Intellectual disabilities moderate sex/gender differences in autism spectrum disorder: a systematic review and meta-analysis.

BACKGROUND: Girls/women with autism spectrum disorder (ASD) are suggested to exhibit different symptom profiles than boys/men with ASD. Accumulating evidence suggests that intellectual disability (ID) may affect sex/gender differences in ASD. However, a systematic review and meta-analysis on this topic is missing. METHODS: Two databases (MEDLINE and PsycINFO) were used to search for studies reporting sex/gender differences (girls/women versus boys/men) in social communication and interaction, restrictive and repetitive behaviour and interests (RRBIs), sensory processing, and linguistic and motor abilities in ASD. The final sample consisted of 79 studies. The meta-analysis was performed with Review Manager using a random-effects model. Participants with ASD without and with ID were analysed as separate subgroups, and the effects in these two subgroups were also compared with each other. RESULTS: Girls/women with ASD without ID displayed fewer RRBIs, more sensory symptoms and less problems in linguistic abilities than their boys/men counterparts. In contrast, girls/women with ASD with ID displayed more social difficulties and RRBIs, poorer linguistic abilities and more motor problems than boys/men with ASD with ID. Comparisons of groups of participants with ASD without ID versus participants with ASD with ID confirmed differences in sex/gender effects on social difficulties, sensory processing, linguistic abilities and motor abilities. CONCLUSIONS: Our results clearly suggest that the female phenotype of ASD is moderated by ID. Among individuals with ASD with ID, girls/women seem to be more severely affected than boys/men, whereas among individuals with ASD without ID, girls/women with ASD may have less symptoms than boys/men. Such phenotypic differences could be a potential cause of underrecognition of girls/women with ASD, and it is also possible that observed phenotypic differences may reflect underdiagnosing of girls/women with ASD.

Attenuation over 24 hours of the efficacy of thrombolysis of pulmonary embolism among patients with cancer.

The efficacy and safety of thrombolysis in patients with cancer with pulmonary embolism is uncertain. Therefore we studied the effects of thrombolysis in 57 patients with cancer and 254 patients without cancer who were treated in five clinical trials with tissue plasminogen activator or urokinase for pulmonary embolism. Immediately after thrombolysis, the proportion of patients with and without cancer who improved on follow-up angiography (77% vs 73%; p = 0.65) was similar. The angiogrophic reduction in clot burden (1.83 +/- 0.27 vs 1.38 +/- 0.13; p = 0.13) was somewhat greater in patients with cancer than in patients without cancer. Twenty-four hours after initiation of thrombolytic therapy, the proportion of patients who improved on follow-up perfusion scan continued to be similar (72% vs 78%; p = 0.40). However, the extent of reperfusion at 24 hours was less in patients with cancer than in patients without cancer (6% vs 13% reperfusion of lung tissue; p = 0.007). These data suggest that patients with cancer should receive effective anticoagulation in the upper portion of the therapeutic range immediately after thrombolysis. It is possible that such a strategy might preserve initial improvement from thrombolysis and prevent attenuation of benefit during the ensuing 24 hours.

Increasing age is a major risk factor for hemorrhagic complications after pulmonary embolism thrombolysis.

We reviewed our database of 312 patients with pulmonary embolism who received thrombolysis in five clinical trials. At baseline, none had a history of stroke, internal bleeding within 6 months, surgery within 10 days, or occult blood in stool. Sixty-six major bleeding episodes occurred within 72 hours of administering thrombolysis in 61 (20%) patients: bleeding at the catheterization site (34 cases), gross hematuria (9), intracranial hemorrhage (5), and 18 other bleeding episodes that led to at least a 10% hematocrit decrease. Patients with a major bleeding complication were on average older than patients with no hemorrhagic complication (mean age 62.9 +/- 1.9 years vs 56.2 +/- 1.1 years; p = 0.005). In an adjusted analysis, there was a fourfold increased risk of bleeding among patients older than 70 years compared with patients younger than 50 years (relative risk [RR] 3.9; 95% confidence interval [CI] 1.7 to 8.9). By using age as a continuous variable, we found a 4% (RR 1.04; 95% CI 1.02 to 1.06) increase in risk of bleeding for each incremental year of age. In addition, patients with higher body mass index had an increased risk of bleeding. Patients who had undergone catheterization had a five times greater risk of bleeding (RR 5.2; 95% CI 1.5 to 17.8). In summary, increasing age, larger body mass index, and catheterization predisposed to bleeding complications after pulmonary embolism thrombolysis.

Thrombolytic therapy for pulmonary embolism. Frequency of intracranial hemorrhage and associated risk factors.

STUDY OBJECTIVES: To determine the risk factors and frequency of intracranial hemorrhage among patients undergoing thrombolysis for pulmonary embolism. DESIGN: A retrospective descriptive and controlled analysis. SETTING: Hospitalized patients at centers in the United States, Canada, and Italy. PATIENTS: All had evidence of pulmonary embolism on perfusion scans or angiography. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Data were analyzed on 312 patients from five previously reported studies of pulmonary embolism thrombolysis. The frequency of intracranial hemorrhage up to 14 days after pulmonary embolism thrombolysis was 6 of 312 or 1.9% (95% confidence interval, 0.7 to 4.1%). Two of six intracranial hemorrhages were fatal. Two of the six patients received thrombolysis in violation of the protocol because they had pre-existing, known intracranial disease. Average diastolic BP at the time of hospital admission was significantly elevated in patients who developed an intracranial hemorrhage (90.3 +/- 15.1 mm Hg) compared with those who did not (77.6 +/- 10.9 mm Hg; p = 0.04). Other baseline characteristics and laboratory data were similar in both groups. Decreased level of consciousness, hemiparesis, and visual field deficits were the most common clinical signs of intracranial hemorrhage. CONCLUSIONS: Intracranial hemorrhage after pulmonary embolism thrombolysis is an infrequent but often grave complication. Meticulous patient screening before administering thrombolysis is imperative. Diastolic hypertension at the time of hospital admission is a risk factor for intracranial hemorrhage after pulmonary embolism thrombolysis.

Indications for operation in ulcerative colitis in the era of the pouch and before.

OBJECTIVE: To find out if the change in the operation of choice for ulcerative colitis from proctocolectomy with conventional ileostomy to restorative proctocolectomy which occurred during the 1980s had any influence on the indications for operation. DESIGN: Retrospective analysis. SETTING: University hospital, Finland. SUBJECTS: 430 consecutive patients who underwent operations for ulcerative colitis: 154 patients during 1976-85, when conventional proctocolectomy was the first choice, and 276 patients in 1986-94, when restorative proctocolectomy was the operation of choice. INTERVENTIONS: Comparison of the main surgical indications between the two periods. MAIN OUTCOME MEASURES: The indication for the first operation for three groups of patients: acute colitis, chronic colitis, and carcinoma (or at risk of cancer). RESULTS: The annual number of patients operated on roughly doubled even though the duration of colitis became longer and the age of patients older. The percentage of patients with "acute colitis" decreased from 29% (45/154) to 20% (55/276) (p = 0.032) and that of "chronic colitis" increased from 52% (80/154) to 65% (179/276) (p = 0.01) during the study period, while patients operated on for risk of carcinoma decreased slightly (19%, 29/154, compared with 15%, (42/276) p = 0.35). CONCLUSION: The adoption of restorative proctocolectomy has not caused any significant changes in indications for operation in ulcerative colitis. On the contrary, the medical control is better than before, but dealing with the risk of cancer remains difficult.

Pulmonary embolism and deep venous thrombosis during pregnancy or oral contraceptive use: prevalence of factor V Leiden.

Activated protein C resistance caused by factor V Leiden mutation is the most common inherited cause of an underlying predisposition to pulmonary embolism (PE) and deep venous thrombosis (DVT). We studied the frequency of the factor V Leiden mutation in 50 women who had PE and/or DVT during or after pregnancy or during oral contraceptive use. Ten (20%; 95% CI 10% to 34%) of the 50 women were heterozygous for the mutation. First-trimester PE or DVT developed in 6 (60%; 95% CI, 26% to 88%) of the 10 women with the mutation compared with 3 (8%; 95% CI 2% to 20%) of 40 women without the mutation (p = 0.0009). These data indicate that the factor V Leiden mutation is an important risk factor for PE or DVT during pregnancy (especially the first trimester), after pregnancy, or during oral contraceptive use.

Restorative compared with conventional proctocolectomy for the treatment of ulcerative colitis.

OBJECTIVE: To evaluate the clinical differences between conventional and restorative proctocolectomy in the treatment of ulcerative colitis. DESIGN: Retrospective analysis. SETTING: University hospital, Finland. SUBJECTS: 240 consecutive patients with ulcerative colitis who underwent elective proctocolectomy between 1976 and 1990. INTERVENTIONS: Proctocolectomy and conventional ileostomy (n = 119) or restorative proctocolectomy (n = 121). MAIN OUTCOME MEASURES: Early and late surgical morbidity and recovery time. RESULTS: There were no postoperative deaths after restorative proctocolectomy and one patient (1%) died after conventional proctocolectomy. Two other patients (2%) with ileostomies died of late complications. Delayed perineal would healing after conventional ileostomy (n = 45, 38%) and either early (n = 31, 26%) or late (n = 19, 16%) defects of the ileoanal anastomosis after restorative proctocolectomy caused most problems. Reoperations (early or late) were needed in 45 (38%) and 44 (36%) patients after Brooke ileostomy and restorative proctocolectomy, respectively. Major complications, however, were more common and the duration of sick leave was a month longer in the pouch group. CONCLUSION: Ulcerative colitis can safely be managed with either conventional or restorative proctocolectomy. In most cases the patient's preference should dictate the choice of procedure.

Liver involvement and its course in patients operated on for ulcerative colitis.

The prevalence of associated liver involvement in 214 patients with ulcerative colitis undergoing definitive surgery was evaluated, with special emphasis on the subsequent course of liver changes. At the time of colectomy or proctocolectomy 45 patients (21%) had more than transient liver involvement, and 13 (6.1%) fulfilled the criteria of primary sclerosing cholangitis (PSC). Of the other 32 patients with minor liver involvement four had steatosis, one chronic active hepatitis, one viral A hepatitis, and 14 possibly early sclerosing cholangitis or unspecific reactive hepatitis. During a mean follow-up of nine years, four patients with PSC (31%) showed clinical progression, but none of those with minor histological changes or those with no liver disease at surgery did so. Alkaline phosphatase levels showed a decreasing tendency, and minor histological changes improved after surgery, while repeated cholangiography mostly demonstrated progression or a static state. The results indicate that asymptomatic sclerosing cholangitis in association with ulcerative colitis is not always a progressive disease, and proctocolectomy may have a beneficial effect on the long-term course of sclerosing cholangitis in its early phase.

Long-term results of restorative proctocolectomy for ulcerative colitis.

To study the long-term effects of restorative proctocolectomy with J-pouch for ulcerative colitis 100 consecutive patients were examined a mean of 5.6 years after ileal pouch-anal anastomosis (IPAA). Seventy-three percent of patients were on steroids and 22% had a preceding severe attack of colitis before IPAA. The overall early and late complication rates were 40% and 33%, respectively. Failure rate was 5% and all failures requiring pouch excision occurred within the first three postoperative years. Pouchitis (36%) was the commonest late complication. A preceding severe attack of colitis was an important prognostic sign of late anastomotic complications, troublesome incontinence and ultimate failure. The daily mean stool frequency varied from 4.5 to 6.9. After a short learning period continence-stabilised and minor incontinence was common (57%). The majority of patients (72%) were either very satisfied or had no problems in daily activities after IPAA. Ten patients were dissatisfied after surgery due to obvious medical reasons in most of them.

Management of fulminating ulcerative colitis.

A series of 69 patients with fulminating ulcerative colitis (UC), treated in 1976-89, was reviewed to evaluate the lines of conservative and surgical methods used. Fifty-six of the patients (81%) were operated on during the first hospitalization period: 33 patients (48%) underwent an emergency or urgent operation, and 23 (33%) received elective surgical treatment. The mortality rate was 4.3%; three patients died after emergency operations. Excluding the 14 patients who underwent immediate surgery within the first 48 hours, a significant difference could be observed in the response to conservative treatment with and without TPN: with TPN remission was achieved in 34 of 44 cases (77%), without it in only two cases of 11 (18%), P less than 0.001. Proctocolectomy used as an emergency or urgent measure resulted in two deaths, and 93% of the patients showed complications, whereas subtotal colectomy with ileostomy resulted in no deaths and significantly fewer patients (31%) had complications, P less than 0.001. The findings suggest that TPN and bowel rest, in addition to corticosteroid treatment, may be advantageous in all cases of fulminant UC. If this 'Oxford regimen' is insufficient, subtotal colectomy with ileostomy is the safest emergency operation.