Nutritional status according to the mini nutritional assessment (MNA)® as potential prognostic factor for health and treatment outcomes in patients with cancer - a systematic review.

BACKGROUND: Patients with cancer have an increased risk of malnutrition which is associated with poor outcome. The Mini Nutritional Assessment (MNA®) is often used in older patients with cancer but its relation to outcome is not known. METHODS: Four databases were systematically searched for studies relating MNA-results with any reported outcome. Two reviewers screened titles/abstracts and full-texts, extracted data and rated the risk of bias (RoB) independently. RESULTS: We included 56 studies which varied widely in patient and study characteristics. In multivariable analyses, (risk of) malnutrition assessed by MNA significantly predicts a higher chance for mortality/poor overall survival (22/27 studies), shorter progression-free survival/time to progression (3/5 studies), treatment maintenance (5/8 studies) and (health-related) quality of life (2/2 studies), but not treatment toxicity/complications (1/7 studies) or functional status/decline in (1/3 studies). For other outcomes - length of hospital stay (2 studies), falls, fatigue and unplanned (hospital) admissions (1 study each) - no adjusted results were reported. RoB was rated as moderate to high. CONCLUSIONS: MNA®-result predicts mortality/survival, cancer progression, treatment maintenance and (health-related) quality of life and did not predict adverse treatment outcomes and functional status/ decline in patients with cancer. For other outcomes results are less clear. The moderate to high RoB calls for studies with better control of potential confounders.

Prevention of anastomotic leak in rectal cancer surgery with local antibiotic decontamination: a prospective, randomized, double-blind, placebo-controlled single center trial.

PURPOSE: Anastomotic leak and other infectious complications are septic complications of rectal cancer surgery caused by bacteria. Data from registry analysis show a beneficial effect of local antimicrobial administration on anastomotic leaks, but data are inconsistent in recent clinical trials. Therefore, our aim was to study the efficacy of topical antibiotic treatment on the incidence of anastomotic leaks in rectal cancer surgery. METHODS: A prospective, randomized, double-blind and placebo-controlled, single center trial was conducted. Patients received either placebo and amphotericin B or decontamination with polymyxin B, tobramycin, vancomycin, and amphotericin B four times per day starting the day before surgery until postoperative day 7. If a protective ileostomy was created, a catheter was placed transanally and the medication was administered locally to the anastomotic site. All patients received an intravenous perioperative antibiotic prophylaxis. RESULTS: The trial had to be stopped for ethical reasons after first interim analysis with 80 patients instead of the initially planned 280 patients. Of the 40 patients randomized to receive placebo, eight (20%) developed anastomotic leak compared to only 2 (5%) in the treatment group of 40 patients (decontamination) with significant difference in the χ2 test (p = 0.0425). Twenty percent of the placebo group and 12.5% in the treatment group developed infectious complications not associated with anastomotic leak (p = 0.5312). One patient (2.5%) in the placebo group died (p = 0.3141). CONCLUSION: Local decontamination with polymyxin, tobramycin, vancomycin, and amphotericin B is safe and effective in the prevention of anastomotic leak in rectal cancer surgery.

Activity of Von Willebrand factor and levels of VWF-cleaving protease (ADAMTS13) in preterm and full term neonates.

Von Willebrand Factor (VWF) has a central role in primary hemostasis. Its biological activity is related to the size of VWF multimers, spontaneously binding to platelets and inducing circulating microthrombi formation. This process is down-regulated by the VWF cleaving protease ADAMTS13 (A Disintegrin and Metalloprotease with ThromboSpondin motif). To date, information regarding the levels of ADAMTS13 in neonates and preterm infants is scarce. Our aim was to study ADAMTS13, VWF antigen (Ag) and Ristocetin cofactor (RiCof) activity in neonates and evaluate potential correlations with perinatal complications. Our cohort consisted of 128 (48/128: born preterm) neonates, born in Sheba Medical Center and followed until hospital discharge. Control group consisted of 20 healthy adults. As expected, a significant elevation of VWF:Ag was observed in preterm and term infants compared to adults. VWF:Ag levels were highest in full term infants (Median 129.0 IQR 33.8) and lowest in adults (Median 119.0 IQR 58.5) (p<0.05), and RiCoF levels in neonates were higher than in adults. ADAMTS13 was significantly (p<0.05) higher in preterm babies in comparison to full term and adult controls. Neonates that underwent stressful conditions or experienced vascular complications such as IUGR, ROP, NEC, had lower levels of ADAMTS13 in our study. Further studies are required to validate and asses potential significance of these findings.

Antiphospholipid antibodies in neonates with stroke--a unique entity or variant of antiphospholipid syndrome?

OBJECTIVE: YB current affiliation: Department of Pediatrics, Hadassah-Hebrew University Medical Center, Mount Scopus, Israel YB and MJS contributed equally to the study and should be regarded as joint first authors on this manuscript. Antiphospholipid syndrome (APS) may present with thrombosis and persistently elevated titers of antiphospholipid antibodies (aPL) in the neonatal period. Our aim was to investigate the course and impact of elevated titers of aPL in a cohort of infants presenting with either perinatal arterial ischemic stroke (PAS) or cerebral sinus vein thrombosis (CSVT) during the perinatal period. STUDY DESIGN: Sixty-two infants with clinically and radiologically confirmed PAS or CSVT presenting in the neonatal period underwent thrombophilia workup that included Factor V Leiden (FVL), PII20210A mutation, MTHFR 677T polymorphism, protein C, protein S, aPL namely either circulating lupus anticoagulant (CLA), anticardiolipin antibodies (aCL) or anti-ß2-glycoprotein-1 (ß2GP1). Mothers also underwent thrombophilia workup. RESULTS: Twelve infants with persistently elevated aPL were prospectively followed. Infants with positive aPL showed no concordance with presence of maternal aPL. All children were followed for a median of 3.5 years (range: nine months to 19 years) with repeated aPL testing every three to six months. Anticoagulant therapy initiation and therapy duration varied at the physician's discretion. In 10/12 cases aPL decreased to normal range within 2.5 years; one female with complex thrombophilia risk factors required indefinite prolonged anticoagulation. None of the infants showed recurrent thrombosis or any other APS manifestations, despite lack of prolonged anticoagulation. CONCLUSIONS: The presence of aPL may be important in the pathogenesis of cerebral thrombosis in neonates. Nevertheless, the nature of thrombophilia interactions in this period and their therapeutic impact warrants further investigation.

Recombinant factor concentrates may increase inhibitor development: a single centre cohort study.

Recent reports have raised concerns regarding potential risk factors for inhibitor development. In Israel, all haemophilia patients (n = 479) are followed by the National Hemophilia Center. Most children are neonatally exposed to factor concentrate (due to circumcision performed at the age of 8 days). The impact of early exposure and recombinant FVIII products (rFVIII) administration (approved in Israel since 1996) upon inhibitor occurrence in our cohort of haemophilia A (HA) patients was analysed. Two hundred ninety-two consecutive paediatric cases with a first symptomatic onset of HA were enrolled and followed over a median time of 7 years [min-max: 9 months to 17 years]. Study endpoint was inhibitor development against factor VIII. In addition, the treatment regimens applied, i.e. bolus administration or 'continuous infusion' and the family history of inhibitor development were investigated. During the follow-up period 31/292 children (10.6%) developed high titre inhibitors. Inhibitors occurred in 14/43 (32.5%) HA patients neonatally exposed to rFVIII, as compared to 22/249 previously treated with Plasma Derived (PD) products (8.8%). The odds ratio for inhibitor formation in rFVIII treated HA patients was 3.43 (95% CI: 1.36-8.65). Transient inhibitor evolved among 2/43 paediatric HA patients, only among those treated with rFVIII. The risk of inhibitor detection significantly increased among HA children treated by continuous infusion (P = 0.025). Our experience shows that the risk of inhibitor formation may be increased by early exposure to recombinant concentrates. The multiple variables affecting inhibitor incidence deserve further attention by larger prospective studies.

Impaired platelet function in neonates born to mothers with diabetes or hypertension during pregnancy.

OBJECTIVE: In a recent pilot study, platelet function of 4 neonates born to mothers with pregnancy-induced hypertension (PIH) was found to display lower platelet adhesion compared to healthy neonates. The present study aimed at confirming and validating these findings. STUDY DESIGN: Platelet adhesion was measured using a Cone Platelet Analyzer (CPA). The platelet function in the cord blood of 35 term infants born to mothers with PIH or gestational diabetes (GD) was compared with the platelet function of 196 infants born to healthy mothers. All neonates were monitored for perinatal complications until hospital discharge. RESULTS: Neonates born to mothers with PIH and with GD displayed poorer platelet function, with decreased platelet surface coverage as tested by CPA (control group 8.53+/-3.81%; PIH: 5.9+/-3.91%, p=0.003; GD: 6.64+/-3.64%, p=0.005). No association was found between CPA values and post-natal complications. CONCLUSIONS: Maternal PIH or GD is associated with impaired platelet function in neonates. The clinical impact of these findings is yet to be studied.

[Economic consequences of complications in abdominal and thoracic surgery in the German DRG payment system]. / Betriebswirtschaftliche Bedeutung von Komplikationen in der Viszeral- und Thoraxchirurgie im DRG-System.

BACKGROUND: The Surgical Department of the University Hospital Grosshadern has been making a systematic record of complications since 2005. With respect to the ongoing problem of under-financing from DRG reimbursements, an analysis of the relationship between surgical cases with severe complications and insufficient reimbursement warranted a detailed analysis. MATERIAL AND METHODS: Out of 16 762 in-house patients during 2005-2007 we assigned 6707 cases into four divisions - hepato-pancreato-biliary, colorectal, minimal invasive and general abdominal surgery as well as 1469 cases of thoracic surgery, for costs and reimbursement. In all groups patients with mandatory treament of complications were compared to the remaining cases without complications. Within these, further subgroups were analysed: patients with a need for artificial ventilation (partition A of the G-DRG system), cases with excessive loss (underfunding above 10 000 Euro) and their intersections. RESULTS: With the exception of minimal invasive surgery, each division featured 10-15 % of serious complications. Losses for these cases ranged from 159 % (thoracic surgery) to 102 % (other abdominal surgery) of the overall loss in each division. Cases with excessive losses, representing 1.5 % of all patients, caused 80 % to 100 % of this deficit. Complicated cases alloted to DRGs for artificial ventilation still represented 50 % of the under-fund-ing. CONCLUSION: Cases with mandatory complication treatment can be discerned as separate economic entities. They are considerably overlapping cases with excessive underfunding, so further analysis might lead to an improved reimbursement policy. In addition, the connection between quality management and economic efficiency is highlighted.

Size matters - The olfactory bulb as a marker for depression.

BACKGROUND: Major Depression is mainly related to structural and functional alterations in brain networks involving limbic and prefrontal regions. Reduced olfactory sensitivity in depression is associated with reduced olfactory bulb (OB) volume. We determined if the OB volume reduction is a specific biomarker for depression and whether its diagnostic accuracy allows its use as a valid biomarker to support its diagnosis. METHODS: 84 in-patients with mixed mental disorders and 51 age-matched healthy controls underwent structural MR imaging with a spin-echo T2-wheighted sequence. Individual OB volume was calculated manually (interrater-reliability = .81, p < .001) and compared between groups. Multiple regression analysis with OB volume as dependent variable and Receiver Operator Characteristic analysis to obtain its diagnostic accuracy for depression were ruled out. RESULTS: Patients exhibited a 13.5% reduced OB volume. Multiple regression analysis showed that the OB volume variation was best explained by depression (ß = -.19), sex (ß = -.31) and age (ß = -.29), but not by any other mental disorder. OB volume attained a diagnostic accuracy of 68.1% for depression. LIMITATIONS: The patient group mainly contained highly comorbid patients with mostly internalizing disorders which limits the generalisability of the results of the regression analysis. CONCLUSION: The OB may serve as a marker for depression. We assume that reduced neural olfactory input to subsequent limbic and salience processing structures moderates this relation. However, the OB was in an inferior position compared to conventional questionnaires for diagnosis of depression. Combination with further structural or functional measurements is suggested.

Outcome of preterm infants born to overweight and obese mothers†.

OBJECTIVES: To evaluate perinatal morbidity and mortality among preterm neonates who were born to overweight and obese mothers compared to preterm neonates who were born to mothers with normal pre-pregnancy body mass index (BMI). METHODS: Retrospective recordings of medical charts of 110 preterm infants born to overweight (n = 68) and obese (n = 42) mothers at gestational age (GA) 28-34 weeks, as well as 110 controls matched for GA and birth weight. All infants were born at the Sheba Medical Center between 2007 and 2014. Data regarding maternal pre-pregnancy weight and height were recorded, as well as maternal and neonatal complications and feeding methods. RESULTS: Obese mothers had more pregnancy-induced hypertension (52.4% versus 21.4%, p = 0.006) and caesarean section deliveries (81% versus 52.4%, p = 0.018). Overweight mothers had more gestational diabetes (20.6% versus 2.9%, p = 0.001). The study and control groups were similar on all neonatal outcome parameters. No differences between the groups were recorded throughout hospitalization with respect to Apgar score, respiratory distress and support, hypotension, cardiac manifestations, brain pathologies, infection, feeding type and total hospitalization days. CONCLUSIONS: Although the maternal complications are greater among obese and overweight women, it seems that preterm infants born to these women are not at increased risk for neonatal complications.

Development of a cost-effective system for digital off-line analysis of transrectal ultrasound.

BACKGROUND: Transrectal ultrasound (TRUS) is the most sensitive and accurate technique for preoperative staging and follow-up of rectal cancer. One of the most relevant problems of this technique is that the assessment of TRUS is possible only during real-time examination. Furthermore, interpretation of the ultrasound findings is difficult and requires long experience. We show the development of a new, cost-effective software solution for off-line examination and documentation of transrectal ultrasound. METHODS: The ultrasound device is connected to a frame-grabber card in a standard PC. Video capturing is done using a freeware software solution and various video codecs. The whole examination course is recorded. The examiner only has to concentrate on producing an artifact-free realization of the examination. RESULTS: The software solution offers a flexible review of each individual "frame" of the investigation on the personal computer, very similar to CT and MRI scans. Infiltration depth and lymph node status can be assessed at any time, independently of the investigation and the investigator. The picture quality is excellent even if a lossy codec is used. It is not necessary to do definitive assessment of the TRUS during the examination. CONCLUSIONS: This new technique gives a cost-effective possibility for high-quality off-line staging, re-examination, re-evaluation, and documentation of rectal cancer. TRUS becomes an examiner-independent objective examination technique for staging and follow-up of rectal cancer.

Risk factors and associated diseases among preterm infants with isolated lenticulostriate vasculopathy.

OBJECTIVE: To determine the prevalence, risk factors and diseases associated with isolated lenticulostriate vasculopathy (LSV) among preterm infants. STUDY DESIGN: Medical records of 84 preterm infants (gestational age (GA) 25 to 34 weeks) with isolated LSV in a case-control retrospective study over a period of 6.5 years were reviewed and compared with matched control infants. LSV was defined as 'early' if it was documented in head ultrasound (HUS) before or on the fifth day of life and 'late' if it was not present in the first HUS and recorded later during neonatal hospitalization. RESULTS: A 3.9% prevalence of LSV was recorded among preterm infants (GA⩽34 weeks). Study and control groups were similar for all maternal parameters, neonatal outcomes and length of hospitalization. Infants with late LSV had more neonatal complications than control infants and were born with younger GA and lower birth weight in comparison to infants with early LSV. More infants with late LSV needed mechanical ventilation, were diagnosed with bronchopulmonary dysplasia and were hospitalized longer in comparison to infants with early LSV. Urine cytomegalovirus was negative in the entire study group. CONCLUSIONS: No risk factors or specific associated morbidities were identified among preterm infants with early isolated LSV. Infants with late isolated LSV were younger and had overall increased associated morbidities. Long-term outcome studies are needed to determine LSV impact.

The use of short message services (SMS) to provide medical updating to parents in the NICU.

OBJECTIVE: Premature delivery and prolonged hospitalization of infants in the neonatal intensive care unit (NICU) are very stressful for parents. As technology has advanced, short message services (SMS) have been used increasingly in the medical disciplines. To date, the use of SMS for updating patients and families regarding medical information has not been reported. We implemented the SMS technique to daily update the parents regarding the health status of their preterm infant. The objective of this study was to evaluate the use of SMS technology and to assess its impact on the parents and the nursing staff. STUDY DESIGN: Parents and nurses completed questionnaires at two time periods: pre-SMS implementation (pre-SMSi) and post-SMS implementation (post-SMSi). The parent questionnaires included statements about medical information delivery, communication and trust between parents and medical staff, parental anxiety and overall satisfaction. The nurse questionnaires included statements about the expected and actual impact on their workload. RESULTS: Comparison of the parents' responses at the two time periods indicated that in the post-SMSi time period, they felt that the physician was more available when needed (P=0.002), they were more comfortable about approaching the physician (P=0.001) and more satisfied with the medical information provided by the staff (P=0.03). In the post-SMSi period, 78.1% of the nurses noted that the SMS communication is a convenient and user-friendly method. CONCLUSIONS: SMS updating is an easy and user-friendly technology that enriches the modalities of information delivery to parents of hospitalized preterm infants. It is a complementary and useful tool for encouraging and improving personal communication between parents and medical staff and should be considered part of quality improvement in health care.

The minimum detectable difference (MDD) and the interpretation of treatment-related effects of pesticides in experimental ecosystems.

In the European registration procedure for pesticides, microcosm and mesocosm studies are the highest aquatic experimental tier to assess their environmental effects. Evaluations of microcosm/mesocosm studies rely heavily on no observed effect concentrations (NOECs) calculated for different population-level endpoints. Ideally, a power analysis should be reported for the concentration-response relationships underlying these NOECs, as well as for measurement endpoints for which significant effects cannot be demonstrated. An indication of this statistical power can be provided a posteriori by calculated minimum detectable differences (MDDs). The MDD defines the difference between the means of a treatment and the control that must exist to detect a statistically significant effect. The aim of this paper is to expand on the Aquatic Guidance Document recently published by the European Food Safety Authority (EFSA) and to propose a procedure to report and evaluate NOECs and related MDDs in a harmonised way. In addition, decision schemes are provided on how MDDs can be used to assess the reliability of microcosm/mesocosm studies and for the derivation of effect classes used to derive regulatory acceptable concentrations. Furthermore, examples are presented to show how MDDs can be reduced by optimising experimental design and sampling techniques.

Modulation of swimming in the lamprey, Petromyzon marinus, by serotonergic and dopaminergic drugs.

The effects of serotonergic and dopaminergic drugs on free swimming behavior in adult sea lampreys (Petromyzon marinus) were investigated using video image analysis. Injections of the serotonin precursor 5-hydroxy-L-tryptophan along with the serotonin reuptake blocker clomipramine into the visceral cavity of lampreys resulted in significant increases in the cycle period of swimming, but had no significant effects on the propagation time of the swim waves down the body (normalized to cycle period), or on the degree of body curvature. Injections of the dopamine agonist apomorphine resulted in significant decreases of cycle period and body curvature with no significant effects on the normalized wave propagation time. The effects on cycle period are consistent with previous findings using serotonin and apomorphine on swimming activity in the isolated spinal cord.

[Janeway laparoscopic gastrostomy]. / Die laparoskopische Gastrostomie nach Janeway.

The percutaneous endoscopic gastrostomy is the procedure of first choice for the creation of a gastrostomy. If that is not possible a laparoscopic access should be preferred to a laparotomy. In tumor patients there seem to be some advantages of the laparoscopic Janeway gastrostomy compared to Kader-Stamm fistulas. We describe the technique and discuss the results of 5 patients without complications referring to current publications. In conclusion the Janeway gastrostomy is a good palliation because it is an effective, safe and simple method with easy handling, and little requirement for nursing care.

Neonatal isolated rectal bleeding and the risk of hypersensitivity syndromes.

OBJECTIVE: When rectal bleeding occurs in an otherwise asymptomatic child, it can be classified as isolated rectal bleeding (IRB). Among the different etiologies suggested for IRB, one of the most common is a hypersensitivity reaction of the bowel mucosa to digested antigens. The objective of this study was to assess the long-term outcomes and the risk of developing hypersensitivity syndromes among infants following an IRB event. STUDY DESIGN: A historical prospective comparative study was carried out. The study compared 77 infants who were born at the Sheba Medical Center in Israel during the period 2002 to 2009 and who experienced a neonatal IRB event to 77 infants with the same gestational age, but without IRB. Data were obtained from hospital records and from phone interviews with the parents regarding hypersensitivity syndrome between the ages of 3 and 10 years. RESULT: The IRB group was not at an increased risk of developing a hypersensitivity syndrome or gastrointestinal symptoms compared to the control group. Longer duration of breast-feeding was found to be related to a lower incidence of hypersensitivity symptoms. CONCLUSION: An IRB event in the neonatal period does not increase the risk of developing hypersensitivity syndromes or food allergies during childhood.

Maternal anti-D prophylaxis during pregnancy and risk of hemolysis among preterm infants.

OBJECTIVE: To evaluate whether Rh-positive preterm newborn infants born to Rh-negative mothers treated with prophylactic anti-D immunoglobulins exhibited signs of hemolytic reaction, including anemia and hyperbilirubinemia. STUDY DESIGN: Retrospective data were collected for 94 Rh-positive preterm newborns born at gestational age (GA) 28 to 34 weeks to 76 Rh-negative mothers and for matched controls. RESULT: We found 11.7% positive Coombs' tests among infants in the study group and slightly higher bilirubin levels at birth and on the following 3 days. No differences were recorded between the study and the control groups for hematocrit levels throughout hospitalization, maximal bilirubin level, phototherapy treatment or the need for blood transfusion. CONCLUSION: Among preterm Rh-positive newborn infants born to Rh-negative mothers, there appears to be no evidence of significant hemolytic reaction derived from placental anti-D transfer. Further prospective studies are needed to confirm these findings in order to support anti-D administration close to preterm birth.

Developmental hemostasis: primary hemostasis and evaluation of platelet function in neonates.

Hemostasis is a dynamic process and physiologic concentrations of coagulation proteins gradually increase with gestational age. Nevertheless, the risk for bleeding in term neonates is counterbalanced by the protective effects of physiologic deficiencies of the inhibitors of coagulation. Although laboratory diagnosis of coagulation disorders in infants may be difficult to establish, due to the need to adapt all assays for small amounts of blood and the age-related interpretation required for test results - evaluation of infants with secondary hemostatic defects is quite feasible, whereas laboratory assessment of primary hemostasis in neonates remains a challenge. While platelet number and volume are similar in neonates as compared to adult values, neonatal platelets certainly exhibit hyporesponsiveness. Analysis of platelet function may include aggregation studies or flow cytometry assays, using fluorescence-stained monoclonal antibodies against platelet membranes and cellular antigens. Data on platelet function in correlation with gestational age are scarce and the duration of platelet hyporeactivity and its clinical significance have not yet been completely elucidated. Whole-blood-based platelet function assays have shown in neonates as well as in premature infants progressive improvement of clot formation with gestational age. This article reviews platelet function, assessed by various techniques, and its development in the premature as well as healthy term neonate.

Enhancement of nasal and intestinal calcitonin delivery by the novel Pheroid fatty acid based delivery system, and by N-trimethyl chitosan chloride.

Therapeutic peptides are highly potent and specific in their functions, but difficulties in their administration require parallel development of viable delivery systems to improve their bioavailability. In this study the potential of a novel lipid-based colloidal delivery system for improving the absorption of nasally and intestinally administered salmon calcitonin (sCT) was investigated. Two types of delivery vehicles based on Pheroid technology was prepared and characterized. Liposome-like bilayer vesicles had a mean diameter of 1.0 microm and microsponges were 1.6 microm. Doses of 10 IU/kg and 500 IU/kg bodyweight sCT were administered intranasally and intestinally to rats, respectively. The obtained absorption enhancement with Pheroid vesicles and Pheroid microsponges were also compared with the absorption enhancement obtained with N-trimethyl chitosan chloride (TMC). With the inclusion of 0.5% (w/v) TMC the maximum plasma concentration (C(max)) of sCT increased from 72.6+/-6.1 pg/ml to 478.5+/-6.1 pg/ml after nasal administration. Pheroid vesicles and Pheroid microsponges increased the C(max) values of sCT to 262.64+/-17.1 pg/ml and 202.66+/-28.6 pg/ml, respectively. The time to reach the maximum concentration (T(max)) was also significantly decreased from 35 min to approximately 14 min. Intestinal administration of Pheroid formulations increased the C(max) of sCT from 249.1+/-21.5 pg/ml to 386.2+/-45.5 and 432.1+/-18.9 pg/ml, respectively for Pheroid vesicles and Pheroid microsponges. TMC increased the C(max) of sCT to 738.9+/-277.1 pg/ml. TMC and Pheroid technology could offer the potential to significantly improve intranasal and intestinal absorption of sCT and reduce the variability in absorption.