Comparison of Hem-o-lok and Endoloop for Appendiceal Stump Closure in Laparoscopic Appendectomy: An Observational Retrospective Study.

BACKGROUND: Laparoscopic appendectomy has gained prominence in the management of acute appendicitis, necessitating secure closure of the appendiceal stump. Two common techniques for this purpose are Hem-o-lok clips (HC) and endoloops (EL), each offering distinct advantages. AIMS: This retrospective study aimed to compare the outcomes of the HC and EL closure techniques. Specifically, the study focused on postoperative complications, hospital stays, and readmission rates. MATERIALS AND METHODS: A retrospective database review was conducted from November 2022 to August 2023. The study compared outcomes, postoperative complications, and the length of hospital stay in 123 patients who underwent appendiceal stump closure with HC and EL at the General Surgery Department of the Turkish Hospital in Doha, Qatar. RESULTS: Among the 123 patients who underwent laparoscopic appendectomy, appendiceal stump closure was performed with HC in 50 patients and EL in 73 patients. Six patients experienced infectious complications associated with the procedure. The hospital stays were similar in both groups (Group HC: 1.3 ± 2 days, Group EL: 1.4 ± 2 days), and there were two readmissions in each group.  Conclusion: The study supports the equivalence of HC and EL closure techniques. Both methods demonstrate comparable postoperative complications, hospital stays, and readmission rates. Surgeons can make informed decisions based on patient profiles and available resources.

The Effect of Bariatric Surgery on Exocrine Pancreatic Function.

INTRODUCTION: After bariatric surgery (BS), patients might suffer from nutrient maldigestion, malabsorption, and vitamin deficiencies. In this study, our aim was to assess pancreatic functions after BS using fecal elastase-1 assay (FE-1). MATERIAL AND METHODS: Sixty patients (21M) undergoing BS and 20 (6M) healthy controls were included into the study. Stool samples were collected 1 year after surgery. Ten patients from one anastomosis gastric bypass (OAGB) and single anastomosis duodenal switch (SADS) groups with the lowest value of FE-1 and GIQLI scores were given pancreatic enzyme replacement therapy (PERT). After PERT, FE-1, excess weight loss (EWL), BMI, GIQLI scores, and vitamin D levels were measured. RESULTS: Vitamin D levels were detected as 19.04 (9-46.5) pg/ml, 15.1 (8.4-23.6) pg/ml, 17.8 (5-30) pg/ml, and 21.79 (11-40.3) pg/ml after sleeve gastrectomy (SG), OAGB, SADS, and control groups, respectively (p = 0.04). GIQLI scores in the first year were found to have increased in all patients (p = 0.02). FE-1 levels were found as 642.35 (566.3-711.4) µg/g, 378.52 (183.5-561.1) µg/g, 458.88 (252.5-593, 5) µg/g, and 518.2 (351.6-691) µg/g for the SG, OAGB, SADS, and control groups, respectively. There was a strong inverse correlation between EWL and FE-1 levels at the end of the first year (Spearman's rho = - 0.688, p = 0.003). After having performed PERT for patients with the lowest FE-1 levels, the levels increased to 683.39 (615.5-720) µg/g in the OAGB and 691.5 (643.1-720) µg/g in the SADS groups (p = 0.011). CONCLUSION: FE-1 measurements demonstrated that many patients suffer from malabsorption after OAGB or SADS, whereas functions remain normal after SG. PERT corrects pancreatic functions without affecting weight loss and also contributes to the normal serum level of vitamin D.

Obesity and appendicitis: Laparoscopy versus open technique.

OBJECTIVES: The clinical results of obese patients who have undergone open or laparoscopic appendectomy, whether one technique is superior to the other is still not clearly known.In our study, we compared the clinical results of obese patients operated with laparoscopic or open technique for acute appendicitis. MATERIAL AND METHODS: We performed retrospective analyses of patients operated for acute appendicitis between the dates of July 2016 and July 2019 at Istinye University Faculty of Medicine Bahcesehir Liv Training and Research Hospital and Liv Hospital Ankara. Of the 241 patients whose height and weight information was accessible, 57 had a body mass index of 30 kg/m2 or higher. Eighteen of these patients underwent open surgery while the other 39 underwent laparoscopic surgery. The primary result criterion was complication ratio. Secondary criteria were operation time and length of hospital stay. RESULTS: Upon comparison of laparoscopic and open techniques in terms of intraoperative-postoperative complications (p= 0.01), operation time (p= 0.02) statistically significant differences were found between the groups. However the mean length of hospital stay (p= 0.181) was similar in both groups. CONCLUSION: In obese appendicitis patients, the laparoscopic technique proved to be superior to the open technique in criteria such as perioperative-postoperative complications, operation time, and etc. Length of hospital stay was determined to be similar between the groups.

Changes in HOMA-IR index levels after bariatric surgery: Comparison of Single Anastomosis Duodenal Switch-proximal approach (SADS-p) and One Anastomosis Gastric Bypass-Mini Gastric Bypass (OAGB-MGB).

BACKGROUND: Bariatric surgery plays a major role in ameliorating metabolic abnormalities of type 2 diabetes (T2DM). The aim of this study was to evaluate the early effects of "Single Anastomosis Duodenal Switch-proximal approach" (SADS-p) and "One Anastomosis Gastric Bypass-Mini Gastric Bypass (OAGB-MGB) on the "homeostasis model assessment of insulin resistance" (HOMA-IR) index levels in morbidly obese patients with T2DM. METHODS: In this retrospective 3-year trial, outcomes of SADS-p and OAGB-MGB patients were compared considering the changes in HOMA-IR index levels. All bariatric procedures were performed by a single primary surgeon recognized as a surgeon of excellence by IFSO-EC with the assistance of one or two additional attending surgeons. SADS-p was performed on 60(10 males) patients, and 200(27 males) patients underwent OAGB-MGB. Forty-six patients (78%) in the SADS-p group and 125 (63%) in the OAGB-MGB group had T2DM. Patients were evaluated before surgery and 1,3,9,12 months after surgery. RESULTS: In both groups, the HOMA-IR index levels decreased significantly after surgery (p < 0.05), and both procedures markedly improved glycemic control. In the SADS-p group the HOMA-IR index levels significantly decreased from 6.2 to 1.4 after the 12th month of surgery (p < 0.05), in OAGB-MGB group HOMA-IR index levels significantly decreased from 5,9 to 1.7 after the 12th month of surgery (p < 0.05). CONCLUSION: Both procedures are promising operations which offer excellent control on weight, HOMA-IR index and diabetes.

A bibliometric analysis of publications on trauma in critical care medicine during 1980-2018: A holistic view.

BACKGROUND: There is not a holistic bibliometric study evaluating the publications in the literature even though trauma is a paramount subject in the field of critical care. This study aimed to investigate the important articles and journals receiving the most citations and publishing the most articles, revealing international cooperation and uncovering trend topics in this subject as a consequence of analyzing articles on trauma in the field of critical care published between 1980 and 2018 using bibliometric analysis methods. METHODS: Publication scan in this study was performed using Web of Science (WoS) database. Literature review was limited to only publications indexed in the field of Critical Care. "Trauma" was used as the keyword to reach relevant publications. Linear regression analysis was performed to predict the number of articles foreseen to be published in the upcoming years in the subject of trauma. RESULTS: As a result of the literature review, a total of 10851 publications were found. Six thousand four hundred and eighty-nine (59.8%) of these publications were under the category of article. First three countries with the most publications were respectively as the United States of America (4096) (63.1%), Canada (401) and Germany (380). Turkey ranked 21 with 41 publications. The article titled "Evaluating trauma care - the triss method" published in 1987 had received the most citations. The journal with the most publications and citations was "Journal of Trauma Injury Infection and Critical Care". CONCLUSION: This study will be a useful guide to all scientists and clinicians conducting research on trauma in critical care.

Analysis of factors associated with mortality in major burn patients.

OBJECTIVES: Major burn injury is a type of trauma with high morbidity and mortality rates at all age groups. There is no consensus on the provided guidelines regarding the prediction of severity of the victims. Not being accessible to sophisticated clinical and blood monitoring in developing countries, it remains a challenge for them. The aim of the present study was to analyze the factors that have an effect on mortality and serve as a guide for burn treatment. Factors affecting mortality in major burn patients treated in a burn treatment center of a third step hospital with over 30% of burns of the total body surface area were evaluated, and parameters indicating severity were specifically determined. MATERIAL AND METHODS: Medical records and follow-up notes of patients hospitalized in Ankara Numune Education and Research Hospital Burn Center between 2008 and 2014 were evaluated retrospectively. Data on age, gender, comorbidities, burn percentage, locality, type of burn, process of the burn (suicide or accident), presence of inhalation injury, results of blood hemogram and biochemical tests, length of hospitalization, type of surgical procedures performed, presence of multitrauma, and ventilatory support requirement were analyzed to determine the factors affecting mortality. White blood cell count, hemoglobin count, platelet count, and lactate dehydrogenase level were examined at admission, at the middle of the clinical course, and at the end of treatment (at both exitus date or discharge date). RESULTS: A total of 224 patients were hospitalized with burns ≥ 30% total body surface area. Of the 224 patients, 81.7% were males, and 18.4% were females. In the mortality group, 41.3% were males, and 58.5% were females. Gender (female, p <0.041), age (p <0.001), age group (0-14/15-59/> 60 years, p <0.001), total body surface area (p <0.001), type of burn (flame, p <0.002), presence of inhalation injury (p <0.001), process of the burn (p <0.002), time spent between the event and admission to the hospital (p <0.001), length of hospitalization (p <0.001), presence of comorbidity (p <0.038), diabetes mellitus (p <0.05), ventilation support (p <0.001), lactate dehydrogenase values (lactate dehydrogenaseadmission, p <0.001; lactate dehydrogenasemiddle, p <0.015; lactate dehydrogenaselast, p <0.001), white blood cell count (p <0.001), and platelet count (p <0.043) were found to be significant for univariate analyses. These parameters were further evaluated using multivariate analyses. Lactate dehydrogenaselast level (p <0.001), age (p <0.001), length of hospitalization (negative odds ratio), p <0.001), presence of inhalation injury (p <0.029), total body surface area burned (p <0.029), and leukocytosis (p <0.006) were found to be significantly associated with mortality; however, leukocytosis and length of hospitalization did not pose risk for mortality with regard to odds ratios. CONCLUSION: Early recognition of the factors affecting morbidity and mortality in patients and taking preventive measures, in addition to earlier detection and prevention of complications in long-time intensive care unit patients, could reduce complication and mortality rates in major burn trauma patients. Parameters for the indication of severity and mortality are important; however, lactate dehydrogenase is an easily studied parameter and is found to have a predictive value on prognosis.

Analysis of factors associated with mortality in major burn patients.

OBJECTIVE: Major burn injury is a type of trauma that still has high morbidity and mortality rates at all age groups. There is no consensus on the provided guidelines regarding the prediction of the severity of the victims. It is sometimes not easy to have sophisticated clinical and blood monitoring for developing countries. It is still a challenge for them. The aim of the present study was to analyze the factors that have an effect on mortality and serve as a guide for burn treatment. Factors affecting mortality in major burn patients with over 30% of burns of the total body surface area who were treated in a burn treatment center of a third step hospital were evaluated, and parameters indicating severity were specifically determined. MATERIAL AND METHODS: Medical records and follow-up notes of patients hospitalized in in Ankara Numune Education and Research Hospital Burn Center between 2008 and 2014 were evaluated retrospectively. Data on age, gender, comorbidities, burn percentage, locality, type of burn, process of the burn (suicide or accident), presence of inhalation injury, results of blood hemogram and biochemical tests, length of hospitalization, type of surgical procedures performed, presence of multitrauma, and ventilatory support requirement were analyzed to determine the factors affecting mortality. White blood cell count, hemoglobin count, platelet count, and lactate dehydrogenase level were examined at admission, at the middle of the clinical course, and at the end of treatment (at both exitus date or discharge date). RESULTS: A total of 224 patients were hospitalized with burns ≥30% total body surface area. Of the 224 patients, 81.7% were males, and 18.4% were females. In the mortality group, 41.3% were males, and 58.5% were females. Gender (female, p<0.041), age (p<0.001), age group (0-14/15-59/>60 years, p<0.001), total body surface area (p<0.001), type of burn (flame, p<0.002), presence of inhalation injury (p<0.001), process of the burn (p<0.002), time spent between the event and admission to the hospital (p<0.001), length of hospitalization (p<0.001), presence of comorbidity (p<0.038), diabetes mellitus (p<0.05), ventilation support (p<0.001), lactate dehydrogenase values (lactate dehydrogenaseadmission, p<0.001; lactate dehydrogenasemiddle, p<0.015; lactate dehydrogenaselast, p<0.001), white blood cell count (p<0.001), and platelet count (p<0.043) were found to be significant for univariate analyses. These parameters were further evaluated using multivariate analyses. lactate dehydrogenaselast level (p<0.001), age (p<0.001), length of hospitalization (negative odds ratio), p<0.001), presence of inhalation injury (p<0.029), total body surface area burned (p<0.029), and leukocytosis (p<0.006) were found to be significantly associated with mortality; however, leukocytosis and length of hospitalization did not pose risk for mortality with regard to odds ratios. CONCLUSION: Early realization of the factors affecting morbidity and mortality in patients and taking preventive measures, in addition to earlier detection and prevention of complications in long-time intensive care unit patients, could reduce complication and mortality rates in major burn trauma patients. Parameters for the indication of severity and mortality are important; however, lactate dehydrogenase is an easily studied parameter and is found to have a predictive value on prognosis.

Clinical infection in burn patients and its consequences.

BACKGROUND: Burn injuries facilitate invasive infections and sepsis not only by destroying the continuity of the protective skin barrier but also through systemic effects. The burn wound, blood, and urine samples are frequently cultured to determine the pathogen agent. The aim of this study was to analyze pathogen growth in patients' cultures confirmed as "infection positive" by the hospital Infection Control Committee and to assess the clinical implications of these growths. METHODS: Hospitalized patients included in the study were those with a total burned body surface area of >10% and "presence of infection" confirmed by the Infection Control Committee. The patients were evaluated with respect to age, gender, burn etiology, the total body surface area burned (TBSA), the presence of inhalation injury, sepsis, positive cultures, the microorganisms cultured in wound-blood-urine samples, and septic focus. RESULTS: Of the total 36 (10.3%) "infection-positive" patients, 26 (72.2%) were male; the mean age of patients was 44±21 years. The mean burned TBSA of the whole group was 45.58%±23.1%. Acinetobacter baumannii was the most isolated organism in the wound cultures. In patients with confirmed infection, there was a correlation between the pathogen isolated in urine cultures and mortality rates (p=0.023). Sepsis was diagnosed in 23 (63.9%) patients, of whom 21 had inhalation injuries. There was a significant correlation between inhalation injury and sepsis (p=0.015), and both the presence of sepsis or inhalation injury increased mortality (p=0.027 and p=0.009, respectively). CONCLUSION: According to the study data, the TBSA burned demonstrated a greater significance for mortality, although the presence of sepsis and/or urinary tract infection should also be noted as a cause of mortality in burned patients.

Correlation between ischemia-modified albumin and Ranson score in acute pancreatitis.

BACKGROUND: Although Ranson score is the most commonly used prognostic model in the severity of acute pancreatitis (AP), ischemia-modified albumin (IMA) has been reported as a novel biomarker of various ischemia-based diseases in recent years. The aim of the present study is to investigate the correlation between Ranson score and IMA in patients with AP. METHODS: Forty-three patients with AP were included in the study. All patients were classified as mild and severe AP. Plasma IMA level was measured after diagnosis and before treatment. The correlation between IMA level and amylase level, Ranson score, and disease severity was evaluated. RESULTS: Twenty-nine (67.4%) patients were diagnosed as mild AP; the remaining 14 (32.6%) patients had moderately severe or severe form of disease, and were classified as severe AP. There was no significant difference in the IMA levels between the patient groups (p=0.737). No correlation between IMA levels and amylase levels (p=0.470), Ranson score (p=0.664), and disease severity (p=0.741) was found. CONCLUSION: According to the results from the study, IMA does not seem as a useful marker in earlier prediction of disease severity in AP. Despite important disadvantages, Ranson score still indicates the disease severity more accurately.

Concomitant thyroid cancer in patients with primary hyperparathyroidism in an endemic goitre region.

OBJECTIVE: Primary hyperparathyroidism (pHPT) is often accompanied by underlying thyroid pathology and 1 to 36% of these thyroid pathologies are malignant. How the identification of these lesions affects patient management is unclear. We present a single-center experience with the prevalence of concomitant thyroid cancer in patients who underwent parathyroidectomy for pHPT. MATERIALS AND METHODS: This was a retrospective cohort study. Two hundred-two patients with primary hyperparathyroidism included study. Demographic data, clinical findings, and final histopathological diagnosis were recorded retrospectively. RESULTS: Preoperative cervical ultrasound examination revealed co-existent thyroid abnormalities in 117 (57.9%) patients. Mean age of these patients was 57.8 ± 12.2 years and 88% were female. Sixty-three (53.9%) of the patients with thyroid abnormalities, underwent preoperative fine needle aspiration biopsy (FNAB). Cytology result was malignant in one (1.6%) patient, benign in 47(85.7%) patients, indeterminate in six (9.5%) patients and Hurthle cell neoplasm in two (3.2%) patients. Ninety-four (80.3%) of the patients underwent simultaneous thyroid surgery. Final pathology of the thyroid specimen was malignant in 26 (12.9%) patients. Sixteen of the malignant patients had preoperative FNAB. Preoperative FNAB result of these patients was malignant in one patient, indeterminate in two patients and benign in 13 patients. CONCLUSION: By implementing a comprehensive approach to patients with pHPT who present with thyroid disease, concomitant pathology may be elucidated preoperatively. But, this approach will not facilitate the detection of otherwise unsuspected thyroid cancer in an endemic goitre region. KEY WORDS: Cancer, Parathyroid adenoma, Parathyroidectomy, Thyroid, Thyroidectomy.

Does the preoperative prognostic nutritional index predict postoperative complications in patients with colorectal cancer who underwent curative resection?

AIM: Malnutrition is a common and very important issue in colorectal cancer patients.The immunological and nutritional status of these patients have been reported to be correlated with the postoperative complications.The prognostic nutritional index (PNI) is an effective and simple parameter, initially created to evaluate preoperative surgical risks. The aim of this study was to evaluate the predictive value of PNI in patients with colorectal cancer who underwent surgery. METHODS: One hundred eighty patients who underwent curative colorectal resections for colorectal cancer were included in this retrospective study. Demographic characteristics of the patients, biochemical parameters, intra-operative findings, operation type, postoperative surgical complications, and PNI values were collected Results:The median PNI value was 44,4(range 19-60,5).Receiver Operating Characteristics demonstrated that a value below 39,75 was the optimal cut-off value for the prediction of major complications. The median PNI values were significantly lower in patients with major complications (Clavien-Dindo grade 3 to 5). CONCLUSION: The PNI can predict severe complications in patients with colorectal cancer who are undergoing primary tumor resection. Investigation of the nutritional status by using the PNI could be a useful approach for clinical follow-up. KEY WORDS: Colorectal, Nutritional index, Postoperative complications.

The evaluation of the complications observed in patients with bilateral total and bilateral near total thyroidectomy.

AIM: The objective was to compare the recurrent laryngeal nerve (RLN) and superior laryngeal nerve (SLN) injuries in patients with bilateral total thyroidectomy (BTT) and bilateral near total thyroidectomy (BNTT) with the frequency of the hypocalcemic complications regarding the operation procedures. MATERIALS AND METHODS: Patients, who underwent BTT and BNTT in our clinic between January 1999 and January 2011, were included in this retrospective clinical study. Patients' files are evaluated. Demographic information, pre-operative complete blood cell count and biochemical analysis, thyroid function tests, ultrasonographic results, results of the fine needle aspiration biopsy, implemented operative procedures (BTT or BNTT), vocal cord investigation, post-operative calcium levels, postoperative complications were analyzed. RESULTS: In 328 of 408 (80.4%) patients BTT was the preferred method and 80 underwent BNTT (19.6 %). Postoperative hypocalcemia was observed in 59 patients in the BTT group (17.9 %) and in 11 patients in the BNTT group (13.7 %) . Hypocalcemia persisted in 8 patients in BTT group (2.4 %) and in 6 patients in BNTT group (7.5%). Unilateral RLN paralysis was observed in 22 patients in BTT group (6.7 %) and in 13 patients in the BNTT group (16.2 %). CONCLUSION: In this study, the likelihood of the temporary RLN paralysis and permanent hypoparathyroidism is found to be higher in the patients with BNTT compared to the patients with BTT. BNTT may be the preferred choice of treatment in suitable patients. KEY WORDS: Complication, Hypocalcemia, Nervus laryngealis recurrens, Nervus laryngealis superior, Thyroidectomy.

Ischemia-modified albumin as a predictor of the severity of acute appendicitis.

BACKGROUND: The early prediction of gangrenous/perforated appendicitis is of great importance for the surgical planning, further treatments, and predicting the course of disease. Ischemia-modified albumin (IMA) was previously reported as a biomarker of various ischemia-based diseases. Our aim is to determine the predictive value of serum IMA in the severity of acute appendicitis. METHODS: Sixty-two patients who underwent urgent appendectomy were included in the study. Plasma level of IMA was measured after diagnosis and before treatment. All patients were classified as noncomplicated (acute) appendicitis and complicated (gangrenous/perforated) appendicitis according to histopathological findings, and comparisons were made between the groups. RESULTS: The data of 62 patients with a mean age of 30.1 years were statistically evaluated. The pathological diagnoses were acute appendicitis in 33 (53.2%), and gangrenous/perforated appendicitis in 29 (46.8%) patients. There were significant differences in computed tomography (CT) findings (P = .031) and IMA (P = .012) levels between the groups. A strong positive correlation between IMA levels and CT findings was also found (Spearman ρ = +0.688, P = .003). CONCLUSIONS: The IMA can be considered as a novel and useful marker to distinguish gangrenous/perforated appendicitis from noncomplicated appendicitis. The correlation of IMA with CT findings also enhances the predictive value of IMA.

Etiology of childhood burns and parental awareness in Turkey.

OBJECTIVE: Burns continue to be a devastating trauma worldwide. Most of the childhood burns are due to preventable injuries. Burns occurring as a result of negligence of the parents'/carers' may cause mortality or life-long morbidities. Identification of the etiologies will direct the precautions that should be undertaken. MATERIAL AND METHODS: One hundred consequent burn patients admitted to our clinics were included to the study. A questionnaire was filled in with the information gathered from the parents/carers. RESULTS: The mean age of the patients was 3.74±3.07 years, and 52% was male. Most of the injuries occurred in the noon (median 12:45). Seventy-eight percent of the burns occurred at children's own home. Parents/carers were close enough to prevent the child from injury in 66% of the cases. While there was no first intervention in 21% of burns, 14% applied ice and 1% yoghurt. Taxi was the means to reaching the hospital in 45%. Hot liquids were the leading etiology (p<0.003). Sixty-two percent of the patients were dining at the living room and on the floor. CONCLUSION: The occurrence of the majority of injuries near parents/carers can be related to inadvertence or lack of awareness. To decrease burns incidence among children in our country, dining at the floor and stove heating should be avoided as much as possible. Not cooling the burn with running tap water at the time of injury leads to deepening of the burn, which consequently makes management more complex. Based on our study, there is an apparent need for determination of preventive measurements and to raise public awareness.

Outpatient burn management and unnecessary referrals.

BACKGROUND: This study aimed to determine the profile of burn patients presented in our polyclinic and evaluate the current status in comparison to the treatment methods of past series. METHODS: Burn patients presented in the polyclinic in a one-year period were included into this prospective study. The records of all patients were examined in respect of gender, age, burn percentage, burn location, cause of burn, degree of burn, dressing material, number of dressings, type of treatment, place of trauma, and month of trauma. RESULTS: From a total of one thousand seven hundred and ninety-five patients presented, management was completed in the polyclinic for one thousand five hundred and eleven cases with a mean age of 27.9 years, with a female: male ratio of 0.88. While most patients were in the 18-64 age group, hot liquid burn was the leading cause in all age groups (p<0.05, p<0.001). Of the total patients, 89.6% were injured at home (p<0.001). The extremities were determined as the body area most often burned (p<0.001). While a single dressing was applied to 446 patients (29.5%), in 64.9% of cases polyclinic follow-up was terminated after the first 3 dressings. The mean number of dressings was greater in patients with deep dermal burns (mean 14.5, median 14, p<0.001). CONCLUSION: A higher incidence of burns was found due to increasing urban populations compared to previous years. Currently, the majority of patients are referred to a healthcare facilty near their residences for follow-up after a few dressings. Unneccessary presentation at specialist centres increases the workload of these centres and creates a burden of wasted time and transport expense for the patients. The application of current burn treatment principles in primary and secondary health facilities will reduce the workload of reference centres.