Significant Increase In Side Effects Research Articles

Current Data and Future Perspectives on Patients with Atrial Fibrillation and Cancer.

Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with cancer. Indeed, cancer patients have a significantly higher incidence of AF than that observed in the general population. A reciprocal relationship between these two diseases has been observed, as much as some assume AF to be a marker for occult cancer screening, especially in older adults. The pathophysiological mechanisms are many and varied, including the underlying pro-inflammatory state, specific treatments (chemo- and radiotherapy), and surgery. The therapeutic management of patients with cancer and AF involves the same rhythm and frequency control strategies as the general population; however, the numerous interactions with chemotherapeutics, which lead to a significant increase in side effects, as well as the extreme fragility of the patient, should be considered. Anticoagulant therapy is also a complex challenge to address, as bleeding and stroke risk scores have not been fully assessed in this subpopulation. Furthermore, in large studies establishing the efficacy of direct oral anticoagulants (DOACs), cancer patients have been underrepresented. In this review, we elaborate on the mechanisms linking AF to cancer patients with a particular focus on the therapeutic challenges in this population.

Comparison of Clonidine with Bupivaicaine vs Plain Bupivaicaine in Transversus Abdominis Plane (TAP) Block in Women Undergoing Cesarean Delivery Under Spinal Anesthesia: Randomized Clinical Trial.

Transversus abdominis plane (TAP) block is a technique of regional anesthesia, introduced by Rafi in 2001. Various additives have been added to prolong the duration of effect of TAP block. We conducted this study to see if addition of clonidine to bupivacaine significantly increases the duration of effect of TAP block. This randomized, parallel group, placebo controlled double blind clinical trial was conducted on 100 healthy participants (ASAII) undergoing LSCS under Spinal anesthesia (SA) from Jan 2021 to July 2021 after consent of Institutional Ethics Committee. Women with contraindications to spinal anesthesia, allergy to any of the drugs or not-suitable for cesarean under SA were excluded. After written informed consent, eligible participants were randomly allocated into two groups using computer generated random number tables using serially numbered opaque sealed envelopes. 48 out of 50 participants in group A (Bupivacaine) were given TAP block with 20 ml of 0.25% bupivacaine bilaterally. 2 women were excluded because of conversion to General Anesthesia. Similarly, 47 out of 50 participants in Group B (Bupivacaine + Clonidine) were given TAP block with 20 ml of 0.25% bupivacaine plus 1.0 mcg/kg clonidine bilaterally after completion of surgery using 18 G Tuohy needle. Separate person used to fill the drugs for block. Participants were assessed for duration of analgesic effect of TAP block measured as the time to request for additional analgesia. Additional analgesic requirement was noted. Participants were assessed for side effects of clonidine like hypotension, bradycardia, sedation and dryness of mouth. Overall patient satisfaction was also noted. Data was analysed using Graphpad Prism 9, using Student's t-test for primary outcome and Mann-Whitney U test for secondary outcomes. The mean 'duration of analgesic effect with TAP block' was 6.34 (SD1.26) hrs for 'Bupivacaine' group and 10.56 (SD2.12) hrs for 'Bupivacaine + Clonidine' group. None of the patients developed hypotension or bradycardia. 25% participants in Bupivacaine only group and 40.42% in Bupivacaine + Clonidine group were sedated (P < 0.05). 20.8% in 'Bupivacaine' group and 51.06% in 'Bupivacaine + Clonidine' group had dryness of mouth (P < 0.001). Patient satisfaction was equal in both the groups. Addition of clonidine to bupivacaine in the dose of 1 mcg/kg significantly increases the duration of analgesic effect of TAP block, decreases analgesic usage without significant increase in side effects.

Effect of Selective Serotonin Reuptake Inhibitors on Motor Recovery After Stroke: A Systematic Meta-analysis.

We conducted a meta-analysis to determine the effectiveness of SSRIs in improving motor outcomes after stroke. For accuracy, we only included studies in which SSRIs were administered to patients in the recovery phase after stroke (<6 months after stroke). Meta-analyses were conducted according to the tools used to measure motor function. We searched the SCOPUS, PubMed, Embase, and Cochrane Library databases for studies which compared motor recovery in patients who receive SSRI medication in the recovery phase after stroke with a control group that did not receive any SSRI. A total of 3,715 publications were assessed, and nine studies met the study criteria. The group which received SSRI showed improved Fugl-Meyer Motor Scale and Barthel index scores compared to the control group. However, there was no significant difference in the modified Rankin Scale scores between the SSRI and control groups. The incidence of adverse effects after the administration of SSRIs did not differ from that in the control group. Our study showed that the use of SSRI in the recovery phase of stroke improved motor function without significant increase in side effects.

Nurse-Led Telephone Follow-Up Intervention for Titrating and Tapering Opioids in Chronic Pain Patients – A Feasibility Study

Opioids in chronic non-cancer pain are debated, but remain a part of the pain treatment for selected patients. Research is scarce on the relieving and adverse effects of opioids, and how to deliver opioid treatment in this patient group. This study's purpose was to assess the feasibility of a nurse-led telephone follow-up intervention for titrating or tapering opioids, including a pilot study of the intervention outcomes. The feasibility assessment and process evaluation were performed according to the UK Medical Research Council (MRC) framework for evaluating complex interventions. A pilot study of the intervention outcomes was also performed. With a retrospective, descriptive, and longitudinal approach, we analyzed reports from 32 patients who titrated or tapered opioids. Information on demography, sleep satisfaction, health status, pain intensity/bothersomeness, opioid doses, and side effects was derived from the Oslo Pain Registry. Descriptive statistics, t-tests, and chi-square tests were used to analyze registry data. The study findings indicate that the intervention is feasible. Areas of impact were lack of a sound theory basis, unclear allocation criteria, and inconsistent and non-validated measurement tools. Mechanisms of change were interprofessional collaboration, nurses' knowledge and competencies, predictability, and availability. Statistical analyses showed no between-groups differences in demographical-, clinical-, and pain characteristics, except those who titrated opioids were significantly older than patients tapering opioids (P=0.010). All patients reported poor health and side effects at baseline. Those who tapered opioids had a significant reduction in opioid use (P=0.004). Titrating opioids was associated with a significant increase in side effects (P=0.038). Considering the limitations and the strengths of the intervention, the present study indicates that the nurse-led telephone follow-up program is a feasible intervention. With the right adjustments and improvements, the intervention is eligible for a larger efficacy study.

Treatment of Congenital Hypothyroidism: Impact of Secular Changes in Levothyroxine Initial Dose on Early Growth

Introduction: Newborn screening of congenital hypothyroidism (CH) has enabled early treatment with levothyroxine (LT4), ensuring normal growth and development. The initial LT4 dose recommendation has increased over decades. We evaluated whether the increased LT4 dosing influenced thyroid-stimulating hormone (TSH) and thyroxine (fT4) concentrations, growth, or treatment-related symptoms. Methods: LT4 doses, TSH, fT4, anthropometrics, and treatment-related symptoms until age 2 years were evaluated in 172 Finnish CH patients born between 1980 and 2018. The patients were grouped according to birth decade: 1980s (n = 19, mean LT4 starting dose 6.8 μg/kg/day), 1990s (n = 50, 7.4 μg/kg/day), 2000s (n = 59, 9.7 μg/kg/day), and 2010s (n = 44, 10.8 μg/kg/day). Results: TSH concentrations were higher during the first 2 years of life in children born in the 1980s compared to children born later. TSH concentrations were often subnormal in children receiving higher LT4 doses (children born in the 2000s and 2010s). However, symptoms of overtreatment were uncommon. Linear or head growth showed no differences between the groups during the first 2 years of life. Although growth was within the normal spectrum, children in all groups were shorter than their target length at 2 years and their weight-for-length was above the mean through the first 2 years of life. Discussion: Current treatment practice with higher LT4 dose normalizes TSH rapidly without significant increase in side effects. However, irrespective of initial LT4 dose, children were shorter than expected at 2 years of age. Effects of different initial LT4 dose on cognitive development urges further investigation.

Application of Dexmedetomidine combined with Propofol Intravenous Anesthesia in Laparoscopic Day Surgery in Pediatric Urology.

ABSTRACTObjectives:To evaluate the sedative and analgesic effects of dexmedetomidine combined with propofol intravenous anesthesia in laparoscopic day surgery in pediatric urology.Methods:Eighty male children with cryptorchidism and hydrocele who underwent laparoscopic daytime surgery in our hospital from January 2019 to January 2021 were selected and randomly divided into two groups: the experimental group and the control group. Children in the experimental group ranged in age from 5.7 to 11.3, with an average of 8.52±2.17 years old, while those in the control group ranged in age from 5.3 to 12.0, with an average of 8.60±2.07 years old. There were 12 cases of cryptorchidism and 28 cases of hydrocele in the experimental group, and 14 cases of cryptorchidism and 26 cases of hydrocele in the control group. Children in the control group received conventional propofol intravenous combined anesthesia, while those in the experimental group were given dexmedetomidine (2-5 ug/kg) intranasally on the basis of conventional propofol intravenous anesthesia. The anesthetic effect, analgesic effect, serum levels of inflammatory cytokines before and after surgery and adverse drug reactions in the two groups were compared and analyzed.Results:The awakening time, extubation time and retention time in the resuscitation room of the experimental group were shorter than those of the control group, with a statistically significant difference (P<0.05); The VAS pain scores of the experimental group were significantly lower than those of the control group at 15minutes, 12hour and 24hour after awakening, with a statistically significant difference (P<0.05). In addition, the levels of TNF-a, CRP, IL-6 and other inflammatory factors in the control group were significantly higher compared with those in the experimental group 24h after surgery, with a statistical significance (TNF-a, P=0.02; CRP, P=0.00; IL-6, P=0.03); The incidence of adverse drug reactions in the experimental group was 17.5%, while that in the control group was 12.5%, which was not statistically significant (P=0.53).Conclusion:Dexmedetomidine combined with intravenous propofol anesthesia may be helpful to shorten the extubation time, the recovery time and the stay time in the anesthesia resuscative room, improve the analgesic effect, and may reduce the inflammatory response and the expression of serum inflammatory cytokines, with no significant increase in side effects.

Ondansetron compared with doxylamine and pyridoxine for treatment of nausea and vomiting in pregnancy

Background: Nausea and vomiting affects up to 80% of the pregnant women population and are the third leading causes of maternal hospitalization during pregnancy. Many pregnant females, and even some healthcare professionals, dread using antiemetic drugs due to a false beliefof their teratogenicrisk. Aim of the work:This study aimed to evaluate ondansetron to a combination of doxylamine and pyridoxine in controlling pregnancy-related nausea and vomiting. Patients and Methods:This randomized controlled trial included 156 pregnant women, at 16 weeks of gestation, with mild-to-moderate nausea and vomiting. Meanwhile, women with severe symptoms indicating admission, those already on anti-emetics, and those who wouldn’t be able to show up for follow-up visits were excluded. Seventy-eight patients received intravenous injection of ondansetron [Zofran] at a dose of 8 mg once daily for 5 days, whereas the other 78 patients received oral pyridoxine at a dose of 25 mg plus doxylamine at a dose of 12.5 mg [Diclegis] twice daily for 5 days. Each patient was subjected to full history taking, complete clinical examination and investigations. Results: Women on Ondansetron reported better alleviation of nausea compared to those receiving pyridoxine and doxylamine [96.2% vs. 52.6%, P<0.001, respectively]. The most frequently reported side effects were headache, dry mouth, gastrointestinal [GI] disturbances, and abdominal pain, and the differences in their occurrence between the two groups were statistically insignificant. Conclusion: Ondansetron was found superior to the combination of pyridoxine and doxylamine in improving pregnancy-related nausea and vomiting occurring without a significant increase in side effects.

200-OR: Effects of Glucose Target on the Performance of a Bihormonal Bionic Pancreas

We performed a non-blinded, random-order, cross-over study in 20 volunteers with type 1 diabetes comparing glycemic regulation by the bihormonal bionic pancreas (BHBP) at three glucose targets (130, 115, and 100 mg/dl). Subjects went about their daily routines during each 3-day test period. In the BHBP arms, lower glucose targets (130 to 115 to 100 mg/dl) were associated with correspondingly lower mean CGM glucose levels (156±12 to 146±14 to 135±14 mg/dl, p&amp;lt;0.005 for each comparison). There was no corresponding difference in percent time &amp;lt;60 mg/dl (0.6±1.0 % to 0.9±1.2% to 0.8±1.1%, p≥0.22 for each comparison). However, there was a corresponding significant increase in glucagon total daily dose (2.2±1.2 to 5.3±2.3 to 8.3±3.0 µg/kg/day, p≤0.001 for each comparison). Mean daily nausea scores reported on a 10 cm visual analog scale were low and not significantly different between BHBP arms (0.5, 0.8 and 1.1 cm for the 130, 115, and 100 mg/dl glucose targets, respectively, p&amp;gt;0.05 for each comparison). There were no significant differences between the different BHBP arms in average hypoglycemia symptoms per day, average hypoglycemia interventions per day, or average grams of oral carbohydrates taken by subjects to prevent or treat hypoglycemia. The 100 mg/dl glucose target had a higher satisfaction score when compared to the 115 and 130 mg/dl glucose targets (4.3 versus 4.15 and 4.18, respectively; p&amp;lt;0.005 for both comparisons). There was no significant difference in satisfaction score between the 115 and 130 mg/dl glucose targets. The results of the present study show that for the BHBP, the lowest glucose target in this comparison was associated with better glycemic control, no statistically significant increase in side effects, and greater user satisfaction than higher glucose targets. Disclosure M. Tuffaha: None. C.A. Balliro: None. M. Hillard: None. F. El-Khatib: Other Relationship; Self; Beta Bionics, Inc. R. Selagamsetty: Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. E. Damiano: Board Member; Self; Beta Bionics, Inc. Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S.J. Russell: Consultant; Self; Beta Bionics, Inc., ConvaTec Inc., Novo Nordisk A/S, Senseonics. Research Support; Self; Beta Bionics, Inc., Novo Nordisk A/S, Zealand Pharma A/S. Stock/Shareholder; Self; Companion Medical. Other Relationship; Self; Ascensia Diabetes Care, Roche Diabetes Care. Funding The Leona M. and Harry B. Helmsley Charitable Trust

Effect on Morphine Requirement of Early Administration of Oral Acetaminophen vs. Acetaminophen/Tramadol Combination in Acute Pain.

To evaluate the effect on opioid requirement of pain treatment starting at triage, and to evaluate satisfaction in emergency department (ED) patients with acute pain. This is a single-blind, randomized, prospective study conducted in the ED. The included patients were randomly assigned to single oral doses of placebo, acetaminophen, or a tramadol/acetaminophen combination. Protocol treatment was given at triage. The primary outcome was the need for rescue morphine during ED stay. The secondary outcome included patient satisfaction, ED length of stay, and percentage of patients discharged from the ED with a VAS score of <30. We included 1,485 patients: 496 patients in the placebo group, 497 in the acetaminophen group, and 492 in the tramadol/acetaminophen combination group. The groups were similar regarding demographic and clinical characteristics and baseline VAS pain scores. Rescue morphine was significantly decreased in the tramadol/acetaminophen combination group compared to that in the placebo and acetaminophen groups (11.5%, 23.2%, and 18.9%, respectively; P=0.03). Patient satisfaction was higher in the tramadol/acetaminophen combination group (77% vs. 69% in the acetaminophen group and 68% in the placebo group). A VAS score of <30 was observed in 84% of patients in the placebo group, 83% in the acetaminophen group, and 87% in the tramadol/acetaminophen combination group (P=0.01 between the acetaminophen group and tramadol/acetaminophen combination group). The ED length of stay was 60minutes for the acetaminophen group and tramadol/acetaminophen combination group and 71minutes for the placebo group (P=0.04). Oral tramadol/acetaminophen combination administered early in triage was associated with a decrease in intravenous morphine requirement and increase in satisfaction among ED patients with acute pain when compared with patients taking acetaminophen. No significant increase in side effects was found. This intervention may be considered in EDs with an aim of similar benefits.

Effectiveness of bezafibrate and ursodeoxycholic acid in patients with primary biliary cholangitis: a meta-analysis of randomized controlled trials.

Background:Ursodeoxycholic acid (UDCA) and obeticholic acid are currently approved treatments for primary biliary cholangitis (PBC). Since some patients do not respond adequately to UDCA, other therapies, such as bezafibrate, have been developed. In this meta-analysis we evaluated the efficacy and safety of using both UDCA and bezafibrate in patients with an inadequate response to UDCA.Methods:We evaluated all randomized controlled trials comparing the combination of UDCA and bezafibrate with UDCA monotherapy. Standardized mean difference (SMD) was used to assess the treatment effect of combination therapy compared with UDCA alone.Results:Ten trials with a total of 369 patients were analyzed. UDCA and bezafibrate combination therapy was more effective than UDCA monotherapy in improving alanine aminotransferase (SMD -2.04, 95% confidence interval [CI] -3.30 to -0.79), alkaline phosphatase at both less than 12 months (SMD -3.63, 95%CI -6.43 to -0.84) and more than 12 months (SMD -2.33, 95%CI -4.03 to -0.63), gamma-glutamyltransferase (SMD -1.29, 95%CI -2.67 to 0.08), triglyceride (SMD -0.80, 95%CI -1.41 to -0.19), immunoglobulin M (SMD -1.48, 95%CI -2.39 to -0.56), and cholesterol (SMD -4.61, 95%CI -7.34 to -1.89). There was no difference between the 2 groups in bilirubin, aspartate aminotransferase or albumin. None of the adverse effects differed statistically between the 2 groups.Conclusion:UDCA and bezafibrate combined treatment is superior to UDCA alone in UDCA non-responders with regard to decreasing liver biochemistry markers, without any significant increase in side effects in patients with PBC.

Does a single dose of pregabalin help with postoperative pain after septoplasty?

Does a single dose of pregabalin help with postoperative pain after septoplasty?

Using of Magnesium Sulphate for Fetal Neuroprotection in Patients Presenting by Intrapartum Fetal Distress at Term : A Randomized Controlled Trial

Background: labour is a stressful event for the fetus but is well tolerated by most fetuses. However, in some infants stress of labour in terms of metabolic acidosis can lead to Hypoxic Ischemic Encephalopathy (HIE). HIE around term remains a major cause of neonatal mortality and morbidity with lifelong chronic disabilities. Such insults are not limited to high risk pregnancies but can also occur in about 50% of low risk pregnancies. On current evidence, it is estimated that in about 10 of brain damaged infants, the cause is hypoxia during labour.There has been considerable interest in magnesium sulfate (MgSO4) because magnesium alleviates excitotoxic damage by binding to the magnesium site on the NMDA (N-methyl-D-aspartate) glutamate channel. Aim of the Work: magnesium sulphate (MgSo4) for fetal neuroprotection in patients presenting by intrapartum fetal distress at term. Patient and Methods:this is a randomized controlled trial (RCT). The current study was conducted to single term pregnant women who developed intrapartum fetal distress (as defined later) and need emergency CS (ceaseran section) according to Ain Shams protocol. This study was carried on 200 pregnant females, recruited from observation and labour wards of Ain Shams University Maternity Hospital. The current study was conducted to single term 200pregnant women who developed intrapartum fetal distress and needs emergency CS (cesarean section) according to Ain Shams protocoltoexaminethe effects of administered magnesium sulphate .patient were invited to participate in the study after providing clear explanation of the study and its expected values. Result: patients were invited to participate in this study after providing clear explanation of the study and its expected values. The demographic data of included women showed no significant difference between groups in the age and gestational age There was a significant difference in Apgar score at 5 min between MgSo4 and placebo.MgSo4 had significantly lower the risk of decrease Apgar score < 7 at 5min(p:0.029) .Mgso4 also had significantly lower seizure attacks (p:0.002) and had highly significantly reduce NICU admission rate (MgSo4 group 20(20%) and placebo group 43(43%)(p: 0.001)).In MgSo4 group, 23 women reported adverse reactions associated with procedure. Among them, 16 (16%) reported only flushing and 7 (7%) reported only nausea. In placebo group, were 8 (8%) reported flushing and 2 (2%) reported nausea. Conclusion and Recommendation: magnesium sulfate is effective in reducing risk of Apgar score <7 at 5min. Magnesium sulfate appear to be effective in reducing seizure and NICU admission. Magnesium sulphate is associated with maternal morbidity rather than non exposure in the form of nausea and flushing. The improvement in short-term outcomes without significant increase in side effects indicate the need for further trials to determine if there are long-term benefits of magnesium and to confirm its safety.

Addition of buprenorphine to local anesthetic in adductor canal blocks after total knee arthroplasty improves postoperative pain relief: a randomized controlled trial

Background and ObjectivesFor the hundreds of thousands of patients who undergo total knee arthroplasty (TKA) in the United States each year, early mobilization has been demonstrated to improve functional outcomes and reduce complications. Management of postoperative pain is a critical factor in achieving early mobilization. Recent studies have shown that the use of an adductor canal block (ACB) after TKA results in increased preservation of quadriceps muscle strength, without significant difference in postoperative pain when compared to femoral nerve block. This increased preservation of quadriceps muscle strength leads to earlier mobilization. Studies have also demonstrated a prolongation of analgesia with the addition of buprenorphine to local anesthetic for regional block placement. This study examined the effect on postoperative opioid consumption when adding buprenorphine to an ACB vs an ACB with local anesthetic alone, for postoperative analgesia after unilateral TKA. MethodsA total of 100 patients scheduled for TKA were randomized to receive postoperative ACB with local anesthetic alone or with local anesthetic and buprenorphine. The primary outcome examined was total opioid analgesic (milligrams of hydrocodone equivalent) consumption in the first 24 hours postsurgery. The secondary outcomes examined were the reported incidence of the opioid side effects nausea, vomiting, and pruritis. ResultsPostoperative opioid consumption decreased significantly in the group that received an ACB with local anesthetic and buprenorphine compared to an ACB with local anesthetic only (25.34±2.62 vs 35.84±2.86; P=.0076). Secondary outcomes showed no statistical difference between the 2 groups in terms of the incidence of nausea, vomiting, or pruritus. ConclusionThe addition of buprenorphine to an adductor canal block decreases postoperative opioid consumption when compared to an ACB with local anesthetic alone. This reduction in opioid consumption, without significant increase in side effects, makes this an attractive anesthetic adjunct for TKA.

Safety and Efficacy of Adding Ribavirin to Interferon or Peginterferon in Treatment of Hepatitis C Infection in Patients With Thalassemia: A Systematic Review on Randomized Controlled Trials

ContextHepatitis C virus (HCV) infection is a major cause of liver-morbidity and mortality among patients with thalassemia. Peginterferon plus ribavirin is currently the recommended therapy for hepatitis C infection in patients do not have thalassemia, but using ribavirin in patients with thalassemia is restricted due to its hemolytic effect. To evaluate the efficacy and safety of adding ribavirin to peginterferon or interferon, authors performed a systematic review on the available literatures.Evidence AcquisitionTrials were identified through electronic database, manual searches of journals and bibliographies and approaching authors of trials. Randomized trials that enrolled patients with a diagnosis of thalassemia and chronic hepatitis C infection treated with interferon or peginterferon with or without ribavirin were included. Two investigators independently evaluated the trials for inclusion criteria, risk of bias and data extraction. The primary outcomes were sustained virological response (SVR), liver-related morbidity, mortality and adverse events. The odds ratios from each trial were calculated individually and in the subgroup analysis of trials. Data were analyzed with fixed-effect model.ResultsThree randomized clinical trials with 92 patients were included. All three trials had unclear risk of bias. Compared with peginterferon monotherapy, adding ribavirin to peginterferon had significant beneficial effect on sustained virological response (OR = 3.44, 95% CI: 1.18 - 10.06). There was no significant difference between combination therapy and monotherapy in the end of treatment achievement response. Other than about 30% increase in blood transfusion due to anemia that returned to normal level 2 - 3 months after treatment, there was no significant increase in side effects followed by adding ribavirin to pegylated interferon (Peg-IFN). Data were insufficient to determine the impact of genotype, viral load and age on the response to treatment.ConclusionsCompared with monotherapy, adding ribavirin to treatment is more effective in removing hepatitis C virus from the bloodstream in patients with thalassemia, it is also more effective in reducing the relapse rate after treatment. Except the increase in blood transfusion, there was no significant increase in side effects followed by adding ribavirin.

Nitric oxide donors improve the ovulation and pregnancy rates in anovulatory women with polycystic ovary syndrome treated with clomiphene citrate: A RCT

Clomiphene citrate (CC) is the first line agent used for ovulation induction in patients with polycystic ovarian syndrome (PCOS). However, there is marked discrepancy between the ovulation and pregnancy rates achieved, which may be attributed to the undesirable effect of CC on cervical mucus and endometrium. The aim of this study was to evaluate the effect of Isosorbid monoitrate (ISMN) as nitric oxide (NO) donors on the ovulation and pregnancy rates in an ovulatory women with PCOS treated with CC. Ninety patients with PCOS were randomly allocated into three groups. Patients in group A) were treated with 100 mg CC for five days starting from the fifth day of the cycle. Patients in group B) and C) received 10 mg and 20 mg of ISMN respectively in addition to CC, applied vaginally till the diagnosis of ovulation. There was a significant increase in the ovulation and pregnancy rates in the patients treated with CC+ISMN as compared with patients treated with CC alone (p< 0.001). Concomitant use of NO with CC seems to improve the ovulation and pregnancy rates in the patients with PCOS with no significant increase in side effects as compared with CC alone.

English

BACKGROUND: Intrathecal adjuvants have gained popularity with the aim of prolonging the duration of block and quality of analgesia. Dexmedetomidine is relatively selective alpha2-agonist with sympatholytic, sedative, amnestic and analgesic properties. The study is designed to evaluate the efficacy of intrathecal administration of different doses of dexmedetomidine on duration of subarachnoid block and postoperative analgesia. METHODS: 60 female patients scheduled for hysterectomy, randomized in 3 groups of 20 each. Each patient was given 2.5ml of 0.5% bupivacaine with 5μg of dexmedetomidine in Group-A, 7.5μg in Group-B and 12μg in Group-C. Onset and regression time of sensory and motor block, hemodynamic change, sedation score, requirement of rescue analgesics and incidence of adverse effects were assessed perioperatively upto 24hours. RESULTS: Demographic data was statistically comparable. Sensory block onset was statistically highly significant between Group-A & C and Group-B & C (p>0.05). The time for 2 segment sensory regression and bromage scale 0 was increased by adding dexmedetomidine in a dose dependent manner (p<0.001).Postoperative VAS and analgesic requirement was significantly lower in Group-C (p<0.001). Sedation scores were significantly higher in Group-C (p<0.05). A significant decrease in heart rate and blood pressure was observed by increasing dose of dexmedetomidine with respect to base line in all the three groups. However, the results were comparable on intergroup analysis. CONCLUSION: Dexmedetomidine when used as an adjuvant to intrathecal bupivacaine hastens the onset of sensory block prolongs the duration of sensory and motor block in a dose dependent manner without any significant increase in side effects.

Optimal chemotherapy for advanced gastric cancer: is there a global consensus?

The optimal medical treatment for advanced gastric cancer is currently the source of debate. Cytotoxic treatment has been shown to prolong survival and provide improved symptom control compared with best supportive care alone, but a global standard has not yet been defined. A literature research was undertaken. Results were evaluated by an international author team. The conclusions of this are presented in this paper. Combination chemotherapy with cisplatin and 5-fluorouracil was the preferred first-line chemotherapy, but oxaliplatin has shown equivalent efficacy to cisplatin. Oral fluoropyrimidines, especially S-1 and capecitabine, can substitute for 5-fluorouracil. Modern doublet regimens are preferred in the majority of patients on the basis of a balanced benefit-to-risk ratio. In selected fit and compliant patients, especially those with a high tumor burden or potential secondary resectability, a third drug may be added because triplet chemotherapy led to higher responses rates and enhanced efficacy. However, docetaxel also adds a significant increase in side effects. Monotherapy and early dose modifications should be considered in elderly and infirm patients. Beyond that, our understanding of gastric cancer tumor biology is increasing. In HER2-positive gastric cancer, the addition of the monoclononal anti-HER2 antibody trastuzumab to cisplatin and fluoropyrimidines has prolonged survival duration. Second-line chemotherapy with single agents has now become a proven treatment option. Alternatively, anti-angiogenic treatment with ramucirumab is on the horizon. In conclusion, combination chemotherapy is regarded as the global standard of care for the first-line treatment of advanced gastric cancer. Molecularly targeted treatments are being explored, preferably in combination with a backbone of chemotherapy doublets.

HPS2-THRIVE results: Bad for niacin/laropiprant, good for ezetimibe?

During the American College of Cardiology meeting held in San Francisco (USA) in March 2013, Professor Jane Armitage presented data on the HPS2-THRIVE study (www.thrivestudy.org). The results were negative from two perspectives. First, niacin/laropiprant (ERN/LRPT) was neutral in terms of its effect on reduction of cardiovascular events. Second, ERN/LRPT therapy was associated with a significant increase in side effects. As a result of this data, ERN/LRPT has been withdrawn from the market, and an intense debate continues regarding the usefulness of niacin to prevent cardiovascular disease.

Magnesium for newborns with hypoxic-ischemic encephalopathy: a systematic review and meta-analysis

Magnesium may have a role in neuroprotection in neonatal hypoxic-ischemic encephalopathy (HIE). The objective of this study was to systematically review the efficacy and safety of postnatal magnesium therapy in newborns with HIE. MEDLINE, EMBASE, CINAHL and CCRCT were searched for studies of magnesium for HIE. Randomized controlled trials that compared magnesium to control in newborns with HIE were selected. The primary outcome was a composite outcome of death or moderate-to-severe neurodevelopmental disability at 18 months. When appropriate, meta-analyses were conducted using random effects model and risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. Five studies with sufficient quality were included. There was no difference in the primary outcome between the magnesium and the control groups (RR 0.81, 95% CI 0.36 to 1.84). There was significant reduction in the unfavorable short-term composite outcome (RR 0.48, 95% CI 0.30 to 0.77) but no difference in mortality (RR 1.39, 95% CI 0.85 to 2.27), seizures (RR 0.84, 95% CI 0.59 to 1.19) or hypotension (RR 1.28, 95% CI 0.69 to 2.38) between the magnesium and the control groups. The improvement in short-term outcomes without significant increase in side effects indicate the need for further trials to determine if there are long-term benefits of magnesium and to confirm its safety. Mortality was statistically insignificant between the magnesium and the control groups. However, the trend toward increase in mortality in the magnesium group is a major clinical concern and should be monitored closely in future trials.

Quantifying the Effect of Metformin Treatment and Dose on Glycemic Control

OBJECTIVEMetformin is the first-line oral medication recommended for glycemic control in patients with type 2 diabetes. We reviewed the literature to quantify the effect of metformin treatment on glycated hemoglobin (HbA1c) levels in all types of diabetes and examine the impact of differing doses on glycemic control.RESEARCH DESIGN AND METHODSMEDLINE, EMBASE, and the Cochrane Library were searched from 1950 to June 2010 for trials of at least 12 weeks’ duration in which diabetic patients were treated with either metformin monotherapy or as an add-on therapy. Data on change in HbA1c were pooled in a meta-analysis. Data from dose-comparison trials were separately pooled.RESULTSA total of 35 trials were identified for the main analysis and 7 for the dose-comparison analysis. Metformin monotherapy lowered HbA1c by 1.12% (95% CI 0.92–1.32; I2 = 80%) versus placebo, metformin added to oral therapy lowered HbA1c by 0.95% (0.77–1.13; I2 = 77%) versus placebo added to oral therapy, and metformin added to insulin therapy lowered HbA1c by 0.60% (0.30–0.91; I2 = 79.8%) versus insulin only. There was a significantly greater reduction in HbA1c using higher doses of metformin compared with lower doses of metformin with no significant increase in side effects.CONCLUSIONSEvidence supports the effectiveness of metformin therapy in a clinically important lowering of HbA1c used as monotherapy and in combination with other therapeutic agents. There is potential for using higher doses of metformin to maximize glycemic control in diabetic patients without increasing gastrointestinal effects.