Mesenteric angiography for the localization and treatment of acute lower gastrointestinal bleeding

Background

There is limited evidence regarding the effectiveness and complications of mesenteric angiography in the diagnosis and management of acute lower gastrointestinal bleeding (ALGIB). Our objective was to determine the complications and outcomes of mesenteric angiography in patients with ALGIB and to identify predictors of a positive result at angiography.

Methods

We identified and reviewed the records of all patients who underwent mesenteric angiography for ALGIB at our institution during a 10-year period. We compared potential predictors of positive versus negative angiograms.

Results

Of 47 mesenteric angiograms in 35 patients, 22 (47%, 95% confidence interval [CI] 33%–61%) revealed a source of bleeding, most commonly the colon. Hematomas developed in the groins of 3 patients (6.4%, 95% CI 0%–18%), and 1 of these patients also experienced a myocardial infarction during the procedure. None of the potential predictors were significantly associated with a positive result at angiography, although the confidence intervals were wide. Twenty patients (57%, 95% CI 41%–74%) continued to bleed after the angiogram, and 18 of the patients (51%, 95% CI 35%–68%) were discharged without a definitive diagnosis.

Conclusion

With a diagnostic success of about 50%, mesenteric angiography may play an important part in the diagnosis and management of patients with ALGIB; however, one or more large, prospective multicentre studies are needed to more clearly define its role. Canadian surgeons have the opportunity to initiate collaborative multicentre studies to address such diagnostic and therapeutic clinical questions.     

Late conversion of endovascular to open repair of abdominal aortic aneurysms

Background

Failure of endovascular repair (EVAR) of an abdominal aortic aneurysm can result in significant risk of morbidity and mortality. We review our experience with late conversions to open repair.

Methods

We conducted a retrospective database review to identify all EVAR procedures performed between 1997 and 2010 and the number converted to open repair at our university-affiliated medical centre. Late conversion was defined as those occurring at least 30 days after initial EVAR.

Results

In all, 892 EVARs took place during the study period. Six patients (0.7%) required late conversion to open repair. Their mean age was 71 (range 58–83) years, and half were women. Half of the initial EVARs were for ruptured aneurysms. The median time to conversion was 15.6 (range 1.7–61.3) months. Indications for secondary conversion (50% urgent, 50% elective) included persistent type I endoleak (n = 3), combined type II and III endoleak (n = 1), graft thrombosis (n = 1) and aneurysm rupture (n = 1). Supraceliac clamping was required in most patients (67%), and the mean transfusion requirement was 2.6 units. Total endograft explantation occurred in 2 patients (33%), whereas partial or total endograft preservation occurred in 4 (67%). Median length of stay in hospital after conversion was 7 (range 6–73) days. There were no instances of early or in-hospital mortality following conversion.

Conclusion

Our EVAR experience includes a low rate of late conversion to open repair, with most conversions being a result of persistent aneurysm perfusion. Although technically challenging, late conversion can be safe. Our experience supports ongoing surveillance after EVAR.     

Specialist outreach service for on-table repair of iatrogenic bile duct injuries--a new kind of 'travelling surgeon'

INTRODUCTION

The objective of this study was to determine the outcome of on table repair of iatrogenic bile duct injuries (IBDIs) following laparoscopic cholecystectomy, by specialist hepatobiliary surgeons as an outreach service.

PATIENTS AND METHODS

Prospectively collected data on IBDI managed as an outreach service, was analysed retrospectively. The Strasberg classification was used to define types of injury.

RESULTS

There were 22 patients. Twenty (91%) had type E ‘classical’ excision injuries, two had types B and D. Two type E cases had co-existent vascular injury both with right hepatic artery injuries; one also had a co-existent portal vein injury. A Roux-en-Y hepaticojejunostomy was used to repair the IBDI in 21 (95%) patients. One type D injury had duct repair over a T-tube. No attempt was made to reconstruct the injured hepatic arteries, while the portal vein injury was primarily repaired. The median follow-up was 210 days (range, 47–1088 days). Two patients developed bile leak and cholangitis while another developed transient jaundice. There were no postoperative mortalities. All patients were followed up at our centre.

CONCLUSIONS

Repair of IBDI as an outreach service by specialist surgeons is feasible and safe, with minimal disruption to the patient pathway. Prompt recognition and definitive management may help reduce complaints and medicolegal litigation.     

Future of vascular surgical training: the trainees' views

INTRODUCTION

In the UK, surgical training includes all aspects of general surgery. Vascular surgery is not an independent specialty. We wished to assess the views of vascular trainees in UK on the future of vascular surgery and training.

MATERIALS AND METHODS

Trainees were surveyed in 2003, 2004 (after introduction of the European Working Time Directive) and 2005, concentrating on four areas – future practise of vascular surgery, role of endovascular training, vascular specialisation and future training.

RESULTS

The majority of trainees want to practise vascular surgery alone. In 2003, 80% thought training should include endovascular techniques. By 2005, all trainees regarded training as mandatory as endovascular techniques would represent a significant part of their future work. Opinion changed on training; from 4 years general then 2 years vascular surgery (qualification in general surgery) to 2 years general and 4 years vascular surgery (specialist qualification in vascular surgery; P < 0.0001). Opinion also changed, that vascular surgery should spilt from general surgery to form its own speciality (P < 0.0007).

CONCLUSIONS

Trainees now regard training in endovascular techniques and endovascular aneurysm repair as mandatory. The majority wish to specialise from general surgery and achieve a separate qualification in vascular surgery.     

Parastomal Hernia Repair: a Single Center Experience

Background/Objectives:

Despite multiple options for operative repair of parastomal hernia, results are frequently disappointing. We review our experience with parastomal hernia repair.

Methods:

A retrospective chart review was performed on all patients with parastomal hernia who underwent LAP or open repair at our institution between 1999 and 2006. Information collected included demographics, indication for stoma creation, operative time, length of stay, postoperative complications, and recurrence.

Results:

Twenty-five patients who underwent laparoscopic or open parastomal hernia repair were identified. Laparoscopic repair was attempted on 12 patients and successfully completed on 11. Thirteen patients underwent open repair. Operative time was 172±10.0 minutes for laparoscopic and 137±19.1 minutes for open cases (P=0.14). Lengths of stay were 3.1±0.4 days (laparoscopic) and 5.1±0.8 days (open), P=0.05. Immediate postoperative complications occurred in 4 laparoscopic patients (33.3%) and 2 open patients (15.4%), P=0.38. Parastomal hernia recurred in 4 laparoscopic patients (33.3%) and 7 open patients (53.8%) after 13.9±4.5 months and 21.4±4.3 months, respectively, P=0.43.

Conclusion:

Laparoscopic modified Sugarbaker technique in the repair of parastomal hernia affords an alternative to open repair for treating parastomal hernia.     

Adding an endovascular aortic surgery program to a rural regional medical centre

Background

Abdominal aortic aneurysms requiring surgical intervention are generally treated by endovascular means. Such procedures are not always offered in rural hospitals, possibly leaving patients underserved. We reviewed our experience initiating an endoaortic surgery program.

Methods

A surgeon in a rural centre was credentialed to perform endovascular aortic aneurysm repair through collaboration with a university centre and was proctored locally for the first 5 abdominal aneurysm repairs. Web-based image storage was used to review complex cases as part of an ongoing partnership. Referred patients were screened for multiple aneurysms and underwent long-term monitoring.

Results

In all, 160 patients were evaluated for 176 aortic pathologies. Twenty-five patients (17 men) aged 55–89 years underwent 26 endovascular abdominal (n = 23) or thoracic (n = 3) aortic procedures. Emergent endovascular procedures were not performed. There were no operative deaths, requirements for dialysis or conversions to open repair. Two endoleaks required early reintervention. The median length of stay in hospital for endovascular procedures was 2.5 days. Chronic endoleaks were observed in 7 patients. An additional 8 patients underwent open abdominal aneurysm repair locally and 15 patients were referred to the university program.

Conclusion

Creation of an endovascular aortic surgery program in a rural hospital is feasible through collaboration with a high-volume centre. Patient safety is enhanced by obtaining second opinions using web-based image review. Most interventions are for abdominal aortic aneurysms, but planning for a comprehensive aortic clinic is preferable.     

Should Vascular Surgeons be Trained in Endovascular Techniques? – An Observational Study

INTRODUCTION

The aim of this study was to determine if there is a satisfactory cover for interventional radiology and whether vascular surgeons have received sufficient training in endovascular techniques.

MATERIALS AND METHODS

This was an observational study based on questionnaires sent to radiology and vascular trainers and vascular trainees in England. A total of 50 NHS trusts were chosen randomly to take part in the study and 320 questionnaires were sent out with an overall consultant response rate of 57%.

RESULTS

Of vascular consultants in the study group, 53% have had experience in endovascular procedures. Overall, 87% felt that there were not enough radiologists to fulfil the demand and 64% would like further training in endovascular procedures. In addition, 69% would like to be involved in a vascular rota without the general component. Similarly, 81% of radiologists felt that the demand was not being met, as emergency interventional radiology cover was not available on most nights in 65% of the trusts. Of responders, 72% would not object to training of vascular trainees in interventional work and 43% would be happy to be involved in training. Some 33% would accept a vascular trainee for 1 year.

CONCLUSIONS

Integrated fellowship in vascular surgery and interventional radiology has been implemented and tested in a number of centres in the US. This approach could be implemented in some of the larger vascular units in the UK.     

Meta-analysis of randomised controlled trials comparing unipolar with bipolar hemiarthroplasty for displaced femoral-neck fractures

Purpose

Unipolar and bipolar hemiarthroplasty (HA) are used to treat displaced femoral-neck fractures. However, which type is best for treating displaced femoral-neck fractures in elderly patients remains a subject for debate. Our aim was to review randomised controlled trials to establish which type provides superior clinical outcome for this patient population.

Methods

We searched PubMed, Embase and Cochrane Register of Controlled Trials databases and Web of Science for randomised controlled trials (RCTs) comparing unipolar with bipolar HA to treat femoral-neck fracture in the elderly. Risk ratios (RRs) and mean differences (MDs) from each trial were pooled using random-effects or fixed-effects models depending on study heterogeneity. Analysis was performed using RevMan5.2 from the Cochrane Collaboration.

Results

A total of 1,100 patients from nine studies were assessed in this meta-analysis. Results showed no significant differences in function score [MD = −0.14, 95% confidence interval (CI) −2.42–2.13], mortality (RR = 0.97, 95% CI 0.65–1.46), dislocation (RR = 1.33, 95 % CI 0.53–3.34), deep infection (RR = 0.79, 95 % CI 0.35–1.79), acetabular erosion (RR = 1.99, 95 % CI 0.61–6.52), operating time (MD = 2.14, 95 % CI −9.85 to14.14), blood loss (MD = 13.40, 95 % CI −49.60 to 76.39) and length of hospital stay (MD = 0.12, 95 % CI −0.49to0.73) between unipolar and bipolar HA.

Conclusions

Unipolar and bipolar HA achieved similar clinical outcomes in patients with displaced femoral-neck fractures.     

Initial Achilles tendon repair strength-synthesized biomechanical data from 196 cadaver repairs

Purpose

The study aim was to describe what kind of operative technique performs best with respect to initial strength after the surgical repair of acute Achilles tendon ruptures.

Methods

We performed a systematic search of the keywords “Achilles tendon AND (suture strength OR biomechanics) AND (cadaver NOT animal)” in the online databases PubMed, EMBASE, CINAHL, and the Cochrane Library. We included studies that employed open, mini-open, or percutaneous Achilles tendon repair in human cadavers, and assessed some measure of tensile strength as a primary outcome.

Results

Our search produced 11 relevant papers reporting results for Kessler, Bunnell, and Krackow sutures in open repair, as well as the Achillon device, the Ma-Griffith repair technique, the triple bundle technique and the “giftbox” technique. The weighted tensile strengths ranged from 81 to 453 N (mean 222.7 N) with the Triple Bundle technique in combination with # 2 Ethibond performing best with a mean of 453 N.

Conclusions

Due to the small sample sizes, different study designs, and heterogeneity of strength measurement techniques, definite recommendations on surgical technique cannot be made but presented information might help in the decision making process for foot and ankle surgeons.     

Prevalence of abdominal aortic aneurysms in over 65-year-old men with inguinal hernias

INTRODUCTION

The aim of this study was to determine the prevalence of abdominal aortic aneurysms (AAAs) in over 65-year-old men who have inguinal hernias and discuss if pre-operative selective screening of this population is appropriate.

PATIENTS AND METHODS

A prospective study on 70 consecutive male patients with an age range of 65–88 years (mean, 74 years) who were referred to a single vascular consultant''s out-patient clinic with an inguinal hernia were screened for the presence of an AAA with an ultrasound scan before hernia repair over a period of 3 years.

RESULTS

Two patients were found to have an AAA measuring 3.8 cm and 6.0 cm giving an AAA prevalence of 3% (exact 95% confidence interval = 0–10%).

CONCLUSIONS

This study does not demonstrate an increased AAA prevalence in over 65-year-old male patients with inguinal hernias, scanned pre-operatively when compared to screening programmes. Selective screening of this cohort cannot be justified on this evidence.     

Treatment preferences for trigger digit by members of the American Association for Hand Surgery

Background

Trigger digit is a common pathology encountered by hand surgeons, but there is a lack of evidence-based guidelines. We investigated the treatment preferences of hand surgeons and explored whether geographic location, type of residency training, or clinical experience is associated with differences in practice.

Methods

An online survey was distributed via email by the American Association for Hand Surgery to 615 members. The survey consisted of 17 questions related to conservative and operative management of trigger digits.

Results

One hundred thirty-nine unique responses were received (22.6 %). Geographic distribution of respondents encompassed the entire USA and was not associated with variations in practice. Of the respondents, 56.8 % were trained in orthopedic surgery while 37.4 % had plastic surgery training. In regards to duration of practice, 8.6 % were in practice for up to 5 years, 29.5 % for 6–15 years, 33.8 % for 16–25 years, and 28.1 % for more than 25 years. Notably, the great majority of respondents preferred corticosteroid injections for initial treatment. Those who were willing to give three or more injections prior to surgery were more likely to be plastic surgeons in practice for 16 years or more. A large minority of surgeons utilized splinting in their conservative management. Orthopedic surgeons were more likely to perform tenolysis during pulley release and more likely to use monitored anesthesia care.

Conclusions

Variation exists between the treatment algorithms of hand surgeons when managing a trigger digit. Some of these differences may be attributable to the type of training or the duration of clinical practice.     

Evolution in the management of Hirschsprung��s disease in the UK and Ireland: a national survey of practice revisited

INTRODUCTION

The management of Hirschsprung’s disease continues to evolve. This questionnaire survey aimed to determine current surgical management strategies for Hirschsprung’s disease in Britain.

SUBJECTS AND METHODS

The survey was sent electronically to all British paediatric surgeons. Initial questions explored individual experience and regional service provision. Additional questions, reserved for surgeons who perform definitive Hirschsprung’s disease surgery, addressed specific clinical scenarios.

RESULTS

Surveys were sent to 142 surgeons yielding 85 responses. After exclusions, 64 surveys from 21 centres were analysed. Forty-seven respondents worked in centres with designated ‘Hirschsprung’s disease surgeons’. Forty respondents perform definitive Hirschsprung’s disease surgery. In a well neonate with left-sided Hirschsprung’s disease, 34 of 40 surgeons favour primary pull-through following bowel decompression with rectal washouts; 35 of 40 surgeons aim to perform definitive surgery at less than 3 months of age, with 17 favouring laparoscopic-assisted Soave–Boley and 15 favouring an open Duhamel pull-through. Of the 40 surgeons, 36 use a staged approach to right-sided/total colonic Hirschsprung’s disease with 23 favouring a Duhamel or Long Duhamel pull-through.

CONCLUSIONS

The primary pull-through, using an open Duhamel or laparoscopic-assisted Soave–Boley technique, during the first 3 months of life, has become the operative strategy of choice in rectosigmoid Hirschsprung’s disease in Britain. Marked variation in practice remains for right-sided Hirschsprung’s disease.     

Scorpio single radius total knee arthroplasty. A minimal five-year follow-up multicentric study

Purpose

Our goal was to evaluate the five-year follow-up results of the Scorpio single radius total knee arthroplasty.

Method

We performed a retrospective study based upon a multicentre database to evaluate the minimum five-year follow-up clinical and radiological results of 747 patients (831 knees) who underwent primary Scorpio single radius total knee arthroplasty.

Results

The mean age of the patients was 71.9 years. At a minimal five-year follow-up, 141 patients were lost to follow-up, 83 patients had died, eight patients had undergone revision of a component, and the remaining 589 patients (602 knees) had a complete clinical and radiological evaluation after a median of six years (range, 5–8). The mean clinical component of the knee score was 92.2 points, and the mean functional component of the knee score was 76.9 points. At last follow-up, 530 of the 602 knees were rated as excellent or good. Only four knees developed patellar complications requiring revision. The survival rate at six years was 95.2% ± 1.9% and 98.3% ± 0.6 with revision for any reason and revision for mechanical failure as the end point, respectively.

Conclusion

This medium-term study indicates favourable clinical and radiological results for this single flexion-extension radius design arthroplasty, with a low complication rate on the patellar side.     

The Effect of Product Safety Courses on the Adoption and Outcomes of LESS Surgery

Background and Objectives:

As technology in surgery evolves, the medical instrument industry is inevitability involved in promoting the use and appropriate (ie, effective and safe) application of its products. This study was undertaken to evaluate industry-supported product safety courses in laparoendoscopic single-site (LESS) surgery, by using the metrics of surgeons'' adoption of the technique, safety of the procedure, and surgeons'' perception of the surgery.

Methods:

LESS surgery courses that involved didactic lectures, operative videos, operation observation, collaborative learning, and simulation, were attended by 226 surgeons. With Florida Hospital Tampa Institutional Review Board approval, the surgeons were queried before and immediately after the course, to assess their attitudes toward LESS surgery. Then, well after the course, the surgeons were contacted, repeatedly if necessary, to complete questionnaires.

Results:

Before the course, 82% of the surgeons undertook more than 10 laparoscopic operations per month. Immediately after the course, 86% were confident that they were prepared to perform LESS surgery. Months after the course, 77% of the respondents had adopted LESS surgery, primarily cholecystectomy; 59% had added 1 or more trocars in 0–20% of their procedures; and 73% held the opinion that operating room observation was the most helpful learning experience. Complications with LESS surgery were noted 12% of the time. Advantages of the technique were better cosmesis (58%) and patient satisfaction (38%). Disadvantages included risk of complications (37%) and higher technical demand (25%). Seventy-eight percent viewed LESS surgery as an advancement in surgical technique.

Conclusion:

In multifaceted product safety courses, operating room observation is thought to provide the most helpful instruction for those wanting to undertake LESS surgery. The procedure has been safely adopted by surgeons who frequently perform laparoscopies. The tradeoff is in performing a more difficult technique to obtain better cosmesis for the patient. We must continue to conduct critical evaluations of product safety courses for the introduction of new technology in surgery.     

Inguinal Hernia Repair: Local or General Anaesthesia?

INTRODUCTION

Specialist hernia centres and public hospitals with a dedicated hernia service (Plymouth Hernia Service) have achieved remarkable results for inguinal hernia repair with the use of local anaesthesia and set the standards for groin hernia surgery. There is minimal data in the literature as to whether such results are reproducible in the National Health Service in the UK.

PATIENTS AND METHODS

A retrospective analysis of all inguinal hernia repairs performed in one district general hospital over a 9-year period was performed. The outcome measures were type of anaesthesia used, early and late postoperative complications and recurrence. A postal questionnaire survey was conducted to obtain satisfaction rates. In addition, a postal questionnaire survey of consultant surgeons in Wales was performed to determine the use of local anaesthesia and day-case rates for inguinal hernia repair.

RESULTS

A total of 577 hernia repairs were performed during the study period. Of these, 369 (64%) repairs were performed under local anaesthesia (LA) and 208 (36%) under general anaesthesia (GA). Day-case repair was achieved in 70% (400) of cases. The day-case rates were significantly higher under LA compared to GA (82.6% versus 42.6%; P < 0.05). Patients operated under LA had lower postoperative analgesic requirements and lower incidence of urinary retention compared with the GA group (P < 0.05). There were 7 (1.2%) recurrences at a median follow-up of 5.1 years (range, 10.3–2.5 years). Postal questionnaire revealed higher satisfaction rates with LA compared to GA repair. Only 15% of surgeons in Wales offer the majority of their patients local anaesthetic repair.

CONCLUSIONS

The use of LA results in increased day-case rates, lesser postoperative analgesic requirements and fewer micturition problems. The excellent results obtained by specialist hernia centres can be reproduced by district general hospitals by increasing the use of LA to repair inguinal hernias.     

The management of vertebral artery injury in anterior cervical spine operation: a systematic review of published cases

Purpose

Anterior cervical spine operations (ACSO) are generally considered to be safe and effective, but the vertebral artery (VA) is at risk during the procedure. Because the consequences of VA injury can be catastrophic, properly managing a VA injury is very important. However, due to the rarity of these injuries, there is no agreed upon treatment strategy.

Methods

Studies were identified for inclusion in the review via sensitive searches of electronic databases through 31 December 2011. All cases included in the review were qualitatively analyzed to explore the relationship between type of VA injury management and neurological complications.

Results

Seventeen articles describing 39 cases of VA injury during ACSO were included in this study. Seven patients (17.9 %) had neurological complications followed by VA insufficiency. Two patients (5.1 %) had root damage due to ligation. One case (2.6 %) resulted in intraoperative death due to fatal bleeding. Delayed vascular complications were identified in nine (45.0 %) of the 20 patients that underwent only tamponade or hemostatic agent during the operation. Four patients underwent intraoperative endovascular treatment, and three of these patients had a cerebral infarction. All three patients who underwent clipping also had neurological complications. The five patients treated by direct repair did not have any complications.

Conclusion

Our review suggests the management of VA injury should be considered in order listed: (1) performing tamponade with a hemostatic agent, (2) direct repair, (3) postoperative endovascular procedures to prevent delayed complications. If tamponade fails to achieve proper hemostasis, additional procedures as endovascular embolization, clipping and ligation should be considered but carry the risk of neurological complications. Because of the limitations of this review, further studies are recommended with larger sample sizes.     

Laparoscopic Cholecystectomy Conversion Rates Two Decades Later

Background and Objectives:

Now nearly 2 decades into the laparoscopic era, nationwide laparoscopic cholecystectomy conversion rates remain around 5% to 10%. We analyzed patient- and surgeon-specific factors that may impact the decision to convert to open.

Methods:

We retrospectively analyzed 2205 LCs performed at a large tertiary community hospital over a 52-month period (May 2004 through October 2008).

Results:

The overall conversion rate was 4.9%. The most common reason for conversion was adhesions, and the majority of these patients had prior abdominal surgery. Males and patients >50 years old had a significantly higher likelihood of open conversion. The conversion rate of high-volume surgeons (≥100 total cases) in comparison to low-volume surgeons (40 to 99 total cases) was significantly lower. Conversion rates were lower among surgeons with fellowship training and those who completed residency training after 1990. Interestingly, the percentage of conversions due to technical difficulty was lower among those with fellowship training but higher among those who completed training after 1990.

Conclusion:

Conversion occurred in ∼5% of all laparoscopic cholecystectomies. Males, patients >50 years old, and cases performed by low-volume surgeons had a higher likelihood of conversion. Other surgeon-specific factors did not have a significant impact on conversion rate.     

Randomized controlled trial to investigate the impact of anticoagulation on the incidence of splenic or portal vein thrombosis after laparoscopic splenectomy

Background

Splenic and portal vein thrombosis (SPVT) is a potentially life-threatening complication of splenectomy. There is a paucity of studies examining the role of prophylactic pre- and postoperative anticoagulation in the prevention of this complication. We designed a prospective randomized controlled trial (RCT) to more rigorously address the impact of prophylactic anticoagulation on the incidence of asymptomatic or symptomatic SPVT, detected on Doppler ultrasound, after laparoscopic splenectomy.

Methods

This 2-centre, phase II, prospective, open-label, parallel-assignment RCT compared no postoperative anticoagulation to a regimen of 40 mg of enoxaparin subcutaneously once daily for 21 days. All patients underwent Doppler ultrasonography of the splenoportal system preoperatively and again 14–28 days after surgery to screen for nonocclusive or occlusive thrombosis.

Results

From November 2006 to November 2008, 35 patients were enrolled in the RCT. Four patients withdrew, 1 required conversion to an open procedure and 1 died at 3 months (the cause of death was not related to the study). Of the 29 patients remaining, 15 were randomly assigned to the anticoagulation group and 14 to the nonanticoagulation group. One (3.4%) patient in the treatment group experienced portal thrombosis. Rates of postoperative bleeding were similar in both groups.

Conclusion

This RCT of anticoagulation found a low overall risk of SPVT after laparoscopic splenectomy; however, this is an underpowered study, and further multi-centred clinical trials are needed.