Pattern of Peritoneal Permeability in Continuous Ambulatory Peritoneal Dialysis Patients in Brunei

2003 ◽  
Vol 23 (2_suppl) ◽  
pp. 11-13
Author(s):  
Ranganathan Dwarakanathan ◽  
Hjh Zarah Yaakob ◽  
Hasnani Hadi
Keyword(s):  
Patient Population ◽  
Diabetic Patients ◽  
Peritoneal Membrane ◽  
Dialysis Patients ◽  
Peritoneal Equilibration Test ◽  
Permeable Membrane ◽  
Brunei Darussalam ◽  
Patients With Diabetes ◽  
Peritoneal Permeability ◽  
Different Populations

Objective Peritoneal permeability may be dissimilar in different populations. The present study identified the pattern of peritoneal permeability in continuous ambulatory dialysis (CAPD) patients treated at the Department of Renal Medicine, RIPAS Hospital, Brunei Darussalam. Methods Data were collected from patients on CAPD in 2001 ( n = 65). Four children were excluded from the study. The remaining 61 patients underwent a 4-hour peritoneal equilibration test (PET) as prescribed by Twardowski et al. For those patients, adequacy of dialysis (Kt/V) was estimated. A retrospective analysis of the peritoneal membrane characteristics of those CAPD patients was also conducted. The membrane characteristics were compared with the urea clearance results. Results Of the 61 patients, 40 were non diabetic, and 21 (34.43%) were diabetic. More than half of our patients (55.74%) had membranes classified as high-average, followed by low-average (22.95%), high (18.03%), and low (3.28%). When the patient population was grouped separately into non diabetic and diabetic patients, peritoneal permeability differed between the groups ( p = 0.000585). No relationship was observed between weekly Kt/V and transport characteristics in the group with diabetes ( p = 0.219306), the group without diabetes ( p = 0.74179), or the entire patient population ( p = 0.376832) Conclusion We conclude that peritoneal permeability among Bruneian CAPD patients is probably different from that among patients from other regions of Asia (more than half of our Bruneian patients had a peritoneal membrane classified as high average). We believe that the observed difference may be related to a difference in ethnicity. In general, patients with diabetes have a highly permeable membrane. Adequacy of dialysis had no correlation to PET results in our study. A larger prospective study is required to confirm our findings.

scholarly journals Mortality after amputation in dialysis patients is high but not modified by diabetes status

2019 ◽  
Vol 13 (6) ◽  
pp. 1077-1082 ◽  
Author(s):  
Marielle A Schroijen ◽  
Merel van Diepen ◽  
Jaap F Hamming ◽  
Friedo W Dekker ◽  
Olaf M Dekkers
Keyword(s):  
Mortality Risk ◽  
Interaction Analysis ◽  
Diabetic Patients ◽  
Comorbid Conditions ◽  
Dialysis Patients ◽  
Diabetes Status ◽  
Patients With Diabetes ◽  
Stage Renal Disease ◽  
End Stage ◽  
Incident Cases

Abstract Background Survival among dialysis patients with diabetes mellitus (DM) is inferior to survival of non-diabetic dialysis patients, probably due to the higher prevalence of diabetes-related comorbid conditions. One could hypothesize that these comorbid conditions also contribute to a decreased survival after amputation in diabetic patients compared with non-diabetic patients on dialysis. Methods Data were collected from the Netherlands Cooperative Study on the Adequacy of Dialysis, a multicentre, prospective cohort study in which new patients with end-stage renal disease were monitored until transplantation or death. Amputation rates (incident cases) were calculated in patients with and without DM. The primary endpoint was all-cause survival after first amputation during dialysis therapy in diabetic patients compared with non-diabetic dialysis patients with an amputation. This was formally assessed using interaction analysis (Poisson regression). Results During follow-up (mean duration 2.9 years), 50 of the 413 diabetic patients had a new amputation (12.1%), compared with 20 of 1553 non-diabetic patients (1.2%). Amputation rates/1000 person-years were 47.9 [95% confidence interval (CI) 36.3–63.2] and 4.1 (95% CI 2.7–6.4), respectively, for diabetic patients and non-diabetic patients. Amputation increased mortality risk more than 4-fold in patients without diabetes [hazard ratio (HR) 4.6 (95% CI 2.8–7.6)] as well as in patients with diabetes [HR 4.6 (95% CI 3.3–6.4)]. No formal interaction between diabetes and amputation was found (P = 0.12). Conclusions Amputation in dialysis patients is associated with a 4-fold increased mortality risk; this mortality risk was similar for diabetes and non-diabetes patients. Importantly, the risk for amputation is 10-fold higher in DM compared with non-diabetic dialysis patients.

Peritoneal Accumulation of Age and Peritoneal Membrane Permeability

2000 ◽  
Vol 20 (4) ◽  
pp. 452-460 ◽  
Author(s):  
Min Sun Park ◽  
Hyon Ah Lee ◽  
Won Suk Chu ◽  
Dong Ho Yang ◽  
Seung Duk Hwang
Keyword(s):  
Membrane Permeability ◽  
High Glucose ◽  
Diabetic Patients ◽  
Peritoneal Membrane ◽  
Exit Site Infection ◽  
Peritoneal Tissue ◽  
Ultrafiltration Failure ◽  
Peritoneal Permeability ◽  
Dialysis Solutions

Background In continuous ambulatory peritoneal dialysis (CAPD), the peritoneal membrane is continuously exposed to high-glucose-containing dialysis solutions. Abnormally high glucose concentration in the peritoneal cavity may enhance advanced glycosylation end-product (AGE) formation and accumulation in the peritoneum. Increased AGE accumulation in the peritoneum, decreased ultrafiltration volume, and increased peritoneal permeability in long-term dialysis patients have been reported. Aim The purpose of the study was to evaluate the relation between peritoneal membrane permeability and peritoneal accumulation of AGE. Methods Peritoneal membrane permeability was evaluated by peritoneal equilibration test (PET) using dialysis solutions containing 4.25% glucose. Serum, dialysate, and peritoneal tissue levels of AGE were measured by ELISA method using polyclonal anti-AGE antibody. Peritoneal biopsy was performed during peritoneal catheter insertion [new group (group N), n = 18] and removal [long-term group (group LT), n = 10]. Peritoneal catheters were removed due to exit-site infection not extended into the internal cuff ( n = 6) and ultrafiltration failure ( n = 4) after 51.6 ± 31.5 months (13 – 101 months) of dialysis. PET data obtained within 3 months after the initiation of CAPD or before catheter removal were included in this study. Ten patients in group N and 4 patients in group LT were diabetic. Patients in group LT were significantly younger (46.5 ± 11.1 years vs 57.5 ± 1.3 years) and experienced more episodes of peritonitis (3.5 ± 2.1 vs 0.2 ± 0.7) than group N. Results Peritoneal tissue AGE level in group LT was significantly higher than in group N, in both nondiabetic (0.187 ± 0.108 U/mg vs 0.093 ± 0.08 U/mg of hydroxyproline, p < 0.03) and diabetic patients (0.384 ± 0.035 U/mg vs 0.152 ± 0.082 U/mg of hydroxyproline, p < 0.03), while serum and dialysate levels did not differ between the groups in both nondiabetic and diabetic patients. Drain volume (2600 ± 237 mL vs 2766 ± 222 mL, p = 0.07) and D4/D0 glucose (0.229 ± 0.066 vs 0.298 ± 0.081, p < 0.009) were lower, and D4/P4 creatinine (0.807 ± 0.100 vs 0.653 ± 0.144, p < 0.0001) and D1/P1 sodium (0.886 ± 0.040 vs 0.822 ± 0.032, p < 0.0003) were significantly higher in group LT than in group N. On linear regression analysis, AGE level in the peritoneum was directly correlated with duration of CAPD ( r = 0.476, p = 0.012), number of peritonitis episodes ( r = 0.433, p = 0.0215), D4/P4 creatinine ( r = 0.546, p < 0.027), and D1/P1 sodium ( r = 0.422, p = 0.0254), and inversely correlated with drain volume ( r = 0.432, p = 0.022) and D4/D0 glucose ( r = 0.552, p < 0.0023). AGE level in the peritoneal tissue and dialysate were significantly higher in diabetics than in nondiabetics in group LT, while these differences were not found in group N. Serum AGE level did not differ between nondiabetics and diabetics in either group N or group LT. Drain volume and D4/D0 glucose were lower and D4/P4 creatinine and D1/P1 sodium higher in diabetics than in nondiabetics in both groups. Conclusion Peritoneal accumulation of AGE increased with time on CAPD and number of peritonitis episodes, and was directly related with peritoneal permeability. Peritoneal AGE accumulation and peritoneal permeability in diabetic patients were higher than in nondiabetic patients from the beginning of CAPD.

Intraperitoneal Administration of Phospha Tidylcholine Improves Ul Trafil Tration in Continuous Ambulatory Peritoneal Dialysis Patients

1992 ◽  
Vol 12 (4) ◽  
pp. 359-364 ◽  
Author(s):  
Genevieve Krack ◽  
Giusto Viglino ◽  
Pier Luigi Cavalli ◽  
Carmen Gandolfo ◽  
Giuseppe Magliano ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Driving Force ◽  
Clinical Evidence ◽  
Intraperitoneal Administration ◽  
Glucose Load ◽  
Dialysis Patients ◽  
Peritoneal Equilibration Test ◽  
Dialysis Solution ◽  
Peritoneal Permeability

Reports in the literature have linked a low phosphatidylcholine content in continuous ambulatory peritoneal dialysis {CAPD) effluent to ultrafiltration loss. Clinical evidence suggests that adding phosphatidylcholine to the dialysis solution enhances ultrafiltration. A clinical study has been designed to clarify the effect of phosphatidylcholine on ultrafiltration in CAPD patients with normal ultrafiltration. A weekly measurement of the peritoneal equilibration test was conducted per patient in the hospital. A comparison between the control dialysis solution {three-week period) and the phosphatidylcholine premixed solution {three-week period) was performed on a total of 12 patients. This study shows that a phosphatidylcholine premixed dialysis solution significantly enhances ultrafiltration. Since ultrafiltration per osmotic driving force (mUg glucose) is enhanced, the patient's glucose load per day is reduced to achieve equal ultrafiltration. In the presence of phosphatidylcholine, peritoneal permeability remained unchanged, as indicated by membrane transport characteristics. No side effects were observed.

scholarly journals Association between the Cardio-Ankle Vascular Index and Diabetes Mellitus-Related Peripheral Arterial Disease in Chronic Hemodialysis Patients

2019 ◽  
Vol 47 (Suppl. 2) ◽  
pp. 25-30
Author(s):  
Fumihiko Furuya ◽  
Ai Motosugi ◽  
Kazutaka Haraguchi ◽  
Shunichiro Hanai ◽  
Toshihisa Ishii ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
Hemodialysis Patients ◽  
Chronic Hemodialysis ◽  
Diabetic Patients ◽  
Dialysis Patients ◽  
Cross Sectional ◽  
Patients With Diabetes ◽  
History Of ◽  
Peripheral Arterial

Background: Peripheral arterial disease (PAD) has increased in association with the increase in the numbers of patients with kidney disease or diabetes. The aim of this study was to assess the prevalence of PAD in hemodialysis patients with diabetes. Methods: To examine the usefulness of the cardio-ankle vascular index (CAVI) to screen for the presence of PAD, cross-sectional studies of 100 patients undergoing chronic hemodialysis were performed. The CAVI and other inflammatory markers were evaluated. Results: The CAVI was markedly elevated in patients with a history of PAD or cardiovascular disease. When dialysis patients were classified on the basis of CAVI quartiles, increased CAVI was associated with other risk factors for PAD. Conclusion: The prevalence of PAD is high in elderly diabetic patients on hemodialysis. The present findings suggest that the CAVI can be a useful index that predicts the occurrence of macrovascular complications in dialysis patients with diabetes.

Assessment of Dialysis Dose by Measured Clearance versus Extrapolated Data

1993 ◽  
Vol 13 (3) ◽  
pp. 184-188 ◽  
Author(s):  
John M. Burkart ◽  
Jean R. Jordan ◽  
Michael V. Rocco
Keyword(s):  
Peritoneal Dialysis ◽  
University Teaching ◽  
Peritoneal Membrane ◽  
Dialysis Patients ◽  
Peritoneal Equilibration Test ◽  
Dialysis Dose ◽  
Dialysis Unit ◽  
Daily Dialysis ◽  
The Individual ◽  
Chronic Ambulatory Peritoneal Dialysis

Objective To determine whether estimates of daily dialysis clearance of creatinine and urea, based on data from the 4-hour peritoneal equilibration test, correlate well with daily dialysis clearance measured by 24-hour dialysate collection in chronic ambulatory peritoneal dialysis patients. Design Prospective study in which each subject collected all dialysate from a 24-hour period and then immediately thereafter underwent a standard peritoneal equilibration test (PET). Daily clearances of creatinine and urea were calculated from 24-hour dialysate collections by standard methods and then were compared with several estimates of 24-hour clearance based on PET data. Setting Single peritoneal dialysis unit of a university teaching hospital. Patients Thirty-six stable patients on continuous ambulatory peritoneal dialysis (CAPD). Main Outcome The estimated values for daily dialysis clearance both overestimated and underestimated the measured 24-hour clearance. The correlation coefficient between the extrapolations and the actual 24-hour clearances ranged from 0.63–0.68. The range of discordance for daily creatinine clearance was from -2530 mL/dayto +2199 mL/day. For daily urea clearance, the range of discordance was from -21 03 mL/ day to +1940 mL/day. The peritoneal membrane transport characteristics of the individual patient did not predict whether the extrapolation overestimated orunder estimated the measured daily clearance. Conclusion Extrapolation of PET data is not a reliable method to estimate the dose of dialysis delivered to the patient. A 24-hour collection of dialysis is necessary for this determination.

The Relationship between Ultrafiltrate Volume with Icodextrin and Peritoneal Transport Pattern according to the Peritoneal Equilibration Test

2002 ◽  
Vol 22 (2) ◽  
pp. 229-233 ◽  
Author(s):  
Maria Regina Teixeira Araújo ◽  
Roberto Flávio Silva Pecoits–Filho ◽  
João Egidio Romão Junior ◽  
Emil Sabbaga ◽  
Marcello Machado Marcondes ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Negative Correlation ◽  
Significant Negative Correlation ◽  
Peritoneal Membrane ◽  
Dialysis Patients ◽  
Peritoneal Equilibration Test ◽  
Peritoneal Transport ◽  
The Mean ◽  
The Difference ◽  
The Relationship

♦ Objective To establish a relationship between peritoneal transport membrane pattern, analyzed by the peritoneal equilibration test (PET), and drained volume using icodextrin (7.5% Ico) and glucose (3.86% Glu) solutions. ♦ Design Thirty peritoneal dialysis patients were submitted to a standard 4-hour PET and divided into 4 transport categories based on dialysate-to-plasma ratio of creatinine (D/Pcr) and dialysate ratio of glucose at 4 and zero hours of the dwell (D4/D0). Patients were asked to perform exchanges for 2 consecutive nights in 10-hour dwells (2 L 3.86% Glu solution on the first night, and 2 L 7.5% Ico solution on the second night). The drained volume was measured and dialysate samples from the overnight exchanges were obtained for β2-microglobulin (B2M) levels. ♦ Results PET classification using D/Pcr showed that 46.6% of the patients were high and high-average transporters, or 23.3% when D4/D0 was used. In spite of this difference, both methods showed significant correlation ( p = 0.0001, r = 0.862). The mean drained volumes were similar for both solutions (for 3.86% Glu, 2696 ± 369 mL; for 7.5% Ico, 2654 ± 424 mL). The high and high-average transport patients classified by D4/D0 achieved a higher ultrafiltration with 7.5% Ico than with 3.86% Glu ( p = 0.0235). When classified by D/Pcr, the difference was not significant ( p = 0.2243). In the low and low-average transport patients classified by D/Pcr, we observed a significantly lower ultrafiltration when 7.5% Ico was used compared to 3.86% Glu solution ( p = 0.0197). Using D4/D0, we saw a tendency toward lower ultrafiltration ( p = 0.0719) in the same group. We then correlated the PET results and the difference between drained volume with 7.5% Ico and 3.86% Glu solution [ΔV (I–G)]. We found a significant negative correlation between D4/D0 and ΔV (I–G) ( p = 0.002, r = –0.5390), and a positive correlation between D/Pcr and ΔV (I–G) ( p = 0.005, r = 0.4932). The levels of B2M obtained with 7.5% Ico were higher than those obtained with 3.86% Glu solution (for 7.5% Ico, 9.47 ± 6.71 μg/vol; for 3.86% Glu, 7.29 ± 4.91 μg/vol; p = 0.004). Furthermore, we found significant correlation between the total amount of B2M obtained with 7.5% Ico solution and D4/D0 ( p < 0.0001, r = –0.4493), and D/Pcr ( p < 0.0001, r = 0.5431). ♦ Conclusion Mean drained volume was similar between the two solution groups. High transporters, as defined by D4/D0, achieved higher ultrafiltration with 7.5% Ico than with 3.86% Glu solution. This is most likely due to the higher number of small pores in the peritoneal membrane. Low transporters, as classified by D/Pcr, achieved lower ultrafiltration with 7.5% Ico than with 3.86% Glu solution. The ΔV (I–G) and the PET results showed significant correlation, confirming that high transporters have a higher ultrafiltration volume with 7.5% Ico. The total B2M mass obtained with 7.5% Ico was greater than with 3.86% Glu solution and significantly higher in the high transport patients, indicating a larger number of small pores. Thus, the ΔV (I–G) could give us an idea of the peritoneal transport pattern in peritoneal dialysis patients.

Intramuscular Nerve and Neuromuscular Junction Alteration In Extraocular Muscles of Diabetic Mice

1985 ◽  
Vol 43 ◽  
pp. 682-683
Author(s):  
Bruce R. Pachter
Keyword(s):  
Diabetes Mellitus ◽  
Peripheral Nerves ◽  
Sudden Onset ◽  
Extraocular Muscles ◽  
Diabetic Patients ◽  
Oculomotor Palsy ◽  
Third Nerve Palsy ◽  
Patients With Diabetes ◽  
Intramuscular Nerve ◽  
Oculomotor Nerves

Diabetes mellitus is one of the commonest causes of neuropathy. Diabetic neuropathy is a heterogeneous group of neuropathic disorders to which patients with diabetes mellitus are susceptible; more than one kind of neuropathy can frequently occur in the same individual. Abnormalities are also known to occur in nearly every anatomic subdivision of the eye in diabetic patients. Oculomotor palsy appears to be common in diabetes mellitus for their occurrence in isolation to suggest diabetes. Nerves to the external ocular muscles are most commonly affected, particularly the oculomotor or third cranial nerve. The third nerve palsy of diabetes is characteristic, being of sudden onset, accompanied by orbital and retro-orbital pain, often associated with complete involvement of the external ocular muscles innervated by the nerve. While the human and experimental animal literature is replete with studies on the peripheral nerves in diabetes mellitus, there is but a paucity of reported studies dealing with the oculomotor nerves and their associated extraocular muscles (EOMs).

Management of the Asymptomatic Diabetic Patient with Evidence of Ischaemia

2010 ◽  
Vol 6 (1) ◽  
pp. 62
Author(s):  
Dimitrios Bliagos ◽  
Ajay J Kirtane ◽  
Jeffrey W Moses ◽  
◽  
◽  
...  
Keyword(s):  
Coronary Artery ◽  
Medical Therapy ◽  
Artery Bypass ◽  
Coronary Intervention ◽  
Diabetic Patients ◽  
Ageing Population ◽  
Patients With Diabetes ◽  
Risk Patients ◽  
Asymptomatic Diabetic Patient ◽  
Artery Disease

In the US, a total of 23.6 million people have diabetes, representing 7.8% of the population, and the prevalence of diabetes is on the rise due to an increasingly sedentary lifestyle, increasing obesity and an ageing population. Coronary artery disease is the leading cause of death in patients with diabetes, despite a reduction in cardiovascular events over the last 50 years, due in part to better medical therapy. Asymptomatic diabetic patients with evidence of ischaemia on stress testing have higher cardiac mortality; increasing amounts of ischaemia are associated with higher mortality rates. Revascularisation of high-risk patients, or those with significant ischaemia, has the potential to improve outcomes in this patient population. The choice of which revascularisation strategy to choose – either percutaneous coronary intervention (PCI) or coronary artery bypass grafting – should be carefully individualised, and must always be implemented against the background of optimal medical therapy.

The cost-effectiveness of insulin analogs and regular insulin for diabetes control: a case study in Iran

2020 ◽  
Vol 33 (4/5) ◽  
pp. 323-331
Author(s):  
Mohsen pakdaman ◽  
Raheleh akbari ◽  
Hamid reza Dehghan ◽  
Asra Asgharzadeh ◽  
Mahdieh Namayandeh
Keyword(s):  
Cost Effectiveness ◽  
Cost Effective ◽  
Regular Insulin ◽  
Diabetes Control ◽  
Diabetic Patients ◽  
Insulin Analogs ◽  
Content Type ◽  
Patients With Diabetes ◽  
The Government ◽  
The Cost

PurposeFor years, traditional techniques have been used for diabetes treatment. There are two major types of insulin: insulin analogs and regular insulin. Insulin analogs are similar to regular insulin and lead to changes in pharmacokinetic and pharmacodynamic properties. The purpose of the present research was to determine the cost-effectiveness of insulin analogs versus regular insulin for diabetes control in Yazd Diabetes Center in 2017.Design/methodology/approachIn this descriptive–analytical research, the cost-effectiveness index was used to compare insulin analogs and regular insulin (pen/vial) for treatment of diabetes. Data were analyzed in the TreeAge Software and a decision tree was constructed. A 10% discount rate was used for ICER sensitivity analysis. Cost-effectiveness was examined from a provider's perspective.FindingsQALY was calculated to be 0.2 for diabetic patients using insulin analogs and 0.05 for those using regular insulin. The average cost was $3.228 for analog users and $1.826 for regular insulin users. An ICER of $0.093506/QALY was obtained. The present findings suggest that insulin analogs are more cost-effective than regular insulin.Originality/valueThis study was conducted using a cost-effectiveness analysis to evaluate insulin analogs versus regular insulin in controlling diabetes. The results of study are helpful to the government to allocate more resources to apply the cost-effective method of the treatment and to protect patients with diabetes from the high cost of treatment.

scholarly journals A preliminary study on diabetes self-management education and glycemic control among patients with diabetes mellitus

2019 ◽  
Vol 9 (9) ◽  
pp. 98 ◽  
Author(s):  
Kisokanth G. ◽  
Indrakumar J. ◽  
Prathapan S. ◽  
Joseph J. ◽  
Ilankoon I.M.P.S.
Keyword(s):  
Diabetes Mellitus ◽  
Glycemic Control ◽  
Management Education ◽  
Self Management ◽  
Rank Test ◽  
Diabetic Patients ◽  
Effective Measure ◽  
Before And After ◽  
Patients With Diabetes ◽  
Preliminary Study

This study was aimed to assess the effectiveness of diabetes self-management education (DSME) in the improvement of glycemic control among patients with type 2 Diabetes Mellitus (T2DM) in Batticaloa District, Sri Lanka. The study was a prospective interventional study and conducted as a preliminary study at medical clinic, Base hospital, Kaluwanchikudy, Batticaloa. Thirty patients with T2DM were included based on inclusion and exclusion criteria. A structured individual diabetes self-management education for 10 hours (one hour per week) was delivered to diabetic patients by the trained Nurse Health Educator. Glycosylate hemoglobin (HbA1c) was assessed as a main outcome measure and Fasting Blood Sugar (FBS), Body Mass Index (BMI) of each patient were also measured and recorded before and after the intervention. The respondent rate was 96.7% (n = 29). Majority of them were females (n = 25, 86.2%). A Wilcoxon signed rank test showed that DSME had a statistically significant reduction in HbA1c [8.60 (IQR 2.60) vs. 7.40 (IQR 2.10), p = .000] and FBS level [159.00 (IQR 77.50) vs. 134.00 (IQR 40.50), p = .002] at 3 months of intervention. The mean BMI at baseline was higher compared to 3 months of intervention [24.88 (SD ± 3.06) vs. 24.19 (SD ± 2.79)] which was statistically significant (p = .000). Majority of participants (n = 22, 75.9%) had improved their HbA1c level by ≥ 0.5% in 3 months. The diabetes self-management education is an effective measure in improving glycemic control and other clinical parameters among patients with T2DM. Thus, DSME needs to be implemented among clinic patients with T2DM for the better outcome and the preventions of complications.

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