Prevalent Side Effects Research Articles

Oxaliplatin-induced blood brain barrier loosening: a new point of view on chemotherapy-induced neurotoxicity

Oxaliplatin is a key drug in the treatment of advanced metastatic colorectal cancer. Despite its beneficial effects in tumor reduction, the most prevalent side-effect of oxaliplatin treatment is a chemotherapy-induced neuropathy that frequently forces to discontinue the therapy. Indeed, along with direct damage to peripheral nerves, the chemotherapy-related neurotoxicity involves also the central nervous system (CNS) as demonstrated by pain chronicity and cognitive impairment (also known as chemobrain), a newly described pharmacological side effect.The presence of the blood brain barrier (BBB) is instrumental in preventing the entry of the drug into the CNS; here we tested the hypothesis that oxaliplatin might enter the endothelial cells of the BBB vessels and trigger a signaling pathway that induce the disassembly of the tight junctions, the critical components of the BBB integrity.By using a rat brain endothelial cell line (RBE4) we investigated the signaling pathway that ensued the entry of oxaliplatin within the cell. We found that the administration of 10 μM oxaliplatin for 8 and 16 h induced alterations of the tight junction (TJs) proteins zonula occludens-1 (ZO-1) and of F-actin, thus highlighting BBB alteration. Furthermore, we reported that intracellular oxaliplatin rapidly induced increased levels of reactive oxygen species and endoplasmic reticulum stress, assessed by the evaluation of glucose-regulated protein GRP78 expression levels. These events were accompanied by activation of caspase-3 that led to extracellular ATP release.These findings suggested a possible novel mechanism of action for oxaliplatin toxicity that could explain, at least in part, the chemotherapy-related central effects.

Pharmacological interaction of Galphimia glauca extract and natural galphimines with Ketamine and Haloperidol on different behavioral tests

Due to the high prevalence of psychiatric disorders and the prevalent side effects produced by the antipsychotic drugs available, it is necessary to search for new therapeutic options. Galphimia glauca has been used for many years in Mexican traditional medicine for treating mental diseases. From this plant, some compounds, denominated galphimines, have been discovered and have shown to possess the ability of modifying the frequency of discharge of dopaminergic neurons in the Ventral tegmental area.The objective of the present work was to evaluate the effect produced by the G. glauca extract, a Galphimine rich fraction (GRF), as well as the pure galphimines (G-A, G-B, and G-E) on behavioral models in mice.Products obtained from G. glauca were evaluated in the Haloperidol-induced catalepsy test and in the acute schizophrenia-like symptoms-induced with Ketamine (KET) in mice. Catalepsy was evaluated through the bar test, and schizophrenia-like symptoms, by means of the Open Field Test (OFT), Passive Avoidance Test (PAT), and the Forced Swimming Test (FST).The methanolic extract from G. glauca, GRF, and the pure galphimines were able to interact with the dopaminergic pathway and modify the behavioral response such as to potentiate the cataleptic effect induced with Haloperidol and to inhibit the behavior induced by KET in mice exposed to OFT, and FST. Moreover, the G. glauca extract and GRF were capable of blocking the cognitive decline that was induced with KET in mice (evaluated by PAT). Based on these results, it is possible to assume that part of the effect of G. glauca is due to the interaction of Galphimines with the dopaminergic and glutamatergic systems in vivo.It can be concluded that the products obtained from G. glauca potentiate the cataleptic effect induced with Haloperidol and show a protector effect on some of the symptoms generated by KET in mice (KET is capable of provoking halucinations in humans and psychosis-like behaviour in mice). With this basis, the metanolic extract from G. glauca, and the GRF are capable of blocking positive and cognitive symptoms associated with psychosis induced by KET. In addition, it could be suggested that the galphimines are responsible for the inhibition of the positive symptoms observed.

Dissatisfaction with opioid maintenance treatment partly explains reported side effects of medications

BackgroundDrop-out is a core problem in opioid maintenance treatment (OMT), but patients’ reactions to and acceptance of the various OMT medications are insufficiently investigated. In Norway, there has been vocal patient resistance to the newest medication, buprenorphine-naloxone (BNX), and complaints have focused on the side effect profile. There has been no comparison of patient satisfaction and side effects of the three most common OMT medications. AimTo compare patient satisfaction with OMT and side effects of BNX, buprenorphine monopreparate (BUP), and methadone (MET) as reported by patients. MethodsData were drawn from a national peer-to-peer survey developed by a patient advocacy group. The survey engaged more than 1000 OMT patients, corresponding to one seventh of OMT patients in Norway. The associations between side effects, treatment satisfaction, and patient characteristics were tested in multinomial logistic regressions. ResultsHigh patient satisfaction with OMT overall was reported despite lower satisfaction with medication itself and widely prevalent side effects. Among each medication group, dissatisfaction with medications or OMT in general along with poor health status increased the relative risk ratio of reporting the heaviest side effect burden. MET users reported the highest side effect burden and BNX users the lightest, but BNX users were more dissatisfied with their medication. ConclusionsSide effects are a concern for nearly all OMT patients, and they do not appear to accumulate with age or length of treatment. BNX users’ dissatisfaction with their medication is of particular concern, and expectations and preferences of medication may be influencing their dissatisfaction.

An Epidemiologic and Clinical Study of Snake Bites during a Five-Year Period in Karoon, Iran

Background:Snakebite is one of the most common health problems in endemic regions such as Iran. Due to the potential life-threatening impact of snake envenomation and biodiversity of snakes, it seems that epidemiological studies are required, as the primary step to design standard and local therapeutic protocols, regarding the national and regional facilities and therapeutic needs. Methods:This investigation was conducted with a retrospective design, by studying all the records of patients affected by snakebite and hospitalized in Sina Hospital during 2006 to 2011. Epidemiological data and also the outcomes of patients (including side effects and survivals) were collected. The data were analyzed by SPSS software version 18, using descriptive statistics and Chi-Square test. P < 0.05 was considered as significant. Results:A total of287 snakebite patients were studied. 73.5% of patients were men and most of them belonged to the age group of 15-34 years. Most common complaints of patients once admitted were pain (74.6%) and edema (43.9%). 96.5% of the patients received 5-10 vials of anti-venom. The most prevalent side effect observed was coagulopathy (70.7%). A significant relationship was found between the anti-venom onset after the bite and the rate of coagulopathy occurrence (p=0.035). Three deaths had occurred in general. Conclusion:Early referral to medical centers and administration of anti-venom has been accompanied by significant improvement in outcomes, and would reduce the hematological side effects, need for administrating blood products, and probably the need for administration higher anti-venom doses.

Seizures and Anticonvulsants in Brain Tumours: Frequency, Mechanisms and Anti-Epileptic Management.

In cancer, epilepsy can be the manifestation of a primary brain tumour, metastatic disease, vascular or surgical complications, opportunistic infection or secondary to anti-tumour therapy. Seizures are frequently the first symptom of a brain tumour. The epilepsy is related to elevated extracellular glutamate stimulating NMDAand AMPA-receptors and to the formation of D-2HG which resembles glutamate in IDH1 mutated gliomas. Epilepsy as presenting sign is associated with a longer survival in low- and high- grade gliomas, particularly with the IDH1 mutation. Anti-tumour treatment by surgery, radiotherapy or chemotherapy strongly contributes to seizure control. Symptomatic management of brain tumour-related epilepsy (BTE) by evidenced-based anti-epileptic drugs (AEDs) as indicated for focal epilepsy depends on individual patient factors including age, sex, weight, co-morbidity and cotherapy. Levetiracetam followed by lacosamide or valproic acid are the agents of choice. Both can be combined with levetiracetam in case monotherapy is inactive or produces side-effects. Lamotrigine, perampanel, zonisamide or clobazam are other good choices. On seizure prophylaxis, there is some evidence for its application in the peri-operative period. The most prevalent side-effects of AEDs in neuro-oncology are cognitive dysfunction, bone marrow toxicity and skin hypersensitivity. Combining anti-epileptic drugs with chemotherapy, tyrosinekinase inhibitors or steroids increases the risks of drug-drug interactions. Plasma monitoring of AEDs for detecting drug insufficiency, interactions or toxicity helps in choosing the proper dose regimen. For practical use, tables on drug interactions between AEDs and cancer therapy are added together with a guideline on the medical management of seizure control including dose regimens.

Investigating Esophageal Stent-Placement Outcomes in Patients with Inoperable Non-Cervical Esophageal Cancer.

Background: Esophageal stent insertion in patients with inoperable esophageal cancer is usually accompanied with relatively high adverse symptoms and even mortality. The current study aims at investigating the outcomes of esophageal stenting in patients with inoperable non-cervical esophageal cancer.Materials and Methods: The current descriptive-analytical research evaluates 25 patients with esophageal cancer. The stent was placed in esophagus based upon endoscopy analysis with or without fluoroscopy and then the stent position and its opening was investigated by making use of CXRand Gastrografin studies. Demographic characteristics, dysphagia scores, stent placement side effects and the dysphagia-related indices were recorded and examined by taking advantage of a questionnaire which was administered pre and post stent insertion.Results: The study population was comprised of 15 women and 10 men. The individuals' average age was 69.20 ± 11.25 years. Dysphagia mean score was lowered from a value of 4.32 ± 0.80 to 2.00 ± 1.22 (P-value<0.05). The prevalent side effects were chest pain (64%), dysphagia recurrence (40%), stent blockage (20%), stent migration (16%), GI bleeding (8%), and malposition (8%). Also, it was found out that 64% of the patients survived for 6 months.Conclusion: The results indicated that although esophageal stenting is accompanied with side effects in patients with inoperable esophageal cancer, but it is the most frequently used and the most reliable method in relieving dysphagia and improving dysphagia-related life indices.

The KATP channel in migraine pathophysiology: a novel therapeutic target for migraine

BackgroundTo review the distribution and function of KATP channels, describe the use of KATP channels openers in clinical trials and make the case that these channels may play a role in headache and migraine.DiscussionKATP channels are widely present in the trigeminovascular system and play an important role in the regulation of tone in cerebral and meningeal arteries. Clinical trials using synthetic KATP channel openers report headache as a prevalent-side effect in non-migraine sufferers, indicating that KATP channel opening may cause headache, possibly due to vascular mechanisms. Whether KATP channel openers can provoke migraine in migraine sufferers is not known.ConclusionWe suggest that KATP channels may play an important role in migraine pathogenesis and could be a potential novel therapeutic anti-migraine target.

Abstract 3132: Inhibition of the integrin αVβ3 improves the effect of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL)

Abstract CTCL are exposed to a complex paracrine and endocrine environment that influence their progression from skin to visceral disease. One of the most common treatments for CTCL is RXR agonists or “rexinoids” such as bexarotene (BEX). The most prevalent side effect of rexinoids (~95% of patients) is the development of hypothyroidism hence these patients are prophylactically treated with thyroid hormone (TH). Paradoxically, we recently found (PMID: 25488971) that TH can activate transcriptional programs required for proliferation of CTCL. We also found that the effects of TH on CTCL are mediated through the activation of two different receptors, the classical nuclear TR and a membrane receptor integrin αVβ3. Our aim was to study how the anti-lymphoma activity of BEX is modified by the activation of TR and αVβ3 during the TH replacement therapy, and unknown topic with clinical implications. We first evaluate the cell viability of CTCL cells HuT78 and MJ treated with BEX in presence and absence of physiological levels of TH. As expected, BEX decreased the viability of CTCL cells, however in presence of TH both effects decreased by 25-60% and 20-50% on HuT78 and MJ cells. However, hypothyroidism is associated with a higher dissemination of TCL cells in syngeneic mice. Thus, to evaluate the impact of TH replacement therapy in BEX-treated mice, we implanted TCL EL-4 cells subcutaneously in C57BL/6 mice. When tumors reached ~75 mm3, mice were randomized in three groups: vehicle, bexarotene alone (BEX) and bexarotene with T4 replacement (to reach euthyroidism) (BEX-T4). Tumor growth significantly decreased in both bexarotene arms (vs. vehicle). However, in contrast to mice receiving BEX-T4, mice receiving BEX alone showed a decreased infiltration of tumor-suppressive immune cells. Specifically, these tumors had decreased NK and CD3+CD8+ cells due to BEX-induced hypothyroidism. This indicates that although TH could decrease the effect of BEX in CTCL cells, the hypothyroidism would impact in the local antitumor response. Thus determine if the inhibition of the non-canonical TH membrane receptor integrin αVβ3 would decrease the pro-survival effect of TH on CTCL treated with BEX. We found that either, αVβ3 silencing or the pharmacological inhibitor Cilengitide, not only avoided the pro-survival effect of TH but increased the anti-lymphoma activity of BEX-T4 by 15-35% in CTCL cells. To evaluate the molecular program underpinning these effects, we conducted RNA-sequencing in HuT78 cells treated with BEX-T4 in presence of siRNA for TR, αVβ3 or controls. Among the top pathways we identified genes involved in “apoptosis”, “angiogenesis” and “IL6-JAK-STAT3 signaling” as differentially expressed in si-αVβ3 vs. the others. These genes were independently validated by using Cilengitide. Our data suggest that inhibition of the non-canonical TH receptor, the integrin αVβ3, could be an effective strategy to improve BEX treatment in CTCL Citation Format: Florencia Cayrol, Victoria Revueta, Alejandra Paulazo, Mercedes Debernardi, Maria Celeste Diaz Flaque, Helena Sterle, Leandro Cerchietti, Graciela Cremaschi. Inhibition of the integrin αVβ3 improves the effect of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3132. doi:10.1158/1538-7445.AM2017-3132

The most prevalent side effects of pegylated liposomal doxorubicin monotherapy in women with metastatic breast cancer: a systematic review of clinical trials.

Despite benefits of systemic chemotherapy in breast cancer treatment, several patients with early-stage breast cancer will develop metastatic breast cancer (MBC). Doxorubicin is among the most active agents against MBC. However, the use of doxorubicin is related to some life-threatening side effects including cardiotoxicity. Many efforts were made to lessen the side effects of doxorubicin and improve its efficacy. Pegylated liposomal doxorubicin (PLD) is a product claimed to achieve these two objectives because of its different pharmacokinetic profile. The aim of this study was to determine the side-effect profile of PLD in MBC through a systematic review of phase II clinical trials. A literature search in PubMed-MEDLINE was performed using terms covering nano-based pharmaceutical systems, 'breast cancer' and 'doxorubicin'. Articles were evaluated according to the inclusion criteria. Reported hematological and non-hematological side effects were categorized. Out of 718 articles that were initially identified, 8 were in accordance with the inclusion criteria. We found that the most important side effects of PLD were skin toxicity and mucositis, but the proportion of patients who showed grade III and IV of these side effects was relatively low. On the other hand, the occurrence of cardiotoxicity, the most important problem with doxorubicin, was considerably reduced in patients treated with PLD. Although PLD has demonstrated a lower toxicity profile than conventional anthracyclines, it has also new side effects. However, it seems that the reduced cardiotoxicity of PLD has made it a more appropriate option in patients with MBC, especially in those with risk factors for cardiac diseases.

Latent Inhibition Reduces Nocebo Nausea, Even Without Deception.

Nocebo nausea is a debilitating and prevalent side effect that can develop after conditioning occurs between cues present in the treatment context and the experience of nausea. Interventions that retard conditioning may therefore be able to reduce nocebo nausea. To test whether 'latent inhibition', where pre-exposing cues in the absence of an outcome retards subsequent learning about those cues, could reduce nocebo nausea in healthy adults. We examined this possibility using a Galvanic Vestibular Stimulation (GVS) model of nausea in healthy participants, with pre-exposure to the treatment cues achieved using a placebo version of GVS. In Experiment 1 we found clear evidence of conditioned nocebo nausea that was eradicated by latent inhibition following pre-exposure to placebo stimulation. Experiment 2 tested whether deception, which may be unethical in clinical settings, was necessary to produce latent inhibition by including an open pre-exposure group informed they were pre-exposed to placebo stimulation. Experiment 2 replicated the latent inhibition effect on nocebo nausea following deceptive pre-exposure from Experiment 1 and found that open pre-exposure was just as effective for reducing nocebo nausea. In both experiments, there was an interesting discrepancy found in expectancy ratings whereby expectations appeared to drive the development of conditioned nocebo nausea, but were not responsible for its suppression through latent inhibition. These findings have significant clinical implications. Applying open pre-exposure in clinical settings may effectively and ethically reduce the development of nocebo effects for nausea and other conditions via latent inhibition.

Assessment of Cognition and Quality of Life in Non-Hodgkin’s Lymphoma Patients One Year Post-Treatment

Objectives: An increasing number of patients with cancer are offered chemotherapy given either alone or in combination with radiotherapy, surgery, or both as neo-adjuvant, concomitant, or adjuvant treatment. Cognitive dysfunction is a prevalent side effect of cancer treatments that may persist for years following treatment and has negative impact on quality of life. Thus, the present study was planned to investigate the prevalence of cognitive impairment, assess the quality of life (QOL) and determine the socioeconomic status in NHL patients one year post chemotherapy treatment. Methods: This was an observational study. All the prospective participants were screened on the basis of inclusion and exclusion criteria and the participants who met all the study inclusion criteria and had none of the exclusion criteria were enrolled in the study. Cognitive function was evaluated using Mini Mental State Examination (MMSE) or Hindi Mental State Examination (HMSE), socioeconomic status was determined by Kuppuswamy scale and quality of life (QoL) was assessed by EORTC QLQ. Results: A total of 90 subjects (45 cases and 45 controls) were enrolled in the study. The control group scored more on MMSE/HMSE scale than the Non-Hodgkin’s Lymphoma (NHL) patient group, suggesting difference in cognitive functioning between the groups (26.6 ± 2.4 vs. 27.8 ± 2.1, p=0.019), respectively. Socio-economic status did not have any impact on the prevalence of cognitive impairment in NHL patients; however, NHL was found to be more prevalent in upper-middle class. No significant difference was found between case and control for QoL. Conclusion: Cognitive dysfunction is a prevalent side effect of cancer treatment that may persist for a year following treatment. Further studies are needed to clarify the effect on quality of life.

Botulinum toxin in spinal cord injury patients with neurogenic detrusor overactivity.

Evidence for the efficacy and safety of intravesical onabotulinum toxin A (onabotA) injections has led to them being licensed in many countries, including Korea, for the treatment of patients with urinary incontinence due to neurogenic detrusor overactivity (NDO) resulting from spinal cord injury or multiple sclerosis who are refractory or intolerant to anticholinergic medications. OnabotA injections have an inhibitory effect on acetylcholine release for up to 10 months, with a recommended dose of 200 U. OnabotA treatment has a beneficial effect not only on urinary symptoms, but also on quality of life. Several clinical studies have shown onabotA to have better effects than placebo in achieving continence, reducing incontinence episodes, improving urodynamic parameters, and improving health-related quality of life. Urinary tract infections and postvoid residual volume are the most prevalent side effects. In patients with residual volume, clean intermittent catheterization may be necessary. In patients with spinal cord injury or multiple sclerosis, it is recommended to evaluate physical and cognitive function before intravesical onabotA injection to ensure that the patient and caregiver are able to perform catheterization if necessary. Further controlled trials should assess the optimal dose, injection technique, long-term safety of repeated injections, and optimal timing of onabotA treatment in the treatment of NDO.

Fertility: A Control Factor for Post Mastectomy Pain Syndrome in Breast Cancer Patients

Background: Normally, surgery is the first choice of treatment for breast cancer which brings about side effects as chronic pain. Post mastectomy pain syndrome (PMPS) is one of the most prevalent side effects in breast cancer survivors as a chronic neuropathic pain lasting more than three months. The precise mechanisms and risk factors connected to chronic pain after breast surgery are not identified. Objectives: This study is aimed at identifying the effects of fertility on PMPS after breast surgery in breast cancer patients. Methods: In this case-control study, a total number of 111 women were studied. Of these, 56 women were diagnosed with positive PMPS and place in the case group, and 55 patients without pain were selected as the control group. The patients’ demographic and clinical information were collected by means of a questionaire and their medical files. Descriptive statistics and inferential statistics, chi-square, Mann-whitney U, Regression Logisitic (Backward), were used to analyze the data in SPSS 22 software. Results: According to the acquired results, the mean age of the study population was 49.77 ± 10.94, the mean weight was 69.5 ± 11.45 kg, the mean height was 160 ± 8.14 centimeter and mean BMI was 27.4 ± 5.4. All in all, the results showed that fertile women were more likely not to suffer from PMPS compared to nulipar women, and there was not a correlation between psychological disorders or other diseases, and PMPS. Conclusions: Fertility is not only a decrescent factor of breast cancer, but also reduces PMPS in breast cancer patients. Encouraging timely fertility, and pregnancy and lactation cares must be the major part of reproductive health education programs.

Use of Complementary Therapies for Side Effect Management in Breast Cancer: Evidence and Rationale

Women diagnosed with breast cancer can experience chronic side effects after curative treatment concludes, negatively impacting survivorship. The most prevalent side effects addressed in the medical and nursing literature include symptoms such as hot flashes, fatigue, myalgias/arthralgias and cognitive impairment. Complementary therapies, particularly natural products including herbs, dietary supplements, vitamins, minerals, and probiotics, and mind–body techniques that include such modalities as yoga, meditation, massage, acupuncture, relaxation, tai chi and hypnosis show promise for treatment of some of these symptoms associated with cancer care. However, the research in this area is nascent and much more work is needed to understand symptom physiology and mechanisms of action of complementary therapies. The purpose of this paper was to summarize key evidence from Phase II and III randomized clinical trials in order to provide guidance to distinguish promising versus nonpromising interventions for symptom management.

Health Related Quality of Life in Patients with Side-Effects after Antimuscarinic Treatment for Overactive Bladder.

Drug therapy is the mainstay of treatment for overactive bladder (OAB), but antimuscarinic agents possess side-effects. These side-effects decrease the patients' quality of life. We therefore assessed the impact of side-effects on health-related quality of life (HR-QoL) through an analysis of EQ-5D questionnaire. This study was designed to investigate the patients' satisfaction by quality weight of health status as affected by the side-effects of OAB medications. Patients who had OAB symptoms lasting longer than 3 months and have experienced side-effects after any antimuscarinic treatments filled in the EQ-5D questionnaire. The enrolled patients had two EQ-5D questionnaires for two different health statuses, i.e., presence or absence of side-effects. Quality weight was calculated using the ED-5D health status score with Korean tariff. One hundred patients were enrolled and completed the HR-QoL questionnaire. The most prevalent side-effect was dry mouth (61%) and 28% patients had dry mouth and constipation concurrently. Most of the patients with side-effects tried to endure and overcome these side-effects (79%), but 10% desired a change in medication, and 6% stopped medication altogether. The quality weight of EQ-5D without side-effects was 0.863, while the quality weight with side-effects was 0.666 (P < 0.001). The VAS score was 79 in patient without side-effects and 57 in those with side-effects, supporting the results of quality weight assessment. Overactive bladder patients may enjoy a better quality of life if side-effects associated with antimuscarinic therapy are fewer.

Comparison of Efficacy and Side Effects of Azithromycin and Co-Amoxiclav in the Treatment of Acute Sinusitis in Adults: A Randomized Clinical Trial

&lt;p&gt;&lt;strong&gt;BACKGROUND:&lt;/strong&gt; Regarding high prevalence of common cold and sinusitis in Chaharmahal and Bakhtiari Province and the lack of studies on patients referring hospitals in this province, this study was conducted to determine and compare the efficacy and side effects of azithromycin and co-amoxiclav.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;METHODS:&lt;/strong&gt; This study was a double-blinded randomized clinical trial. The study population of this clinical trial was consisted of 90 patients with acute sinusitis aged 12-65 years. At least two major criteria or one major criterion and two minor criteria with duration of at least 7 days and at most 28 days, were some of the sinusitis diagnostic criteria for inclusion of the patients into the study. The patients were examined for symptoms prior to and twice after the treatment. The treatment was administration with &lt;strong&gt;500 mg&lt;/strong&gt; azithromycin tablet per day for three days in group 1 (G1) and &lt;strong&gt;625 mg&lt;/strong&gt; co-amoxiclav tablet every &lt;strong&gt;8 h&lt;/strong&gt; for 10 days in group 2 (G2). The data were analyzed by repeated measures analysis of variance, independent t-test, and chi-square in Stata software and P &amp;lt; 0.05 was considered significant.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;RESULTS: &lt;/strong&gt;Mean±Standard deviation age of all patients was 32.14±9.91 years. Out of 90 participants in the study, 50 (55.56%) were male and the rest were female. The patients’ symptoms were quantitatively similar in the two groups (22.3±2 and 22.2±1.9 in G1 and G2, respectively) prior to the intervention. The score at second examination decreased to 3.7±2.1 in G1 and to 9.4±2.7 in G2, significantly different from that prior to intervention and between the two groups (P&amp;lt;0.001). Although the score decreased in the two groups at third examination, it was not significant in the two groups (P=0.652). The cure rate in azithromycin group was derived 87.5% and 88%, and in co-amoxiclav group 32.4% and 83.3% at the days 5 and 10 of treatment, respectively. The most prevalent side effects in the two groups were diarrhea and nausea. The prevalence of diarrhea was obtained 21% and 33% in G1 and G2, respectively. &lt;/p&gt;&lt;strong&gt;CONCLUSION: &lt;/strong&gt;No significant difference in side effects was seen between the two groups. Although the cure was faster in the patients treated with azithromycin than those treated with co-amoxiclav, co-amoxiclav is still considered as adequately working against acute sinusitis bacterial pathogens. In view of this efficacy, co-amoxiclav seems to lead to no drug resistance and could be used to treat the patient

Intricate Assessment and Evaluation of Dental Implants in Patients on Bisphosphonate Therapy: A Retrospective Analysis.

Osteonecrosis is one of the prevalent side effects of bisphosphonate (BP) therapy in oral cancer patients. In case of patients with various oncologic lesions, standard guidelines contraindicate the use of dental implants if the patients are on BP therapy. Literature also quotes studies that emphasize on the safety of dental implants in patients on BP therapy. Hence, this study aimed to retrospectively evaluate the clinical outcome of dental implants in patients on BP therapy. In this retrospective analysis, a total of 140 dental implants in 112 patients were included. Inclusion criteria included only those patients who were on or had history of BP therapy. Calculation of implant failure and survival rate was done. Ten cases of implant failure occurred, giving a success rate of above 92%, which was comparable to the results found in previous studies in patients who were not on BP therapy. No significant risk of implant failure is seen in patients on BP therapy compared with other patients.

Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance.

The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp) has been targeted for antiviral development. Direct acting antivirals (DAA) have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly effective and well tolerated antiviral treatment for HCV infection. Here we review the different classes of RdRp inhibitors and their mode of action against HCV. Furthermore, the mechanism of antiviral resistance to each class is described, including naturally occurring resistance-associated variants (RAVs) in different viral strains and genotypes. Finally, we review the impact of these RAVs on treatment outcomes with the newly developed regimens.

Topical antioxidants in radiodermatitis: a clinical review

Radiation-induced skin toxicity is the most prevalent side effect of radiation therapy. Not only does it have a significant effect on patients' quality of life, but it also results in poor follow-up and early termination of radiotherapy treatment. Several skin care practices and topical applications have been studied in the field of radiodermatitis, including skin washing, topical steroids, and mechanical skin barriers. Aside from these methods, many patients turn to complementary and alternative medicine for the prevention and treatment of radiodermatitis. Many of these alternative therapies are topically applied antioxidants. While the rationale behind the use of antioxidants in treating radiodermatitis is strong, clinical studies have been far less consistent. Even in large scale randomised controlled trials, findings have been limited by the inconsistent use of topical vehicles and placebos. In this article, the authors review the role of topical antioxidants to better help the practitioner navigate through different available skin directed antioxidants.

Behavioral and electrophysiological abnormalities in two rat models of antiretroviral drug-induced neuropathy.

Painful peripheral neuropathy due to the antiretroviral therapy used to treat HIV is one of the most prevalent side effects occurring in at least 30% of patients living with this infection. We have evaluated the electrophysiological and behavioral effects of d4T and ddC on peripheral large and small nerve fibers in male rats treated with d4T (Sprague-Dawley, 50 mg/kg, twice within 1 week), ddC (Wistar, 50 mg/kg, 3 times per week for 3 weeks), or vehicle. The effect of the interventions was assessed using behavioral measures of mechanical sensitivity, conventional nerve conduction studies, and microneurographic single nerve C-fiber recordings. To mimic as much as possible the human clinical condition, all treated animals were included in the study. No statistically significant differences were observed in behavioral parameters of mechanical sensitivity. Nerve conduction studies did not reveal any significant change in the ddC-treated group. In contrast, we observed electrophysiological evidence of significant demyelinating neuropathy 1 week after the start of d4T treatment. Additionally, spontaneous activity in mechanoinsensitive C-nociceptors was observed in both drug-treated groups. No relationship could be established between measures of spontaneous activity in C-nociceptors and the results of the behavioral tests. Our results show that both models of antiretroviral-induced neuropathy differ in their effects on peripheral nerves. However, both groups present abnormal spontaneous activity in mechanoinsensitive C-nociceptors that can be used as a model for pharmacological intervention.