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Concept: Adverse effect


BACKGROUND: Pre-eclampsia/eclampsia is one of the most common causes of maternal and perinatal morbidity and mortality in low and middle income countries. Magnesium sulfate is the drug of choice for prevention of seizures as part of comprehensive management of the disease. Despite the compelling evidence for the effectiveness of magnesium sulfate, concern has been expressed about its safety and potential for toxicity, particularly among providers in low- and middle-income countries. The purpose of this review was to determine whether the literature published in these global settings supports the concerns about the safety of use of magnesium sulfate. METHODS: An integrative review of the literature was conducted to document the known incidences of severe adverse reactions to magnesium sulphate, and specific outcomes of interest related to its use. All types of prospective clinical studies were included if magnesium sulfate was used to manage pre-eclampsia or eclampsia, the study was conducted in a low- or middle-income country, and the study included the recording of the incidence of any adverse side effect resulting from magnesium sulfate use. RESULTS: A total of 24 studies that compared a magnesium sulfate regimen against other drug regimens and examined side effects among 34 subject groups were included. The overall rate of absent patellar reflex among all 9556 aggregated women was 1.6%, with a range of 0-57%. The overall rate of respiratory depression in 25 subject groups in which this outcome was reported was 1.3%, with a range of 0–8.2%. Delay in repeat administration of magnesium sulfate occurred in 3.6% of cases, with a range of 0-65%. Calcium gluconate was administered at an overall rate of less than 0.2%. There was only one maternal death that was attributed by the study authors to the use of magnesium sulfate among the 9556 women in the 24 studies. CONCLUSION: Concerns about safety and toxicity from the use of magnesium sulfate should be mitigated by findings from this integrative review, which indicates a low incidence of the most severe side effects, documented in studies that used a wide variety of standard and modified drug regimens. Adverse effects of concern to providers occur infrequently, and when they occurred, a delay of repeat administration was generally sufficient to mitigate the effect. Early screening and diagnosis of the disease, appropriate treatment with proven drugs, and reasonable vigilance for women under treatment should be adopted as global policy and practice.

Concepts: Pharmacology, Effectiveness, Magnesium sulfate, Sulfur, Morphine, Adverse effect, Salt, Iatrogenesis


Concern exists regarding the potential for chiropractic treatment to cause adverse effects in individuals with scoliosis. The aim of this paper is to present the self-reported responses of 189 scoliosis patients over 3198 unique visits, collected over one calendar year from nine chiropractic clinics, regarding how they felt and the side effects they experienced immediately after chiropractic treatment.

Concepts: Philosophy of science, Alternative medicine, Adverse effect


In vitro-based search for promising anti-cancer drug combinations may provide important leads to improved cancer therapies. Currently there are no integrated computational-experimental methods specifically designed to search for combinations, maximizing a predefined therapeutic index (TI) defined in terms of appropriate model systems. Here, such a pipeline is presented allowing the search for optimal combinations among an arbitrary number of drugs while also taking experimental variability into account. The TI optimized is the cytotoxicity difference (in vitro) between a target model and an adverse side effect model. Focusing on colorectal carcinoma (CRC), the pipeline provided several combinations that are effective in six different CRC models with limited cytotoxicity in normal cell models. Herein we describe the identification of the combination (Trichostatin A, Afungin, 17-AAG) and present results from subsequent characterisations, including efficacy in primary cultures of tumour cells from CRC patients. We hypothesize that its effect derives from potentiation of the proteotoxic action of 17-AAG by Trichostatin A and Afungin. The discovered drug combinations against CRC are significant findings themselves and also indicate that the proposed strategy has great potential for suggesting drug combination treatments suitable for other cancer types as well as for other complex diseases.

Concepts: Therapeutic effect, Pharmacology, Cancer, Oncology, Effectiveness, Chemotherapy, Model, Adverse effect


Abstract Background The oral tetracyclines, especially minocycline hydrochloride, are often used as an effective treatment for perioral dermatitis, however they are sometimes difficult to use because of the side effects, especially in children. Objective The effectiveness of β-lactam antibiotics was evaluated in three cases of perioral dermatitis. Methods Three Japanese patients with perioral dermatitis were treated with cefcapene pivoxil hydrochloride hydrate per os 100 to 300 mg per day. They were one girl (age 10) and two adult women (age 32, 37). One of the adult patients had a past history of Meniere’s disease and the other had had a side effect, vertigo, from minocycline hydrochloride treatment. The presence of fusobacteria before and after the treatment was examined using the tape-stripping toluidine blue method. Results These patients showed the improvement in 1 to 2 weeks and were much improved or cured after 2 to 5 weeks. No side effects were found during the treatment. Fusobacteria were positive before treatment but became negative after the treatment in all of them. Conclusion β-lactam antibiotics might be a useful treatment for perioral dermatitis, especially in cases who cannot take tetracyclines.

Concepts: Effect, Effectiveness, Ménière's disease, Adverse effect, Acne vulgaris, Rosacea, Tetracycline antibiotics, Minocycline


Cantharidin is a widely used treatment for molluscum contagiosum (MC) that is often favored because of its speed of application and lack of pain at the time of application. Previous studies have supported its safety and reported high parental and dermatologist satisfaction with its use. Nonetheless, a lack of safety data has contributed to ambiguous U.S. Food and Drug Administration status that has made it increasingly difficult to obtain. All children treated with cantharidin for MC at a tertiary care center between January 1, 2005, and December 31, 2011, who had at least one follow-up visit or telephone call were included in the current study. Information related to treatment with cantharidin and adverse effects was abstracted from medical records. Of 512 children identified, 405 had at least one follow-up visit or telephone call after treatment and were included in this study. Cantharidin was applied to 9,688 lesions over 1,056 visits. Fifty-seven percent of children experienced blistering, an expected effect of therapy. Eleven percent of patients experienced adverse events. The most common adverse events were pain (7%) and significant blistering (2.5%). Other side effects were rare (<1%) and included pruritus, possible mild infection, significant irritation, id reactions, and bleeding. Eighty-six percent of parents reported satisfaction with cantharidin or opted to use it again. Cantharidin is a safe treatment modality for MC and should be considered when symptomatic infection necessitates treatment. The cantharidin application protocol used in this study may serve as a model protocol with a known side-effect profile.

Concepts: Immune system, Medicine, Adverse effect, Tertiary referral hospital, Molluscum contagiosum, Iatrogenesis, Wart, Cantharidin


Cancer disease is one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and around 8 million cancer-related deaths yearly. Estimates expect to increase these figures over the next few years. Therefore, it is very important to develop more effective and targeted therapies. Polysaccharides are widely used for biomedical and pharmaceutical applications due to their interesting properties, and can be utilised in the production of nanovehicles for drug delivery, since they frequently extend the half-life and improve the stability of chemotherapeutic agents in bloodstream allowing them to reach the tumour tissue. Moreover, polysaccharide-based nanovehicles are generally expected to increase the therapeutic benefit by reducing the undesired side effects and promoting a more efficient cellular uptake. Here, we highlight the application of various polysaccharides as nanovehicles in cancer therapy, focusing mainly on in vivo applications and describing the main advantages of each designed system in a critical way. The use of different polysaccharides interacting with metal nanoparticles to develop new nanovehicles for cancer therapy will also be discussed.

Concepts: Pharmacology, Medicine, Cancer, Oncology, Cure, Chemotherapy, Adverse effect, Targeted therapy


Not all women initiate clinically indicated breast cancer adjuvant treatment. It is important for clinicians to identify women at risk for noninitiation.

Concepts: Cancer, Breast cancer, Metastasis, Oncology, Chemotherapy, Chemotherapy regimens, Alternative medicine, Adverse effect


Gastrointestinal (gi) symptoms are the most notable side effects of chemotherapeutic drugs; such symptoms are currently treated with drugs. In the present study, we investigated the effect of acupuncture on gi symptoms induced by chemotherapy in patients with advanced gastric cancer.

Concepts: Immune system, Cancer, Metastasis, Oncology, Chemotherapy, Lymphoma, Adverse effect


Cellular senescence suppresses cancer by irreversibly arresting cell proliferation. Senescent cells acquire a pro-inflammatory senescence-associated secretory phenotype. Many genotoxic chemotherapies target proliferating cells non-specifically, often with adverse reactions. In accord with prior work, we show that several chemotherapeutic drugs induce senescence of primary murine and human cells. Using a transgenic mouse that permits tracking and eliminating senescent cells, we show that therapy-induced senescent (TIS) cells persist and contribute to local and systemic inflammation. Eliminating TIS cells reduced several short- and long-term effects of the drugs, including bone marrow suppression, cardiac dysfunction, cancer recurrence and physical activity and strength. Consistent with our findings in mice, the risk of chemotherapy-induced fatigue was significantly greater in humans with increased expression of a senescence marker in T-cells prior to chemotherapy. These findings suggest that senescent cells can cause certain chemotherapy side effects, providing a new target to reduce the toxicity of anti-cancer treatments.

Concepts: Immune system, Cancer, Oncology, Cell division, Bone marrow, Chemotherapy, Leukemia, Adverse effect


Controversy has arisen regarding the effectiveness of neuraminidase inhibitors (NIs), especially against influenza-related complications. A literature search was performed to critically assess the evidence collected by the available systematic reviews (SRs) regarding the benefits and disadvantages of NIs (oseltamivir, zanamivir) compared to placebos in healthy and at-risk individuals of all ages for prophylaxis and treatment of seasonal influenza. A SR was done using the Cochrane Database of Systematic Reviews, Health Technology Assessment Database, Database of Abstracts of Reviews of Effects, and Medline (January 2006-July 2012). Two reviewers selected SRs based on randomized clinical trials, which were restricted to intention-to-treat results, and they assessed review (AMSTAR) and study quality indicators (GRADE). The SRs included (N = 9) were of high quality. The efficacy of NIs in prophylaxis ranged from 64% (16-85) to 92% (37-99); the absolute risk reduction ranged from 1.2% to 12.1% (GRADE moderate to low). Clinically relevant treatment benefits of NIs were small in healthy adults and children suffering from influenza-like illness (GRADE high to moderate). Oseltamivir reduced antibiotic usage in healthy adults according to one SR, but this was not confirmed by other reviews (GRADE low). Zanamivir showed a preventive effect on antibiotic usage in children (95% (77-99);GRADE moderate) and on the occurrence of bronchitis in at-risk individuals (59% (30-76);GRADE moderate). No evidence was available on the treatment benefits of NIs in elderly and at-risk groups and their effects on hospitalization and mortality. In oseltamivir trials, nausea, vomiting and diarrhea were significant side-effects. For zanamivir trials, no adverse effects have been reported. The combination of diagnostic uncertainty, the risk for virus strain resistance, possible side effects and financial cost outweigh the small benefits of oseltamivir or zanamivir for the prophylaxis and treatment of healthy individuals. No relevant benefits of these NIs on complications in at-risk individuals have been established.

Concepts: Epidemiology, Evidence-based medicine, Systematic review, Randomized controlled trial, Influenza, Adverse effect, Oseltamivir, Neuraminidase