Context: Cholera causes acute watery diarrhoea and death if not properly treated. Outbreaks occur in areas with poor sanitation, including refugee camps. Several vaccines have been developed and tested over the last 50 years. This is an update of a Cochrane review, originally published in 1998, which explored the effects of all vaccines for preventing cholera. This review examines oral vaccines made from killed bacteria.

To assess the effectiveness and safety of the available World Health Organization (WHO)-prequalified oral killed cholera vaccines among children and adults.

We included randomized controlled trials (RCTs), including cluster-RCTs. There were no restrictions on the age and sex of the participants or the setting of the study. We considered any available WHO-prequalified oral killed cholera vaccine as an intervention. The control group was given a placebo, another vaccine, or no vaccine. The outcomes were related to vaccine effectiveness and safety. We included articles published in English only.

Two-year study of the protective efficacy of the oral whole cell plus recombinant B subunit cholera vaccine in Peru.

Abstract: The protective efficacy of an oral inactivated whole cell Vibrio cholerae plus recombinant B subunit cholera vaccine was determined against El Tor cholera among Peruvian children and adults (2-65 years old) in a randomized, double-blind manner. Study subjects received 2 doses of vaccine or placebo 2 weeks apart, followed by a booster dose 10 months later. Surveillance for cholera was performed actively, with 2 visits per week to each household, and passively, at a local hospital. Stool samples were collected during diarrhea episodes and were cultured for V. cholerae. A total of 17,799 persons received 2 doses of vaccine or placebo, and 14,997 of these persons received the booster dose. After 2 doses (first surveillance period), V. cholerae biotype O1 was isolated from 17 vaccinees and 16 placebo recipients, demonstrating vaccine efficacy (VE) of -4%. After 3 doses (second surveillance period), V. cholerae O1 was isolated from 13 vaccinees and 32 placebo recipients, demonstrating VE of 61% (95% confidence interval ¿CI, 28%-79%). In the second surveillance period, the VE for illness requiring hospitalization was 82% (95% CI, 27%-96%). VE was also higher for persons >15 years old (VE, 72%; 95% CI, 28%-89%).

Efficacy and safety of a modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-randomised, double-blind, placebo-controlled trial.

Abstract:
Oral cholera vaccines consisting of killed whole cells have been available for many years, but they have not been used extensively in populations with endemic disease. An inexpensive, locally produced oral killed-whole-cell vaccine has been used in high-risk areas in Vietnam. To expand the use of this vaccine, it was modified to comply with WHO standards. We assessed the efficacy and safety of this modified vaccine in a population with endemic cholera.

In this double-blind trial, 107 774 non-pregnant residents of Kolkata, India, aged 1 year or older, were cluster-randomised by dwelling to receive two doses of either modified killed-whole-cell cholera vaccine (n=52 212; 1966 clusters) or heat-killed Escherichia coli K12 placebo (n=55 562; 1967 clusters), both delivered orally. Randomisation was done by computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for the patient to seek treatment in a health-care facility. We undertook an interim, per-protocol analysis at 2 years of follow-up that included individuals who received two completely ingested doses of vaccine or placebo. We assessed first episodes of cholera that occurred between 14 days and 730 days after receipt of the second dose. This study is registered with ClinicalTrials.gov, number NCT00289224.

31 932 participants assigned to vaccine (1721 clusters) and 34 968 assigned to placebo (1757 clusters) received two doses of study treatment. There were 20 episodes of cholera in the vaccine group and 68 episodes in the placebo group (protective efficacy 67%; one-tailed 99% CI, lower bound 35%, p<0.0001). The vaccine protected individuals in age-groups 1.0-4.9 years, 5.0-14.9 years, and 15 years and older, and protective efficacy did not differ significantly between age-groups (p=0.28). We recorded no vaccine-related serious adverse events.

This modified killed-whole-cell oral vaccine, compliant with WHO standards, is safe, provides protection against clinically significant cholera in an endemic setting, and can be used in children aged 1.0-4.9 years, who are at highest risk of developing cholera in endemic settings.

Bill & Melinda Gates Foundation, Swedish International Development Cooperation Agency, Governments of South Korea, Sweden, and Kuwait.

Efficacy of a low-cost, inactivated whole-cell oral cholera vaccine: results from 3 years of follow-up of a randomized, controlled trial.

Abstract:
Killed oral cholera vaccines (OCVs) have been licensed for use in developing countries, but protection conferred by licensed OCVs beyond two years of follow-up has not been demonstrated in randomized, clinical trials.

We conducted a cluster-randomized, placebo-controlled trial of a two-dose regimen of a low-cost killed whole cell OCV in residents 1 year of age and older living in 3,933 clusters in Kolkata, India. The primary endpoint was culture-proven Vibrio cholerae O1 diarrhea episodes severe enough to require treatment in a health care facility. Of the 66,900 fully dosed individuals (31,932 vaccinees and 34,968 placebo recipients), 38 vaccinees and 128 placebo-recipients developed cholera during three years of follow-up (protective efficacy 66%; one-sided 95%CI lower bound = 53%, p<0.001). Vaccine protection during the third year of follow-up was 65% (one-sided 95%CI lower bound = 44%, p<0.001). Significant protection was evident in the second year of follow-up in children vaccinated at ages 1-4 years and in the third year in older age groups.

The killed whole-cell OCV conferred significant protection that was evident in the second year of follow-up in young children and was sustained for at least three years in older age groups. Continued follow-up will be important to establish the vaccine's duration of protection.

ClinicalTrials.gov NCT00289224.

5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial.

Abstract:
Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India.

In our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment.

69 of 31 932 recipients of vaccine and 219 of 34 968 recipients of placebo developed cholera during 5 year follow-up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74; p<0·0001), and point estimates by year of follow-up suggested no evidence of decline in protective efficacy.

Sustained protection for 5 years at the level we reported has not been noted previously with other oral cholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings.

Bill & Melinda Gates Foundation and the governments of South Korea and Sweden.

Feasibility and effectiveness of oral cholera vaccine in an urban endemic setting in Bangladesh: a cluster randomised open-label trial.

Abstract:
Cholera is endemic in Bangladesh with epidemics occurring each year. The decision to use a cheap oral killed whole-cell cholera vaccine to control the disease depends on the feasibility and effectiveness of vaccination when delivered in a public health setting. We therefore assessed the feasibility and protective effect of delivering such a vaccine through routine government services in urban Bangladesh and evaluated the benefit of adding behavioural interventions to encourage safe drinking water and hand washing to vaccination in this setting.

We did this cluster-randomised open-label trial in Dhaka, Bangladesh. We randomly assigned 90 clusters (1:1:1) to vaccination only, vaccination and behavioural change, or no intervention. The primary outcome was overall protective effectiveness, assessed as the risk of severely dehydrating cholera during 2 years after vaccination for all individuals present at time of the second dose. This study is registered with ClinicalTrials.gov, number NCT01339845.

Of 268,896 people present at baseline, we analysed 267,270: 94,675 assigned to vaccination only, 92,539 assigned to vaccination and behavioural change, and 80,056 assigned to non-intervention. Vaccine coverage was 65% in the vaccination only group and 66% in the vaccination and behavioural change group. Overall protective effectiveness was 37% (95% CI lower bound 18%; p=0·002) in the vaccination group and 45% (95% CI lower bound 24%; p=0·001) in the vaccination and behavioural change group. We recorded no vaccine-related serious adverse events.

Our findings provide the first indication of the effect of delivering an oral killed whole-cell cholera vaccine to poor urban populations with endemic cholera using routine government services and will help policy makers to formulate vaccination strategies to reduce the burden of severely dehydrating cholera in such populations.

Bill & Melinda Gates Foundation.

Efficacy of a Single-Dose, Inactivated Oral Cholera Vaccine in Bangladesh.

Abstract:
A single-dose regimen of the current killed oral cholera vaccines that have been prequalified by the World Health Organization would make them more attractive for use against endemic and epidemic cholera. We conducted an efficacy trial of a single dose of the killed oral cholera vaccine Shanchol, which is currently given in a two-dose schedule, in an urban area in which cholera is highly endemic.

Nonpregnant residents of Dhaka, Bangladesh, who were 1 year of age or older were randomly assigned to receive a single dose of oral cholera vaccine or oral placebo. The primary outcome was vaccine protective efficacy against culture-confirmed cholera occurring 7 to 180 days after dosing. Prespecified secondary outcomes included protective efficacy against severely dehydrating culture-confirmed cholera during the same interval, against cholera and severe cholera occurring 7 to 90 versus 91 to 180 days after dosing, and against cholera and severe cholera according to age at baseline.

A total of 101 episodes of cholera, 37 associated with severe dehydration, were detected among the 204,700 persons who received one dose of vaccine or placebo. The vaccine protective efficacy was 40% (95% confidence interval [CI], 11 to 60%; 0.37 cases per 1000 vaccine recipients vs. 0.62 cases per 1000 placebo recipients) against all cholera episodes, 63% (95% CI, 24 to 82%; 0.10 vs. 0.26 cases per 1000 recipients) against severely dehydrating cholera episodes, and 63% (95% CI, -39 to 90%), 56% (95% CI, 16 to 77%), and 16% (95% CI, -49% to 53%) against all cholera episodes among persons vaccinated at the age of 5 to 14 years, 15 or more years, and 1 to 4 years, respectively, although the differences according to age were not significant (P=0.25). Adverse events occurred at similar frequencies in the two groups.

A single dose of the oral cholera vaccine was efficacious in older children (≥5 years of age) and in adults in a setting with a high level of cholera endemicity. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02027207.).

Safety of the oral cholera vaccine in pregnancy: Retrospective findings from a subgroup following mass vaccination campaign in Dhaka, Bangladesh.

Abstract:
Pregnant women are vulnerable to complications of cholera. Killed oral cholera vaccines (OCV) are not recommended for pregnant women though there is no evidence of harmful effects during pregnancy. We evaluated the effect of a killed OCV, Shanchol™, on pregnancy outcomes during an effectiveness trial of the vaccine in urban Bangladesh.

Individuals ⩾1year were invited to participate in the trial, conducted in 2011 in Dhaka, Bangladesh. Pregnancy by history was an exclusion criterion and all women of reproductive age (15-49years) were verbally questioned about pregnancy at enrollment and prior to vaccination. Out of 48,414 women of reproductive age 286 women received the OCV unknowingly while pregnant. Out of these, we could recruit 69 women defined as exposed to OCV. Accordingly, we selected 69 pregnant women randomly from those who did not take the OCV (non-exposed to OCV). We evaluated adverse pregnancy outcome (spontaneous miscarriages, still births, or congenital malformations) between those who were exposed to OCV and those who were not exposed to OCV.

About 16% of pregnant women exposed to OCV had pregnancy loss, as compared to 12% of unvaccinated pregnant women (P=0.38). One congenital anomaly was observed and occurred in women non-exposed to OCV group. Models that adjusted for baseline characteristics that were unbalanced between the exposed and non-exposed groups, revealed a no elevation of risk of adverse pregnancy outcomes in vaccinees versus non-vaccinees (Adj. OR (95% CI): 0.45 (0.11-1.88).

No excess of adverse fetal outcomes associated with receipt of OCV was observed in this study.

Clinical Trials.gov number NCT01339845.

Efficacy of a bivalent killed whole-cell cholera vaccine over five years: a re-analysis of a cluster-randomized trial.

Abstract:
Oral cholera vaccine (OCV) is a feasible tool to prevent or mitigate cholera outbreaks. A better understanding of the vaccine's efficacy among different age groups and how rapidly its protection wanes could help guide vaccination policy.

To estimate the level and duration of OCV efficacy, we re-analyzed data from a previously published cluster-randomized, double-blind, placebo controlled trial with five years of follow-up. We used a Cox proportional hazards model and modeled the potentially time-dependent effect of age categories on both vaccine efficacy and risk of infection in the placebo group. In addition, we investigated the impact of an outbreak period on model estimation.

Vaccine efficacy was 38% (95% CI: -2%,62%) for those vaccinated from ages 1 to under 5 years old, 85% (95% CI: 67%,93%) for those 5 to under 15 years, and 69% (95% CI: 49%,81%) for those vaccinated at ages 15 years and older. Among adult vaccinees, efficacy did not appear to wane during the trial, but there was insufficient data to assess the waning of efficacy among child vaccinees.

Through this re-analysis we were able to detect a statistically significant difference in OCV efficacy when the vaccine was administered to children under 5 years old vs. children 5 years and older. The estimated efficacies are more similar to the previously published analysis based on the first two years of follow-up than the analysis based on all five years.

ClinicalTrials.gov identifier NCT00289224.

Efficacy of a single-dose regimen of inactivated whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trial.

Abstract:
A single-dose regimen of inactivated whole-cell oral cholera vaccine (OCV) is attractive because it reduces logistical challenges for vaccination and could enable more people to be vaccinated. Previously, we reported the efficacy of a single dose of an OCV vaccine during the 6 months following dosing. Herein, we report the results of 2 years of follow-up.

In this placebo-controlled, double-blind trial done in Dhaka, Bangladesh, individuals aged 1 year or older with no history of receipt of OCV were randomly assigned to receive a single dose of inactivated OCV or oral placebo. The primary endpoint was a confirmed episode of non-bloody diarrhoea for which the onset was at least 7 days after dosing and a faecal culture was positive for Vibrio cholerae O1 or O139. Passive surveillance for diarrhoea was done in 13 hospitals or major clinics located in or near the study area for 2 years after the last administered dose. We assessed the protective efficacy of the OCV against culture-confirmed cholera occurring 7-730 days after dosing with both crude and multivariable per-protocol analyses. This trial is registered at ClinicalTrials.gov, number NCT02027207.

Between Jan 10, 2014, and Feb 4, 2014, 205 513 people were randomly assigned to receive either vaccine or placebo, of whom 204 700 (102 552 vaccine recipients and 102 148 placebo recipients) were included in the per-protocol analysis. 287 first episodes of cholera (109 among vaccine recipients and 178 among placebo recipients) were detected during the 2-year follow-up; 138 of these episodes (46 in vaccine recipients and 92 in placebo recipients) were associated with severe dehydration. The overall incidence rates of initial cholera episodes were 0·22 (95% CI 0·18 to 0·27) per 100 000 person-days in vaccine recipients versus 0·36 (0·31 to 0·42) per 100 000 person-days in placebo recipients (adjusted protective efficacy 39%, 95% CI 23 to 52). The overall incidence of severe cholera was 0·09 (0·07 to 0·12) per 100 000 person-days versus 0·19 (0·15 to 0·23; adjusted protective efficacy 50%, 29 to 65). Vaccine protective efficacy was 52% (8 to 75) against all cholera episodes and 71% (27 to 88) against severe cholera episodes in participants aged 5 years to younger than 15 years. For participants aged 15 years or older, vaccine protective efficacy was 59% (42 to 71) against all cholera episodes and 59% (35 to 74) against severe cholera. The protection in the older age groups was sustained throughout the 2-year follow-up. In participants younger than 5 years, the vaccine did not show protection against either all cholera episodes (protective efficacy -13%, -68 to 25) or severe cholera episodes (-44%, -220 to 35).

A single dose of the inactivated whole-cell OCV offered protection to older children and adults that was sustained for at least 2 years. The absence of protection of young children might reflect a lesser degree of pre-existing natural immunity in this age group.

Bill & Melinda Gates Foundation to the International Vaccine Institute.

Safety of a bivalent, killed, whole-cell oral cholera vaccine in pregnant women in Bangladesh: evidence from a randomized placebo-controlled trial.

Abstract:
Cholera increases the risk of harmful effects on foetuses. We prospectively followed pregnant women unaware of their pregnancy status who received a study agent in a clinical trial evaluating the association between exposure to an oral cholera vaccine (OCV) and foetal survival.

Study participants were selected from a randomized placebo-controlled trial conducted in Dhaka, Bangladesh. The vaccination campaign was conducted between January 10 and February 4, 2014. We enrolled women who were exposed to an OCV or placebo during pregnancy (Cohort 1) and women who were pregnant after the vaccination was completed (Cohort 2). Our primary endpoint was pregnancy loss (spontaneous miscarriage or stillbirth), and the secondary endpoints were preterm delivery and low birth weight. We employed a log-binomial regression to calculate the relative risk of having adverse outcomes among OCV recipients compared to that among placebo recipients.

There were 231 OCV and 234 placebo recipients in Cohort 1 and 277 OCV and 299 placebo recipients in Cohort 2. In Cohort 1, the incidence of pregnancy loss was 113/1000 and 115/1000 among OCV and placebo recipients, respectively. The adjusted relative risk for pregnancy loss was 0.97 (95% CI: 0.58-1.61; p = 0.91) in Cohort 1. We did not observe any variation in the risk of pregnancy loss between the two cohorts. The risks for preterm delivery and low birth weight were not significantly different between the groups in both cohorts.

Our study provides additional evidence that exposure to an OCV during pregnancy does not increase the risk of pregnancy loss, preterm delivery, or low birth weight, suggesting that pregnant women in cholera-affected regions should not be excluded in a mass vaccination campaign.

The study is registered at ( http://clinicaltrials.gov ). Identifier: NCT02027207 .


Context: Over 1.3 million people die each year as a result of traffic collisions and hundreds of thousands of others are permanently and seriously injured. Most of these deaths occur in low- and middle-income countries, where mortality rates can be up to 10 times higher than those of some high-income countries. Seat belts are designed to accomplish two key functions - to prevent the occupant from being ejected from the vehicle by the force of impact, and to extend the time that the decelerating force is applied to a person. Seat belts also spread the area of impact both to larger and less vulnerable parts of the body. Since the 1950s, seat belts have been factory-fitted to most vehicles, and today around 90% of high-income countries have adopted seat belt legislation that makes it mandatory for some, if not all, vehicle occupants to wear seat belts. However, the simple passing of laws is not sufficient to ensure seat belt use, and, while the enforcement of seat belt laws does increase seat belt use, other interventions have been developed to encourage voluntary - and hence sustainable - behaviour change.

To evaluate the benefits of behavioural-change interventions (educational-based, incentive-based, engineering-based, or a combination, but not enforcement-based) that promote the use of seat belts, and to determine which types of interventions are most effective.

We included randomised controlled trials (RCTs), both individually randomised and cluster-randomised, that evaluated education, engineering, incentive-based interventions (or combinations) that promoted seat belt use.

A statewide intervention to increase safety belt use: adding to the impact of a belt use law.

Effectiveness of a comprehensive multisector campaign to increase seat belt use in the greater Athens area, Greece. Hellenic Road Traffic Police Department.

Abstract:
This study assessed the effectiveness of a comprehensive campaign to increase seat belt use in Athens.

In 1996 a survey focusing on seat belt use was undertaken among occupants of 1400 passenger cars. From October 1997 to June 1998 the campaign was implemented; during the campaign, seat belt law enforcement was not intensified. In 1998 another inspection survey of 2250 cars was undertaken.

The program brought only a 6% increase in compliance, but there was an estimated gain of about 50 averted deaths and 1500 averted injuries.

An intensive campaign to increase seat belt use, conducted in the absence of increased law enforcement, resulted in moderate gains.

Evaluation of a brief intervention for increasing seat belt use on a college campus.

Abstract: The authors evaluated a brief intervention for increasing seat belt use among the front seat occupants of cars at a junior college, in a jurisdiction with a mandatory belt use law. The intervention included public posting of performance feedback and distribution of an informational flyer to cars in target parking lot. Feedback was the display of the proportion of drivers observed wearing seat belts on the previous observation day. Seat belt use among drivers increased from 64% during the baseline phase to 71% during the intervention phase. Seat belt use among front passengers increased from 49% during the baseline phase to 67% during the intervention phase. In both cases, seat belt use at follow-up was comparable to seat belt use during the intervention phase, although a trend toward decreasing belt use was noted. Also found was higher seat belt use among females as compared with males irrespective of their front seat occupant status (driver or passenger). Effects of the intervention are discussed in the context of increasing seat belt use in a hardcore nonuser population of predominantly young adults.

A program to increase seat belt use along the Texas-Mexico border.

Abstract: A school-based, bilingual intervention was developed to increase seat belt use among families living along the Texas-Mexico border. The intervention sought to increase seat belt use by changing perceived norms within the community (i.e., making the nonuse of seat belts less socially acceptable). The intervention was implemented in more than 110 classrooms and involved more than 2100 children. Blind coding, validity checks, and reliability estimates contributed to a rigorous program evaluation. Seat belt use increased by 10% among children riding in the front seat of motor vehicles in the intervention community, as compared with a small but nonsignificant decline in use among control community children. Seat belt use among drivers did not increase.

Increasing the screening and counseling of adolescents for risky health behaviors: a primary care intervention.

Abstract:
To determine whether a systems intervention for primary care providers resulted in increased preventive screening and counseling of adolescent patients, compared with the usual standard of care.

The intervention was conducted in 2 outpatient pediatric clinics; 2 other pediatric clinics in the same health maintenance organization served as comparison sites. The intervention was implemented in 2 phases: first, pediatric primary care providers attended a training workshop (N = 37) to increase screening and counseling of adolescents in the areas of tobacco, alcohol, drugs, sexual behavior, and safety (seatbelt and helmet use). Second, screening and charting tools were integrated into the intervention clinics. Providers in the comparison sites (N = 39) continued to provide the usual standard of care to their adolescent patients. Adolescent reports were used to assess changes in provider behavior. After a well visit, 13- to 17-year olds (N = 2628) completed surveys reporting on whether their provider screened and counseled them for risky behavior.

Screening and counseling rates increased significantly in each of the 6 areas in the intervention sites, compared with rates of delivery using the usual standard of care. Across the 6 areas combined, the average screening rate increased from 58% to 83%; counseling rates increased from 52% to 78%. There were no significant increases in the comparison sites during the same period. The training component seems to account for most of this increase, with the tools sustaining the effects of the training.

The study offers strong support for an intervention to increase clinicians' delivery of preventive services to a wide age range of adolescent patients.

Cost effectiveness of a dealer's intervention in retrofitting rollover protective structures.

Abstract:
To evaluate the cost effectiveness of a 4.5 year education campaign that promoted farmers' adoption of rollover protective structures (ROPS) to prevent tractor overturn injuries.

Randomized controlled trial, decision analysis, and cost effectiveness analysis.

One treatment county and one control county in the State of Kentucky.

A campaign by a local tractor and equipment dealership to encourage farmers to purchase and install ROPS and seatbelt retrofit kits for older tractors.

Number of injuries averted and cost per injury averted.

The dealership's 4.5 year intervention was shown to potentially reduce both fatal (0.26) and non-fatal (1.50) injuries by 2.6% in its county over the intervention period using a 20 year analytic horizon. When extrapolated statewide, 6.7 lives would be saved and 39 non-fatal injuries would be averted over the combined 24.5 year combined intervention period and analytic horizon. The intervention for this period was cost effective with a "savings" of 35,713 dollars per injury (fatal plus non-fatal) averted at a 4% discount rate.

Tractor manufacturer promotions can influence their dealerships to promote ROPS retrofits by their customers. A manufacturer backed dealer ROPS retrofit campaign was cost effective in reducing overturn related injuries.

Safety halls--an evaluation.

Abstract:
In most countries, drivers licensing systems usually include teaching some aspects of using safety equipment (e.g., airbags and seat belts). However, there is now evidence worldwide that such education is inadequate, as indicated by, for example, the overrepresentation of young drivers who do not use seat belts.

A randomized controlled study was conducted in Sweden to evaluate the effects of visiting a facility known as a "safety hall" in combination with the mandatory skid training. The results were assessed to determine the effects of the knowledge and attitudes of learner drivers in the following subjects: airbags, securing loads, seat belts, sitting posture, speed, and tires. An experimental group and a control group comprising 658 and 668 learners, respectively, answered identical questionnaires on three different occasions (pretest, posttest 1, and posttest 2).

The results show that, for most of the topics considered, knowledge and attitudes in both groups were better at posttest 2 than at the pretest, and in general, the best knowledge and attitudes were found in the experimental group. The combined safety/skid training seems to have had the greatest effect on seat belts and loads. The findings also indicate that the safety halls can be further improved to achieve an even better effect.

The use of safety halls has improved the knowledge and attitudes of learner drivers concerning several important areas related to traffic safety. Since knowledge and attitudes are important predictors of behavior, implementing safety halls can be expected to lead to improvements, especially regarding the use of safety belts and securing loads.

An emergency department intervention to increase booster seat use for lower socioeconomic families.

Abstract:
To evaluate the effectiveness of booster seat education within an emergency department (ED) setting for families residing in lower socioeconomic neighborhoods.

This was a prospective, randomized study of families with children aged 4 to 7 years and weighing 40 to 80 lb who presented to a pediatric ED without a booster seat and resided in lower socioeconomic communities. Subjects were randomly assigned to one of three groups: 1) received standard discharge instructions, 2) received five-minute booster seat training, and 3) received five-minute booster seat training and free booster seat with installation. Automobile restraint practices were obtained initially and by telephone at one month.

A total of 225 children were enrolled. Before randomization in the study, 79.6% of parents reported that their child was usually positioned in the car with a lap/shoulder belt and 13.3% with a lap belt alone. Some parents (16.4%) had never heard of a booster seat, and 44.9% believed a lap belt was sufficient restraint. A total of 147 parents (65.3%) were contacted for follow-up at one month. Only one parent (1.3%) in the control group and four parents (5.3%) in the education group purchased and used a booster seat after their ED visit, while 55 parents (98.2%) in the education and installation group reported using the booster seat; 42 (75.0%) of these parents reported using the seat 100% of the time.

Education in a pediatric ED did not convince parents to purchase and use booster seats; however, the combination of education with installation significantly increased booster seat use in this population.

Reducing the burden of road traffic injury: translating high-income country interventions to middle-income and low-income countries.

Abstract:
To increase seat belt restraint use in Guangzhou City, People's Republic of China.

Comparison group pre-test, post-test design.

Guangzhou City.

Interventions to increase the prevalence of seat belt use in high-income countries (enhanced training and enforcement practices along with raising of public awareness) were adapted and implemented in Guangzhou. The prevalence of seat belt use was determined before and after the introduction of the 12-month intervention. Seat belt prevalence was also examined over the same time period in the neighboring city of Nanning, and an incremental cost-effectiveness analysis of the intervention was undertaken.

Prevalence rates and incremental cost effectiveness ratios.

A 12% increase in seat belt use was observed in Guangzhou over the study period, increasing from a prevalence of 50% before (error range 30-62%) to 62% after (error range 60-67%) (p<0.001) the intervention; an absolute change difference between the intervention and reference city of 20% was achieved. The incremental cost-effectiveness ratio of the intervention was yen 3246 (US dollars 418) per disability-adjusted life year saved.

This city-wide intervention demonstrates that it is possible to increase the prevalence of seat belt use using similar methods to those used in high-income countries and, importantly, that such an approach is cost-effective.

Encouraging the installation of rollover protective structures in New York State: the design of a social marketing intervention.

Abstract:
Increasing the percentage of rollover protective structure (ROPS) equipped tractors has been the focus of many agricultural safety campaigns. Traditionally efforts have attempted to persuade farmers through education or community awareness interventions. These efforts have lead to marginal change. In response, a social marketing approach was tested as a means for increasing interest in ROPS retrofitting in New York.

An initial phone survey was conducted with a random sample of New York farmers to identify a potential target population. Following target selection, in-depth interviews were conducted to isolate barriers and motivators to retrofitting. This information was used to develop message prototypes which were tested in small focus group discussions. Selected and revised messages, as well as various other incentives developed in response to feedback from interviews, were then tested in a prospective, quasi-randomized controlled trial.

Small crop and livestock farms were selected as the intervention target since they represent 86% of New York farms with none or only one ROPS protected tractor. Barriers to retrofitting which were identified in interviews were: 1) constant exposures normalize risk, 2) risk is modeled by significant others and 3) safety in general and retrofitting in particular requires too much time and money. The piloting of ROPS incentives led to a marked increase in ROPS sales in New York.

Social Marketing provides a promising framework for the design of agricultural injury prevention programs. The potential implications for other health initiatives seeking to promote behaviour change are also discussed.


Context: Emotional and behavioural difficulties (EBD) in children are common, characterised by externalising or internalising behaviours that can be highly stable over time. EBD are an important cause of functional disability in childhood, and predictive of poorer psychosocial, academic, and occupational functioning into adolescence and adulthood. The prevalence, stability, and long-term consequences of EBD highlight the importance of intervening in childhood when behavioural patterns are more easily modified. Multiple factors contribute to the aetiology of EBD in children, and parenting plays an important role. The relationship between parenting and EBD has been described as bidirectional, with parents and children shaping one another's behaviour. One consequence of bidirectionality is that parents with insufficient parenting skills may become involved in increasingly negative behaviours when dealing with non-compliance in children. This can have a cyclical effect, exacerbating child behavioural difficulties and further increasing parental distress. Behavioural or skills-based parenting training can be highly effective in addressing EBD in children. However, emotional dysregulation may intercept some parents' ability to implement parenting skills, and there is recognition that skills-based interventions may benefit from adjunct components that better target parental emotional responses. Mindful parenting interventions have demonstrated some efficacy in improving child outcomes via improvements in parental emotion regulation, and there is potential for mindfulness training to enhance the effectiveness of standard parent training programmes.

To assess the effectiveness of mindfulness-enhanced parent training programmes on the psychosocial functioning of children (aged 0 to 18 years) and their parents.

We included randomised and quasi-randomised trials. Participants were parents or caregivers of children under the age of 18. The intervention was mindfulness-enhanced parent training programmes compared with a no-intervention, waitlist, or attentional control, or a parent training programme with no mindfulness component. The intervention must have combined mindfulness parent training with behavioural or skills-based parent training. We defined parent training programmes in terms of the delivery of a standardised and manualised intervention over a specified and limited period, on a one-to-one or group-basis, with a well-defined mindfulness component. The mindfulness component must have included mindfulness training (breath, visualisation, listening, or other sensory focus) and an explicit focus on present-focused attention and non-judgemental acceptance.

Reducing potential for child abuse among methadone-maintained parents: results from a randomized controlled trial.

Abstract: High rates of child abuse and neglect occur in many families in which either or both parents abuse illicit drugs. This study reports on the results of a randomized controlled trial with families having a parent on methadone maintenance (N = 64), in which an intensive, home-based intervention, the Parents Under Pressure (PUP) program, was compared to standard care. A second brief intervention control group of families received a two-session parenting education intervention. The PUP intervention draws from the ecological model of child development by targeting multiple domains of family functioning including the psychological functioning of individuals in the family, parent-child relationships, and social contextual factors. Mindfulness skills were included to address parental affect regulation, a significant problem for this group of parents. At 3- and 6-month follow-up, PUP families showed significant reductions in problems across multiple domains of family functioning, including a reduction in child abuse potential, rigid parenting attitudes, and child behavior problems. Families in the brief intervention group showed a modest reduction in child abuse potential but no other changes in family function. There were no improvements found in the standard care group and some significant worsening was observed. Results are discussed in terms of their implications for improved treatment.

Pilot study to gauge acceptability of a mindfulness-based, family-focused preventive intervention.

Abstract: The purpose of the present study was to conduct a test of acceptability of a new model for family-focused drug prevention programs for families of early adolescents. An existing evidence-based behavioral intervention, the Strengthening Families Program: For Parents and Youth 10-14 (SFP), was adapted to include concepts and activities related to mindfulness and mindful parenting (an extension of mindfulness to the interpersonal domain of parent-child relationships). The foundation for this innovative intervention approach stems from research on the effects of mind-body treatments involving mindfulness meditation and the function of stress and coping in relation to parenting and parent well-being. One group of families participated in a seven-week pilot of this mindfulness-enhanced version of SFP. Results of a mixed-method implementation evaluation suggest that the new intervention activities were generally feasible to deliver, acceptable to participants, and perceived to yield positive benefits for family functioning and parent psychological well-being. The next phase of this research will involve curriculum refinement based upon results of this initial study, and a larger pilot efficacy trial will be conducted.

Changing Parent's Mindfulness, Child Management Skills and Relationship Quality With Their Youth: Results From a Randomized Pilot Intervention Trial.

Abstract: We evaluated the efficacy of a mindful parenting program for changing parents' mindfulness, child management practices, and relationships with their early adolescent youth and tested whether changes in parents' mindfulness mediated changes in other domains. We conducted a pilot randomized trial with 65 families and tested an adapted version of the

Interventions to reduce behavioral problems in children with cerebral palsy: an RCT.

Abstract:
To test Stepping Stones Triple P (SSTP) and Acceptance and Commitment Therapy (ACT) in a trial targeting behavioral problems in children with cerebral palsy (CP).

Sixty-seven parents (97.0% mothers; mean age 38.7 ± 7.1 years) of children (64.2% boys; mean age 5.3 ± 3.0 years) with CP (Gross Motor Function Classification System = 15, 22%; II = 18, 27%; III =12, 18%; IV = 18, 27%; V = 4, 6%) participated and were randomly assigned to SSTP, SSTP + ACT, or waitlist. Primary outcomes were behavioral and emotional problems (Eyberg Child Behavior Inventory [ECBI], Strengths and Difficulties Questionnaire [SDQ]) and parenting style (Parenting Scale [PS]) at postintervention and 6-month follow-up.

SSTP with ACT was associated with decreased behavioral problems (ECBI Intensity mean difference [MD] = 24.12, confidence interval [CI] 10.22 to 38.03, P = .003; ECBI problem MD = 8.30, CI 4.63 to 11.97, P < .0001) including hyperactivity (SDQ MD = 1.66, CI 0.55 to 2.77, P = .004), as well as decreased parental overreactivity (PS MD = 0.60, CI 0.16 to 1.04, P = .008) and verbosity (PS MD = 0.68, CI 0.17 to 1.20, P = .01). SSTP alone was associated with decreased behavioral problems (ECBI problems MD = 6.04, CI 2.20 to 9.89, P = .003) and emotional symptoms (SDQ MD = 1.33, CI 0.45 to 2.21, P = .004). Decreases in behavioral and emotional problems were maintained at follow-up.

SSTP is an effective intervention for behavioral problems in children with CP. ACT delivers additive benefits.

Integrating mindfulness with parent training: effects of the Mindfulness-Enhanced Strengthening Families Program.

Abstract: There is growing support for the efficacy of mindfulness training with parents as an intervention technique to improve parenting skills and reduce risk for youth problem behaviors. The evidence, however, has been limited to small scale studies, many with methodological shortcomings. This study sought to integrate mindfulness training with parents into the Strengthening Families Program: For Parents and Youth 10-14 (SFP 10-14), an empirically-validated family-based preventive intervention. It used a randomized-controlled comparative effectiveness study design (N = 432 families, 31% racial/ethnic minority) to test the efficacy of the Mindfulness-Enhanced Strengthening Families Program (MSFP), compared to standard SFP 10-14 and a minimal-treatment home study control condition. Results indicated that, in general, MSFP was as effective as SFP 10-14 in improving multiple dimensions of parenting, including interpersonal mindfulness in parenting, parent-youth relationship quality, youth behavior management, and parent well-being, according to both parent and youth reports at both postintervention and 1-year follow-up. This study also found that in some areas MSFP boosted and better sustained the effects of SFP 10-14, especially for fathers. Although the pattern of effects was not as uniform as hypothesized, this study provides intriguing evidence for the unique contribution of mindfulness activities to standard parent training.

Mindfulness training effects for parents and educators of children with special needs.

Abstract: Parents and teachers of children with special needs face unique social-emotional challenges in carrying out their caregiving roles. Stress associated with these roles impacts parents' and special educators' health and well-being, as well as the quality of their parenting and teaching. No rigorous studies have assessed whether mindfulness training (MT) might be an effective strategy to reduce stress and cultivate well-being and positive caregiving in these adults. This randomized controlled study assessed the efficacy of a 5-week MT program for parents and educators of children with special needs. Participants receiving MT showed significant reductions in stress and anxiety and increased mindfulness, self-compassion, and personal growth at program completion and at 2 months follow-up in contrast to waiting-list controls. Relational competence also showed significant positive changes, with medium-to-large effect sizes noted on measures of empathic concern and forgiveness. MT significantly influenced caregiving competence specific to teaching. Mindfulness changes at program completion mediated outcomes at follow-up, suggesting its importance in maintaining emotional balance and facilitating well-being in parents and teachers of children with developmental challenges.

Mindfulness-based stress reduction for parents of young children with developmental delays: implications for parental mental health and child behavior problems.

Abstract:
Parents of children with developmental delays (DD) typically report elevated levels of parental stress compared with parents of typically developing children. Children with DD are also at high risk for exhibiting significant behaviour problems. Parental stress has been shown to impact the development of these behaviour problems; however, it is rarely addressed in interventions aimed at reducing child behaviour problems. The current study examined the efficacy of mindfulness-based stress reduction (MBSR) for parents of children with DD by investigating whether this intervention is effective in reducing parenting stress and whether decreases in parenting stress lead to reductions in behaviour problems among children with DD.

Forty six parents of children with DD were randomly assigned to an immediate treatment or wait list-control group. Participants completed questionnaires assessing parental stress and child behaviour problems at intake and at a second assessment, which took place after only the immediate treatment group had received the MBSR.

Parents who participated in MBSR reported significantly less stress and depression as well as greater life satisfaction compared with wait list-control parents. Regarding child outcomes, children whose parents participated in MBSR were reported to have fewer behaviour problems following the intervention, specifically in the areas of attention problems and ADHD symptomatology.

Results indicated that MBSR may be an effective intervention for ameliorating parental stress and mental health problems among parents of children with DD. Additionally, these benefits may 'spill over' and improve behaviour challenges among these children.

The effect of a family-based mindfulness intervention on children with attention deficit and hyperactivity symptoms and their parents: design and rationale for a randomized, controlled clinical trial (Study protocol).

Abstract:
About 4 % of children in Hong Kong have attention deficit hyperactivity disorder (ADHD). The parents of children with ADHD report higher levels of stress and show more negative parenting behavior. Medication and behavior training are evidence-based treatments, but both show significant limitations. In short, medical treatment is not suitable for preschool children and would suppress growth, whereas parents under stress may not be capable of consistently applying behavior management skills. Mindfulness training can improve attention and facilitate cognitive development and overall functioning. It has been widely adopted as a treatment option in health care, but its application in a family context is limited. In this context, a family-based mindfulness intervention (FBMI) has been developed to promote the attention and mental health of children with attention symptoms and to reduce the stress experienced by their parents. This article describes the design and conduct of the trial.

A multicenter, 8-week, waitlist, randomized controlled trial of FBMI is currently being conducted in Hong Kong (from mid-2015 to mid-2016). Its effectiveness will be examined by comparing the participants who receive treatment to those in a waitlist control group. The study population consists of one hundred twenty children with ADHD, or with symptoms of inattention and hyperactivity, between 5 and 7 years of age and their parents. To be included in the study, the children are required to meet or exceed the borderline cutoff score of the Chinese version of the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviors Rating Scale (SWAN-C). The primary outcome measures are the children's ADHD symptoms and behavior and the parents' stress. The secondary outcome measures include the children's overall behavioral problems and performance on the Attention Network Test, the parents' ADHD symptoms, the parents' mindful parenting scores, and heart rate variability of parents.

This study is probably the first randomized controlled trial of FBMI for young children and their caregivers. A rigorous design and multiple outcome measures are used to examine the effectiveness of FBMI. If the hypotheses are confirmed, FBMI may serve as an additional treatment option for children with ADHD.

This study is registered with the Chinese Clinical Trial Registry (reference number: ChiCTR-IOR-15007292 ). Registered 28 October 2015.

Effectiveness of mindfulness-based interventions on quality of life and positive reappraisal coping among parents of children with autism spectrum disorder.

Abstract:
Previous research has supported mindfulness-based interventions (MBIs) to enhance quality of life (QOL) in different populations, but no studies have been found to examine the effectiveness of MBIs on QOL among parents of children with ASD.

The purpose of the current study was to examine the effectiveness of brief MBI on perceived QOL and positive stress reappraisal (PSR) among parents of children with ASD.

A quasi-experimental, with nonequivalent control group design was used. One hundred and four parents of children with ASD were equally assigned to the intervention and control groups. The study groups were matched on measures of their gender and age, and level of severity of ASD in children. The intervention group participated in MBI program for 5 weeks, while the control group had not attended the program.

After the intervention program, results of paired samples t-test indicated that parents in the intervention group demonstrated significant improvements in measures of psychological health domain of QOL, social health domain of QOL, mindfulness, and positive stress reappraisal with medium to large effect size (P<0.01). The control group demonstrated improvement in measures of the dependent variables with small effect size.

MBI is culturally adaptable, acceptable, and effective method to improve QOL and PSR in parents of children with ASD.

Manual Development and Pilot Randomised Controlled Trial of Mindfulness-Based Cognitive Therapy Versus Usual Care for Parents with a History of Depression.

Abstract: Parental depression can adversely affect parenting and children's development. We adapted mindfulness-based cognitive therapy (MBCT) for parents (MBCT-P) with a history of depression and describe its development, feasibility, acceptability and preliminary estimates of efficacy. Manual development involved interviews with 12 parents who participated in MBCT groups or pilot MBCT-P groups. We subsequently randomised 38 parents of children aged between 2 and 6 years to MBCT-P plus usual care (


Context: The prevalence of peripheral artery disease (PAD) in the general population is about 12% to 14% and it increases with age. PAD increased from 164 million people in 2000 to 202 million people in 2010. More than two-thirds of people with PAD are based in low- or middle-income countries. Critical limb ischaemia (CLI) occurs in 1% to 2% of people with intermittent claudication over five years. One third of people with CLI have isolated below the knee (BTK) lesions. CLI and isolated BTK lesions are associated with a higher incidence of limb loss when compared with people with multilevel arterial disease. Endovascular procedures such as angioplasty (with or without stenting) are widely used to treat isolated BTK lesions, aiming to improve blood flow and limb salvage. The technical success of any angioplasty procedure depends on the ability to cross the target lesion. Failed attempts are underestimated in the literature and failures in the real world appear to be higher than reported. People with isolated BTK lesions undergoing angioplasty by conventional femoral access present a high failure rate to cross these lesions. Retrograde distal access may provide some advantages that can lead to successful crossing of the target lesion.

To evaluate the benefits and harms of retrograde distal access versus conventional femoral access for people undergoing below the knee angioplasty.

We planned to include randomised or quasi-randomised controlled trials comparing people undergoing retrograde distal access versus people undergoing conventional femoral access (ipsilateral antegrade or contralateral retrograde) for BTK angioplasty.

Percutaneous transluminal angioplasty of infrapopliteal arteries in patients with intermittent claudication: acute and one-year results.

Abstract: In advanced stages of infrapopliteal peripheral arterial occlusive disease with critical ischemia of the lower limb, the efficacy of percutaneous transluminal angioplasty (PTA) is well established. In contrast, PTA is currently not the therapy of choice in intermittent claudication (IC). In this prospective study, patients with IC were treated percutaneously. Technical aspects and long-term results are presented. In 78 patients (61 males, or 78.2%; age, 71 +/- 11 years) with IC (Rutherford grade 2 or 3), 104 interventions were performed. At baseline, the initial/absolute walking distance (IWD/AWD) was 49 +/- 34/102 +/- 88 m; the ankle-brachial index (ABI) was 0.61 +/- 0.2 before and 0.49 +/- 0.2 after exercise. A crossover approach was used in 74% and an antegrade access in 26% of the cases. In 19 interventions (18.3%), the excimer laser technique was used, and in 26 interventions (25%) a total of 39 stents were implanted. Procedural success rate was 89.4%. IWD and AWD improved to 107 +/- 67 m and 167 +/- 74 m (P < 0.0001 vs. baseline each), respectively, and the ABI at rest and after exercise increased to 0.88 +/- 0.13 and 0.72 +/- 0.19 (P < 0.0001 vs. baseline each). Six complications occurred (5.8%). One embolic occlusion, two minor groin hematoma, one arteriovenous fistula, one compartment syndrome, and one perforation. All were treated conservatively. After 12 months, the primary patency rate was 66.3%, cumulative primary assisted patency rate was 81.9%, and secondary patency rate was 91.5%. Percutaneous revascularization of infrapopliteal arteries in patients with IC is feasible and associated with good acute clinical results and an encouraging long-term patency rate. The complication rate is low.

Sirolimus-eluting versus bare stents after suboptimal infrapopliteal angioplasty for critical limb ischemia: enduring 1-year angiographic and clinical benefit.

Abstract:
To report the 1-year angiographic and clinical outcome from a prospective single-center study investigating the infrapopliteal application of sirolimus-eluting versus bare metal stents in patients with critical limb ischemia (CLI) who underwent below-the-knee endovascular revascularization.

Stenting was performed as a bailout procedure for suboptimal angioplasty results (flow-limiting dissection, elastic recoil, or postangioplasty residual stenosis >30%). In the first 29 patients, infrapopliteal stenting was performed with bare metal stents (group B) and with sirolimus-eluting stents in the other 29 patients (group S).

Below-the-knee angioplasty and stenting involved 65 lesions in 40 infrapopliteal arteries of 29 limbs in group B and 66 lesions in 41 infrapopliteal arteries of 29 limbs in group S. Baseline comorbidities (hyperlipidemia and symptomatic cardiac and carotid disease) were more pronounced in group S (p<0.05). At 6 months, sirolimus-eluting stents demonstrated significantly higher primary patency (OR 5.625, 95% CI 1.711 to 18.493, p = 0.004) and decreased in-stent binary restenosis (OR 0.067, 95% CI 0.021 to 0.017, p<0.001) and in-segment binary restenosis (OR 0.229, 95% CI 0.099 to 0.533, p = 0.001). After 1 year, sirolimus-eluting stents were steadily associated with increased primary patency (OR 10.401, 95% CI 3.425 to 31.589, p<0.001) and significantly less in-stent (OR 0.156, 95% CI 0.060 to 0.407, p<0.001) and in-segment (OR 0.089, 95% CI 0.023 to 0.349, p = 0.001) binary restenosis. In addition, sirolimus-eluting stents were associated with significantly fewer cumulative target lesion reinterventions at 6 months (OR 0.057, 95% CI 0.008 to 0.426, p = 0.005) and 1 year (OR 0.238, 95% CI 0.067 to 0.841, p = 0.026). No significant differences between groups B and S were noted at 1 year with respect to mortality (10.3% versus 13.8%, respectively), minor amputation (17.2% versus 10.3%), or limb salvage (100% versus 96%).

The application of sirolimus-eluting stents reduces the restenosis rate in the infrapopliteal arteries and the rate of repeat endovascular procedures the first year after treatment.

Clinical results of below-the knee intervention using pedal-plantar loop technique for the revascularization of foot arteries.

Abstract:
Recent registries and randomized trials support the role of percutaneous revascularization in patients with critical limb ischemia (CLI) due to below-the-knee (BTK) atherosclerotic disease, as percutaneous transluminal angioplasty (PTA) for BTK disease has shown to be feasible and safe in this setting. Nonetheless, succes rates remain suboptimal with current techniques. The authors aimed to appraise clinical results following PTA of foot vessels exploiting a novel technique, based on the recanalization of both pedal and plantar arteries and their anatomical anastomosis in order to restore direct arterial in-flow from both anterior and posterior tibial vessels, defined as the pedal-plantar loop technique.

Baseline, procedural and mid-term outcome data of all consecutive patients with CLI due to BTK disease in which PTA was attempted using the pedal-plantar loop technique were prospectively collected between January 2007 and September 2008. The primary end-point was acute success (i.e. the composite of technical, angiographic and procedural success). Secondary end-points included limb salvage rate, major (above the ankle) and minor (below the ankle) amputation, change in Rutherford class and transcutaneous oxygen tension, reocclusion/restenosis, rehospitalization, and repeat revascularization after 12 months.

A total of 1331 consecutive patients with CLI were treated using BTK PTA and 135 (10.1%) were approached with the pedal-plantar loop technique in order to recanalize the foot arteries. Target lesions were mostly occlusive and diffusely diseased, involving in most cases the tibial arteries as well as the in-flow and out-flow vessels. Acute success was achieved for tibial PTA in 100% of the cases, with ability to position and inflate the balloon and achieve adequate angiographic results without peri-procedural complications in all, whereas acute success for the pedal-plantar loop technique was 85%. Clinical improvement in functional status was obtained and maintained after an average of 12 months, with a significant improvement of transcutaneous oxygen tension after 15 days, 59+/-16 mmHg in the group of patients in which the foot arteries revascularization was successfully feasible, versus 42+/-12 mmHg in patients achieving patency of two BTK vessels at the ankle level with partial out-flow in the foot (P<0.001).

Percutaneous revascularization of foot arteries in patients with CLI is feasible and safe, and appears to provide positive clinical results at both acute and mid-term follow-up.

Alternative techniques for treatment of complex below-the knee arterial occlusions in diabetic patients with critical limb ischemia.

Abstract:
The purpose of this study was to describe alternative endovascular (EV) techniques and assess their feasibility and efficacy in minimizing failure rates in limb salvage for the treatment of complex below-the knee (BTK) occlusions that could not be crossed with a conventional antegrade access.

Between December 2007 and November 2010, 1,035 patients (557 male) underwent EV treatment for critical limb ischemia in our institution. In 124 (12% [83 male], mean age 68.2 ± 0.5 years) patients, transfemoral antegrade revascularization attempt failed, and an alternative approach was used. Follow-up was performed at 1 and 6 months. Results were compared with 56 patients treated between November 2002 and November 2007, in whom conventional technique was unsuccessful and unconventional techniques were not adopted.

Technical success was achieved in 119 (96%) patients. The limb-salvage rates were 96.8% and 83% at 1- and 6-month follow-up, respectively. Sixteen (12.9%) and 33 (26.6%) patients underwent reintervention at 1- and 6-month follow-up, respectively. Transcutaneous oxygen tension increased at 1 month (44.7 ± 1.1 vs. 15.7 ± 0.8 mmHg; p < 0.001) and remained stable at follow-up. Twenty (16.1%) patients required major amputation. Thirteen (10.4%) patients died during follow-up. In our previous experience, percutaneous transluminal angioplasty failure, amputation, and death rates were 10.9, 39.2, and 23.2%, respectively. Alternative techniques allowed a significant decrease of major amputation and death rates (p = 0.0001 and p = 0.02, respectively).

The use of alternative techniques seems feasible in case of a failed antegrade BTK revascularization attempt and could minimize failure rates in the treatment of complex occlusions while providing satisfying clinical success rates at 6 months.

Incidence and risk factors of vascular complications following endovascular treatment of peripheral arterial disease via the popliteal artery.

Abstract: To evaluate vascular complications associated with endovascular treatment (EVT) of peripheral arterial disease (PAD) through the popliteal artery and to identify the risk factors for these complications. Between November 2005 and January 2009, 63 patients with PAD received EVT via the popliteal artery. Retrograde (n = 58) and antegrade (n = 5) transpopliteal procedures were performed to target 77 lesions, including 12 distal to the trifurcation. Thirty-five punctures were performed under ultrasound guidance and 7 under angiographic guidance; 21 punctures were performed without any guidance. Vascular complications were evaluated by physical examination and duplex ultrasonography. Vascular complications at the popliteal puncture site occurred in 8 patients (12.7%): 6 hematomas and 2 arteriovenous fistulas (AVF). Seven of 24 patients receiving hemodialysis (HD) (29%) had significantly higher complications (P = 0.004) compared with 1 of 39 patients not receiving hemodialysis (non-HD) (2.6%). HD alone was also a significant risk factor for hematoma (P = 0.010). Both AVF occurred in HD patients (P = 0.141), and one occurred despite ultrasound-guided puncture. Ultrasound-guided puncture showed no significant improvement in reducing both complications. The combination of antiplatelet and anticoagulant therapy showed no statistical significance in overall complications. In non-HD patients, the transpopliteal approach in the EVT of PAD seems to be safe. More attention should be paid to HD patients when using the transpopliteal approach due to a higher complication rate.

Retrograde transplantar arch angioplasty of below-the-knee arterial occlusions: outcomes compared to anterograde recanalization.

Abstract:
To compare the clinical outcomes of retrograde transplantar arch angioplasty and conventional below-the-knee (BTK) anterograde recanalization.

One hundred twelve limbs in 96 patients underwent attempt at antegrade tibial angioplasty. Among 27 technical failures, retrograde trans-dorsal or -planter percutaneous transluminal angioplasty was attempted in 22 limbs. Ankle-brachial index (ABI), thrombolysis in myocardial infarction (TIMI) flow grade, and dorsal/plantar arterial pulse score improvement were compared immediately after the procedures between patients received successful anterograde angioplasty (anterograde angioplasty group [AAG], 85 limbs in 71 patients) and retrograde angioplasty (retrograde angioplasty group [RAG], 22 limbs in 20 patients). Target vessel restenosis and limb salvage were observed during follow-up.

Primary technical success rate was 75.9% in the RAG (vs. 74.0% AAG, P > .05). ABI improved from 0.55 ± 0.21 to 0.93 ± 0.19 in the RAG (vs. 0.56 ± 0.14 to 0.89 ± 0.18 AAG, P > .05). TIMI flow grade demonstrated greater reperfusion of distal foot tissue in the RAG (2.3 ± 0.8 vs. 1.0 ± 0.8, P < .05). Primary patency rates at 12 and 24 months were 63.6% (14 of 22) and 45.5% (10 of 22) in the RAG and 52.9% (45 of 85) and 37.6% (32 of 85) in the AAG, respectively (P > .05). Kaplan-Meier analysis after 24 months found limb salvage rates of 93.8% in the RAG and 96.5% in the AAG (P > .05).

Retrograde transplantar arch angioplasty achieved better immediate blood flow and similar ABI improvement, primary patency rate, and limb salvage rate compared to conventional transtibial angioplasty for BTK occlusions. This could become a supplementary technique when anterograde angioplasty fails.

Use of Tapered Balloons to Recanalize Occluded Below-the-Knee Arteries in Diabetic Patients with Critical Limb Ischemia.

Abstract:
The aim of this study was to evaluate the outcome of tapered balloon use in recanalization of long occlusions of below-the-knee (BTK) arteries in diabetic patients with critical limb ischemia (CLI).

Forty-nine occluded BTK arteries in 35 diabetic patients with CLI were revascularized in our Diabetic Foot Center between January and September 2014 using tapered balloons. Twelve-month outcomes were evaluated in terms of healing of the lesions, survival, limb salvage, primary patency, primary assisted patency, and secondary patency.

The patients were predominantly male (27/35, 77.1%) with a mean age of 70.9 years (±10.3 standard deviation [SD]). During the follow-up (mean duration 12.4 months ± 4 SD), healing of the lesions was obtained in 27 of the 35 cases (77.1%). Estimated 12-month survival and limb salvage were 85.7% and 91.1%, respectively. Estimated 12-month primary patency, primary assisted patency, and secondary patency were 78.3%, 79%, and 88.9%, respectively. Univariate analysis demonstrated that the presence of chronic renal failure affected survival (P = 0.005), and assignment to Rutherford class 6 affected limb salvage (P = 0.005), primary patency (P < 0.001), and primary assisted patency (P < 0.001). Furthermore, the presence of coronary artery disease affected primary patency (P = 0.001) and primary assisted patency (P = 0.05).

Tapered balloons are a safe and effective means to recanalize long occlusions of BTK arteries in diabetic patients with CLI. Outcomes are poorer in patients with major tissue loss and with a history of coronary artery disease. Further experience with larger groups is needed to validate these outcomes.

Outcomes of Endovascular Therapy With the Controlled Antegrade Retrograde Subintimal Tracking (CART) or Reverse CART Technique for Long Infrainguinal Occlusions.

Abstract:
To compare the safety, efficacy, and clinical outcomes associated with the controlled antegrade retrograde subintimal tracking (CART) or reverse CART (r-CART) technique to the conventional retrograde approach in the treatment of patients with long infrainguinal occlusions.

From May 2008 to April 2014, 121 patients failed antegrade recanalization and underwent a retrograde approach to recanalize long infrainguinal occlusions. Patients who underwent successful endovascular therapy (EVT) by the conventional retrograde approach (CRA group) were compared to patients who had successful EVT using the CART/r-CART technique (CART group) after failure of a bidirectional approach. The efficacy, safety, vessel patency, and other clinical outcomes were compared between the groups.

Fifty-eight patients (mean age 71.6 ± 12.2 years; 32 men) underwent successful EVT (47.9%, 58/121) using the conventional retrograde approach (CRA group), while 44 patients (mean age 70.8 ± 11.1 years; 31 men) among the 50 patients who underwent the CART/r-CART technique were successfully treated (88.0%, 44/50). Both groups had similar average occlusion lengths and gained 100% immediate hemodynamic success after EVT. There was no significant difference between the groups regarding procedure-related complications. During follow-up, 28 patients died (p=0.380), but there were no differences in the rates of major (p=0.279) or minor amputation (p=0.417) between the groups. There was no difference in the 2-year primary patency (31% vs 24%, p=0.686), assisted primary patency (66% vs 76%, p=0.251), target vessel revascularization (65% vs 54%, p=0.845), or sustained clinical success (52% vs 46%, p=0.995) rates between the CRA and CART groups, respectively.

Based on acceptable safety, efficacy, and follow-up results in this study, the CART/r-CART technique can salvage patients with long peripheral occlusions after failure of the conventional antegrade or retrograde approach.

Outcome of a drug-eluting stent in longer below-the-knee lesions in patients with critical limb ischemia.

Abstract:
The superiority of drug eluting stents versus bare metal stents or balloon angioplasty in the treatment of patients with critical limb ischemia and infrapopliteal lesions has been established. However, only shorter lesions were evaluated. This study was designed to evaluate the immediate and long-term (up to 12 months) outcome of the Xience Prime™ Everolimus-Eluting Coronary Stent System (Abbott Vascular) in a controlled, prospective, multi-center investigation for long lesions up to 10 cm.

All patients with critical limb ischemia and long infrapopliteal lesions between 30 and 100 mm, who met the inclusion criteria, were included in this study. The primary endpoint was primary patency at 12 months, defined as absence of restenosis (≥50% stenosis) or occlusion based on quantitative analysis of contrast angiography.

Between August 2011 and October 2013, 60 patients were enrolled in this study with a mean lesion length of 47.40±25.06 mm (range 2-100 mm). The primary patency rate at 12 months was 75.4%. Freedom from target lesion revascularization was 84.9%. The amputation rate was rare (94.4% freedom from amputation). At the 12-month follow-up time point, a total of 36 out of 42 (85.7%) patients improved in their Rutherford classification by at least 1 class.

The use of everolimus-eluting stents in longer infrapopliteal lesions in the treatment of critical limb ischemia is safe and effective with a comparable primary patency, freedom from target lesion revascularization and amputation free survival as in short lesions.

Tibiopedal Access for Crossing of Infrainguinal Artery Occlusions: A Prospective Multicenter Observational Study.

Abstract:
To report a prospective, multicenter, observational study (ClinicalTrials.gov identifier NCT01609621) of the safety and effectiveness of tibiopedal access and retrograde crossing in the treatment of infrainguinal chronic total occlusions (CTOs).

Twelve sites around the world prospectively enrolled 197 patients (mean age 71±11 years, range 41-93; 129 men) from May 2012 to July 2013 who met the inclusion criterion of at least one CTO for which a retrograde crossing procedure was planned or became necessary. The population consisted of 64 (32.5%) claudicants (Rutherford categories 2/3) and 133 (67.5%) patients with critical limb ischemia (Rutherford category ≥4). A primary antegrade attempt to cross had been made prior to the tibiopedal attempt in 132 (67.0%) cases. Techniques used for access, retrograde lesion crossing, and treatment were at the operator's discretion. Follow-up data were obtained 30 days after the procedure.

Technical tibiopedal access success was achieved in 184 (93.4%) of 197 patients and technical occlusion crossing success in 157 (85.3%) of the 184 successful tibial accesses. Failed access attempts were more common in women (9 of 13 failures). The rate of successful crossing was roughly equivalent between sexes [84.7% (50/59) women compared to 85.6% (107/125) men]. Technical success did not differ significantly based on a prior failed antegrade attempt: the access success rate was 92.4% (122/132) after a failed antegrade access vs 95.4% (62/65) in those with a primary tibiopedal attempt (p=0.55). Similarly, crossing success was achieved in 82.8% (101/122) after a failed antegrade access vs 90.3% (56/62) for patients with no prior antegrade attempt (p=0.19). Minor complications related to the access site occurred in 11 (5.6%) cases; no patient had access vessel thrombosis, compartment syndrome, or surgical revascularization.

Tibiopedal access appears to be safe and can be used effectively for the crossing of infrainguinal lesions in patients with severe lower limb ischemia.


Context: Haemodialysis (HD) requires safe and effective anticoagulation to prevent clot formation within the extracorporeal circuit during dialysis treatments to enable adequate dialysis and minimise adverse events, including major bleeding. Low molecular weight heparin (LMWH) may provide a more predictable dose, reliable anticoagulant effects and be simpler to administer than unfractionated heparin (UFH) for HD anticoagulation, but may accumulate in the kidneys and lead to bleeding.

To assess the efficacy and safety of anticoagulation strategies (including both heparin and non-heparin drugs) for long-term HD in people with kidney failure. Any intervention preventing clotting within the extracorporeal circuit without establishing anticoagulation within the patient, such as regional citrate, citrate enriched dialysate, heparin-coated dialysers, pre-dilution haemodiafiltration (HDF), and saline flushes were also included.

Randomised controlled trials (RCTs) and quasi-randomised controlled studies (quasi-RCTs) evaluating anticoagulant agents administered during HD treatment in adults and children with kidney failure.

Comparison of low-molecular-weight heparin (enoxaparin sodium) and standard unfractionated heparin for haemodialysis anticoagulation.

Abstract:
Low-molecular-weight heparin (LMWH) has been suggested as providing safe, efficient, convenient and possibly more cost-effective anticoagulation for haemodialysis (HD) than unfractionated heparin, with fewer side-effects and possible benefits on uraemic dyslipidaemia.

In this prospective, randomized, cross-over study we compared the safety, clinical efficacy and cost effectiveness of Clexane (enoxaparin sodium; Rhône-Poulenc Rorer) with unfractionated heparin in 36 chronic HD patients. They were randomly assigned to either Clexane (1 mg/kg body weight, equivalent to 100 IU) or standard heparin, and followed prospectively for 12 weeks (36 dialyses) before crossing over to the alternate therapy for a further 12 weeks. Heparin anticoagulation was monitored using activated coagulation times.

Dialysis with Clexane resulted in less frequent minor fibrin/clot formation in the dialyser and lines than with heparin (P<0.001), but was accompanied by increased frequency of minor haemorrhage between dialyses (P<0.001). Clexane dose reduction (to a mean of 0.69 mg/kg) eliminated excess minor haemorrhage without increasing clotting frequencies. Mean vascular compression times were similar in both groups. Over 24 weeks, no changes in standard serum lipid profiles were observed.

This study suggests that a single-dose protocol of Clexane is an effective and very convenient alternative to sodium heparin, but currently direct costs are about 16% more. We recommend an initial dose of 0.70 mg/kg.

Comparison of different routes of administration of nadroparin in hemodialysis.

Abstract:
In an open, crossover, randomized study in hemodialysis patients, we investigated possible differences of the effect of the low molecular weight heparin (LMWH) nadroparin/fraxiparine in relation to the route of administration.

The effect of nadroparin, administered by the venous line or by the arterial line after priming of the extracorporeal circuit with a part of the total dose administered, was compared with administration of the same dose by the arterial line as recommended by the manufacturer. Twelve stable, chronic hemodialysis patients were studied during 3 dialysis sessions for each treatment option. Concomitant medication was kept constant.

Results obtained after administration of nadroparin by the venous line were comparable to those obtained after administration by the arterial line. When a part of the dose was added to the priming solution, the anti-Xa activity, measured after 2 hours of dialysis, was somewhat lower (p = 0.09). There was also a tendency towards longer manual compression time in this group. There was no difference in hemoglobin, serum urea and creatinine before the study and at the end of each treatment option.

We therefore conclude that the safety and efficacy of administration of LMWH by the arterial and by the venous route are identical. There is no need for addition of a small dose of LMWH to the priming fluid.

Effect of anticoagulation on blood membrane interactions during hemodialysis.

Abstract:
Adequate anticoagulation is a precondition to prevent extracorporeal blood clotting and to improve biocompatibility during hemodialysis. In this study, we performed a morphologic analysis by using scanning electron microscopy to compare three modes of anticoagulation-conventional unfractionated heparin (UFH), low molecular weight heparin (LMWH; dalteparin sodium), or sodium citrate during hemodialysis-on membrane-associated coagulation activation.

Fifteen patients on regular hemodialysis therapy were investigated. Five patients received UFH, five patients LMWH, and five patients sodium citrate as an anticoagulant during a standardized hemodialysis protocol using a single-use polysulfone capillary dialyzer. Membrane-associated clotting was evaluated using a scanning electron microscope. A dialyzer clotting score was used for quantitative description of coagulation activation on membrane segments.

Using UFH as an anticoagulant revealed the most pronounced cell adhesion and thrombus formation and the highest dialyzer clotting score (11.5 +/- 1.3 of a maximal 20 points). LMWH had a lower dialyzer clotting score than UFH (10.4 +/- 1.2 of 20 points). During the use of sodium citrate, a negligible thrombus formation and the lowest dialyzer clotting score (1.6 +/- 0.6 of 20 points, P < 0.05) were observed.

The results of this investigation indicate that using sodium citrate as an anticoagulant during hemodialysis induces a lower activation of coagulation than both conventional and fractionated heparin, which might contribute to an improvement of biocompatibility of hemodialysis extracorporeal circulation.

A randomized trial of minidose warfarin for the prevention of late malfunction in tunneled, cuffed hemodialysis catheters.

Abstract:
Minidose warfarin (1 mg/day) has been associated with a 74% reduction in the thrombosis rate of central venous catheters used in oncology patients. To determine the efficacy of minidose warfarin on late malfunction caused by thrombosis or fibrin sheath formation in tunneled, cuffed catheters (TCC) used for hemodialysis (HD), we performed a randomized, placebo-controlled trial.

One hundred five chronic HD patients with TCCs were initially randomized. Of these, 85 (warfarin 41 and placebo 44) completed the first two weeks of the protocol and were followed for the first year of TCC life or until TCC removal.

Sixteen TCCs failed with late TCC malfunction, eight in each group. In a multivariate analysis, there was no significant effect of warfarin on thrombosis-free TCC survival or time to the first urokinase (UK) instillation for incipient thrombosis. The presence of a low hemoglobin (Hgb; <10.5 g/dL) or a low international normalized ratio (INR; <1.00) was significantly associated with a higher risk of late TCC malfunction (RR 5.2 and 4.0, respectively), a higher risk of incipient TCC thrombosis requiring UK (RR 2.0 and 2.8, respectively), and higher rates of UK dosing. Diabetics had a 3.6-fold higher risk of late TCC malfunction and a twofold higher risk of incipient thrombosis requiring UK, although these findings were not statistically significant. Aspirin use, race, age, number of hospitalizations, erythropoietin dose, intradialytic heparin dose, serum albumin, and the number of episodes of TCC-associated infection were not significantly associated with late TCC malfunction.

Thrombosis prophylaxis using fixed minidose warfarin is not efficacious in TCCs used for HD. However, the present data suggest improved TCC survival in patients with an INR> 1.00. Patients with diabetes and those with a low Hgb or INR have a higher risk of late TCC malfunction.

Low-intensity warfarin is ineffective for the prevention of PTFE graft failure in patients on hemodialysis: a randomized controlled trial.

Abstract: Polytetrafluoroethylene (PTFE) dialysis grafts in patients with end-stage renal disease (ESRD) are prone to thrombotic failure. The objective of this multicenter, randomized, double-blind, placebo-controlled clinical trial was to determine if warfarin reduces the risk of failure of PTFE dialysis grafts. Patients with ESRD and newly placed PTFE grafts were studied at community and academic dialysis centers in Southwestern Ontario. Patients were allocated to receive warfarin or matching placebo, with the warfarin administered to achieve a target INR of 1.4 to 1.9. Time to graft failure was the main outcome measure. A total of 107 patients (56 allocated to warfarin) were randomized. The time-to-event analysis revealed no significant difference in the likelihood of graft survival between the two groups (odds ratio, 1.76 in favor of placebo; 95% confidence interval, 0.72 to 4.34). Six major bleeds occurred in five patients allocated to warfarin compared with none in the patients who received placebo (P = 0.03). In conclusion, low-dose warfarin was associated with an excess of clinically important major bleeding in patients with ESRD enrolled in this study. Furthermore, low-intensity, monitored-dose warfarin does not appear to prolong PTFE graft survival.

Dermatan sulphate in haemodialysis.

Abstract: Experimental work suggests that dermatan sulphate has potential as an antithrombotic agent: it can inhibit venous thrombi yet has less effect upon bleeding than heparin. While heparin functions as an anticoagulant primarily by its ability to accelerate the action of the plasma protein inhibitor antithrombin III, dermatan sulphate acts selectively through a structurally related inhibitor, heparin co-factor II, to inhibit thrombin. We have done a series of dose-finding studies of the use of dermatan sulphate as an anticoagulant/antithrombotic agent in patients on maintenance haemodialysis. Dermatan sulphate proved to be an effective anticoagulant in this setting.

Antithrombotic properties of dermatan sulphate (MF 701) in haemodialysis for chronic renal failure.

Abstract: The therapeutic potential of the glycosaminoglycan (GAG), dermatan sulphate (DS), as an antithrombotic agent in humans has yet to be established. We have performed dose ranging studies of DS to determine its effectiveness as an antithrombotic agent in patients (n = 6-8) undergoing haemodialysis for chronic renal failure. In an initial study, Study 1, i.v. bolus doses of 2-4 mg/kg and 5-6 mg/kg DS were given to patients dialysing with polyacrylonitrile hollow fibre (PAN HF) membranes. In a second crossover study, Study 2, performed using cuprophane hollow fibre (CHF) membranes, i.v. bolus doses of 3 mg/kg and 6 mg/kg DS were compared to a standard unfractionated heparin (UFH) regime that has been shown previously to inhibit fibrin formation. Further infusion studies, Study 3 and Study 4 evaluated the antithrombotic efficacy of an i.v. DS bolus of 3 mg/kg plus an i.v. infusion of DS 0.6 mg kg-1 h-1 and a DS bolus of 5 mg/kg plus an infusion of 1 mg kg-1 h-1 over 5 h, respectively. These studies were compared to standard UFH regimes in a randomised crossover design. Plasma levels of fibrinopeptide A (FPA) and thrombin-antithrombin (TAT) were used as markers of fibrin formation and thrombin generation during dialysis using both membranes. The changes in DS concentration following administration of the different doses were similar in Studies 1 and 2. However, the effectiveness of DS as an anticoagulant appeared to depend markedly on the different dialyser types used in the two studies.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of oral anticoagulation on clotting during hemodialysis.

Abstract:
Between 5% and 10% of hemodialysis patients are treated with oral anticoagulants. It is currently unknown whether additional anticoagulation with heparin or low-molecular-weight heparin (LMWH) is needed to prevent clotting during hemodialysis.

In this prospective, randomized, cross-over study 10 patients treated with oral anticoagulants (phenprocoumon) received either no additional anticoagulation or low dose dalteparin (bolus of 40 IU/kg body weight) before dialysis. Efficacy of hemodialysis was measured by normalized weekly Kt/V and urea reduction rate (URR). Thrombus formation was evaluated by measurement of D-dimer and inspection of air traps and dialyser.

The median international normalized ratio (INR) did not differ between both observation periods (phenprocoumon 2.2(2 to 3) vs. dalteparin 2.1(2 to 2.9). The anti-Xa level in dalteparin patients was 0.33 (0.27 to 0.38) IU/mL after 2 hours and 0.16 (0.03 to 0.23) IU/mL after 4 hours of hemodialysis. The median increase of D-dimer was significantly higher in patients without additional dalteparin therapy during hemodialysis (DeltaD-dimer 0.23 microg/mL vs. 0.03 mug/mL) (P= 0.0004). Complete thrombosis of the dialyser membrane occurred in one patient in the phenprocoumon group but in none with combined treatment. The extent of thrombosis in the arterial and venous air trap and dialyser was significantly less in patients with additional dalteparin therapy (P= 0.0014, P= 0.0002, and P= 0.0005, respectively). Weekly Kt/V and URR was similar in both groups.

Standard oral anticoagulation with an INR between 2 and 3 is insufficient to prevent clotting during hemodialysis. Additional low dose anticoagulation with a LMWH or heparin is necessary to facilitate treatment.

Assessment of the heparin-binding AN69 ST hemodialysis membrane: II. Clinical studies without heparin administration.

Abstract: Binding polyanionic unfractionated heparin over the modified AN69 polyacrylonitrile membrane, the surface electronegativity of which has been neutralized by polyethyleneimine (AN69-ST), renders the membrane more hemocompatible. This property was tested in two groups of long-term hemodialysis patients. Results were rated as massive or partial clotting of a dialyzer at the end of the session. Group I patients were included in a prospective, cross-over study comparing standard dialysis with hemodialysis without systemic administration of unfractionated heparin (n = 12, 123 sessions). In all instances, priming was made with 2 I saline containing 5,000 IU/l heparin. Only patchy or partial clotting was observed in 11% and 39% of the sessions with standard and heparin-free administration, respectively. Group II patients were included in an open, observational pilot study testing the effects of the heparin-coated membrane, without systemic administration of heparin, in patients at high risk of bleeding (n = 68, 331 sessions). Massive clotting was observed in six sessions only (less than 2%) and normal or slightly patchy dialyzers were found in 88% of the sessions. It is concluded that the dialysis AN69 ST membrane, after adequate priming at bedside, can be used without systemic administration of heparin for hemodialysis in patients at high risk of bleeding.