Misoprostol plus isosorbide mononitrate versus misoprostol alone for cervical ripening during labor induction: A systematic review and meta-analysis of randomized controlled trials.

AIM: To conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that examined the maternal and neonatal outcomes of misoprostol+isosorbide mononitrate (ISMN) versus misoprostol alone (control) in promoting cervical ripening during labor induction. METHODS: We searched five databases from inception until 05-May-2021. We assessed risk of bias of RCTs, meta-analyzed 23 endpoints, and pooled them as mean difference or risk ratio with 95% confidence interval. RESULTS: Overall, five RCTs met the inclusion criteria, comprising 850 patients (426 and 424 patients were allocated to misoprostol+ISMN and misoprostol group, respectively). Overall, the RCTs had a low risk of bias. Pertaining to maternal delivery-related outcomes, there was no significant difference between both groups regarding the mean interval from drug administration to delivery, rate of vaginal delivery, rate of cesarean section delivery, and rate of need for oxytocin augmentation. Pertaining to maternal drug-related side effects, the rate of maternal headache was significantly higher in disfavor of the misoprostol+ISMN compared with misoprostol alone. However, the rates of maternal nausea, hypotension, flushing, palpitation, dizziness, postpartum hemorrhage, and uterine tachysystole did not differ between both groups. Pertaining to neonatal outcomes, there was no significant difference between both groups regarding rates of NICU admission, meconium-stained amniotic fluid, and Apgar score <7 at five minutes. CONCLUSION: Compared with misoprostol alone, co-administration of misoprostol+ISMN did not correlate with superior maternal delivery-related outcomes. The rate of maternal headache was significantly higher in disfavor of the misoprostol+ISMN group. There was no significant difference between both groups regarding neonatal endpoints.

Rapid Improvement in Jaundice Using Transdermal Isosorbide Tape as a Nitric Oxide Donor in Two Adult Patients with Transplantation-associated Microangiopathy Related to Graft-versus-host Disease.

Two adult patients with acute leukemia developed transplantation-associated microangiopathy (TAM) related to graft-versus-host disease (GVHD). Both patients were resistant to standard therapy for TAM and GVHD, which led to markedly elevated serum total bilirubin levels of 47.5 and 10.6 mg/dL, respectively. Transdermal isosorbide tape as a nitric oxide donor was applied to Patients 1 and 2 on post-transplantation days 60 and 66, respectively, which rapidly improved their jaundice after 1 day. This is the first report to describe the efficacy of transdermal isosorbide tape for adult patients with jaundice associated with TAM related to GVHD.

Comparative analysis of cost-effectiveness between isosorbide-5-mononitrate and isosorbide: a retrospective real-world evaluation.

Aim: The cost-effectiveness of isosorbide-5-mononitrate (5-ISMN) and isosorbide dinitrate (ISDN) in real-world use in patients with coronary heart disease (CHD; either angina pectoris or myocardial infarction) was retrospectively compared. Method: In this retrospective real-world evaluation, patients with established CHD satisfying the following criteria were selected from information system of two tertiary hospitals in China: with pharmacy claiming for at least one injection of 5-ISMN or ISDN between July 2008 and May 2017; and, CHD patients. By using propensity score matching (PSM), we compared clinical aspects of efficacy, safety, length of hospital stay and cost during hospitalization between 5-ISMN and ISDN group. All data were processed by R statistical package v.2.13.1 (R Foundation for Statistical Computing, Vienna, Austria). Result: Of 5609 patients selected, 4047 received 5-ISMN and 1562 received ISDN. After PSM, we acquired 1555 pairs based on balancing of age, sex, insurance and comorbidities on admission. The frequency (4.2 ± 6.6-times vs 6.5 ± 9.5-times; p < 0.05) and total dosage (47.5 ± 153.4 vs 136.4 ± 261.0 mg; p < 0.05) of sublingual nitroglycerin use decreased and hypotension incidence lowered (8.0 vs 13.0%; p < 0.05) in 5-ISMN group compared with ISDN group. Hospital stay (16.0 ± 11.3 days vs 17.7 ± 13.2; p < 0.05) and hospitalization expenditure ([the ratio of cost in the study to the average hospitalization cost in the city] [odds ratio: 2.5 vs 2.6; p < 0.05]) were reduced in 5-ISMN group as with that of ISDN group. Moreover, the main component of hospitalization cost was medical consumables and medications in both the groups. Conclusion: In the present retrospective real-world evaluation, by using PSM analysis, we found that newer injection agent of 5-ISMN was associated with fewer use of sublingual nitroglycerin, less hypotension incidence, shorter length of hospital stay and less hospitalization expenditure related to its comparator ISDN in patients with established CHD. Further evaluation and clinical experience are need in different circumference for the usage of ISDN.

Nuevas evidencias en el manejo de pacientes con insuficiencia cardiaca con fracción de eyección preservada / New evidence for the management of patients with heart failure with preserved ejection fraction

Introducción: Aunque en ocasiones los nitratos se emplean para el alivio de los síntomas en el paciente con insuficiencia cardiaca, realmente no se conocen sus efectos en el paciente con insuficiencia cardiaca y fracción de eyección preservada, a pesar de que algunas series muestran cómo los nitratos son empleados en el 15-50% de estos pacientes. El estudio (Nitrate's Effect on Activity Tolerance in Heart Failure with Preserved Ejection Fraction (NEAT-HFpEF) comparó el efecto de mononitrato de isosorbida frente a placebo sobre la actividad diaria en pacientes con insuficiencia cardiaca y fracción de eyección preservada. Métodos: Se realizó un ensayo clínico multicéntrico, doble ciego y de diseño cruzado, en el que se incluyó a 110 pacientes ambulatorios con al menos 50 años de edad e insuficiencia cardiaca con una fracción de eyección preservada (≥ 50%) en tratamiento médico estable. Los pacientes fueron aleatorizados a mononitrato de isosorbida, con un régimen de titulación de 6 semanas (de 30mg a 60mg a 120mg una vez al día) o a placebo, con el consiguiente cruce al otro grupo por 6 semanas. La variable primaria del estudio fue el nivel de actividad diaria cuantificada mediante acelerómetro durante la fase de 120mg. Resultados: En comparación con el placebo, los pacientes tratados con 120mg de mononitrato de isosorbida mostraron una tendencia no significativa a presentar una menor actividad diaria (p=0,06) y un descenso significativo en las horas de actividad por día (-0,30 h; p=0,02). Asimismo, la actividad en el grupo de mononitrato de isosorbida durante todas las dosis fue menor que en el grupo placebo. Además, los niveles de actividad disminuyeron significativamente y de manera progresiva conforme aumentaba las dosis de mononitrato de isosorbida. No hubo diferencias significativas entre los grupos ni en el test de los 6 min, ni en la calidad de vida, ni en los niveles de péptidos natriuréticos. Numéricamente hubo más discontinuaciones en los pacientes con tratamiento activo, así como más efectos adversos. Conclusiones: La adición de mononitrato de isosorbida al tratamiento con insuficiencia cardiaca y fracción de eyección preservada se tradujo en una menor actividad diaria. Además, tampoco mejoró la calidad de vida de estos pacientes (AU)

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Fatal Intoxications Due to Administration of Isosorbide Tablets Contaminated with Pyrimethamine.

In January 2012, 664 cases of pyrimethamine toxicity and 151 deaths were reported among cardiac patients that had recently received free medicines from pharmacy of Punjab Institute of Cardiology, Lahore, Pakistan. These patients, ages ranged from 58 to 75 years, were prescribed simvastatin, clopidogrel, aspirin soluble, isosorbide mononitrate, and amlodipine. On examination of medications being given to them, it was found that a particular batch of isosorbide mononitrate tablets was contaminated with 50 mg pyrimethamine. Cardiac patients were taking isosorbide contaminated with pyrimethamine twice daily (100 mg pyrimethamine/day), whereas therapeutic dose of pyrimethamine for malaria is 25 mg/week. Postmortem urine, cardiac blood, and femoral blood specimens of three deceased males were submitted to author's laboratory for analysis. Postmortem toxicological analysis revealed that pyrimethamine concentration fell within the range of 1-10 µg/mL by liquid chromatography. Clinical, autopsy, histopathological, and toxicological findings strongly suggested toxicity due to pyrimethamine accumulation that resulted in deaths of these cardiac patients.

Is dehydration test using isosorbide useful in Meniere's disease?

CONCLUSION: The dehydration test using isosorbide is well tolerated when used to detect endolymphatic hydrops and may also be used to improve the sensitivity of ECoG performed on patients with MD, especially in poor hearing at low-frequency. OBJECTIVE: This prospective study was to explore the diagnostic utility of a dehydration test, administering oral isosorbide, which has been used to treat Meniere's disease (MD). METHOD: Electrocochleography (ECoG) and the dehydration test with isosorbide were performed on 32 patients diagnosed with definite diagnosed MD. Isosorbide (120 mL) was orally administered after baseline audiometric testing, and the testing was repeated 3 h later. The dehydration test was considered positive when improvements in hearing thresholds of 10 dB or more were evident at two or more frequencies, or the speech discrimination score increased by 12% or more. An abnormal ECoG finding was defined as an SP/AP (summating potential/action potential) ratio ≥0.4. RESULTS: The dehydration test using isosorbide was positive in 10 of 32 patients (31.3%). The test was not associated with development of any serious side-effect. Abnormal ECoG findings were noted in 14 of 32 patients (43.8%). When endolymphatic hydrops was defined as an abnormal ECoG or a positive dehydration test, the condition was detected in 21 of 32 patients (65.6%). The positive result in dehydration test was significantly higher in patients with above moderate hearing loss at low-frequency.

Prognostic impact of chronic nitrate therapy in patients with vasospastic angina: multicentre registry study of the Japanese coronary spasm association.

AIMS: Although nitrates are widely used as a concomitant therapy with calcium channel blockers (CCBs) for vasospastic angina (VSA), their prognostic contribution remains unclear. The present study aimed to examine the prognostic impact of chronic nitrate therapy in patients with VSA. METHODS AND RESULTS: A total of 1429 VSA patients (median 66 years; male/female, 1090/339) were enrolled. The primary endpoint was defined as major adverse cardiac events (MACE). The propensity score matching and multivariable Cox proportional hazard model were used to adjust for selection bias for treatment and potential confounding factors. Among the study patients, 695 (49%) were treated with nitrates, including conventional nitrates [e.g. nitroglycerin (GTN), isosorbide mono- and dinitrate] in 551 and nicorandil in 306. Calcium channel blockers were used in >90% of patients. During the median follow-up period of 32 months, 85 patients (5.9%) reached the primary endpoint. Propensity score-matched analysis demonstrated that the cumulative incidence of MACE was comparable between the patients with and those without nitrates [11 vs. 8% at 5 years; hazard ratio (HR): 1.28; 95% confidence interval (CI): 0.72-2.28, P = 0.40]. Although nicorandil itself had a neutral prognostic effect on VSA (HR: 0.80; 95% CI: 0.28-2.27, P = 0.67), multivariable Cox model revealed the potential harm of concomitant use of conventional nitrates and nicorandil (HR: 2.14; 95% CI: 1.02-4.47; P = 0.044), particularly when GTN and nicorandil were simultaneously administered. CONCLUSIONS: Chronic nitrate therapy did not improve the long-term prognosis of VSA patients when combined with CCBs. Furthermore, the VSA patients with multiple nitrates would have increased risk for cardiac events.

Vasospastic angina with J-wave pattern and polymorphic ventricular tachycardia effectively treated with quinidine.

BACKGROUND: Myocardial ischemia during coronary spasm may generate malignant ventricular arrhythmias. The J-wave pattern was suggested to be a marker of a disorder associated with life-threatening arrhythmias. RESULTS: We report the case of a patient with vasospastic angina and J-wave pattern in inferior and lateral leads associated with polymorphic ventricular tachycardia which was effectively treated only with quinidine-vasodilating drugs were not able to prevent the arrhythmia although they were effective in preventing ischemic events. CONCLUSION: The J-wave pattern in inferolateral leads may be a sign of electrical vulnerability to lethal ventricular arrhythmia in patients suffering from vasospastic angina--quinidine can effectively prevent such arrhythmias in these patients.

A comparison of the short-term outcome in patients with acute low-tone sensorineural hearing loss.

PURPOSE OF THE STUDY: We aimed to compare the short-term outcome of patients with acute low-tone sensorineural hearing loss (ALHL) treated with steroid alone, diuretics alone or combination treatment. PROCEDURES: Between April 2000 and March 2009, we retrospectively reviewed the medical records of 156 patients with a diagnosis of ALHL. All patients were followed up until improvement or for 8 weeks from the initial examination. Patients were treated with steroid alone (n = 49), diuretics alone (n = 40), combination treatment (n = 46) or they received neither steroid nor diuretics (n = 21). RESULTS: The steroid-diuretic combination therapy for ALHL showed significantly better results than the steroid or diuretic treatments alone (p < 0.05). There were no clinically significant differences in the outcome between the steroid- and diuretic-alone treatments. CONCLUSION AND MESSAGE: The etiology of ALHL is described as both an endolymphatic hydrops and an autoimmunological mechanism so that, as expected, the steroid-diuretic combination therapy was more effective than the steroid or diuretic treatments alone.

Mononitrato de isosorbide o misoprostol vaginal para la maduración cervical en embarazos a término / Vaginal isosorbide mononitrate or misoprostol for cervical ripening in term pregnancies

Objetivo Comparar la efectividad del mononitrato de isosorbide con la del misoprostol vaginal en la maduración cervical en embarazos a término. Método Se seleccionaron y asignaron al azar pacientes para ser tratadas con 40mg de mononitrato de isosorbide (grupo A) o 100 μg de misoprostol (grupo B) que asistieron para maduración cervical e inducción del parto. Se evaluaron la tasa de eficacia, el tiempo entre el inicio de la maduración y la obtención del recién nacido, las complicaciones neonatales y los efectos adversos. Resultados No se encontraron diferencias estadísticamente significativas entre los grupos con relación a las características generales (p=ns). Las pacientes tratadas con misoprostol presentaron un período significativamente menor desde la administración de la primera dosis hasta la obtención del recién nacido que las pacientes tratadas con isosorbide (p<0,05). No se encontraron diferencias significativas con relación al número de partos vaginales entre ambos grupos (p=ns). Los recién nacidos de las pacientes del grupo B presentaron valores promedio significativamente más bajos de Apgar al minuto y a los 5min al compararlos con el grupo A (p<0,05). El efecto adverso más común en el grupo A fue la cefalea (16 casos, 53,3%), mientras que en el grupo B fue la diarrea (5 casos, 16,7%).Conclusiones El misoprostol y el mononitrato de isosorbide vaginal tienen una efectividad similar en la maduración cervical en embarazos a término cuando son administrados (AU)

Objective To compare the effectiveness of vaginal isosorbide mononitrate or misoprostol in cervical ripening in term pregnancies. Methods Patients undergoing cervical ripening and induction of labor were selected and randomly assigned to receive 40mg isosorbide mononitrate (group A) or 100 mcg misoprostol (group B). The efficacy rate, time between cervical ripening and delivery, neonatal outcome and adverse effects were evaluated. Results There were no significant differences between the groups in general characteristics (p=ns). Patients treated with misoprostol showed a shorter period from first dose administration to newborn delivery than those treated with isosorbide (p<0.05). There were no significant differences in the number of vaginal births between the two groups (p=ns). Newborns in group B had significantly lower mean Apgar scores at 1 and 5min than those in group A (p<0.05). The most common adverse effect in group A was headache (16 cases, 53.3%) and diarrhea (five cases, 16.7%) in group B. Conclusion The effectiveness of vaginal misoprostol and isosorbide mononitrate is similar in cervical ripening in term pregnancy (AU)

Effect of nicorandil on proteinuria in well controlled hypertensive patients.

OBJECTIVE: Proteinuria is an important risk factor for cardiovascular and renal morbidity and mortality. The effect of nicorandil on proteinuria in hypertensive patients well controlled by antihypertensive agents containing a low dose of valsartan has not been studied. PATIENTS AND METHODS: A total of 136 proteinuric (300-3000 mg/day), valsartan-treated hypertensive patients with blood pressure less than 140/90 mmHg were randomized into three groups to receive placebo, isosorbide dinitrate (30 mg/day), or nicorandil (15 mg/day) for 6 months. RESULTS: The average dose of valsartan given to the patients was similar in the three groups. Creatinine clearance remained stable throughout the study in the three groups. Nicorandil, but not isosorbide dinitrate, significantly reduced proteinuria by 44% after 6 months (P < 0.0001). Urinary endothelin-1 levels significantly decreased after administration of nicorandil (P = 0.002), whereas placebo and isosorbide dinitrate had no effect. Urinary excretion of endothelin-1 was significantly correlated with improvement in urinary protein excretion in nicorandil-treated patients (r = 0.69, P < 0.0001). The urinary excretion of retinol-binding protein decreased after nicorandil administration, probably reflecting an improvement in tubular function. In contrast, the urinary excretion of immunoglobulin G did not change significantly throughout the study in the three groups. Multivariate analysis revealed that proteinuria was only significantly correlated with the use of nicorandil (model adjusted r = 0.35, P < 0.0001). CONCLUSION: The addition of nicorandil to treatment for patients with well controlled hypertension may have an additive effect on reducing proteinuria independent of hemodynamics and nitric oxide effects, possibly through inhibiting renal endothelin-1 synthesis and improving tubular function.

Vestibular type of Mondini anomalies with BPPV and Meniere's disease-like symptoms.

An extremely rare case with labyrinthine anomaly with normal hearing was demonstrated. This case firstly showed transient positioning vertigo like benign paroxysmal positional vertigo (BPPV) and subsequently episodic vertigo like Meniere's disease. A 55-year-old male attended our hospital, complaining of transient but persistent positioning vertigo in 2004. The apogeotropic positioning nystagmus was observed in spine position. In 2005, he came to feel episodic vertigo continuously for more than 30min like Meniere's disease. We examined CT scan and 3D-MRI, indicating the hypoplastic lateral semicircular canal (L-SCC) fused together with enlarged vestibule on the left side. We finally diagnosed this case as Mondini anomaly on the left side. The imaging analysis is the most useful for differential diagnosis of Mondini anomalies, because symptoms in these patients are actually various due to the individual inner ear condition. The mechanism of generation of BPPV-like vertigo: the otolith in deformed utricle might be transferred into the fused space with vestibule and L-SCC, resulting in the irrigation of the hypoplastic cupula. The mechanism of generation of Meniere's disease-like vertigo: neuro-otologic findings with furosemide test implied endolymphatic hydrops on the left side. Meniere's disease-like episodic vertigo could be due to subsequently generated endolymphatic hydrops.

Current endoscopic therapy of variceal bleeding.

Variceal ligation has proved more effective and safer than sclerotherapy and is currently the endoscopic treatment of choice for oesophageal varices. In acute bleeding, vasoactive drugs should be started before endoscopy and maintained for 2-5 days. The efficacy of drugs is improved when associated with emergency endoscopic therapy. Antibiotic prophylaxis should also be used. To prevent rebleeding, both endoscopic ligation and the combination of beta-blockers and nitrates may be used. Adding beta-blockers improves the efficacy of ligation. Haemodynamic responders to beta-blockers+/-nitrates (those with a decrease in portal pressure gradient HVPG to <12 mmHg or by >20% of baseline) have a marked reduction in the risk of haemorrhage and will not need further treatment. Beta-blockers significantly reduce the risk of a first haemorrhage in patients with large varices, and they improve survival. As compared to beta-blockers, endoscopic ligation reduces the risk of first bleeding without affecting mortality, and should be used in patients with contraindications or intolerance to beta-blockers.

Vestibular evoked myogenic potentials in acute acoustic trauma.

OBJECTIVES: Anatomical proximity of the saccule to the stapedial footplate points to the possibility of acoustic trauma associated with saccular dysfunction. Therefore, it was the authors' premise that abnormal vestibular evoked myogenic potential (VEMP) after acute acoustic trauma may be caused by saccular damage from very high intensity noise; consequently, irreversible hearing loss ensued. The aim of this study was to investigate the VEMP responses in those with acute acoustic trauma. STUDY DESIGN: A prospective study. SETTING: University hospital. PATIENTS: Twenty patients (29 ears) without previous ear disorders diagnosed as acute acoustic trauma were enrolled in this study. MAIN OUTCOME MEASURES: Before treatment, each patient underwent pure tone audiometry and caloric and VEMP tests. Correlations between the hearing outcome and mean hearing level, sources of noise, caloric responses, or VEMP results were investigated. RESULTS: After 3 months of medication, complete recovery was achieved in 4 ears and hearing improvement in 4 ears, whereas hearing in 21 ears (72%) remained unchanged. Eighteen ears presenting normal VEMPs revealed hearing improvement in eight ears (44%) and unchanged hearing in ten ears (56%). However, hearing loss remained unchanged in all 11 ears (100%) with absent or delayed VEMPs, exhibiting a significant relationship between VEMP results and hearing outcome. Thus, VEMP test can predict the hearing outcome after acute acoustic trauma with a sensitivity of 44% and a specificity of 100%. CONCLUSION: The greater the noise intensity, the severer damage on the cochlea and saccule is shown. Absent or delayed VEMPs in ears after acute acoustic trauma may indicate poor prognosis with respect to hearing improvement, whereas normal VEMP is not a powerful indicator for expectation of hearing improvement.