Dialyzer reuse--part II: advantages and disadvantages

Although single dialyzer use and reuse by chemical reprocessing are both associated with some complications, there is no definitive advantage to either in this respect. Some complications occur mainly at the first use of a dialyzer: a new cellophane or cuprophane membrane may activate the complement system, or a noxious agent may be introduced to the dialyzer during production or generated during storage. These agents may not be completely removed during the routine rinsing procedure. The reuse of dialyzers is associated with environmental contamination, allergic reactions, residual chemical infusion (rebound release), inadequate concentration of disinfectants, and pyrogen reactions. Bleach used during reprocessing causes a progressive increase in dialyzer permeability to larger molecules, including albumin. Reprocessing methods without the use of bleach are associated with progressive decreases in membrane permeability, particularly to larger molecules. Most comparative studies have not shown differences in mortality between centers reusing and those not reusing dialyzers, however, the largest cluster of dialysis-related deaths occurred with single-use dialyzers due to the presence of perfluorohydrocarbon introduced during the manufacturing process and not completely removed during preparation of the dialyzers before the dialysis procedure. The cost savings associated with reuse is substantial, especially with more expensive, high-flux synthetic membrane dialyzers. With reuse, some dialysis centers can afford to utilize more efficient dialyzers that are more expensive; consequently they provide a higher dose of dialysis and reduce mortality. Some studies have shown minimally higher morbidity with chemical reuse, depending on the method. Waste disposal is definitely decreased with the reuse of dialyzers, thus environmental impacts are lessened, particularly if reprocessing is done by heat disinfection. It is safe to predict that dialyzer reuse in dialysis centers will continue because it also saves money for the providers. Saving both time for the patient and money for the provider were the main motivations to design a new machine for daily home hemodialysis. The machine, developed in the 1990s, cleans and heat disinfects the dialyzer and lines in situ so they do not need to be changed for a month. In contrast, reuse of dialyzers in home hemodialysis patients treated with other hemodialysis machines is becoming less popular and is almost extinct.     

Influence of Reuse and of Reuse Sterilants on the First-Use Syndrome

Over a 4 year period, five of 98 patients at our dialysis unit developed signs and symptoms consistent with first-use syndrome (FUS). Marked improvement was noted after subjecting new dialyzers to automated processing using either formaldehyde or peracetic acid. No episodes of FUS occurred in patients being treated with reused dialyzers. Use of formaldehyde sterilization was associated with development of anti-N-like antibodies in the blood of four (8%) of 50 patients over a follow-up period of 14 months. In two patients on the reuse program, itching during dialysis resolved after changing from formaldehyde-sterilization to a method using peracetic acid. Our results confirm the beneficial effects of reuse with regard to first-use syndrome. However, our data also suggest that use of formaldehyde, the most common reuse sterilant, continues to be associated with undesirable clinical and laboratory side effects.     

Dialyzer performance over prolonged reuse

Studies were performed in patients on maintenance hemodialysis to evaluate the role of prolonged dialyzer reuse in the management of end-stage renal disease. For this purpose the patients were dialyzed without interruption with the same hollow fiber dialyzers (GambroR 120M) reprocessed with the Lixivitron IIR equipment. The data obtained from in vivo clearances in sixteen patients demonstrate that membrane permeability to small solutes (urea, creatinine, phosphate) is maintained up to thirty dialyzer uses. In vitro studies confirmed this observation and established that clearances of larger solutes (vitamin B12) are also maintained over similar extensive dialyzer reuse. Hematological and blood gas studies were performed serially during dialysis in five additional patients. Although circulating leucocyte and neutrophil counts, hemoglobin concentration as well as arterial pH and partial pressures of oxygen and carbon dioxide changed appropriately during dialysis, there was no observable difference from the first to the twentieth use of the same dialyzer. Thus, these results clearly demonstrate that prolonged dialyzer reuse in end-stage renal disease patients constitutes a stable form of renal replacement therapy provided adequate dialyzer reprocessing is applied.     

Evaluation of Three Dry-Sterilized Hollow Fiber Artificial Kidneys

We investigated three new dry sterilized hollow fiber artificial kidneys (HFAK) (Cordis Dow CDAK 1.3, Travenol CF 1200, Extracorporeal Tri-Ex 1). Dry sterilization makes these dialyzers more economical by shortening set-up time. Dry sterilization also eliminates iatrogenic administration of residual sterilant. Water of imbibition can significantly increase the blood compartment volume of the dialyzer during dialysis. Consequently, a corrected blood volume for each dialyzer was established; these corrected volumes varied from 13-36% greater than the volume determined before dialysate flow. With low dose heparinization of these dialyzers there was between an 18 and 45% decrease in the post dialysis volume, presumably due to fiber clotting during dialysis. This volume added to the residual blood loss measured by a colori-metric technique accounted for a possible blood loss ranging between 26.9 and 53.9 ml per dialysis for these three dialyzers. Our results suggest that a relationship between dialyzer clotting and decreased dialyzer efficiency may exist. These three capillary flow dialyzers had a much lower platelet drop (0-9% pre to post) when compared to 30-40% drop of flat plate dialyzers. These dialyzers were found to be safe and easy to use but the high fiber clotting warrants further investigation in chronic dialysis patients on high dose heparin.     

A Quality and Cost-Benefit Analysis of Dialyzer Reuse in Hemodialysis Patients

Background. To evaluate the benefits of dialyzer reuse for hemodialysis (HD) patients, including the cost of HD treatment and patient's survival, a comparison was made regarding the standard practice of single-use dialysis. Methods. From January 1, 2005, to December 31, 2005, a total of 128,232 successive HD treatments in 822 patients in Chang Gung Memorial Hospital-Kaohsiung Medical Center were included in this study. Results. Approximately 54.25% (446/822) of patients reused dialyzers. The average times of dialyzer reuse was 2.54. The annual hollow fiber cost is reduced by $241,054.08 U.S. dollars (NT $7,834,257.60). The annual cost of hollow fiber was reduced by $540.48 U.S. dollars (NT $17,565.60) in one patient with dialyzer reuse. The mortality rates in dialyzer reuse and single use groups were 3.1% and 10.9% within one year (p < 0.0001). Multiple logistic regressions showed that single use compared with reuse was associated with higher mortality after adjusting co-morbid conditions including age, diabetes mellitus, etc. Conclusions. We concluded that the benefits of dialyzer reuse included safety in our center and reduction in cost during a 12-month period. Dialyzer reuse may be a safe alternative.     

Method of Dialyzer Cleaning and Frequency of Reuse

Several methods exist for cleaning hollow fiber dialyzers for reuse. How important is the cleaning procedure in determining the number of times a dialyzer can be reused?     

Effect of RenNew-D as a sterilant on the performance of reused dialyzers

RenNew-D (Alcide), a novel demand-release sporocidal agent, was employed instead of formaldehyde in the reprocessing for reuse of cuprophan hollow fiber dialyzers (Gambro) and the performance of these dialyzers was evaluated over 40 consecutive dialyses in six patients on maintenance hemodialysis. When RenNew-D was part of automated reprocessing performed with 4.3% bleach as specified by the manufacturer (Lixivitron), dialyzer survival was prolonged (16.7 +/- 7.2 uses) and hemodialysis neutropenia was unchanged with reuse. When RenNew-D was part of manual reprocessing conducted in the absence of bleach, marked improvement in dialyzer biocompatibility was observed but with a decreased survival (4.8 +/- 3.0). The majority of dialyzer failures were due to a fall in fiber bundle volume below a 85% set limit. Small solute clearances were maintained with both types of reprocessing. Dialyses were well tolerated throughout. Our data suggest that RenNew-D is a safe and efficacious product which can serve as a valuable alternative to formaldehyde for the purpose of dialyzer reuse.     

Association of dialyzer reuse and hospitalization rates among hemodialysis patients in the US

OBJECTIVES: To determine if reuse of hemodialyzers is associated with higher rates of hospitalization and their resulting costs among end-stage renal disease (ESRD) patients. METHODS: Noncurrent cohort study of hospitalization rates among 27,264 ESRD patients beginning hemodialysis in the United States in 1986 and 1987. RESULTS: Dialysis in free-standing facilities reprocessing dialyzers was associated with a greater rate of hospitalization than in facilities not reprocessing (relative rate (RR) = 1.08, 95% confidence interval (CI), 1.02-1.14). This higher rate of hospitalization was observed with dialyzer reuse using peracetic/acetic acids (RR = 1.11, CI 1. 04-1.18) and formaldehyde (RR = 1.07, CI 1.00-1.14), but not glutaraldehyde (p = 0.97). There was no difference among hospitalization rates in hospital-based facilities reprocessing dialyzers with any sterilant and those not reprocessing. Hospitalization for causes other than vascular access morbidity in free-standing facilities reusing dialyzers with formaldehyde was not different from hospitalization in facilities not reusing. However, reuse with peracetic/acetic acids was associated with higher rates of hospitalization than formaldehyde (RR = 1.08, CI 1.03-1.15). CONCLUSIONS: Dialysis in free-standing facilities reprocessing dialyzers with peracetic/acetic acids or formaldehyde was associated with greater hospitalization than dialysis without dialyzer reprocessing. This greater hospitalization accounts for a large increment in inpatient stays in the USA. These findings raise important concerns about potentially avoidable morbidity among hemodialysis patients. Copyright Copyright 1999 S. Karger AG, Basel     

Dialyzer Reuse Following Manual Reprocessing with a New Sterilant, RenNew-D

Dialysis patients are at risk for toxicity from formaldehyde used in the reprocessing of dialyzers for reuse; therefore, replacing formaldehyde as a dialyzer sterilant would be advantageous. The potential for RenNew-D as a sterilizing agent was investigated in seven stable in-center hemodialysis patients over 20 consecutive dialyses with cuprammonium cellulose hollow-fiber dialyzers. Treatment with RenNew-D showed no toxicity to patients or dialyzers except for two blood leaks occurring in one patient. The mean number of dialyzer uses was 4.9. In all the dialyzers that passed functional testing small solute clearances were maintained with reuse. The ability of RenNew-D to improve the biocompatibility of reused dialyzers was documented with mean neutrophil counts falling to only 78% of initial values during first reuse of dialyzers processed with RenNew-D compared with a decrease in neutrophil count to 2% of initial values during first use of the same dialyzers. Our results suggest that RenNew-D may be a useful alternative to formaldehyde for the purpose of dialyzer reuse. A reuse procedure that includes processing with RenNew-D is associated with improved biocompatibility, possibly because of maintenance of the blood-derived membrane coating established during prior dialysis.     

Dialyzer reuse-Part I: Historical perspective

The first apparatus for hemodialysis in animals, made painstakingly by Abel et al. in their laboratory at the beginning of 20th century, was cleaned with acid-pepsin to digest blood, disinfected with thymol, and reused for up to 30 experiments for as long as 8 months. The obvious incentive was saving time. In the early years of hemodialysis in patients, dialyzers and lines were assembled and sterilized immediately before dialysis. Various methods of dry and moist heat sterilization and miscellaneous chemical agents were employed for disinfection. Significant time was required to assemble the dialyzers, so there was an incentive to reuse previously assembled dialyzers to save time, especially for home hemodialysis. Bleach to clean and formaldehyde to disinfect the membranes and lines was used for this purpose. Preassembled dialyzers, commercially introduced in the 1950s, were the most expensive components of hemodialysis systems, therefore reprocessing of these dialyzers was the most effective way to save money. Refrigeration of coil dialyzers with blood, introduced in the mid-1960s, was associated with frequent febrile reactions and was soon abandoned. Preassembled coil and plate dialyzers permitted almost complete return of blood after dialysis and led to the introduction of chemical disinfection for dialyzer reprocessing. A variety of disinfectants have been used. Formaldehyde was the most common disinfectant until the end of the 1970s. Sodium hypochlorite was used to clean the majority of dialyzers and to sterilize dialyzers with polyacrylonitrile membranes. In the early 1980s, peracetic acid and glutaraldehyde started to compete with formaldehyde. By the 1990s, formaldehyde had become less popular than peracetic acid. In the mid-1990s, disinfection and membrane cleaning with acetic acid and heat was introduced. Manual reprocessing was replaced by early reuse machines in the mid-1970s and a more sophisticated second generation of automated hemodialyzer reprocessing machines followed in the late 1970s. Recently disinfection of dialyzers with moist heat has resumed. Saving both time for the patient and money for the provider were the main motivations for designing a new machine for daily home hemodialysis. The machine, developed in the 1990s, cleans and moist-heat disinfects the dialyzer and lines in situ so they do not need to be changed for a month. In contrast, the reuse of dialyzers in home hemodialysis patients treated with other hemodialysis machines has become less popular and is almost extinct.     

The effects of reprocessing cuprophane and polysulfone dialyzers on beta 2-microglobulin removal from hemodialysis patients

To further define the relationship between dialyzer reuse and the removal of beta 2-microglobulin (beta 2M) during dialysis, 26 patients who received hemodialysis were studied. Thirteen patients were dialyzed with conventional cuprophane dialyzers, and thirteen patients were dialyzed with high-flux polysulfone dialyzers. Patients in each group were dialyzed with only new dialyzers during the primary-use phase of the study, and reprocessed dialyzers during the reuse phase. Dialyzers were used six times during the reuse phase. Serum beta 2M levels were measured both predialysis and postdialysis, and adjusted for fluid loss. Dialysis with conventional cuprophane new dialyzers during the primary-use phase of the study resulted in a 3.3% increase in serum beta 2M levels, and a 2.4% increase in serum beta 2M levels during the reuse phase. The difference in the change of the concentration of beta 2M between primary-use and reuse phases was not statistically significant. Dialysis with high-flux polysulfone new dialyzers during the primary-use phase was associated with a decrease of 59.5% in the mean postdialysis concentration of serum beta 2M compared with the predialysis level. A corresponding decrease of 62.6% in serum beta 2M levels was observed after dialysis with high-flux polysulfone reprocessed dialyzers during the reuse phase. These data show no evidence of an adverse effect on the clearance of beta 2M during dialysis from the reuse of dialyzers up to six times. The results confirm previous studies that have reported that high-flux dialysis with polysulfone dialyzers removes substantial amounts of beta 2M, and dialysis with conventional cuprophane dialyzers does not.     

Evaluation with micro‐CT of different anticoagulation strategies during hemodialysis in patients with thrombocytopenia: A randomized crossover study

In patients with enhanced risk for bleeding, heparin‐free hemodialysis (HD) with conventional dialyzers is routinely used. To explore the potential benefit of using heparin‐coated dialyzers, we used a reference CT‐scanning technique and registered different clotting parameters to quantify coagulation with heparin‐coated versus non‐coated dialyzers. Six HD patients with thrombocytopenia were dialyzed 240 min in a randomized crossover study with Evodial 1.3 or FX600 Cordiax, each without anticoagulation. Blood samples were taken from the vascular access predialysis, and from the dialyzer inlet and outlet at 5 and 240 min after dialysis start. Predialysis blood samples were analyzed for hemoglobin, hematocrit, thrombocytes, fibrinogen, and activated partial thromboplastin time. On dialyzer inlet and outlet blood samples, a viscoelastic measurement of blood coagulation was performed using a Sonoclot analyzer. After dialysis, dialyzers were visually scored, subsequently dried for 24 h, weighed, and scanned with micro‐CT at a resolution of 25 µm. After image reconstruction, the open, non‐coagulated fibers were counted in a representative cross‐section at the dialyzer outlet. No sessions were terminated prematurely for circuit clotting. Heparin‐coated dialyzers had more patent fibers on micro‐CT versus non‐coated dialyzers and also had a better score of subjective visual assessment of fiber clotting. There was no difference in subjective assessment of clotting at the venous drip chamber. With both dialyzers, all ACT values remained in the normal range, and were lower at the dialyzer outlet versus inlet. In conclusion, dialysis with a heparin‐coated versus non heparin‐coated membrane results in substantially less coagulated fibers during 4 h hemodialysis without systemic anticoagulation. Eventual leaching of heparin, immobilized on the fiber membrane, does not result in measurable systemic anticoagulation.     

Urea kinetics with dialyzer reuse--a prospective study

We performed a prospective study to examine the impact of dialyzer reuse on KT/V under rigidly standardized conditions on 3 membrane types. Heparin dosage was standardized with ACT during an eight week run-in period and remained unchanged through the study. Post dialysis BUN and weight were obtained at five minutes after exactly 80 +/- 0.5 l of blood were processed through the dialyzer. Dialyzers were reused after automated glutaraldehyde processing and after ensuring >80% open fiber bundles. Each membrane type was utilized 3 times on a set of 3 patients; each individual dialyzer was reused 8 times. KT/V was done on the 1st, 2nd, 4th and 8th uses of each dialyzer (36 measurements) starting mid week; BUN measurements were grouped. The KT/V (mean +/- SD) for the 1st, 2nd, 4th, and 8th uses of the cellulose acetate dialyzer were 1.3 +/- 0.2, 1.3 +/- 0.3, 1.3 +/- 0.2, 1.3 +/- 0.2 respectively; the corresponding values of the cuprophane dialyzer were 1.4 +/- 0.3, 1.4 +/- 0.3, 1.3 +/- 0.4, 1.3 +/- 0.3 respectively; and those of the polysulfone dialyzer 1.7 +/- 0.3, 1.6 +/- 0.2, 1.6 +/- 0.2 respectively. By a 3 way ANOVA there were no significant differences between the 1st and subsequent uses of any of the dialyzers tested. Conclusions: Reuse of dialyzers up to 8 times does not result in a loss of urea clearance. We believe this model is useful for further studies on reuse and quality assurance. Copyright Copyright 1999 S. Karger AG, Basel     

Antibody Responses to Hemodialysis-Related Antigens in Chronic Hemodialysis Patients

Allergic-type reactions during hemodialysis are sometimes due to sensitization to ethylene oxide. To examine the possibility that additional antigens might be a basis for unexplained reactions, antibodies to formaldehyde and phthalate-related antigens and to dialyzer extracts were measured. Unselected sera from 113 chronic hemodialysis patients (CHP) and 200 control subjects were tested for IgG antibodies to formaldehyde-treated human serum albumin (HSA). The IgG antibody activity was confirmed in sera of five CHP who had used formaldehyde-treated dialyzers. These antibodies also reacted with formaldehyde-treated red blood cells. Sera from 71 CHP and 80 controls were tested for IgE antibodies to diethylphthalate-treated HSA; antibody was detected in two CHP sera. With extracts from hollow-fiber dialyzers, IgG antibody was detected in approximately 1/3 and IgM antibodies in approximately 1/2 of CHP sera. This antibody was found in comparable numbers of control sera. It was concluded that these additional substances are immunogenic and could be involved in allergic-type reactions.     

Anaphylactoid reactions associated with reuse of hollow-fiber hemodialyzers and ACE inhibitors.

From July 18 through November 27, 1989, 12 anaphylactoid reactions (ARs) occurred in 10 patients at a hemodialysis center in Virginia. One patient required hospitalization; no patients died. ARs occurred within minutes of initiating dialysis and were characterized by peripheral numbness and tingling, laryngeal edema or angioedema, facial or generalized sensation of warmth, and/or nausea or vomiting. All 12 ARs occurred with dialyzers that had been reprocessed with an automated reprocessing system. A cohort study, including all patients undergoing dialysis sessions on the six days when an AR occurred, showed that the patients who experienced ARs were significantly more likely than patients who did not to be treated with angiotensin-converting enzyme (ACE) inhibitors (7/10 vs. 3/33; relative risk = 7.9; 95% confidence interval = 2.5 to 25.2) and to have been exposed to reused dialyzers rather than to new dialyzers (12/70 sessions vs. 0/31; P = 0.016). In those sessions using a reused dialyzer, the mean number of dialyzer uses in case-sessions was significantly higher than for noncase-sessions (10.3 vs. 6.2; P = 0.016). After reuse of dialyzers was discontinued at the center, no further ARs occurred, despite the continued administration of ACE inhibitors. This is the first report of an outbreak of ARs associated exclusively with reused dialyzers. We hypothesize that interactions between a dialyzer that has been repeatedly reprocessed and reused, blood, and additional factors, such as ACE inhibitors, increased the risk of developing ARs.     

Dialyzer reuse: an evolving search for efficiency

The evolution of dialyzer reuse in the United States provides an opportunity to examine the dialysis community's response to changing financial conditions and incentives. As background, we provide a conceptual framework to explain the factors governing the diffusion of dialysis technologies and then describe the clinical context in which reuse programs have developed. Early in its evolution, dialyzer reuse arose principally from the desire to reduce costs under a system of capitated payments. More recently, despite evidence of an adverse health effect, cost-savings from reuse have permitted the adoption of new and expensive technologies. The net effect of the tradeoff's between cost and quality should, ideally, drive the decision to reuse dialyzers. However, even if such tradeoffs can be fully characterized, incentives to implement efficiencies created by capitated systems of payment will continue to influence practice.     

Beta 2-microglobulin kinetics in maintenance hemodialysis: a comparison of conventional and high-flux dialyzers and the effects of dialyzer reuse

beta 2-Microglobulin (beta 2M) forms synovial and bony amyloid deposits in long-term hemodialysis patients. To define the kinetics of beta 2M during hemodialysis and the effects of dialyzer reprocessing, we measured serum beta 2M, plasma C3a, and neutrophil counts immediately predialysis; 15, 90, and 180 minutes after beginning dialysis; and 15 minutes postdialysis in ten chronic hemodialysis patients. The studies were performed during first and third uses of cuprammonium rayon and polysulfone dialyzers processed by rinsing with water, then bleach, in an automated system (Seratronics DRS 4) and then packed in 1.5% formaldehyde. Mean serum beta 2M (corrected for ultrafiltration) decreased by 16.6% +/- 18.1% with new cuprammonium dialyzers and 57.1% +/- 12.8% with new polysulfone dialyzers. Dialyzer reprocessing had no significant effect on this decline. Predialysis serum beta 2M decreased by 30.4% +/- 15.5% 1 month after switching from cuprammonium to polysulfone dialyzers; these levels remained stable after 3 months of dialysis with polysulfone. Complement activation and neutropenia during dialysis were significantly more marked with cuprammonium, but were not affected by reprocessing of either dialyzer. In vitro adsorption of 124I-beta 2M to polysulfone fibers was greater than to cuprammonium; adsorption was not influenced by dialyzer reprocessing.     

Effect of Reuse on Dialyzer Efficacy

The effect of reuse on dialyzer efficacy was examined by measuring blood compartment volume and dialyzer mass transfer coefficient (maximum dialyzer clearance) as a function of dialyzer use number. The 102 polysulfone dialyzers tested (F60 and HF80, Fresenius) were reprocessed on Renatron machines using peroxyacetic acid as the dual cleansing and sterilizing agent. Each dialyzer was used an average of 14.4 +/- 5.7SD times and was tested once (twice for 13/102 dialyzers) during a routine dialysis session at an arbitrary use number (7.6 +/- 5.3; range 1 to 24). The parameters tested were found to decrease only marginally with reuse, corresponding to a blood compartment volume loss of approximately 1% (R = 0.04) over a 5-week/15-use period and a decrease in dialyzer mass transfer coefficient of approximately 3% (R = 0.07 and 0.06) over the same period for urea and creatinine, respectively. It was concluded that the loss in dialyzer efficacy is negligible over the average use period of almost 5 weeks per dialyzer.     

A new scintigraphic method to characterize ultrafiltration in hollow fiber dialyzers.

Ultrafiltration and pressure profiles in hollow fiber dialyzers with different hydraulic permeabilities have been investigated with a new scintigraphic method. Radiolabelled albumin macroaggregates, used as a nondiffusible marker molecule, were added to the blood in an in vitro circuit and circulated through cuprophan and polysulphon dialyzers. Since the marker molecule was too big to cross the dialysis membrane, its changes in concentration were assumed to occur in response to the variation of the blood water content (filtration or back-filtration). These changes in concentration, recorded by a gamma camera, were evaluated to establish the cumulative values of filtration and back-filtration and their relevant profiles along the length of the dialyzer. The achieved data were compared with the experimental values of ultrafiltration empirically measured and with the theoretical values predicted by a classic linear method. Two conditions were analyzed: A) the minimal filtration rate necessary to avoid back-filtration (critical filtration); and B) the condition of zero net filtration in which filtration equals back-filtration. The nuclear method proved to be extremely precise in predicting the ultrafiltration values and significantly more precise than the linear method, especially for the highly permeable dialyzer. The reason for that probably depends on the non-linear pressure and ultrafiltration profile observed with the scintigraphic pattern of the dialyzer. Viscosity changes and local variations in blood flow may in fact interfere with the pressure drop inside the hollow fibers and result in such a complex behavior. The other interesting aspect of this method is the possibility of accurate measurement of the amount of back-filtration that wouldn't be possible with simple calculations. In conclusion, the complex nature of the phenomena regulating the water fluxes in hollow fiber dialyzers requires more complex calculation than a simple linear model to achieve an accurate range of predictability.