Pentoxifylline for intermittent claudication.

BACKGROUND: Intermittent claudication (IC) is a symptom of peripheral arterial disease (PAD) and is associated with high morbidity and mortality. Pentoxifylline, one of many drugs used to treat IC, acts by decreasing blood viscosity, improving erythrocyte flexibility, and promoting microcirculatory flow and tissue oxygen concentration. Many studies have evaluated the efficacy of pentoxifylline in treating people with PAD, but results of these studies are variable. This is the second update of a review first published in 2012. OBJECTIVES: To determine the efficacy of pentoxifylline in improving the walking capacity (i.e. pain-free walking distance and total (absolute, maximum) walking distance) of people with stable intermittent claudication, Fontaine stage II. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 28 January 2020. There were no language restrictions. SELECTION CRITERIA: We included all double-blind, randomised controlled trials (RCTs) comparing pentoxifylline versus placebo or any other pharmacological intervention in people with IC Fontaine stage II. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, assessed the included studies, matched data and resolved disagreements by discussion. Review authors assessed the methodological quality of studies using the Cochrane 'Risk of bias' tool and collected results related to the outcomes of interest, pain-free walking distance (PFWD), total walking distance (TWD), ankle-brachial pressure index (ABI), quality of life (QoL) and side effects. Comparison of studies was based on duration and dose of pentoxifylline. We used GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: We identified no new eligible studies for this update. This review includes 24 studies with 3377 participants. Seventeen studies compared pentoxifylline versus placebo. The seven remaining studies compared pentoxifylline with flunarizine (one study), aspirin (one study), Gingko biloba extract (one study), nylidrin hydrochloride (one study), prostaglandin E1 (two studies), and buflomedil and nifedipine (one study). Risk of bias for the individual studies was generally unclear because there was a lack of methodological reporting for many of the included studies, especially regarding randomisation and allocation methods. Most included studies did not provide adequate information to allow selective reporting to be judged and did not report blinding of assessors. Heterogeneity between included studies was considerable with regards to multiple variables, including duration of treatment, dose of pentoxifylline, baseline walking distance and participant characteristics; therefore, pooled analysis for comparisons which included more than one study, was not possible. Pentoxifylline compared to placebo Of 17 studies comparing pentoxifylline with placebo, 11 reported PFWD and 14 reported TWD; the difference in percentage improvement in PFWD for pentoxifylline over placebo ranged from -33.8% to 73.9% and in TWD ranged from 1.2% to 155.9%. It was not possible to pool the data of the studies because data were insufficient and findings from individual trials were unclear. Most included studies suggested a possible improvement in PFWD and TWD for pentoxifylline over placebo (both low-certainty evidence). The five studies which evaluated pre-exercise ABI comparing pentoxifylline and placebo found no evidence of a difference (moderate-certainty evidence). Two of the three studies that evaluated QoL between people who received pentoxifylline and placebo were larger studies that used validated QoL tools and generally found no evidence of a difference between groups. One small, short-term study, which did not specify which QoL tool was used, reported improved QoL in the pentoxifylline group (moderate-certainty evidence). Pentoxifylline generally was well tolerated; the most commonly reported side effects consisted of gastrointestinal symptoms such as nausea (low-certainty evidence). Certainty of the evidence from this review was low or moderate, with downgrading due to risk of bias concerns, inconsistencies between studies and the inability to evaluate imprecision because meta-analysis could not be undertaken. The seven remaining studies compared pentoxifylline with either flunarizine, aspirin, Gingko biloba extract, nylidrin hydrochloride, prostaglandin E1, or buflomedil and nifedipine; data were too limited to allow any meaningful conclusions to be made. AUTHORS' CONCLUSIONS: There is a lack of high-certainty evidence for the effects of pentoxifylline compared to placebo, or other treatments, for IC. There is low-certainty evidence that pentoxifylline may improve PFWD and TWD compared to placebo, but no evidence of a benefit to ABI or QoL (moderate-certainty evidence). Pentoxifylline was reported to be generally well tolerated (low-certainty evidence). Given the large degree of heterogeneity between the studies, the role of pentoxifylline for people with IC Fontaine class II remains uncertain.

Pentoxifylline for intermittent claudication.

BACKGROUND: Intermittent claudication (IC) is a symptom of peripheral arterial disease (PAD) and is associated with high morbidity and mortality. Pentoxifylline, one of many drugs used to treat IC, acts by decreasing blood viscosity, improving erythrocyte flexibility and promoting microcirculatory flow and tissue oxygen concentration. Many studies have evaluated the efficacy of pentoxifylline in treating individuals with PAD, but results of these studies are variable. This is an update of a review first published in 2012. OBJECTIVES: To determine the efficacy of pentoxifylline in improving the walking capacity (i.e. pain-free walking distance and total (absolute, maximum) walking distance) of individuals with stable intermittent claudication, Fontaine stage II. SEARCH METHODS: For this update, the Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched April 2015) and the Cochrane Register of Studies (2015, Issue 3). SELECTION CRITERIA: All double-blind, randomised controlled trials (RCTs) comparing pentoxifylline versus placebo or any other pharmacological intervention in patients with IC Fontaine stage II. DATA COLLECTION AND ANALYSIS: Two review authors separately assessed included studies,. matched data and resolved disagreements by discussion. Review authors assessed the methodological quality of studies by using the Cochrane 'Risk of bias' tool and collected results related to pain-free walking distance (PFWD) and total walking distance (TWD). Comparison of studies was based on duration and dose of pentoxifylline. MAIN RESULTS: We included in this review 24 studies with 3377 participants. Seventeen studies compared pentoxifylline versus placebo. In the seven remaining studies, pentoxifylline was compared with flunarizine (one study), aspirin (one study), Gingko biloba extract (one study), nylidrin hydrochloride (one study), prostaglandin E1 (two studies) and buflomedil and nifedipine (one study). The quality of the evidence was generally low, with large variability in reported findings.. Most included studies did not report on random sequence generation and allocation concealment, did not provide adequate information to allow selective reporting to be judged and did not report blinding of assessors. Heterogeneity between included studies was considerable with regards to multiple variables, including duration of treatment, dose of pentoxifylline, baseline walking distance and participant characteristics; therefore, pooled analysis was not possible.Of 17 studies comparing pentoxifylline with placebo, 14 reported TWD and 11 reported PFWD; the difference in percentage improvement in TWD for pentoxifylline over placebo ranged from 1.2% to 155.9%, and in PFWD from -33.8% to 73.9%. Testing the statistical significance of these results generally was not possible because data were insufficient. Most included studies suggested improvement in PFWD and TWD for pentoxifylline over placebo and other treatments, but the statistical and clinical significance of findings from individual trials is unclear. Pentoxifylline generally was well tolerated; the most commonly reported side effects consisted of gastrointestinal symptoms such as nausea. AUTHORS' CONCLUSIONS: Given the generally poor quality of published studies and the large degree of heterogeneity evident in interventions and in results, the overall benefit of pentoxifylline for patients with Fontaine class II intermittent claudication remains uncertain. Pentoxifylline was shown to be generally well tolerated.Based on total available evidence, high-quality data are currently insufficient to reveal the benefits of pentoxifylline for intermittent claudication.

Pentoxifylline for intermittent claudication.

BACKGROUND: Intermittent claudication (IC) is a symptom of peripheral arterial occlusive disease (PAD). It is associated with high morbidity and mortality. Pentoxifylline is one of many drugs used to treat IC. Pentoxifylline decreases blood viscosity, improves erythrocyte flexibility, and increases microcirculatory flow and tissue oxygen concentration.Many studies have evaluated the efficacy of pentoxifylline in treating PAD but the results of these studies are very variable. OBJECTIVES: To determine the efficacy of pentoxifylline in improving the walking capacity (that is pain-free walking distance and the total (absolute, maximum) walking distance) of patients with stable intermittent claudication, Fontaine stage II. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched January 2011) and CENTRAL (2011, Issue 1). In addition, we searched MEDLINE (Week 2 January 2011) and EMBASE (2011 Week 03). ClinicalTrials.gov and Current Controlled Trials were searched for ongoing or unpublished trials. SELECTION CRITERIA: All double blind, randomised controlled trials (RCTs) comparing pentoxifylline to placebo or any other pharmacological intervention in patients with IC Fontaine stage II. DATA COLLECTION AND ANALYSIS: Included studies were assessed separately by two review authors. Data were matched and disagreements resolved by discussion. The quality of the studies was assessed using the Jadad score and the Cochrane risk of bias tool. Results relating to pain-free walking distance (PFWD) and total walking distance (TWD) were collected. Studies were compared based on the duration and dose of pentoxifylline. MAIN RESULTS: Twenty-three studies with 2816 participants were included in this review. There was considerable heterogeneity between the included studies with regards to multiple variables including duration of treatment, dose of pentoxifylline, baseline walking distance and patient characteristics, and therefore pooled analysis was not possible. The quality of the included studies was generally low. There was very large variability in the reported findings between the individual studies. In a total of 17 studies which compared pentoxifylline with placebo, of which 14 reported TWD and 11 reported PFWD, the difference in percentage improvement in TWD for pentoxifylline over placebo ranged from 1.2% to 155.9%, and for PFWD the difference ranged from -33.8% to 73.9%. Testing for statistical significance of these results was generally not possible due to the lack of data. There was no statistically significant difference in ankle brachial pressure index (ABI) between the pentoxifylline and placebo groups. Pentoxifylline was generally well tolerated. AUTHORS' CONCLUSIONS: Given the generally poor quality of the published studies and the large degree of heterogeneity in the interventions and the results, the overall benefit of pentoxifylline for patients with Fontaine class II intermittent claudication remains uncertain. Pentoxifylline is generally well tolerated.  Based on the totality of the available evidence, it is possible that pentoxifylline could have a place in the treatment of IC as a means of improving walking distance and as a complimentary treatment assuming all other essential measures such as lifestyle change, exercise and treatment for secondary prevention have been taken into account. However, the response to pentoxifylline should be assessed on an individual basis.

Impact of the COVID-19 pandemic on cardiovascular mortality and catherization activity during the lockdown in central Germany: an observational study.

AIMS: During the COVID-19 pandemic, hospital admissions for cardiac care have declined. However, effects on mortality are unclear. Thus, we sought to evaluate the impact of the lockdown period in central Germany on overall and cardiovascular deaths. Simultaneously we looked at catheterization activities in the same region. METHODS AND RESULTS: Data from 22 of 24 public health-authorities in central Germany were aggregated during the pandemic related lockdown period and compared to the same time period in 2019. Information on the total number of deaths and causes of death, including cardiovascular mortality, were collected. Additionally, we compared rates of hospitalization (n = 5178) for chronic coronary syndrome (CCS), acute coronary syndrome (ACS), and out of hospital cardiac arrest (OHCA) in 26 hospitals in this area. Data on 5,984 deaths occurring between March 23, 2020 and April 26, 2020 were evaluated. In comparison to the reference non-pandemic period in 2019 (deaths: n = 5832), there was a non-significant increase in all-cause mortality of 2.6% [incidence rate ratio (IRR) 1.03, 95% confidence interval (CI) 0.99-1.06; p = 0.16]. Cardiovascular and cardiac mortality increased significantly by 7.6% (IRR 1.08, 95%-CI 1.01-1.14; p = 0.02) and by 11.8% (IRR 1.12, 95%-CI 1.05-1.19; p < 0.001), respectively. During the same period, our data revealed a drop in cardiac catherization procedures. CONCLUSION: During the COVID-19-related lockdown a significant increase in cardiovascular mortality was observed in central Germany, whereas catherization activities were reduced. The mechanisms underlying both of these observations should be investigated further in order to better understand the effects of a pandemic-related lockdown and social-distancing restrictions on cardiovascular care and mortality.

Coronary stents cause high velocity fluctuation with a flow acceleration and flow reduction in jailed branches: an in vitro study using laser-Doppler anemometry.

Flow disturbance and reduced blood flow have been associated with higher restenosis rates and clinical adverse events after coronary interventions. In the present study, we sought to investigate flow alterations that occurred after stent implantation in a coronary model, within and adjacent to the stented segment. Two stents (Carbostent, Tetrastent) with different strut design were deployed in the left anterior descending artery (LAD) of a 1:1 scaled silicon coronary model. The model was mounted into an artificial circulation and showed distensibility and rheologic behavior comparable to human coronaries. Flow profiles were assessed using laser-Doppler anemometry. Both stents induced a transitional flow within the stents, in the jailed branch as well as in the adjacent segments. However, the alterations in flow were less marked using the Carbostent having stents with thinner struts and a larger strut cell area, and thus seem to be more favorable in avoiding bifurcation lesions. This study shows precisely that stent implantation induces flow disturbances in segments known to be prone for restenosis. Investigations using laser-Doppler measurements may enlighten rheologic phenomena inducing restenosis and help in optimizing stent design and deployment techniques.

Not all ovarian cysts in young woman are benign: a case series and review of the management of complex adnexal masses in young women.

While ovarian cancer is a disease that predominately affects postmenopausal women, up to 13% of affected patients are indeed less than 45 years of age. The diagnosis is often delayed because of the non-specific nature of symptoms and a lack of specific and accurate diagnostic tests, that is, CA125 and ultrasound. In premenopausal women these issues are compounded, further reducing the likelihood of an accurate and early diagnosis. It is important for gynaecologists to have a high index of suspicion and appropriately investigate symptomatic patients and interpret test results critically. Not all ovarian cysts in young women are benign, and a low threshold for surgical evaluation is warranted.

Recurrence after treatment for high-grade dysplasia: should we modify our post-treatment surveillance protocols?

A cohort of women, having undergone an excisional procedure for high-grade cervical dysplasia, was studied to identify those patients who developed recurrent high-grade cervical dysplasia post-treatment. We have confirmed that recurrent histologically confirmed high-grade cervical dysplasia is uncommon after complete excision and appears not to occur within the first 6 months post-treatment. Post-treatment surveillance protocols should incorporate these findings.