The relationship between clinical presentation and the nature of care in adults with intellectual disability and epilepsy - national comparative cohort study.

BACKGROUND: A quarter of People with Intellectual Disabilities (PwID) have epilepsy compared with 1% of the general population. Epilepsy in PwID is a bellwether for premature mortality, multimorbidity and polypharmacy. This group depends on their care provider to give relevant information for management, especially epilepsy. There is no research on care status relationship and clinical characteristics of PwID and epilepsy. AIM: Explore and compare the clinical characteristics of PwID with epilepsy across different care settings. METHOD: A retrospective multicentre cohort study across England and Wales collected information on seizure characteristics, intellectual disability severity, neurodevelopmental/biological/psychiatric comorbidities, medication including psychotropics/anti-seizure medication, and care status. Clinical characteristics were compared across different care settings, and those aged over and younger than 40 years. RESULTS: Of 618 adult PwID across six centres (male:female = 61%:39%), 338 (55%) received professional care whereas 258 (42%) lived with family. Significant differences between the care groups existed in intellectual disability severity (P = 0.01), autism presence (P < 0.001), challenging behaviour (P < 0.001) and comorbid physical conditions (P = 0.008). The two groups did not vary in intellectual disability severity/genetic conditions/seizure type and frequency/psychiatric disorders. The professional care cohort experienced increased polypharmacy (P < 0.001) and antipsychotic/psychotropic use (P < 0.001/P = 0.008).The over-40s cohort had lower autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) comorbidity (P < 0.001/P = 0.007), increased psychiatric comorbidity and challenging behaviour (P < 0.05), physical multimorbidity (P < 0.001), polypharmacy (P < 0.001) and antipsychotic use (P < 0.001) but reduced numbers of seizures (P = 0.007). CONCLUSION: PwID and epilepsy over 40 years in professional care have more complex clinical characteristics, increased polypharmacy and antipsychotic prescribing but fewer seizures.

Chronic constipation in people with intellectual disabilities in the community: cross-sectional study.

BACKGROUND: One-third to half of people with intellectual disabilities suffer from chronic constipation (defined as two or fewer bowel movements weekly or taking regular laxatives three or more times weekly), a cause of significant morbidity and premature mortality. Research on risk factors associated with constipation is limited. AIMS: To enumerate risk factors associated with constipation in this population. METHOD: A questionnaire was developed on possible risk factors for constipation. The questionnaire was sent to carers of people with intellectual disabilities on the case-loads of four specialist intellectual disability services in England. Data analysis focused on descriptively summarising responses and comparing those reported with and without constipation. RESULTS: Of the 181 people with intellectual disabilities whose carers returned the questionnaire, 42% reported chronic constipation. Constipation was significantly associated with more severe intellectual disability, dysphagia, cerebral palsy, poor mobility, polypharmacy including antipsychotics and antiseizure medication, and the need for greater toileting support. There were no associations with age or gender. CONCLUSIONS: People with intellectual disabilities may be more vulnerable to chronic constipation if they are more severely intellectually disabled. The associations of constipation with dysphagia, cerebral palsy, poor mobility and the need for greater toileting support suggests people with intellectual disabilities with significant physical disabilities are more at risk. People with the above disabilities need closer monitoring of their bowel health. Reducing medication to the minimum necessary may reduce the risk of constipation and is a modifiable risk factor that it is important to monitor. By screening patients using the constipation questionnaire, individualised bowel care plans could be implemented.

Comparison of coagulation parameters associated with fibrinogen concentrate and cryoprecipitate for treatment of bleeding in patients undergoing cytoreductive surgery for pseudomyxoma peritonei: Subanalysis from a randomized, controlled phase 2 study.

Background and Aims: The FORMA-05 study compared the efficacy and safety of human fibrinogen concentrate (HFC) versus cryoprecipitate for hemostasis in bleeding patients undergoing cytoreductive surgery for pseudomyxoma peritonei (PMP). This subanalysis explores coagulation parameters in the FORMA-05 patients, with a focus on the seven patients who developed thromboembolic events (TEEs). Methods: FORMA-05 was a prospective, randomized, controlled phase 2 study in which patients with predicted blood loss ≥2 L received HFC (4 g) or cryoprecipitate (two pools of five units), repeated as needed. Plasma fibrinogen, platelet count, factor (F) XIII, FVIII, von Willebrand Factor (VWF) antigen and ristocetin cofactor activity levels, EXTEM A20, FIBTEM A20, and endogenous thrombin potential (ETP) were measured perioperatively. Results: Fibrinogen, platelet count, EXTEM and FIBTEM A20, FXIII, FVIII, VWF levels, and ETP were maintained throughout surgery in both the HFC group (N = 21) and the cryoprecipitate group (N = 23). Seven TEEs were observed in the cryoprecipitate group. The two patients developing deep vein thromboses (DVT) appeared to have a procoagulant status preoperatively, with distinctively higher fibrinogen level, FIBTEM A20, and platelet levels, all of which persisted perioperatively. The five patients developing pulmonary embolism (PE) had slightly higher VWF levels preoperatively, with a disproportionate increase intraoperatively (postcryoprecipitate administration) and postoperatively. Conclusions: Patients treated with HFC versus cryoprecipitate showed broad overlaps in coagulation parameters. Patients with PE experienced a disproportionate VWF rise following cryoprecipitate administration, whereas patients developing DVT displayed a procoagulant status before and following surgery. Preoperative testing may allow these patients to be identified.

Peri-operative thrombophilia in patients undergoing liver resection for colorectal metastases.

BACKGROUND: Routine chemical venous thromboembolism (VTE) prophylaxis for liver surgery remains controversial, and often delayed post-operatively due to perceived bleeding risk. This study asked whether patients undergoing hepatectomy for colorectal metastases (CRM) were at risk from VTE pre-operatively, and the impact of hepatectomy on that risk. METHODS: Single-centre prospective observational cohort study of patients undergoing open hepatectomy for CRM, comparing pre-, peri- and post-operative haemostatic variables. RESULTS: Of 336 hepatectomies performed October 2017-December 2019, 60 resections in 57 patients were recruited. There were 28 (46.7%) major resections, with median (interquartile range [IQR]) blood loss 150.0 (76.3-263.7) mls, no blood transfusions, post-operative VTE events or deaths. Patients were prothrombotic pre-operatively (high median factor VIIIC and increased thrombin generation velocity index), an effect exacerbated post-hepatectomy. Major hepatectomies had a significantly greater median drop in Protein C, rise in Factor VIIIC and von Willebrand Factor, versus minor resections (p = 0.001, 0.005, 0.001 respectively). Patients with parenchymal transection times greater than median (40 min), had significantly increased median (IQR) PMBC-TFmRNA expression [1.65(0.93-2.70)2ddCt], versus quicker transections [0.99(0.69-1.28)2ddCt, p = 0.020]. CONCLUSIONS: Patients with CRM are prothrombotic pre-operatively, an effect exacerbated by hepatectomy, particularly longer, complex resections, suggesting chemical thromboprophylaxis be considered early in the patient pathway.

Efficacy of fibrinogen concentrate in major abdominal surgery - A prospective, randomized, controlled study in cytoreductive surgery for pseudomyxoma peritonei.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei (PMP) is associated with excessive bleeding and acquired fibrinogen deficiency. Maintaining plasma fibrinogen may support hemostasis. OBJECTIVES: To compare hemostatic efficacy and safety of human fibrinogen concentrate (HFC) vs cryoprecipitate as fibrinogen sources for bleeding patients with acquired fibrinogen deficiency undergoing PMP CRS. METHODS: FORMA-05 was an off-label single-center, prospective, randomized, controlled phase 2 study. Patients undergoing PMP surgery with predicted intraoperative blood loss ≥2 L received human fibrinogen concentrate (HFC; 4 g) or cryoprecipitate (two pools of 5 units, containing approximately 4.0-4.6 g fibrinogen), repeated as needed. The primary endpoint was a composite of intraoperative and postoperative efficacy, graded using objective 4-point scales and adjudicated by an independent committee. RESULTS: One hundred percent of patients receiving HFC (95% confidence interval: 83.9-100.0, n = 21) or cryoprecipitate (84.6-100.0, n = 22) achieved hemostatic success. HFC demonstrated noninferior efficacy (P = .0095; post hoc) and arrived in the operating room 46 minutes faster. There were significantly greater mean increases with HFC vs cryoprecipitate in plasma fibrinogen (0.78 vs 0.35 g/L; P < .0001) and FIBTEM A20 (3.33 vs 0.93 mm; P = .003). Factor XIII, factor VIII, and von Willebrand factor activity were maintained throughout surgery. Only red blood cells were transfused intraoperatively (median units: HFC group, 1.0; cryoprecipitate group, 0.5). Thromboembolic events were detected with cryoprecipitate only. Safety was otherwise comparable between groups. CONCLUSIONS: Human fibrinogen concentrate was hemostatically efficacious in patients undergoing major abdominal PMP surgery, with a favorable safety profile. These results are relevant to other surgical settings where bleeding and acquired fibrinogen deficiency occur.

Identifying Needs-Based Groupings Among People Accessing Intellectual Disability Services.

There is increasing emphasis on needs-led service provision for people with intellectual disability (ID). This study outlines the statistical cluster analysis of clinical data from 1,692 individuals accessing secondary care ID services in the United Kingdom (U.K.) Using objective needs assessment data from a newly developed ID assessment tool, six clusters were identified. These had clinical face validity and were validated using six concurrently (but independently) rated tools. In keeping with previous studies, the clusters varied in terms of overall level of need as well as specific clinical features (autism spectrum disorder, mental health problems, challenging behaviors and physical health conditions). More work is now needed to further develop these clusters and explore their utility for planning, commissioning and optimizing needs-led services.

Alemtuzumab therapy in T-cell prolymphocytic leukemia: comparing efficacy in a series treated intravenously and a study piloting the subcutaneous route.

Intravenous alemtuzumab is an effective and well-tolerated treatment for T-cell prolymphocytic leukemia (T-PLL). Alemtuzumab given intravenously as first-line treatment in 32 patients resulted in an overall response rate of 91% with 81% complete responses. Studies in B-cell chronic lymphocytic leukemia have shown subcutaneous alemtuzumab to be equally as effective as intravenous alemtuzumab. The UKCLL05 pilot study examined the efficacy and toxicity of this more convenient method of administration in 9 previously untreated patients with T-PLL. Only 3 of 9 patients (33%) responded to treatment. Furthermore, 2 of 9 patients (22%) died while on treatment. Recruitment was terminated because of these poor results. After rescue therapy with intravenous alemtuzumab and/or pentostatin, median progression-free survival and overall survival were similar to the intravenous group. Alemtuzumab delivered intravenously, but not subcutaneously, remains the treatment of choice for previously untreated T-PLL.

Pseudo-Gaucher cells in multiple myeloma.

A case of multiple myeloma is reported in which the bone marrow contained sheets of histiocytes with light microscopic features mimicking Gaucher cells. The patient had no clinical evidence of inherited Gaucher's disease. These pseudo-Gaucher cells obscured neoplastic plasma cells causing diagnostic difficulty.

Quality of evaluation and management of children requiring timely orthopaedic surgery before admission to a tertiary pediatric facility.

The purpose of this study was to investigate the quality of evaluation and management of children requiring timely orthopaedic surgery before admission to a tertiary pediatric facility. A retrospective chart review was performed on 372 consecutive children who underwent orthopaedic surgery for a diagnosis of fracture, infection, slipped capital femoral epiphysis (SCFE), or compartment syndrome during a 22-month period at the authors' facility. Of the 372 children, 142 children (38%) first received medical care elsewhere; these are the subjects of this study. Before being seen at the authors' institution, 27 children (19%) had a problem in treatment or diagnosis and 18 (13%) had a delay in diagnosis or treatment of greater than 48 hours. Problems in diagnosis included five children with unrecognized open fractures, four of whom did not receive antibiotics; six children with missed SCFE, five of whom were not made non-weight-bearing; and six missed closed fractures. Delay in treatment occurred for 15 fractures, with a mean delay of >7 days until surgical treatment. Insurance status and primary language of the family were not associated with problems or delays in treatment. Overall, 32% of children undergoing time-sensitive orthopaedic surgery at a tertiary pediatric center had problems or delays in the medical care they received before transfer.