Severely increased albuminuria in patients with type 2 diabetes mellitus is associated with increased subclinical atherosclerosis in femoral arteries with Na [18F]F activity as a proxy - The DETERMINE study.

BACKGROUND AND AIMS: Sodium [18F]fluoride (Na [18F]F) positron emission tomography imaging allows detailed visualization of early arterial micro-calcifications. This study aims to investigate atherosclerosis manifested by micro-calcification, macro-calcification, and aortic stiffness in patients with type 2 diabetes mellitus (T2DM) with and without albuminuria and severely decreased kidney function. METHODS: A cohort was stratified in four groups (N = 10 per group), based on KDIGO categories (G1-5 A1-3). G1-2A1 non-diabetic controls (median [IQR] estimated glomerular filtration rate (eGFR) in mL/min/1.73 m2 91 [81-104]), G1-2A1 with T2DM (eGFR 87 [84-93], and albumin-creatinin-ratio (ACR) in mg/mmol 0.35 [0.25-0.75]), G1-2A3 with T2DM (eGFR 85 [60-103], and ACR 74 [62-122], and G4A3 with T2DM (eGFR 19 [13-27] and ACR 131 [59-304]). RESULTS: Na [18F]F femoral artery grading score differed significantly in the groups with the highest Na [18F]F activity in A3 groups with T2DM (G1-2A3 with T2DM 228 [100-446] and G4A3 with T2DM 198 [113-578]) from the lowest groups of the G1-2A1 with T2DM (33 [0-93]) and in G1-2A1 non-diabetic controls (75 [0-200], p = 0.001). Aortic Na [18F]F activity and femoral artery computed tomography (CT)-assessed macro-calcification was increased in G4A3 with T2DM compared with G1-2A1 with T2DM (47.5 [33.8-73.8] vs. 17.5 [8.8-27.5] (p = 0.006) and 291 [170-511] vs. 12.2 [1.41-44.3] mg (p = 0.032), respectively). Carotid-femoral pulse wave velocity (PWV)-assessed aortic stiffness was significantly higher in both A3 groups with T2DM compared with G1-2A1 with T2DM (11.15 and 12.35 vs. 8.86 m/s, respectively (p = 0.009)). CONCLUSIONS: This study indicates that the presence of severely increased albuminuria in patients with T2DM is cross-sectionally associated with subclinical arterial disease in terms of micro-calcification and aortic stiffness. Additional decrease in kidney function was associated with advanced macro-calcifications.

Radiological Screening Methods in Deceased Organ Donation: An Overview of Guidelines Worldwide.

Organ transplantation is performed worldwide, but policies regarding donor imaging are not uniform. An overview of the policies in different regions is missing. This study aims to investigate the various protocols worldwide on imaging in deceased organ donation. An online survey was created to determine the current policies. Competent authorities were approached to fill out the survey based on their current protocols. In total 32 of the 48 countries approached filled out the questionnaire (response rate 67%). In 16% of the countries no abdominal imaging is required prior to procurement. In 50%, abdominal ultrasound (US) is performed to screen the abdomen and in 19% an enhanced abdominal Computed Tomography (CT). In 15% of the countries both an unenhanced abdominal CT scan and abdominal US are performed. In 38% of the countries a chest radiographic (CXR) is performed to screen the thorax, in 28% only a chest CT, and in 34% both are performed. Policies regarding radiologic screening in deceased organ donors show a great variation between different countries. Consensus on which imaging method should be applied is missing. A uniform approach will contribute to quality and safety, justifying (inter)national exchange of organs.

Fasting before living-kidney donation: effect on donor well-being and postoperative recovery: study protocol of a multicenter randomized controlled trial.

BACKGROUND: One of the main effectors on the quality of life of living-kidney donors is postoperative fatigue. Caloric restriction (CR) and short-term fasting (STF) are associated with improved fitness and increased resistance to acute stress. CR/STF increases the expression of cytoprotective genes, increases immunomodulation via increased anti-inflammatory cytokine production, and decreases the expression of pro-inflammatory markers. As such, nutritional preconditioning by CR or STF represents a non-invasive and cost-effective method that could mitigate the effects of acute surgery-induced stress and postoperative fatigue. To investigate whether preoperative STF contributes to a reduction in fatigue after living-kidney donation, a randomized clinical trial is indicated. METHODS: We aim to determine whether 2.5 days of fasting reduces postoperative fatigue score in subjects undergoing living-kidney donation. In this randomized study, the intervention group will follow a preoperative fasting regime for 2.5 days with a low-dose laxative, while the control group will receive standard care. The main study endpoint is postoperative fatigue, 4 weeks after living-kidney donation. Secondary endpoints include the effect of preoperative fasting on postoperative hospital admission time, the feasibility of STF, and the postoperative recovery of donor and recipient kidney function. This study will provide us with knowledge of the feasibility of STF and confirm its effect on postoperative recovery. DISCUSSION: Our study will provide clinically relevant information on the merits of caloric restriction for living-kidney donors and recipients. We expect to reduce the postoperative fatigue in living-kidney donors and improve the postoperative recovery of living-kidney recipients. It will provide evidence on the clinical merits and potential caveats of preoperative dietary interventions. TRIAL REGISTRATION: Netherlands Trial Register NL9262 . EudraCT 2020-005445-16 . MEC Erasmus MC MEC-2020-0778. CCMO NL74623.078.21.

[18F]FDG and [18F]NaF as PET markers of systemic atherosclerosis progression: A longitudinal descriptive imaging study in patients with type 2 diabetes mellitus.

BACKGROUND: While [18F]-fluordeoxyglucose ([18F]FDG) uptake is associated with arterial inflammation, [18F]-sodium fluoride ([18F]NaF) is a marker for arterial micro-calcification. We aimed to investigate the prospective correlation between both PET markers over time and whether they are prospectively ([18F]FDG) and retrospectively ([18F]NaF) related to progression of systemic arterial disease in a longitudinal study in patients with type 2 diabetes mellitus (T2DM). METHODS: Baseline [18F]FDG PET/Low Dose (LD) Computed Tomography (CT) scans of ten patients with early T2DM without cardiovascular history (70% men, median age 63 years) were compared with five-year follow-up [18F]NaF/LDCT scans. Systemic activity was expressed as mean target-to-background ratio (meanTBR) by dividing the maximal standardized uptake value (SUVmax) of ten arteries by SUVmean of the caval vein. CT-assessed macro-calcifications were scored visually and expressed as calcified plaque (CP) score. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (PWV). Five-year changes were expressed absolutely with delta (Δ) and relatively with %change. RESULTS: Baseline meanTBR[18F]FDG was strongly correlated with five-year follow-up meanTBR[18F]NaF (r = 0.709, P = .022). meanTBR[18F]NaF correlated positively with ΔCPscore, CPscore at baseline, and follow-up (r = 0.845, P = .002 and r = 0.855, P = .002, respectively), but not with %change in CPscore and PWV. CONCLUSION: This proof-of-concept study demonstrated that systemic arterial inflammation is an important pathogenetic factor in systemic arterial micro-calcification development.

Pancreas Transplantation from Donors after Circulatory Death: an Irrational Reluctance?

PURPOSE OF REVIEW: Beta-cell replacement is the best therapeutic option for patients with type 1 diabetes. Because of donor scarcity, more extended criteria donors are used for transplantation. Donation after circulatory death donors (DCD) are not commonly used for pancreas transplantation, because of the supposed higher risk of complications. This review gives an overview on the pathophysiology, risk factors, and outcome in DCD transplantation and discusses different preservation methods. RECENT FINDINGS: Studies on outcomes of DCD pancreata show similar results compared with those of donation after brain death (DBD), when accumulation of other risk factors is avoided. Hypothermic machine perfusion is shown to be a safe method to improve graft viability in experimental settings. DCD should not be the sole reason to decline a pancreas for transplantation. Adequate donor selection and improved preservation techniques can lead to enhanced pancreas utilization and outcome.

Inguinal microbiome in patients undergoing an endovascular aneurysm repair: Application of next-generation sequencing of the 16S-23S rRNA regions.

BACKGROUND: Surgical site infection (SSI) remains a hazardous complication after vascular surgery. In this pilot study we investigated the inguinal microbiome in skin biopsies using histology and 16S-23S rDNA Next Generation Sequencing (NGS). Our hypothesis was that causative microorganisms of SSI are present in the inguinal microbiome. METHODS: Data on surgical site infections and skin samples from the Percutaneous in Endovascular Repair versus Open (PiERO) trail were evaluated. Two patients with SSI were matched for age and comorbidity to eight matching patients of the PiERO trial. All patients were treated for an abdominal aortic aneurysm with endovascular repair. Nasal and perineal cultures were taken preoperatively to detect Staphylococcus aureus carriage. After disinfection with chlorhexidine, groin biopsies were taken to identify bacteria in deeper skin layers. All samples were subjected to histological analysis and culture-free 16S-23S rDNA NGS. RESULTS: Staphylococcus aureus species were cultured in 5 out of 20 preoperative nasal and perineal swaps. Histology detected only a few bacteria. NGS of the 16S-23S rRNA regions identified DNA of bacterial species in all biopsies (20/20). Most identified genera and species proved to be known skin flora bacteria. No relation was found between SSIs and the preoperative microbiome. CONCLUSION: In this pilot study, an innovative analysis of the preoperative microbiome using 16S-23S rDNA NGS did not show a relation with the occurrence of a surgical site infection. No pathogenic bacterial species were present in the inguinal skin after disinfection with chlorhexidine.

Chronic pain after hand-assisted laparoscopic donor nephrectomy.

BACKGROUND: Data on chronic pain after kidney donation are sparse. The aim of this study was to assess the incidence of chronic pain after hand-assisted laparoscopic nephrectomy. METHODS: Living kidney donors who donated between 2011 and 2017 at the University Medical Centre Groningen were included. All patients underwent hand-assisted laparoscopic donor nephrectomy. Postdonation pain and movement disabilities were assessed using the Carolinas Comfort Scale (CCS) and a visual analogue scale (VAS). The prevalence, severity of pain and the need for analgesics were reported. RESULTS: Some 333 living kidney donors with a mean age of 56 years were included. At a median of 19 (i.q.r. 10-33) months after donation, 82 donors (24·6 per cent) had a CCS score above 0, of which 58 (71 per cent) had a CCS score of at least 2 and 57 (70 per cent) reported movement limitations. Some 110 donors (33·0 per cent) had a VAS score of more than 0. Complaints mainly occurred during bending over (12·3 per cent) and exercising (12·4 per cent). Thirty-two donors (9·7 per cent) required analgesics during follow-up between donation and the time of measurement, and six of 82 (7 per cent) reported chronic inguinal pain. In multivariable analysis, donor age (odds ratio (OR) 0·97, 95 per cent c.i. 0·95 to 0·99; P = 0·020) and length of hospital stay (OR 1·21, 1·01 to 1·51; P = 0·041) were independently associated with chronic pain. CONCLUSION: One-quarter of donors experienced chronic postdonation pain or discomfort, most of which was bothersome. Younger donors and those with a longer postoperative hospital stay had more symptoms.

Parathyroidectomy versus cinacalcet for tertiary hyperparathyroidism; a retrospective analysis.

INTRODUCTION: Tertiary hyperparathyroidism (tHPT), i.e., persistent HPT after kidney transplantation, affects 17-50% of transplant recipients. Treatment of tHPT is mandatory since persistently elevated PTH concentrations after KTx increase the risk of renal allograft dysfunction and osteoporosis. The introduction of cinacalcet in 2004 seemed to offer a medical treatment alternative to parathyroidectomy (PTx). However, the optimal management of tHPT remains unclear. METHODS: A retrospective analysis was performed on patients receiving a kidney transplantation (KT) in two academic centers in the Netherlands. Thirty patients undergoing PTx within 3 years of transplantation and 64 patients treated with cinacalcet 1 year after transplantation for tHPT were included. Primary outcomes were serum calcium and PTH concentrations 1 year after KT and after PTx. RESULTS: Serum calcium normalized in both the cinacalcet and the PTx patients. PTH concentrations remained above the upper limit of normal (median 22.0 pmol/L) 1 year after KT, but returned to within the normal range in the PTx group (median 3.7 pmol/L). Side effects of cinacalcet were difficult to assess; minor complications occurred in three patients. Re-exploration due to persistent tHPT was performed in three (10%) patients. CONCLUSION: In patients with tHPT, cinacalcet normalizes serum calcium, but does not lead to a normalization of serum PTH concentrations. In contrast, PTx leads to a normalization of both serum calcium and PTH concentrations. These findings suggest that PTx is the treatment of choice for tHPT.

18F-sodium fluoride positron emission tomography assessed microcalcifications in culprit and non-culprit human carotid plaques.

BACKGROUND: 18F-NaF positron emission tomography (PET) targets microcalcifications. We compared in vitro microPET assessed 18F-NaF uptake between culprit and non-culprit human carotid plaques. Furthermore, we compared 18F-NaF uptake with calcification visualized on microcomputed tomography (microCT). METHODS: Carotid plaques from stroke patients undergoing surgery were incubated in 18F-NaF and scanned using a microPET and a microCT scan. The average PET assessed 18F-NaF uptake was expressed as percentage of the incubation dose per gram (%Inc/g). 18F-NaF PET volume of interest (VOI) was compared with CT calcification VOI. RESULTS: 23 carotid plaques (17 culprit, 6 non-culprit) were included. The average 18F-NaF uptake in culprit carotid plaques was comparable with the uptake in non-culprit carotid plaques (median 2.32 %Inc/g [IQR 1.98 to 2.81] vs. median 2.35 %Inc/g [IQR 1.77 to 3.00], P = 0.916). Only a median of 10% (IQR 4 to 25) of CT calcification VOI showed increased 18F-NaF uptake, while merely a median of 35% (IQR 6 to 42) of 18F-NaF PET VOI showed calcification on CT. CONCLUSIONS: 18F-NaF PET represents a different stage in the calcification process than CT. We observed a similar PET assessed 18F-NaF uptake and pattern in culprit and non-culprit plaques of high-risk patients, indicating that this method may be of more value in early atherosclerotic stenosis development.

Renal scintigraphy for post-transplant monitoring after kidney transplantation.

BACKGROUND: Clinicians use several diagnostic modalities to recognize post-transplant complications, such as acute tubular necrosis, acute rejection, urologic and vascular complications. Currently, there is no consensus about the best procedural approach to evaluate post-transplant renal dysfunction. Renal needle-biopsy is often required, however, this is invasive and may lead to sample errors and complications, and most clinicians prefer using one of the noninvasive diagnostic modalities. METHODS: A systematic literature search was performed using PubMed, EMBASE, the Cochrane Library, MEDLINE (OvidSP), Web of Science, and Google Scholar to identify relevant articles. This review provides a literature overview of the technical aspects, new developments and clinical value of renal scintigraphy (RS), after kidney transplantation. Additionally, the advantages and limitations of RS in comparison to other diagnostic modalities are addressed. The study protocol is registered with PROSPERO, protocol number CRD42017078391. RESULTS: A total of 32 studies were included. Studies were categorized in the following groups: tracer pharmacokinetics; acute rejection and acute tubular necrosis; vascular complications; urological complications; postoperative fluid collections; early transplant outcomes; one-year transplant outcomes. CONCLUSIONS: Several studies have described the use of RS for the diagnosis of acute rejection, however, differentiating between rejection and acute tubular necrosis remains difficult. For the diagnosis of vascular complications, RS has been described as an alternative for invasive procedures. For urologic complications, studies support the use of RS in combination with routine ultrasonography (US) surveillance. For the diagnosis of postoperative fluid collections, RS provides information to differentiate lymphoceles and urinomas. Altogether, RS should be considered in case of non-acute complications, and if US provides insufficient results.

Editor's Choice - Arteriotomy Closure Devices in EVAR, TEVAR, and TAVR: A Systematic Review and Meta-analysis of Randomised Clinical Trials and Cohort Studies.

OBJECTIVES: Cardiac and vascular surgery benefit from percutaneous interventions. Arteriotomy closure devices (ACDs) enable minimally invasive access to the common femoral artery (CFA). The objective of this review was to assess the differences between ACDs and surgical cut down (SCD) of the CFA regarding the number of complications, duration of surgery (DOS), and hospital length of stay (HLOS). DESIGN: A systematic literature search with predefined search terms was performed using MEDLINE, Embase, and the Cochrane Library (2000-2016). All studies reporting on ACD and SCD for a puncture of the CFA of at least 12 French (Fr.) were assessed for eligibility. METHODS: Included were randomised controlled trials and cohort studies comparing both techniques. Patient characteristics, exclusion criteria, and conversion rates were evaluated. Complications, DOS, and HLOS were compared. MATERIALS: A total of 17 studies were included for meta-analysis, describing 7889 vascular access sites; four studies were randomised trials, two studies reported from a prospective database, and 11 studies reported retrospective cohorts. RESULTS: ACD was associated with fewer post-operative seromas (odds ratio [OR] 0.15, 95% confidence interval [CI] 0.06-0.35), less wound dehiscence (OR 0.14, 95% CI 0.03-0.78), and fewer surgical site infections (OR 0.38, 95% CI 0.23-0.63). Post-operative pseudoaneurysms were significantly more common in the ACD group (OR 3.83, 95% CI 1.55-9.44). In five of 17 studies, DOS and HLOS were not reduced in the ACD group. When all studies reporting a mean DOS and/or HLOS were compared in a non-parametric analysis, neither was significantly different. CONCLUSION: This meta-analysis favours ACD regarding the number of wound complications compared with SCD in endovascular aneurysm repair, thoracic endovascular aneurysm repair, and transcatheter aortic valve repair. Treatment duration (DOS and HLOS) was not reduced in ACD. The differences are of limited clinical significance and with this equivocal quality of evidence, the ACD may be considered safe for CFA access in suitable patients.

Mesenteric ischemia after abdominal aortic aneurysm repair: a systemic review.

Mesenteric ischemia after abdominal aneurysm repair is a devastating complication with mortality rates up to 70%. Incidence however is relatively low. The aim of this review was to provide an overview on current insights, diagnostic modalities and on mesenteric ischemia after abdominal aortic aneurysm repair.

Excellent prognosis of node negative patients after sentinel node procedure in colon carcinoma: a 5-year follow-up study.

AIM: Investigate the prognostic impact and clinical relevance of the sentinel node (SN)-procedure in colon carcinoma. PATIENTS AND METHODS: Between May 2002 and January 2004, the SN-procedure was performed in 55 patients that underwent elective resection for clinically non-advanced colon carcinoma. A control group of 110 patients was identified from a cohort between January 2000 and April 2002. All lymph nodes were analysed by conventional haematoxylin-eosin staining. All negative SNs underwent in-depth analysis using immunohistochemical-staining and automated microscopy with the Ariol-system. Patients with positive lymph nodes were offered adjuvant chemotherapy. All patients were routinely monitored at 6-month intervals and follow-up was more than 5 years. RESULTS: The SN was successfully identified in 98% of the patients, with 94% sensitivity. In-depth analysis with immunohistochemistry and automated microscopy (Ariol-system) upstaged 3 and 4 patients respectively. When only node-negative patients were analysed, overall 5-year-survival was significantly better in the SN group (91% vs. 76%, p = 0.04). Cancer-specific-mortality was even 0% (vs. 8%, p = 0.08). Disease-free-survival was significantly improved to 96% (vs. 77%, p < 0.01). CONCLUSIONS: This study describes the prognostic impact of the SN-procedure in colon carcinoma after 5-year-follow-up. Only one patient had recurrent disease after a negative SN procedure (disease-free-survival 96%). These results indicate that the SN-procedure is of prognostic relevance and might be useful to select patients for adjuvant chemotherapy. Patients that are lymph node negative after an SN-procedure have an excellent prognosis and do not need adjuvant treatment.

New insights in (acute) endovascular abdominal aneurysm repair: when fenestrated devices fall short.

The suitability for endovascular aneurysm repair (EVAR) is determined primarily by abdominal aortic aneurysm (AAA) anatomy. For patients unsuitable for standard EVAR, due to proximal neck anatomy, fenestrated aortic stent-grafting (FEVAR) is a viable alternative to open repair surgery. Initially FEVAR stent-grafts were custom-made to fit the unique anatomical characteristics of each treated individual. This customization leads to production delays therefore excluding acute aneurysms from endovascular treatment. For patients in need for more urgent treatment, several alternatives have currently been developed. The aim of this review is to provide an overview on current developments and results in acute endovascular abdominal aortic aneurysm repair.

Standardised frailty indicator as predictor for postoperative delirium after vascular surgery: a prospective cohort study.

OBJECTIVES: To determine whether the Groningen Frailty Indicator (GFI) has a positive predictive value for postoperative delirium (POD) after vascular surgery. METHODS: Between March and August 2010, 142 consecutive vascular surgery patients were prospectively evaluated. Preoperatively, the GFI was obtained and postoperatively patients were screened with the Delirium Observation Scale (DOS). Patients with a DOS-score ≥3 points were assessed by a geriatrician. Delirium was defined by the DSM-IV-TR criteria. Primary outcome variable was the incidence of POD. Secondary outcome variables were any surgical complication and hospital length of stay (HLOS) (>7 days). RESULTS: Ten patients (7%) developed POD. The highest incidence of POD was found after aortic surgery (17%) and amputation procedures (40%). Increased comorbidities (p = 0.006), GFI score (p = 0.03), renal insufficiency (p = 0.04), elevated C-reactive protein (p = 0.008), high American Society of Anaesthesiologists score (p = 0.05), a DOS-score of ≥3 points (p = 0.001), post-operative intensive care unit admittance (p = 0.01) and HLOS ≥7 days (p = 0.005) were risk factors for POD. The GFI score was not associated with a prolonged HLOS. A mean number of 2 ± 1 (range 0-5) complications were registered. The receiver operator characteristics (ROC) area under the curve for the GFI was 0.70. CONCLUSIONS: The GFI can be helpful in the early identification of POD after vascular surgery in a select group of high-risk patients.

The "bathroom game": a systematic program for the elimination of encopretic behavior.

The present investigation utilized a unique, variable ratio schedule of reinforcement (the "bathroom game") to treat a 10-year-old encopretic male. Dependent measures included confirmed incidents of (a) soiling and (b) appropriate bowel movements monitored across an ABAB design (Baseline 1, "Bathroom Game 1", Baseline 2, "Bathroom Game 2") with one-year follow-up. During "bathroom game" conditions, contingent monetary rewards were provided for non-instances of soiling and appropriate bowel movements. Such rewards were progressively and systematically leaned-out over the course of treatment on a pre-determined variable ratio schedule. Results indicated a clear demonstration of functional control and clinically significant treatment effects during both experimental periods. These findings are discussed with regard to the positive features of the "bathroom game" procedure and recommendations are made for future investigations in the area.

Peer training of safety-related skills to institutional staff: benefits for trainers and trainees.

A peer training program, in which experienced staff trained new staff, was evaluated as a method for teaching and maintaining safety-related caregiver skills in an institutional setting for the developmentally disabled. Three sets of safety-type skills were assessed in simulated emergency situations: responding to facility fires, managing aggressive attacks by residents, and assisting residents during convulsive seizures. Using a multiple-baseline research design, results indicated that the peer training program was an effective method of training the three types of emergency skills to new direct care staff. The program also appeared effective in improving the skills of the peer trainers. Perhaps most importantly, results indicated that if experienced staff functioned as peer trainers for particular emergency skills, then their proficiency in those skills maintained over time whereas their proficiency declined in emergency skills for which they did not act as peer trainers. Social validity information collected from available staff 23 months after the program was completed supported the utility of the training in terms of staff responses during actual emergencies. Also, acceptability measures indicated that staff liked participating in the program. However, some inconsistencies between staff verbal reports and performance-based measures of acceptability were noted. Results are discussed regarding the overall effectiveness of the peer training program, the importance of maintenance strategies for safety-related skills, and the need for multidimensional analyses of staff acceptability in staff training/management research.

A program for increasing manual signing by autistic and profoundly retarded youth within the daily environment.

A program was implemented to increase the manual signing of five profoundly retarded and four autistic youth within their daily environment. Each participant was nonvocal or minimally vocal. The program was based on modified incidental teaching strategies and was implemented by direct care personnel under supervision in an institutional setting. Specific components included rearranging the physical environment to prompt signing, altering routine staff-resident interactions to prompt, manually guide and/or reinforce signing; and conducting mini-training sessions. Additionally, staff modeled signs intermittently throughout the day. The program was sequentially implemented during two staff work shifts on each of two resident living modules. Observations conducted at four separate time periods during the day indicated that significant increases in signing occurred for all participating youth and that the increases generally maintained during follow-up checks at 5 and 17 weeks. Differential effects of the increased signing on frequency of vocalizations were noted across residents. A staff acceptability survey indicated favorable staff reports on the usefulness of signing to communicate with the youth. Results are discussed regarding the significance of manual signing for seriously developmentally disabled persons and the importance of ensuring that signing skills are used in the daily environment and not exclusively in formal training sessions. Also, areas for continued research are noted in terms of more refined analyses of client skills and subsequent progress in manual communication programs.