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Nature Reviews. Rheumatology Apr 2023Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease with multi-organ involvement, fibrosis and vasculopathy. Treatment in SSc, including early... (Review)
Review
Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease with multi-organ involvement, fibrosis and vasculopathy. Treatment in SSc, including early diffuse cutaneous SSc (dcSSc) and the use of organ-specific therapies, has improved, as evident from randomized clinical trials. Treatments for early dcSSc include immunosuppressive agents such as mycophenolate mofetil, methotrexate, cyclophosphamide, rituximab and tocilizumab. Patients with rapidly progressive early dcSSc might be eligible for autologous haematopoietic stem cell transplantation, which can improve survival. Morbidity from interstitial lung disease and pulmonary arterial hypertension is improving with the use of proven therapies. Mycophenolate mofetil has surpassed cyclophosphamide as the initial treatment for SSc-interstitial lung disease. Nintedanib and possibly perfinidone can be considered in SSc pulmonary fibrosis. Pulmonary arterial hypertension is frequently treated with initial combination therapy (for example, with phosphodiesterase 5 inhibitors and endothelin receptor antagonists) and, if necessary, the addition of a prostacyclin analogue. Raynaud phenomenon and digital ulcers are treated with dihydropyridine calcium channel blockers (especially nifedipine), then phosphodiesterase 5 inhibitors or intravenous iloprost. Bosentan can reduce the development of new digital ulcers. Trial data for other manifestations are mostly lacking. Research is needed to develop targeted and highly effective treatments, best practices for organ-specific screening and early intervention, and sensitive outcome measurements.
Topics: Humans; Mycophenolic Acid; Pulmonary Arterial Hypertension; Phosphodiesterase 5 Inhibitors; Scleroderma, Systemic; Cyclophosphamide; Lung Diseases, Interstitial
PubMed: 36849541
DOI: 10.1038/s41584-023-00909-5 -
JRSM Open Aug 2017Buerger's disease is characterized by recurring progressive inflammation and occlusions in small and medium arteries and veins of the limbs. Its cause is unknown, but it... (Review)
Review
Buerger's disease is characterized by recurring progressive inflammation and occlusions in small and medium arteries and veins of the limbs. Its cause is unknown, but it is most common in young men with a history of tobacco use. It is responsible for ischemic ulcers and extreme pain in the hands and feet. In many cases, notably in patients with the most severe presentations, there is no possibility of improving the condition with surgery (limb revascularisation), and therefore, alternative therapies (e.g. sympathectomy) is used. This review assessed the effectiveness of surgical sympathectomy compared with any other therapy in patients with Buerger's disease. As a result, only one randomised controlled study (162 participants) compared sympathectomy with prostacyclin analogue (iloprost) was incorporated to the review. Such comparison shown that iloprost is more effective than sympathectomy to complete healing ulcers at four weeks (risk ratio 0.65; 95% confidence interval 0.45 to 0.95; P = 0.02; very low quality evidence) and at twenty four weeks (risk ratio 0.62; 95% confidence interval 0.48 to 0.82; P < 0.01; very low quality evidence) after the start of treatment and to relief rest pain at four weeks (risk ratio 1.90; 95% confidence interval 1.17 to 3.10; P = 0.01; very low quality evidence) but not more effective at twenty four weeks (risk ratio 1.68; 95% confidence interval 1.00 to 2.84; P = .10; very low quality evidence) after the start of treatment. We concluded, with very low quality of evidence, that intravenous iloprost is more effective than lumbar sympathectomyin the healing of ischemic ulcers and pain at rest in patients with Buerger's disease. Therefore, until now, the preference of the usage of intravenous iloprost over the lumbar sympathectomy (and vice versa) does not find robust evidence for its routine use.
PubMed: 28811905
DOI: 10.1177/2054270417717666 -
CMAJ : Canadian Medical Association... Nov 2021
Topics: Fluorescence; Frostbite; Humans; Iloprost
PubMed: 34810170
DOI: 10.1503/cmaj.202258-f -
Cureus Sep 2023Raynaud's phenomenon (RP) is a vasospastic disorder characterized by an exaggerated vasoconstrictive response to cold or emotional stress. It can be classified as...
Raynaud's phenomenon (RP) is a vasospastic disorder characterized by an exaggerated vasoconstrictive response to cold or emotional stress. It can be classified as primary (PRP) or secondary (SRP) depending on its association with an underlying condition. We present a case of a young female with severe RP, with trophic changes and abnormal capillaroscopy. After a detailed investigation, a diagnosis of secondary RP due to solvent exposure was made. The patient was treated with calcium channel blocker in low doses, due to hypotension, without improvement of symptoms. Vitamin C and pentoxifylline were added with an unsatisfactory response. Given the progressive worsening of RP and the appearance of trophic lesions, the patient's treatment was reviewed, and continuous intravenous iloprost infusion through an elastomeric pump was started. This resulted in significant symptom improvement and normalization on the capillaroscopic examination.
PubMed: 37829986
DOI: 10.7759/cureus.45004 -
Annals of Translational Medicine Apr 2021Pulmonary hypertension (PH) is a severe disease that affects people of all ages. It can occur as an idiopathic disorder at birth or as part of a variety of... (Review)
Review
Pulmonary hypertension (PH) is a severe disease that affects people of all ages. It can occur as an idiopathic disorder at birth or as part of a variety of cardiovascular and pulmonary disorders. Inhaled pulmonary vasodilators (IPV) can reduce pulmonary vascular resistance (PVR) and improve RV function with minimal systemic effects. IPV includes inhaled nitric oxide (iNO), inhaled aerosolized prostacyclin, or analogs, including epoprostenol, iloprost, treprostinil, and other vasodilators. In addition to pulmonary vasodilating effects, IPV can also be used to improve oxygenation, reduce inflammation, and protect cell. Off-label use of IPV is common in daily clinical practice. However, evidence supporting the inhalational administration of these medications is limited, inconclusive, and controversial regarding their safety and efficacy. We conducted a search for relevant papers published up to May 2020 in four databases: PubMed, Google Scholar, EMBASE and Web of Science. This review demonstrates that the clinical using and updated evidence of IPV. iNO is widely used in neonates, pediatrics, and adults with different cardiopulmonary diseases. The limitations of iNO include high cost, flat dose-response, risk of significant rebound PH after withdrawal, and the requirement of complex technology for monitoring. The literature suggests that inhaled aerosolized epoprostenol, iloprost, treprostinil and others such as milrinone and levosimendan may be similar to iNO. More research of IPV is needed to determine acceptable inclusion criteria, long-term outcomes, and management strategies including time, dose, and duration.
PubMed: 33987295
DOI: 10.21037/atm-20-4895 -
European Review For Medical and... Jan 2022Despite its low incidence, pulmonary hypertension in children places a substantial burden on families and society because survival can be shorter than 10 months and... (Review)
Review
OBJECTIVE
Despite its low incidence, pulmonary hypertension in children places a substantial burden on families and society because survival can be shorter than 10 months and treatment options are limited and ineffective. Drugs to treat pulmonary hypertension include endothelin antagonists, phosphodiesterase type 5 inhibitors and prostacyclin, which is the most widely used to treat pediatric pulmonary hypertension. The main aim of this study was to provide a comprehensive overview of the advantages and disadvantages of prostacyclin and its analogs for treating pulmonary hypertension in children.
MATERIALS AND METHODS
To retrieve a thorough collection of studies, we performed a search in PubMed using the following combination of keywords: (Prostacyclins) or (Epoprostenol) or (Iloprost) or (Treprostinil) or (Beraprost), (children) and (pulmonary arterial hypertension). The time limits used for the search were December 1983 to May 2021.
RESULTS
The search retrieved a total of 238 articles. Titles and abstracts of articles were screened for relevance, and all relevant articles published in English were included.
CONCLUSIONS
Epoprostenol can be effective against severe pulmonary hypertension. Iloprost can treat severe persistent pulmonary hypertension in newborns and inhaled iloprost can be used in pulmonary vasoreactivity testing. Treprostinil is a long-acting prostacyclin analog, and it shows the highest antiproliferative activity among prostacyclins. Beraprost may be effective in premature infants, but available evidence comes from only one patient, so more clinical testing is needed.
Topics: Antihypertensive Agents; Child; Endothelin Receptor Antagonists; Humans; Hypertension, Pulmonary; Iloprost; Infant, Newborn; Prostaglandins I; Pulmonary Arterial Hypertension
PubMed: 35049017
DOI: 10.26355/eurrev_202201_27745 -
The Cochrane Database of Systematic... Dec 2017Exercise programmes are a relatively inexpensive, low-risk option compared with other, more invasive therapies for treatment of leg pain on walking (intermittent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Exercise programmes are a relatively inexpensive, low-risk option compared with other, more invasive therapies for treatment of leg pain on walking (intermittent claudication (IC)). This is the fourth update of a review first published in 1998.
OBJECTIVES
Our goal was to determine whether an exercise programme was effective in alleviating symptoms and increasing walking treadmill distances and walking times in people with intermittent claudication. Secondary objectives were to determine whether exercise was effective in preventing deterioration of underlying disease, reducing cardiovascular events, and improving quality of life.
SEARCH METHODS
For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (last searched 15 November 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10) via the Cochrane Register of Studies Online, along with trials registries.
SELECTION CRITERIA
Randomised controlled trials of an exercise regimen versus control or versus medical therapy for people with IC due to peripheral arterial disease (PAD). We included any exercise programme or regimen used for treatment of IC, such as walking, skipping, and running. Inclusion of trials was not affected by duration, frequency, or intensity of the exercise programme. Outcome measures collected included treadmill walking distance (time to onset of pain or pain-free walking distance and maximum walking time or maximum walking distance), ankle brachial index (ABI), quality of life, morbidity, or amputation; if none of these was reported, we did not include the trial in this review.
DATA COLLECTION AND ANALYSIS
For this update (2017), RAL and AH selected trials and extracted data independently. We assessed study quality by using the Cochrane 'Risk of bias' tool. We analysed continuous data by determining mean differences (MDs) and 95% confidence intervals (CIs), and dichotomous data by determining risk ratios (RRs) and 95% CIs. We pooled data using a fixed-effect model unless we identified significant heterogeneity, in which case we used a random-effects model. We used the GRADE approach to assess the overall quality of evidence supporting the outcomes assessed in this review.
MAIN RESULTS
We included two new studies in this update and identified additional publications for previously included studies, bringing the total number of studies meeting the inclusion criteria to 32, and involving a total of 1835 participants with stable leg pain. The follow-up period ranged from two weeks to two years. Types of exercise varied from strength training to polestriding and upper or lower limb exercises; supervised sessions were generally held at least twice a week. Most trials used a treadmill walking test for one of the primary outcome measures. The methodological quality of included trials was moderate, mainly owing to absence of relevant information. Most trials were small and included 20 to 49 participants. Twenty-seven trials compared exercise versus usual care or placebo, and the five remaining trials compared exercise versus medication (pentoxifylline, iloprost, antiplatelet agents, and vitamin E) or pneumatic calf compression; we generally excluded people with various medical conditions or other pre-existing limitations to their exercise capacity.Meta-analysis from nine studies with 391 participants showed overall improvement in pain-free walking distance in the exercise group compared with the no exercise group (MD 82.11 m, 95% CI 71.73 to 92.48, P < 0.00001, high-quality evidence). Data also showed benefit from exercise in improved maximum walking distance (MD 120.36 m, 95% CI 50.79 to 189.92, P < 0.0007, high-quality evidence), as revealed by pooling data from 10 studies with 500 participants. Improvements were seen for up to two years.Exercise did not improve the ABI (MD 0.04, 95% CI 0.00 to 0.08, 13 trials, 570 participants, moderate-quality evidence). Limited data were available for the outcomes of mortality and amputation; trials provided no evidence of an effect of exercise, when compared with placebo or usual care, on mortality (RR 0.92, 95% CI 0.39 to 2.17, 5 trials, 540 participants, moderate-quality evidence) or amputation (RR 0.20, 95% CI 0.01 to 4.15, 1 trial, 177 participants, low-quality evidence).Researchers measured quality of life using Short Form (SF)-36 at three and six months. At three months, the domains 'physical function', 'vitality', and 'role physical' improved with exercise; however this was a limited finding, as it was reported by only two trials. At six months, meta-analysis showed improvement in 'physical summary score' (MD 2.15, 95% CI 1.26 to 3.04, P = 0.02, 5 trials, 429 participants, moderate-quality evidence) and in 'mental summary score' (MD 3.76, 95% CI 2.70 to 4.82, P < 0.01, 4 trials, 343 participants, moderate-quality evidence) secondary to exercise. Two trials reported the remaining domains of the SF-36. Data showed improvements secondary to exercise in 'physical function' and 'general health'. The other domains - 'role physical', 'bodily pain', 'vitality', 'social', 'role emotional', and 'mental health' - did not show improvement at six months.Evidence was generally limited in trials comparing exercise versus antiplatelet therapy, pentoxifylline, iloprost, vitamin E, and pneumatic foot and calf compression owing to small numbers of trials and participants.Review authors used GRADE to assess the evidence presented in this review and determined that quality was moderate to high. Although results showed significant heterogeneity between trials, populations and outcomes were comparable overall, with findings relevant to the claudicant population. Results were pooled for large sample sizes - over 300 participants for most outcomes - using reproducible methods.
AUTHORS' CONCLUSIONS
High-quality evidence shows that exercise programmes provided important benefit compared with placebo or usual care in improving both pain-free and maximum walking distance in people with leg pain from IC who were considered to be fit for exercise intervention. Exercise did not improve ABI, and we found no evidence of an effect of exercise on amputation or mortality. Exercise may improve quality of life when compared with placebo or usual care. As time has progressed, the trials undertaken have begun to include exercise versus exercise or other modalities; therefore we can include fewer of the new trials in this update.
Topics: Amputation, Surgical; Ankle Brachial Index; Exercise Therapy; Female; Humans; Intermittent Claudication; Male; Pain Management; Quality of Life; Randomized Controlled Trials as Topic; Time Factors; Walking
PubMed: 29278423
DOI: 10.1002/14651858.CD000990.pub4 -
Respiratory Care Jun 2015The inhaled route has a number of attractive features for treatment of pulmonary hypertension, including delivery of drug directly to the target organ, thus enhancing... (Review)
Review
The inhaled route has a number of attractive features for treatment of pulmonary hypertension, including delivery of drug directly to the target organ, thus enhancing pulmonary specificity and reducing systemic adverse effects. It can also improve ventilation/perfusion matching by dilating vessels supplying ventilated regions, thus improving gas exchange. Furthermore, it can achieve higher local drug concentrations at a lower overall dose, potentially reducing drug cost. Accordingly, a number of inhaled agents have been developed to treat pulmonary hypertension. Most in current use are prostacyclins, including epoprostenol, which has been cleared for intravenous applications but is used off-label in acute care settings as a continuously nebulized medication. Aerosolized iloprost and treprostinil are both prostacyclins that have been cleared by the FDA to treat pulmonary arterial hypertension (PAH). Both require frequent administration (6 and 4 times daily, respectively), and both have a tendency to cause airway symptoms, including cough and wheeze, which can lead to intolerance. These agents cannot be used to substitute for the infused routes of prostacyclin because they do not permit delivery of medication at high doses. Inhaled nitric oxide (INO) is cleared for the treatment of primary pulmonary hypertension in newborns. It is also used off-label to test acute vasoreactivity in PAH during right-heart catheterization and to treat acute right-heart failure in hospitalized patients. In addition, some studies on long-term application of INO either have been recently completed with results pending or are under consideration. In the future, because of its inherent advantages in targeting the lung, the inhaled route is likely to be tested using a variety of small molecules that show promise as PAH therapies.
Topics: Administration, Inhalation; Adult; Antihypertensive Agents; Bronchodilator Agents; Epoprostenol; Humans; Hypertension, Pulmonary; Iloprost; Infant, Newborn; Nitric Oxide; Off-Label Use; Prostaglandins I; Vasodilator Agents
PubMed: 26070575
DOI: 10.4187/respcare.03927 -
International Journal of Circumpolar... Dec 2023We performed a scoping review to identify the extent of the literature describing the use of iloprost in the treatment of frostbite. Iloprost is a stable synthetic... (Review)
Review
We performed a scoping review to identify the extent of the literature describing the use of iloprost in the treatment of frostbite. Iloprost is a stable synthetic analog of prostaglandin I. As a potent inhibitor of platelet aggregation and vasodilator, it has been used to address the post-rewarming reperfusion injury in frostbite. The search using iloprost and frostbite as key words and MeSH terms yielded 200 articles. We included in our review the literature examining iloprost for the treatment of frostbite in humans in the form of primary research, conference proceedings and abstracts. Twenty studies published from 1994 to 2022 were selected for analysis. The majority were retrospective case series consisting of a homogeneous population of mountain sport enthusiasts. A total of 254 patients and over 1000 frostbitten digits were included among the 20 studies. The larger case series demonstrated a decrease in amputation rates relative to untreated patients. Primary gaps in the literature include a paucity of randomised trials and relatively limited study populations to date. While the case evidence is promising, a multi-centre collaboration would be crucial to adequately power prospective randomised studies to definitively determine if iloprost has a role in the treatment of frostbite.
Topics: Humans; Iloprost; Prospective Studies; Retrospective Studies; Epoprostenol; Frostbite
PubMed: 36966492
DOI: 10.1080/22423982.2023.2189552