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Journal of Hypertension Nov 2017Although medication is generally avoided wherever possible during pregnancy, pharmacotherapy is required for the treatment of pregnancy associated hypertension, which... (Review)
Review
BACKGROUND
Although medication is generally avoided wherever possible during pregnancy, pharmacotherapy is required for the treatment of pregnancy associated hypertension, which remains a leading cause of maternal and fetal morbidity and mortality. The long-term effects to the child of in-utero exposure to antihypertensive agents remains largely unknown.
OBJECTIVE
The aim of this study was to systematically review published studies on adverse outcomes to the child associated with in-utero exposure to antihypertensive medications.
METHODS
OVID, Scopus, EBSCO Collections, the Cochrane Library, and Web of Science databases were searched for relevant publications published between January 1950 and October 2016 and a total of 688 potentially eligible studies were identified.
RESULTS
Following review, 47 primary studies were eligible for inclusion. The Critical Appraisal Skills Programme checklist was used to assess study quality. Five studies were of excellent quality; the remainder were either mediocre or poor. Increased risk of low birth weight, low size for gestational age, preterm birth, and congenital defects following in-utero exposure to all antihypertensive agents were identified. Two studies reported an increased risk of attention deficit hyperactivity disorder following exposure to labetalol, and an increased risk of sleep disorders following exposure to methyldopa and clonidine.
CONCLUSION
The current systematic review demonstrates a paucity of relevant published high-quality studies. A small number of studies suggest possible increased risk of adverse child health outcomes; however, most published studies have methodological weaknesses and/or lacked statistical power thus preventing any firm conclusions being drawn.
Topics: Antihypertensive Agents; Attention Deficit Disorder with Hyperactivity; Birth Weight; Child; Child Health; Female; Gestational Age; Humans; Hypertension, Pregnancy-Induced; Infant, Low Birth Weight; Infant, Newborn; Labetalol; Maternal Exposure; Pregnancy; Premature Birth
PubMed: 28661961
DOI: 10.1097/HJH.0000000000001456 -
Movement Disorders : Official Journal... Jun 2021In the advanced stages of Parkinson's disease (PD), patients frequently experience disabling motor complications. Treatment options include deep brain stimulation (DBS),... (Meta-Analysis)
Meta-Analysis Review
In the advanced stages of Parkinson's disease (PD), patients frequently experience disabling motor complications. Treatment options include deep brain stimulation (DBS), levodopa-carbidopa intestinal gel (LCIG), and continuous subcutaneous apomorphine infusion (CSAI). Choosing among these treatments is influenced by scientific evidence, clinical expertise, and patient preferences. To foster patient engagement in decision-making among the options, scientific evidence should be adjusted to their information needs. We conducted a systematic review from the patient perspective. First, patients selected outcomes for a treatment choice: quality of life, activities of daily living, ON and OFF time, and adverse events. Second, we conducted a systematic review and meta-analysis for each treatment versus best medical treatment using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Finally, the evidence was transformed into comprehensible and comparable information. We converted the meta-analysis results into the number of patients (per 100) who benefit clinically from an advanced treatment per outcome, based on the minimal clinically important difference and the cumulative distribution function. Although this approach allows for a comparison of outcomes across the three device-aided therapies, they have never been compared directly. The interpretation is hindered by the relatively short follow-up time in the included studies, usually less than 12 months. These limitations should be clarified to patients during the decision-making process. This review can help patients integrate the evidence with their own preferences, and with their clinician's expertise, to reach an informed decision. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Activities of Daily Living; Antiparkinson Agents; Apomorphine; Carbidopa; Drug Combinations; Gels; Humans; Levodopa; Parkinson Disease; Quality of Life
PubMed: 33797786
DOI: 10.1002/mds.28599 -
The Cochrane Database of Systematic... 2000Hypertension is a common complication of pregnancy. Antihypertensive drugs are widely used in the belief these will improve outcome for both the woman (such as... (Review)
Review
BACKGROUND
Hypertension is a common complication of pregnancy. Antihypertensive drugs are widely used in the belief these will improve outcome for both the woman (such as decreasing the risk of stroke or eclampsia) and her baby (such as decreasing the risk of preterm birth and its complications). Beta-blockers are a popular choice of antihypertensive agent during pregnancy; other choices include methyldopa and calcium channel blockers.
OBJECTIVES
The aim of this review is to assess whether oral beta-blockers are overall better than placebo, or no beta-blocker, for women with mild-moderate hypertension during pregnancy, and to assess whether oral beta-blockers have any advantages over other antihypertensive agents for women with mild-moderate hypertension during pregnancy. Both maternal outcomes (e.g., the incidence of severe hypertension) and perinatal outcomes (e.g., mortality) were of interest.
SEARCH STRATEGY
Register of trials maintained by the Cochrane Pregnancy and Childbirth Group, MEDLINE 1966-97, bibliographies of retrieved papers, personal files. Date of last search: June 2000.
SELECTION CRITERIA
Trials comparing beta-blockers with (i) placebo or no therapy, or (ii) other antihypertensive agents, for women with mild-moderate pregnancy hypertension (i.e., blood pressure under 170 mm Hg systolic, or 110 mm Hg diastolic).
DATA COLLECTION AND ANALYSIS
All data were extracted independently by two investigators, who were not blinded to outcome or other trial characteristics. Whenever possible, missing data were obtained by personal communication with authors. Discrepancies were resolved by discussion. The overview was divided into two comparisons: (i) beta-blockers versus placebo or no therapy, and (ii) beta-blockers versus other antihypertensives.
MAIN RESULTS
Twenty-seven trials, involving just under 2400 women, are included in this review. Fourteen trials (1516 women) compared beta-blockers with placebo/no beta blocker. Oral beta-blockers decrease the risk of severe hypertension (relative risk (RR) 0.37, 95% confidence interval (CI) 0.26-0.53) and the need for additional antihypertensive drugs (RR 0.44, 95% CI 0.31-0.62). There are insufficient data for any conclusions about the effect on perinatal mortality or preterm delivery. Beta-blockers seem to be associated with an increase in small for gestational age infants (RR 1.34, 95% CI 1.01-1.79). Maternal hospital admission may be decreased, neonatal bradycardia increased and respiratory distress syndrome decreased, but these outcomes are only reported in a very small proportion of trials. Eleven trials (787 women) compared beta-blockers with methyldopa. Beta-blockers appear to be no more effective and probably equally as safe (from maternal and perinatal perspectives) as methyldopa. Single small trials have compared beta-blockers with hydralazine and with nicardipine. It is unusual for women to change drugs due to side effects.
REVIEWER'S CONCLUSIONS
The improvement in control of maternal blood pressure with use of beta-blockers would be worthwhile only if it were reflected in other more substantive benefits for the mother and/or baby, and none have yet been clearly demonstrated. The effect of beta-blockers on perinatal outcome is uncertain, given that the worrying trend to an increase in small for gestational age infants is partly dependent on one small outlying trial. Large, randomised controlled trials are needed to determine whether antihypertensive therapy in general (rather than beta-blocker therapy specifically) results in benefits that outweigh the risks for treatment of mild-moderate pregnancy hypertension. If so, then it would be appropriate to look at which antihypertensive is best. Beta-blockers would remain a candidate class of agents.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Antihypertensive Agents; Female; Humans; Hypertension; Pregnancy; Pregnancy Complications, Cardiovascular; Randomized Controlled Trials as Topic
PubMed: 11034777
DOI: 10.1002/14651858.CD002863 -
Movement Disorders : Official Journal... Aug 2021Advanced Parkinson's disease is inconsistently defined, and evidence is lacking in relation to device-aided therapies. To update existing reviews of intrajejunal... (Review)
Review
Advanced Parkinson's disease is inconsistently defined, and evidence is lacking in relation to device-aided therapies. To update existing reviews of intrajejunal infusion of levodopa/carbidopa (LCIG), we performed a literature search for relevant articles (to November 3, 2020) using PubMed supplemented by hand searching. Retrieved articles were categorized by relevance to identified research questions, including motor complications and symptoms; nonmotor symptoms; functioning, quality of life, and caregiver burden; optimal timing of treatment initiation and administration duration; discontinuation; and complications. Most eligible studies (n = 56) were open-label, observational studies including relatively small patient numbers. LCIG consistently reduces OFF time and increased ON time without troublesome dyskinesia with varying effects regarding ON time with troublesome dyskinesia and the possibility of diphasic dyskinesia. More recent evidence provides some increased support for the benefits of LCIG in relation to nonmotor symptoms, quality of life, activities of daily living, and reduced caregiver burden. Patient age does not appear to significantly impact the effectiveness of LCIG. Discontinuation rates with LCIG (~17%-26%) commonly relate to device-related issues, although the ability to easily discontinue LCIG may represent a potential benefit. LCIG may be a favorable option for patients with advanced Parkinson's disease who show predominant nonmotor symptoms and vulnerability to complications of other advanced therapy modalities. Larger, well-controlled studies, including precise investigation of cost effectiveness, would further assist treatment selection. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Activities of Daily Living; Antiparkinson Agents; Carbidopa; Drug Combinations; Gels; Humans; Levodopa; Parkinson Disease; Quality of Life
PubMed: 33899262
DOI: 10.1002/mds.28595 -
The Cochrane Database of Systematic... Aug 2017Hypertension is an important risk factor for adverse cardiovascular events including stroke, myocardial infarction, heart failure and renal failure. The main goal of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypertension is an important risk factor for adverse cardiovascular events including stroke, myocardial infarction, heart failure and renal failure. The main goal of treatment is to reduce these events. Systematic reviews have shown proven benefit of antihypertensive drug therapy in reducing cardiovascular morbidity and mortality but most of the evidence is in people 60 years of age and older. We wanted to know what the effects of therapy are in people 18 to 59 years of age.
OBJECTIVES
To quantify antihypertensive drug effects on all-cause mortality in adults aged 18 to 59 years with mild to moderate primary hypertension. To quantify effects on cardiovascular mortality plus morbidity (including cerebrovascular and coronary heart disease mortality plus morbidity), withdrawal due adverse events and estimate magnitude of systolic blood pressure (SBP) and diastolic blood pressure (DBP) lowering at one year.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to January 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We contacted authors of relevant papers regarding further published and unpublished work.
SELECTION CRITERIA
Randomized trials of at least one year' duration comparing antihypertensive pharmacotherapy with a placebo or no treatment in adults aged 18 to 59 years with mild to moderate primary hypertension defined as SBP 140 mmHg or greater or DBP 90 mmHg or greater at baseline, or both.
DATA COLLECTION AND ANALYSIS
The outcomes assessed were all-cause mortality, total cardiovascular (CVS) mortality plus morbidity, withdrawals due to adverse events, and decrease in SBP and DBP. For dichotomous outcomes, we used risk ratio (RR) with 95% confidence interval (CI) and a fixed-effect model to combine outcomes across trials. For continuous outcomes, we used mean difference (MD) with 95% CI and a random-effects model as there was significant heterogeneity.
MAIN RESULTS
The population in the seven included studies (17,327 participants) were predominantly healthy adults with mild to moderate primary hypertension. The Medical Research Council Trial of Mild Hypertension contributed 14,541 (84%) of total randomized participants, with mean age of 50 years and mean baseline blood pressure of 160/98 mmHg and a mean duration of follow-up of five years. Treatments used in this study were bendrofluazide 10 mg daily or propranolol 80 mg to 240 mg daily with addition of methyldopa if required. The risk of bias in the studies was high or unclear for a number of domains and led us to downgrade the quality of evidence for all outcomes.Based on five studies, antihypertensive drug therapy as compared to placebo or untreated control may have little or no effect on all-cause mortality (2.4% with control vs 2.3% with treatment; low quality evidence; RR 0.94, 95% CI 0.77 to 1.13). Based on 4 studies, the effects on coronary heart disease were uncertain due to low quality evidence (RR 0.99, 95% CI 0.82 to 1.19). Low quality evidence from six studies showed that drug therapy may reduce total cardiovascular mortality and morbidity from 4.1% to 3.2% over five years (RR 0.78, 95% CI 0.67 to 0.91) due to reduction in cerebrovascular mortality and morbidity (1.3% with control vs 0.6% with treatment; RR 0.46, 95% CI 0.34 to 0.64). Very low quality evidence from three studies showed that withdrawals due to adverse events were higher with drug therapy from 0.7% to 3.0% (RR 4.82, 95% CI 1.67 to 13.92). The effects on blood pressure varied between the studies and we are uncertain as to how much of a difference treatment makes on average.
AUTHORS' CONCLUSIONS
Antihypertensive drugs used to treat predominantly healthy adults aged 18 to 59 years with mild to moderate primary hypertension have a small absolute effect to reduce cardiovascular mortality and morbidity primarily due to reduction in cerebrovascular mortality and morbidity. All-cause mortality and coronary heart disease were not reduced. There is lack of good evidence on withdrawal due to adverse events. Future trials in this age group should be at least 10 years in duration and should compare different first-line drug classes and strategies.
Topics: Adult; Antihypertensive Agents; Bendroflumethiazide; Blood Pressure; Cause of Death; Coronary Disease; Humans; Hypertension; Methyldopa; Middle Aged; Myocardial Infarction; Patient Dropouts; Propranolol; Randomized Controlled Trials as Topic; Stroke; Young Adult
PubMed: 28813123
DOI: 10.1002/14651858.CD008276.pub2 -
Advances in Therapy Jun 2021Levodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in... (Review)
Review
INTRODUCTION
Levodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in levodopa-responsive patients with advanced Parkinson's disease (PD) when other treatments have not given satisfactory results. Reduction in 'off'-time is a common primary endpoint in studies of LCIG, and it is important to assess the durability of this response. This systematic literature review was conducted to qualitatively summarise the data on the long-term effects of LCIG therapy on 'off'-time.
METHODS
Studies were identified by searching PubMed, EMBASE and Ovid on 30 September 2019. Studies were included if they reported on patients with PD, had a sample size of ≥ 10, LCIG was an active intervention and 'off'-time was reported for ≥ 12 months after initiation of LCIG treatment. Randomised clinical trials, retrospective and prospective observational studies, and other interventional studies were included for selection. Data were collected on: 'off'-time (at pre-specified time periods and the end of follow-up), study characteristics, Unified Parkinson's Disease Rating Scale (UPDRS) II, III and IV total scores, dyskinesia duration, quality of life scores, non-motor symptoms and safety outcomes.
RESULTS
Twenty-seven studies were included in this review. The improvement in 'off'-time observed shortly after initiating LCIG was maintained and was statistically significant at the end of follow-up in 24 of 27 studies. 'Off'-time was reduced from baseline to end of follow-up by 38-84% and was accompanied by a clinically meaningful improvement in quality of life. Stratified analysis of 'off'-time demonstrated mean relative reductions of 47-82% at 3-6 months and up to 83% reduction at 3-5 years of follow-up. Most studies reported significant improvements in activities of daily living and motor complications. Most frequent adverse events were related to the procedure or the device.
CONCLUSION
In one of the largest qualitative syntheses of published LCIG studies, LCIG treatment was observed to provide a durable effect in reducing 'off'-time.
INFOGRAPHIC
Video Abstract.
Topics: Activities of Daily Living; Antiparkinson Agents; Carbidopa; Drug Combinations; Gels; Humans; Levodopa; Observational Studies as Topic; Parkinson Disease; Quality of Life; Retrospective Studies
PubMed: 34018146
DOI: 10.1007/s12325-021-01747-1 -
Drug Design, Development and Therapy 2020Levodopa-carbidopa intestinal gel (LCIG) is a new type of administration that results in steadier levodopa plasma concentrations in advanced Parkinson's disease (PD)...
BACKGROUND
Levodopa-carbidopa intestinal gel (LCIG) is a new type of administration that results in steadier levodopa plasma concentrations in advanced Parkinson's disease (PD) patients and effectively reduces poor mobility and dyskinesia.
METHODS
Electronic databases were searched up to January 1, 2018. The inclusion criteria for this review were as follows: LCIG vs oral medication in advanced PD patients.
RESULTS
Five trials, with a total of 198 patients, met all the inclusion criteria. The quality score of these studies ranged from 3 to 5. Two clinical trials showed that compared with oral medication, LCIG had a better treatment effect on on-time with troublesome dyskinesia (TSD) ( = 0.02) and on-time without TSD ( < 0.00001) in advanced PD patients. In addition, four of the 5 studies showed that the LCIG may have better efficacy than oral medication for improving the scores of the UPDRS, and two studies found that LCIG demonstrated better efficacy for improving the PDQ-39 scores. The video recording results indicated a potential decline in both dyskinesia and the "off" state in LCIG-treated patients. The incidence of adverse events was not significantly different between the LCIG and oral medication groups.
CONCLUSION
Compared with oral treatment, LCIG exerts its effectiveness, mostly by reducing the time of on-time with TSD, increasing the time of on-time without TSD and scores of UPDRS and PDQ-39. It is suggesting that LCIG was likely to be a new type of administration used in clinical applications. However, due to methodological flaws, these findings should be viewed with caution, and more RCTs are needed in the field to complement our findings.
Topics: Administration, Oral; Antiparkinson Agents; Carbidopa; Drug Combinations; Gels; Humans; Levodopa; Parkinson Disease
PubMed: 32161444
DOI: 10.2147/DDDT.S229621 -
Neurologia I Neurochirurgia Polska 2023Polyneuropathy (PNP) is a known complication of levodopa-carbidopa intestinal gel (LCIG) therapy of advanced Parkinson's Disease (PD). The overall prevalence of PNP in...
Polyneuropathy (PNP) is a known complication of levodopa-carbidopa intestinal gel (LCIG) therapy of advanced Parkinson's Disease (PD). The overall prevalence of PNP in PD is estimated to be 42.1% (as shown in a review by Romagnolo et al. 2018), and the most common type is chronic axonal polyneuropathy. There is a group of acute/subacute onset demyelinating polyneuropathies, which is far less common, although it seems to be an important factor leading to the rapid discontinuation of LCIG treatment. In this systematic review, we present data on demyelinating polyneuropathy with acute/subacute onset; we identified nine papers including prospective assessments and case reports, with detailed information on 15 patients. In all patients, despite treatment with corticosteroids, intravenous immunoglobulins (IVIG) or plasma exchange (PE), the LCIG therapy was terminated. We also present a case of subacute demyelinating polyneuropathy with effective treatment and continuation of LCIG therapy.
Topics: Humans; Carbidopa; Levodopa; Parkinson Disease; Antiparkinson Agents; Prospective Studies; Polyneuropathies; Drug Combinations; Gels
PubMed: 36628506
DOI: 10.5603/PJNNS.a2023.0001