant urease (rUre) plus 25 μg of Escherichia coli heat-labile enterotoxin (LT) (n = 26) or placebo plus LT (n = 29), given four times at 1-week intervals followed by a booster 1 month later. Ten months after the start of the immunization, the animals were subjected to endoscopy and biopsy samples were obtained. H. pylori negativity was defined as no H. pylori growth by culture and no H. pylori observed at histology. By this criterion, 2 (7%) of 29 animals receiving placebo and 8 (31%) of 26 immunized animals were H. pylori negative (P < 0.035). In addition, antral gastritis score was significantly less in H. pylori-negative immunized monkeys than in H. pylori-positive animals, whether they were given rUre plus LT or placebo plus LT (P < 0.02 orP < 0.01, respectively). Interestingly, antral gastritis was also significantly less in H. pylori-positive animals given rUre plus LT than in H. pylori-positive animals given placebo plus LT (P < 0.02). However, quantitative cultures did not demonstrate significant differences between the two latter groups. It is concluded that oral administration of rUre vaccine plus LT significantly protects nonhuman primates against H. pylori infection while not causing undesirable side effects.

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A Ten-Year Assessment of Methicillin-Associated Side Effects

PEDIATRICS ◽

10.1542/peds.58.3.329 ◽

1976 ◽

Vol 58 (3) ◽

pp. 329-334

Author(s):

Martha D. Yow ◽

Larry H. Taber ◽

Fred F. Barrett ◽

A. Aaron Mintz ◽

G. Richard Blankinship ◽

...

Keyword(s):

Side Effects ◽

Great Majority ◽

Incidence Rates ◽

Term Therapy ◽

Average Dose ◽

True Incidence ◽

Number Of Patients ◽

Chemical Irritation ◽

Long Term Therapy

The exact incidence and importance of side effects associated with methicillin therapy in children is unknown. During the ten-year period from 1964 to 1974 approximately 3,000 Houston children who received methicillin were observed for side effects. The great majority of these patients received the drug for less than ten days; however, side effects were more common in patients receiving long-term therapy. In order to assess these side effects, experiences with 124 children who received methicillin for ten days or longer were reviewed in depth. The average dose of methicillin was 200 mg/kg/day and the average duration was 22 days. In this highly selected group there were no adverse side effects in 54.8% and only eosinophilia in an additional 13%. Leukopenia occurred in 16%, microscopic hematuria in 8%, gross hematuria in 4%, skin rash in 6%, and "drug fever" in 6%. In many instances several of these side effects occurred within a single patient so that the total number of patients with definite side effects was 39 of 124 (31.5%). The true incidence figure of overall side effects is much lower than 31.5%. Corrected incidence rates based on a conservative figure of 3,000 methicillin-treated children are less than 1.5% for all side effects. In some patients the mechanism producing the adverse reactions seemed to be chemical irritation or toxicity and in others hypersensitivity. In nine of the 39 patients follow-up studies were not optimal. In the other 30 patients all side effects were reversible.

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