Clinical Outcomes of Medical Management Options for Chronic Anal Fissures in a Long-Term Follow-up: Systematic Review and Meta-Analysis.

BACKGROUND: Topical treatments and botulinum toxin injections are valid options for the management of patients with chronic anal fissures (CAF), but little is known about the efficacy of these techniques in long-term follow-up. The aim of this meta-analysis was to evaluate the effectiveness, given to clinical outcomes, of medical treatments with calcium antagonists, nitroglycerin, and botulinum toxin on CAF treatment in adults. METHOD: A systemic review and meta-analysis developed according to PRISMA [PLoS Med. 2009 Jul 21;6(7):e1000100; BMJ. 2010 Mar 23;340:c332] and registered in PROSPERO (Registration number: CRD42020120386). A systematic literature search was conducted through MEDLINE, EMBASE, Web of Science, and Cochrane Library databases. Randomized control trials that compared medical treatment were identified; publications had to have a clinical definition of CAF with at least one of the following signs or symptoms: visible sphincter fibers at the base of the fissure, anal papillae, sentinel piles, and indurated margins. The symptoms had to be chronic for at least 4 weeks. Data were independently extracted for each study, and a meta-analysis was drawn using fixed- and random-effects models. RESULTS: 17 randomized trials met the inclusion criteria. Diltiazem showed a superior effect compared with glycerin (RR = 1.16 [95% CI = 1.05-1.30]; I2 = 18%) and with fewer adverse effects (RR = 0.13 [95% CI = 0.04-0.042]; I2 = 87%). Similar results were evidenced with the use of nifedipine compared with lidocaine (RR = 4.53 [95% CI = 2.99-6.86]; I2 = 28%). Botulinum toxin did not show statistically significant differences compared to glycerin (RR = 0.81 [95% CI = 0.02-29.36]; I2 = 93%) or isosorbide dinitrate (RR = 1.45 [95% CI = 0.32-6.54]; I2 = 85%). Regarding recurrence, nifedipine was superior to lidocaine (RR = 0.18 [95% CI = 0.08-0.44]; I2 = 31%). CONCLUSIONS: Calcium channel blockers performed well regarding the healing of CAF when compared to others in long-term follow-up. The superiority of botulinum toxin was not evidenced compared to topical treatments. More studies are needed to better assess recurrence rates.

Pharmacokinetics of the most commonly used antihypertensive drugs throughout pregnancy methyldopa, labetalol, and nifedipine: a systematic review.

PURPOSE: Antihypertensive drugs are among the most prescribed drugs during pregnancy. Methyldopa, labetalol, and nifedipine have been perceived safe to use during pregnancy and are therefore recommended in international guidelines for treatment of hypertension. In this review, we provide a complete overview of what is known on the pharmacokinetics (PK) of the antihypertensive drugs methyldopa, labetalol, and nifedipine throughout pregnancy. METHODS: A systematic search was performed to retrieve studies on the PK of methyldopa, labetalol, and nifedipine used throughout pregnancy. The search was restricted to English and original studies. The systematic search was conducted on July 27, 2021, in Embase, Medline Ovid, Web of Science, Cochrane Library, and Google Scholar. Keywords were methyldopa, labetalol, nifedipine, pharmacokinetics, pregnancy, and placenta. RESULTS: A total of 1459 unique references were identified of which title and abstract were screened. Based on this screening, 67 full-text papers were assessed, to retain 30 PK studies of which 2 described methyldopa, 12 labetalol, and 16 nifedipine. No fetal accumulation is found for any of the antihypertensive drugs studied. CONCLUSION: We conclude that despite decades of prescribing methyldopa, labetalol, and nifedipine throughout pregnancy, descriptions of their PK during pregnancy are hampered by a large heterogeneity in the low number of available studies. Aiming for evidence-based and personalized dosing of antihypertensive medication in the future, further studies on the relationship of both PK and pharmacodynamics (including the optimal blood pressure targeting) during pregnancy and pregnancy-related pathology are urgently needed to prevent undertreatment, overtreatment, and side effects.

Antihypertensive medicine use differs between Ghana and Nigeria.

BACKGROUND: Non-communicable diseases are a growing burden in many African countries; cardiovascular disease is the main disease. Antihypertensive medicines (AHM) are a common treatment option but we know little about community use in most low- and medium-income countries (LMIC). We aimed to describe the use of antihypertensive medicines (AHM) in Ghana and Nigeria using a novel data source. METHODS: We used data from mPharma-a health and pharmaceutical company which distributes pharmaceuticals to hospital and retail pharmacies. We extracted data using the anatomical therapeutic chemical (ATC) classification codes and calculated use in defined daily doses and explored patterns by class, medicines, dose, and originator or generic product. RESULTS: AHM use differed between Ghana and Nigeria. The most used classes in Ghana were angiotensin receptor blockers (ARB) followed by calcium channel blockers (CCB) and angiotensin-converting-enzyme inhibitors (ACEi). The five most used products were 16 mg candesartan, 30 mg nifedipine, 10 mg lisinopril, 5 mg amlodipine and 50 mg losartan. In Nigeria ARB, CCB and diuretics were widely used; the top five products were 50 mg losartan, 10 mg lisinopril, 30 mg nifedipine, 40 mg furosemide, and 5 mg amlodipine. More originator products were used in Ghana than Nigeria. CONCLUSION: The differences between Ghana and Nigeria may result from a combination of medical, contextual and policy evidence and reflect factors related to clinical guidance (e.g. standard treatment guidelines), accessibility to prescribers and the role of community pharmacies, and structure of the health system and universal health coverage including funding for medicines. We show the feasibility of using novel data sources to gain insights on medicines use in the community.

Tocolysis with nifedipine versus atosiban and perinatal outcome: an individual participant data meta-analysis.

BACKGROUND: Worldwide, nifedipine and atosiban are the two most commonly used tocolytic agents for the treatment of threatened preterm birth. The aim of this study was to evaluate the effectiveness of nifedipine and atosiban in an individual participant data meta-analysis (IPDMA). METHODS: We investigated the occurrence of adverse neonatal outcomes in women with threatened preterm birth by performing an IPDMA, and sought to identify possible subgroups in which one treatment may be preferred. We searched PubMed, Embase, and Cochrane for trials comparing nifedipine and atosiban for treatment of threatened preterm birth between 240/7 and 340/7 weeks' gestational age. Primary outcome was a composite of perinatal mortality and neonatal morbidities including respiratory distress syndrome, intraventricular haemorrhage, periventricular leucomalacia, necrotising enterocolitis, and sepsis. Secondary outcomes included NICU admission, prolongation of pregnancy and GA at delivery. For studies that did not have the original databases available, metadata was used. This led to a two-stage meta-analysis that combined individual participant data with aggregate metadata. RESULTS: We detected four studies (N = 791 women), of which two provided individual participant data (N = 650 women). The composite neonatal outcome occurred in 58/364 (16%) after nifedipine versus 69/359 (19%) after atosiban (OR 0.76, 95%CI 0.47-1.23). Perinatal death occurred in 14/392 (3.6%) after nifedipine versus 7/380 (1.8%) after atosiban (OR 2.0, 95%CI 0.80-5.1). Nifedipine results in longer prolongation of pregnancy, with a 18 days to delivery compared with 10 days for atosiban (HR 0.83 (96% CI 0.69-0.99)). NICU admission occurred less often after nifedipine (46%) than after atosiban (59%), (OR 0.32, 95%CI 0.14-0.75). The sensitivity analysis revealed no difference in prolongation of pregnancy for 48 hours (OR 1.0, 95% CI 0.73-1.4) or 7 days (OR 1.3, 95% CI 0.85-5.8) between nifedipine and atosiban. There was a non-significant higher neonatal mortality in the nifedipine-exposed group (OR 1.4, 95% CI 0.60-3.4). CONCLUSIONS: In this IPDMA, we found no differences in composite outcome between nifedipine and atosiban in the treatment of threatened preterm birth. However, the non-significant higher mortality after administering nifedipine warrants further investigation of the use of nifedipine as a tocolytic drug. STUDY REGISTRATION: We conducted this study according to a prospectively prepared protocol, registered with PROSPERO (the International Prospective Register of Systematic Reviews) under CRD42016024244.

Fetal echocardiographic evaluation before and after nifedipine treatment in preterm labor.

OBJECTIVE: To assess the effect of nifedipine used for tocolysis on cardiac morphology and functions. METHODS: The study included 47 pregnant women diagnosed with preterm labor at 32-33 weeks. Fetal echocardiographic evaluation was performed with two-dimensional (2D) imaging, M-mode, pulsed wave (PW) Doppler, and tissue Doppler imaging (TDI) before and after the 48th hour of nifedipine treatment. RESULTS: No significant change was observed in Doppler parameters (pulsatility indices of the umbilical artery, middle cerebral artery, ductus venosus) and cardiac morphology (cardiothoracic ratio, end-diastolic longitudinal diameters, sphericity indices, wall thickness) after nifedipine treatment. The parameters obtained with TDI (e', a', s', e'/a', E/e' of mitral and tricuspid valves), M- mode (TAPSE, MAPSE), pulsed Doppler (myocardial performance index, left cardiac output, right cardiac output, tricuspid E, A waves, tricuspid E/A ratio, mitral E, A waves, mitral E/A ratio) did not change after nifedipine treatment. CONCLUSION: To date, this is the first study to examine the effects of nifedipine on the fetal heart using the TDI. Since nifedipine is a drug that is frequently used and well-tolerated in the prevention of preterm labor, it is crucial that it does not cause changes in fetal cardiac parameters during tocolysis. Therefore, we used TDI in addition to conventional methods to evaluate the effect of nifedipine, which is frequently used in obstetrics, on cardiac functions in the early period. Nifedipine treatment seems not to affect systolic or diastolic functions. This indicates that nifedipine is reliable on cardiac functions and morphology in pregnancies treated for preterm labor.

Oral antihypertensive regimens (nifedipine retard, labetalol, and methyldopa) for management of severe hypertension in pregnancy: an open-label, randomised controlled trial.

BACKGROUND: Hypertension is the most common medical disorder in pregnancy, complicating one in ten pregnancies. Treatment of severely increased blood pressure is widely recommended to reduce the risk for maternal complications. Regimens for the acute treatment of severe hypertension typically include intravenous medications. Although effective, these drugs require venous access and careful fetal monitoring and might not be feasible in busy or low-resource environments. We therefore aimed to compare the efficacy and safety of three oral drugs, labetalol, nifedipine retard, and methyldopa for the management of severe hypertension in pregnancy. METHODS: In this multicentre, parallel-group, open-label, randomised controlled trial, we compared these oral antihypertensives in two public hospitals in Nagpur, India. Pregnant women were eligible for the trial if they were aged at least 18 years; they were pregnant with fetuses that had reached a gestational age of at least 28 weeks; they required pharmacological blood pressure control for severe hypertension (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg); and were able to swallow oral medications. Women were randomly assigned to receive 10 mg oral nifedipine, 200 mg oral labetalol (hourly, in both of which the dose could be escalated if hypertension was maintained), or 1000 mg methyldopa (a single dose, without dose escalation). Masking of participants, study investigators, and care providers to group allocation was not possible because of different escalation protocols in the study groups. The primary outcome was blood pressure control (defined as 120-150 mm Hg systolic blood pressure and 70-100 mm Hg diastolic blood pressure) within 6 h with no adverse outcomes. This study is registered with ClinicalTrials.gov, number NCT01912677, and the Clinical Trial Registry, India, number ctri/2013/08/003866. FINDINGS: Between April 1, 2015, and Aug 21, 2017, we screened 2307 women for their inclusion in the study. We excluded 1413 (61%) women who were ineligible, declined to participate, had impending eclampsia, were in active labour, or had a combination of these factors. 11 (4%) women in the nifedipine group, ten (3%) women in the labetalol group, and 11 (4%) women in the methyldopa group were ineligible for treatment (because they had only one qualifying blood pressure measurement) or had treatment stopped (because of delivery or transfer elsewhere). 894 (39%) women were randomly assigned to a treatment group and were included in the intention-to-treat analysis: 298 (33%) women were assigned to receive nifedipine, 295 (33%) women were assigned to receive labetalol, and 301 (33%) women were assigned to receive methyldopa. The primary outcome was significantly more common in women in the nifedipine group than in those in the methyldopa group (249 [84%] women vs 230 [76%] women; p=0·03). However, the primary outcome did not differ between the nifedipine and labetalol groups (249 [84%] women vs 228 [77%] women; p=0·05) or the labetalol and methyldopa groups (p=0·80). Seven serious adverse events (1% of births) were reported during the study: one (<1%) woman in the labetalol group had an intrapartum seizure and six (1%) neonates (one [<1%] neonate in the nifedipine group, two [1%] neonates in the labetalol group, and three [1%] neonates in the methyldopa group) were stillborn. No birth had more than one adverse event. INTERPRETATION: All oral antihypertensives reduced blood pressure to the reference range in most women. As single drugs, nifedipine retard use resulted in a greater frequency of primary outcome attainment than labetalol or methyldopa use. All three oral drugs-methyldopa, nifedipine, and labetalol-are viable initial options for treating severe hypertension in low-resource settings. FUNDING: PREEMPT (University of British Columbia, Vancouver, BC, Canada; grantee of Bill & Melinda Gates Foundation).

Cost effectiveness of nifedipine compared with atosiban in the treatment of threatened preterm birth (APOSTEL III trial).

OBJECTIVE: To assess the cost-effectiveness of treatment with nifedipine compared with atosiban in women with threatened preterm birth. DESIGN: An economic analysis alongside a randomised clinical trial (the APOSTEL III study). SETTING: Obstetric departments of 12 tertiary hospitals and seven secondary hospitals in the Netherlands and Belgium. POPULATION: Women with threatened preterm birth between 25 and 34 weeks of gestation, randomised for tocolysis with either nifedipine or atosiban. METHODS: We performed an economic analysis from a societal perspective. We estimated costs from randomisation until discharge. Analyses for singleton and multiple pregnancies were performed separately. The robustness of our findings was evaluated in sensitivity analyses. MAIN OUTCOME MEASURES: Mean costs and differences were calculated per woman treated with nifedipine or atosiban. Health outcomes were expressed as the prevalence of a composite of adverse perinatal outcomes. RESULTS: Mean costs per patients were significantly lower in the nifedipine group [singleton pregnancies: €34,897 versus €43,376, mean difference (MD) -€8479 [95% confidence interval (CI) -€14,327 to -€2016)]; multiple pregnancies: €90,248 versus €102,292, MD -€12,044 (95% CI -€21,607 to € -1671). There was a non-significantly higher death rate in the nifedipine group. The difference in costs was mainly driven by a lower neonatal intensive care unit admission (NICU) rate in the nifedipine group. CONCLUSION: Treatment with nifedipine in women with threatened preterm birth results in lower costs when compared with treatment with atosiban. However, the safety of nifedipine warrants further investigation. TWEETABLE ABSTRACT: In women with threatened preterm birth, tocolysis using nifedipine results in lower costs when compared with atosiban.

Effect of nifedipine and atosiban on perinatal brain injury: secondary analysis of the APOSTEL-III trial.

OBJECTIVE: Brain injury in neonates born prematurely is associated strongly with poor neurodevelopmental outcome. The aim of this study was to evaluate whether tocolysis with nifedipine or atosiban in women with threatened preterm birth can reduce the incidence of overall brain injury in neonates born prematurely. METHODS: This was a secondary analysis of the APOSTEL-III trial (Dutch Clinical Trial Registry, no. NTR2947), a randomized clinical trial in which women with threatened preterm labor between 25 and 34 weeks of gestation were allocated to treatment with nifedipine or atosiban. In this secondary analysis, women delivered at ≤ 32 weeks of gestational age in the two main contributing centers were included. Primary outcome was the presence of neonatal brain injury, which was defined as presence of abnormalities on ultrasound investigation and classified into mild and severe. To evaluate type and severity of brain injury, all neonatal ultrasounds performed during neonatal intensive and medium care admission were analyzed. To test the robustness of our results, a sensitivity analysis was performed assessing differences in baseline or known risk factors for brain injury. RESULTS: A total of 117 neonates (from 102 women) were studied, of which 51 had been exposed to nifedipine and 66 to atosiban. Brain injury was observed in 22 (43.1%) neonates in the nifedipine group compared with 37 (56.1%) in the atosiban group (OR, 0.60; 95% CI, 0.29-1.24). Presence of mild brain injury was comparable between the nifedipine (33.3%) and atosiban (48.5%) groups (OR, 0.53; 95% CI, 0.25-1.13). Severe brain injury was also comparable between the groups, observed in 9.8% of neonates in the nifedipine vs 7.6% of those in the atosiban group (OR, 1.33; 95% CI, 0.36-4.85). Intraventricular hemorrhage (≥ Grade I) was the most frequently seen ultrasound abnormality, observed in 18 (35.3%) neonates in the nifedipine group vs 25 (37.9%) in the atosiban group (OR, 0.90; 95% CI, 0.42-1.91). The sensitivity analysis, with adjustment for maternal age and gestational age at randomization, showed no statistical difference between the groups for presence of brain injury (OR, 0.58; 95% CI, 0.27-1.27). CONCLUSION: In children born before 32 weeks of gestation after the use of tocolytics, the prevalence of brain injury was high. No significant differences were found with respect to overall brain injury between neonates exposed to nifedipine and those exposed to atosiban. However, as this study was a secondary analysis of the APOSTEL III trial, it was underpowered for brain injury. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Oral nifedipine versus intravenous labetalol for severe hypertension during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Oral nifedipine is recommended along with labetalol and hydralazine for treatment of severe hypertension during pregnancy by most authorities. Although nifedipine is cheap and easily administered, the usage pattern among health care providers suggests a strong preference for labetalol despite lack of evidence for the same. OBJECTIVES: To determine the efficacy and safety of oral nifedipine for treatment of severe hypertension of pregnancy compared with intravenous labetalol. SEARCH STRATEGY: We systematically searched for articles comparing oral nifedipine with intravenous labetalol for the treatment of severe hypertension during pregnancy in any language, over Medline, Cochrane Central Register of Clinical Trials and Google Scholar from inception till February 2014. SELECTION CRITERIA: We included all RCTs that compared intravenous labetalol with oral nifedipine for treatment of severe hypertension during pregnancy, addressing relevant efficacy and safety outcomes. DATA COLLECTION AND ANALYSIS: Eligible studies were reviewed, and data were extracted onto a standard form. We used Cochrane review manager software for quantitative analysis. Data were analysed using a fixed effect model. MAIN RESULTS: The pooled analysis of seven trials (four from developing countries) consisting of 363 woman-infant pairs showed that oral nifedipine was associated with less risk of persistent hypertension (RR 0.42, 95% CI 0.18-0.96) and reported maternal side effects (RR 0.57, 95% CI 0.35-0.94). However, on sensitivity analysis the outcome 'persistent hypertension' was no longer significant. Other outcomes did not reach statistical significance. CONCLUSION: Oral nifedipine is as efficacious and safe as intravenous labetalol and may have an edge in low resource settings. TWEETABLE ABSTRACT: Although studies to date are few in number and small, nifedipine shows promise for severe hypertension in pregnancy.

Randomized comparison of nifedipine and placebo in fibronectin-negative women with symptoms of preterm labor and a short cervix (APOSTEL-I Trial).

OBJECTIVE: To evaluate whether tocolysis with nifedipine can be omitted in women with symptoms of preterm labor, a shortened cervix, and negative fetal fibronectin test. STUDY DESIGN: A randomized noninferiority trial was performed in all Dutch perinatal centers. Women with symptoms of preterm labor between 24 and 34 weeks, intact membranes, cervical length between 10 and 30 mm, and negative fibronectin test were randomly allocated to nifedipine (80 mg/day) or placebo. The primary outcome was delivery within 7 days. Secondary outcomes were severe neonatal morbidity and mortality. We also followed all eligible nonrandomized women. RESULTS: We allocated 37 women to nifedipine and 36 women to placebo. In the nifedipine group, three women (8.1%) delivered within 7 days, compared with one woman (2.8%) in the placebo group (difference -5.3%; one-sided 95% confidence limit 4.5%). Median gestational age at delivery were respectively 37 + 0 (interquartile range [IQR] 34 + 6 to 38 + 5) and 38 + 2 (IQR 37 + 0 to 39 + 6) weeks (p = 0.008). In the nifedipine group, three pregnancies (8.1%) had a poor outcome; there were no poor outcomes in the placebo group. We observed similar trends in eligible nonrandomized women. CONCLUSION: In symptomatic women with preterm labor, a shortened cervix, and negative fibronectin test, placebo treatment is not inferior to tocolysis with nifedipine.

Comparison of nifedipine and progesterone for maintenance tocolysis after arrested preterm labour.

The aim of our study was to compare the efficacy and safety of nifedipine and progesterone for maintenance tocolysis after arrested preterm labour, in prolonging pregnancy and preventing recurrence of preterm labour. This study was a randomised comparative study conducted on 110 pregnant women with arrested preterm labour, randomised to receive either nifedipine 20 mg Q 8-hourly or progesterone 400 mg daily for maintenance tocolysis. Other than demographic parameters, obstetric parameters like previous history of abortions or preterm deliveries, gestational age, cervical dilatation and effacement, ultrasound measured cervical length at admission, were noted. Outcome measures studied were mean prolongation of pregnancy, mode of delivery, neonatal outcome and side-effects of both the drugs. We found that there was no significant difference in the demographic profile, parity, number of abortions, previous preterm deliveries, gestational age, cervical dilatation and effacement at admission between the two groups. A total of 10% of the patients in the nifedipine group and 61% of the patients in the progesterone group delivered at term (p value 0.000). The mean prolongation of pregnancy in the nifedipine group was 16.63 days and 40.14 days in the progesterone group which was significant (p = 0.000). Neonates in the progesterone group had better birth weight, better Apgar scores at 1 and 5 min, lesser need for ventilation and significantly lesser composite morbidity. Nifedipine was associated significantly with side-effects. We conclude that when compared with nifedipine, progesterone significantly prolongs pregnancy in women with arrested preterm labour with better neonatal outcomes and fewer side-effects.

[Acute mountain sickness : How can it be treated and how can it be avoided?]. / Höhenkrankheit : Wie behandeln, wie vermeiden?

Due to the decreasing partial pressure of oxygen, high altitude sickness can occur at heights over 2,500 m. This can be best avoided by slow adaptation to the altitude (acclimatization). In this way the organism adapts to the chronic hyperventilation and in the further process the oxygen content is normalized by an increase in erythrocytes. The commonest form of high altitude sickness is acute mountain sickness which is characterized by the leading symptom of headache. When additional signs of ataxia occur there is an acute danger of edema which is associated with a high mortality. Stress dyspnea, coughing and rasping breathing noises also occur by the potentially fatal high altitude pulmonary edema. All forms of high altitude sickness can be countered by a rapid descent to a height of at least 500 m. In acute mountain sickness acetazolamide can be administered (2 × 250 mg), for high altitude cerebral edema dexamethasone (3 × 4-8 mg) and for high altitude pulmonary edema nifedipine (initially 10 mg then 20 mg retard).

Description and management of patients with anal fissure: insights on Italian primary care setting coming from real-world data.

To describe patients with anal fissure (AF) and their management in primary care. Retrospective study using the Italian Longitudinal Patient Database on 18 + years old subjects with AF records during 'July 2016-June 2021' (selection period). Index Date (ID) was the first AF record during selection period. Sub-cohorts were defined by presence/absence of prescriptions on ID of the combination of topical nifedipine 0.3% and lidocaine 1.5% (NIF/LID). Patients' information on the 12-month period before (baseline) and after (follow-up) ID was analyzed. Subjects with AF were 8632: 14.0% had NIF/LID on ID. Mean age was 52 (± 17.2) years, there were more women in ' < 50 years' group, and more men in '50-70' one. Prevalences of pregnancy and immunodepression were around 5%; most common comorbidities were hypertension (29.6%) and heart disease (13.1%), while constipation and diarrhea were < 5%. Healthcare resources utilization (HRUs) increased during follow-up, but still few patients were prescribed NIF/LID (2.8%), other treatments for AF (10.3%), or proctological visits (7.7%). NIF/LID patients were younger (< 40 years people: 30.7% versus 23.9%; p value < 0.0001), and more likely to have constipation (4.3% versus 2.5%; p value < 0.001); patients without NIF/LID showed slightly higher prevalences of hypertension (30.0% versus 27.1%; p value: 0.039) and depression (4.0% versus**2.5%; p value: 0.009), and a little higher overall HRUs. Results show that general practitioners are used to manage AF. However, there is still a gap between guidelines' recommendations and actual management. Educational campaigns on common anal problems in primary care might help further improving AF management and optimizing HRUs.

[The efficacy of antihypertension drugs and their combinations in the non-treated hypertension].

In case of non-treated hypertension several medications and their combinations were studied (captopril, and moxonidine as such, captopril + nifedipine, captopril + moxonidine). Moxonidine to be more effective in patients with the prevalence of the sympathetic tone, captopril in patients without increased sympathetic activity. At a combination of captopril + nifedipine efficiency of therapy was reduced, and at a combination moxonidine + nifedipine - increased. Beyond that administration of captopril + nifedipine possessed more side effects, as to compare with the moxonidine + nifedipine.

A randomized controlled trial comparing the efficacy of nifedipine and enalapril in the postpartum period.

BACKGROUND: Postpartum hypertension is a common medical complication of pregnancy and is associated with increased healthcare use, including unplanned interactions with the medical system and readmission, which can add significant stress to both a newly postpartum patient and the medical care delivery system. We currently do not know what the best antihypertensive treatment for postpartum hypertension is and tend to use antihypertensives commonly used during pregnancy. However, the mechanism of action of angiotensin-converting enzyme inhibitors may be well suited for the pathophysiology of hypertension in the postpartum period and may help to provide better control of hypertension and, in turn, decrease healthcare use. OBJECTIVE: This study aimed to determine if enalapril is superior to nifedipine in preventing prolonged hospitalizations, unplanned medical visits, and/or readmission among women with postpartum hypertension. STUDY DESIGN: We performed an open-label, randomized controlled trial (ClinicalTrials.gov registered: NCT04236258) in which patients ≥18 years with chronic hypertension, gestational hypertension, or preeclampsia were recruited to receive either 10 mg enalapril daily or 30 mg extended-release nifedipine daily as an initial antihypertensive agent in the period from delivery to 6 weeks postpartum. Recruitment occurred at a tertiary academic hospital from January 2020 to February 2021. Exclusion criteria included being on an antihypertensive when pregnancy started or requiring ≥2 daily antihypertensives during pregnancy. The antihypertensive regimen was managed by the participants' obstetrical provider after the initial randomization. The primary outcome was a composite of prolonged hospitalization, unplanned clinic visits, triage visits, and/or readmission. A total of 40 patients in each arm were needed to detect a decrease in the primary outcome rate from 70% to 40% (α=0.05; power 0.80). Analyses were performed based on the intention-to-treat principal, and each arm was oversampled because of the risk for participant dropout. RESULTS: A total of 47 patients were randomized to each arm. Aside from the mode of delivery and twin gestation, the maternal demographics were similar between the 2 groups. The primary outcome occurred in 31 of 47 patients (66%) randomized to the nifedipine group and in 30 of 47 (64%) randomized to the enalapril group (P=.83). There was no significant difference in the primary outcome after controlling for mode of delivery and twin gestation. More patients in the enalapril arm had a second antihypertensive added during their primary hospitalization (16 vs 6) and more patients in the nifedipine arm were still on their antihypertensive at 2 weeks postpartum (42 vs 36). There were no adverse events in either group. CONCLUSION: Enalapril was not superior to nifedipine when used as an initial antihypertensive in the immediate postpartum period in terms of decreasing healthcare use.

Trial of Intrapartum Extended-Release Nifedipine to Prevent Severe Hypertension Among Pregnant Individuals With Preeclampsia With Severe Features.

BACKGROUND: Preeclampsia is associated with maternal and perinatal morbidity. Besides acute therapy for severe hypertension, best practices are lacking for intrapartum hypertension management. Our objective was to test the hypothesis that intrapartum initiation of extended-release nifedipine in individuals with preeclampsia with severe features prevents severe hypertension. METHODS: Randomized, triple-blind, placebo-controlled trial of individuals with preeclampsia with severe features undergoing labor induction between 220/7 and 416/7 weeks gestation. Participants were randomized to oral extended-release nifedipine 30 mg or identical placebo every 24 hours. Primary outcome is defined as receipt of ≥1 dose of acute hypertension therapy for severe blood pressure (≥160/110 mm Hg) sustained ≥10 minutes. Secondary outcomes included route of delivery, neonatal intensive care unit admission, and a composite of adverse neonatal outcomes. RESULTS: Of 365 individuals screened, 55 were randomized to nifedipine and 55 to placebo. Primary outcome was observed in 34.0% of individuals in nifedipine group versus 55.1% in placebo group (relative risk [RR] 0.62 [95% CI, 0.39-0.97]); number needed to treat to prevent receipt of acute treatment was 4.7 (95% CI, 2.5-44.3). Fewer individuals in nifedipine group required cesarean delivery compared with placebo group (20.8% versus 34.7%, RR, 0.60 [95% CI, 0.31-1.15]). Neonatal intensive care unit admission rate was lower in nifedipine group compared with placebo (29.1% versus 47.1%; RR 0.62 [95% CI, 0.37-1.02]). Neonatal composite was similar between groups (35.8% versus 41.2%, RR, 0.83 [95% CI, 0.51-1.37]). CONCLUSIONS: Initiation of extended-release nifedipine is effective in reducing intrapartum acute hypertensive therapy among individuals with preeclampsia with severe features. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04392375.

Inhibition of uterine contractility with various tocolytics with and without progesterone: in vitro studies.

OBJECTIVE: Various tocolytics are used to suppress uterine contractility in patients in preterm labor. Progesterone (P4) is used in patients at high risk for preterm delivery. In this study, we evaluated the effects of various tocolytics with and without P4 to examine effects on uterine contractility. STUDY DESIGN: Uterine tissues (n = 280) from women undergoing cesarean at term were exposed in vitro to various agents (vehicle, magnesium sulfate [MgSO(4)], nifedipine, indomethacin, or pinacidil-all with and without P4). Contractility was measured before and after addition of the various agents. RESULTS: P4 alone at 10(-5) mol/L concentration has little effect to inhibit contractility (P ≥ .05). MgSO(4) (2-8 × 10(-3) mol/L) inhibits uterine contractility (P < .05) but there is no change when combined with P4 (P > .05). Nifedipine (10(-8) mol/L) and indomethacin (10(-5) mol/L) inhibit contractions alone (P < .05) and to a greater extent when combined with P4 (P < .05). P4 significantly (P < .05) reduced the effects of pinacidil (10(-6.5) mol/L). CONCLUSION: Combinations of P4 with nifedipine or indomethacin, but not MgSO(4), might be used to effectively suppress preterm labor.

Behcet's disease and IgA nephropathy.

Although Behçet's disease (BD) is a kind of systemic disease, renal involvement is rare, especially IgA nephropathy (IgAN). Renal manifestations in BD range from mild urinary abnormalities to glomerulonephritis with persistent renal failure, which includes minimal change disease, proliferative glomerulonephritis, rapidly crescentic glomerulonephritis, renal amyloidosis and IgA nephropathy. Amyloidosis seems to be the most common type of renal lesion in BD, and several cases of nephrotic syndrome secondary to amyloidosis have been documented. Co-occurrence of BD and IgA nephropathy has only been reported in only few cases. We describe two patients with the rare association of BD and IgAN. We suggested that it is important to periodically perform renal function assessment in patients with BD, through urinalysis and measurement of serum creatinine for detecting any abnormality and providing an early adequate treatment.

The tocolytic role of nifedipine in preventing preterm labour pain.

This study was undertaken to evaluate the efficacy of oral nifedipine to reduce labour pain in patient with preterm labour, to complete the doses of steroids in lung maturity and in utero transfer to the Neonatal Intensive Care Unit (NICU) and to evaluate the maternal adverse effects and neonatal outcome. Diagnosed cases of preterm labour (between 24 to 34 weeks gestation) were randomly selected. Among them 50 patients were given oral nifedipine (n=50) and 50 patients were observed with no treatment (n=50). There were no statistically significant differences in age, race, parity, preterm delivery risk factor between the groups. At first the labour pain were observed through Continuous CTG in first hour, then intermittent CTG. The patient in the Nifedipine group can prolong the pregnancy time 36.0±3.2 wks than 30.6±3.1 wks in the control group (p<0.05) with reduced neonatal complications and admission to NICU. Oral nifedipine in patients with preterm labour pain as Tocolytic therapy has significantly prolonged pregnancy with lesser neonatal problems and fewer maternal adverse effects.