Effectiveness of longstanding exercise therapy compared with usual care for people with rheumatoid arthritis and severe functional limitations: a randomised controlled trial.

OBJECTIVES: To compare the effectiveness of longstanding (>52 weeks), supervised exercise therapy with usual care in adults with rheumatoid arthritis (RA) and severe functional limitations. METHODS: Participants were randomised 1:1 to the intervention (individualised goal-setting, active exercises, education and self-management regarding physical activity) or usual care. Primary endpoint was the change in the Patient-Specific Complaints activity ranked 1 (PSC1, 0-10) at 52 weeks. Secondary endpoints included the PSC activities ranked 2 and 3 (PSC2, PSC3), Health Assessment Questionnaire-Disability Index (HAQ-DI), Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL), 6-minute walk test (6MWT), Patient Reported Outcome Measurement Information System Physical Function-10 (PROMIS PF-10) and the Short Form-36 Physical and Mental Component Summary Scales (SF-36 PCS and MCS). (Serious) Adverse events (AEs) were recorded. Measurements were done by blinded assessors. Analyses at 52 weeks were based on the intention-to-treat principle. RESULTS: In total, 217 people (90% female, age 58.8 (SD 12.9) years) were randomised (n=104 intervention, n=98 usual care available for analyses). At 52 weeks, the improvement of the PSC1 was significantly larger in the intervention group (mean difference (95% CI) -1.7 (-2.4, -1.0)). Except for the SF-36 MCS, all secondary outcomes showed significantly greater improvements favouring the intervention (PSC2 -1.8 (-2.4, -1.1), PSC3 -1.7 (-2.4, -1.0), PROMIS PF-10 +3.09 (1.80, 4.38), HAQ-DI -0.17 (-0.29, -0.06), RAQoL -2.03 (-3.39, -0.69), SF-36 PCS +3.83 (1.49, 6.17) and 6MWT +56 (38, 75) m). One mild, transient AE occurred in the intervention group. CONCLUSION: Longstanding, supervised exercise therapy was more effective than usual care in people with RA and severe functional limitations. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL8235), included in the International Clinical Trial Registry Platform (https://trialsearch.who.int/Trial2.aspx?TrialID=NL8235).

One-year effectiveness of long-term exercise therapy in people with axial spondyloarthritis and severe functional limitations.

OBJECTIVE: To evaluate the effectiveness of long-term, personalized, supervised exercise therapy on functional ability compared with usual care in people with axial spondyloarthritis (axSpA) and severe functional limitations. METHODS: Participants were randomly 1:1 assigned to the intervention(maximal 64 sessions, with 14 additional optional sessions of supervised active exercise therapy(e.g. aerobic and muscle strengthening) with individualized goal-setting, education and self-management regarding physical activity) or usual care(care determined by clinician(s) and participants themselves). Primary end point was the change in the Patient-Specific Complaints activity ranked 1 (PSC1 (0-10)) at 52 weeks. Secondary endpoints were the PSC activities ranked 2 and 3, the Bath Ankylosing Spondylitis Functional Index, 6-min walk test, Patient Reported Outcome Measurement Information System-Physical Function-10 and the Short Form-36 Physical and Mental Component Summary Score (SF-36 PCS and MCS). Statistical comparisons comprised independent student t-tests and linear mixed models, based on intention-to-treat. RESULTS: 214 participants(49% female, age 52 (SD 12) years), were randomized to the intervention (n = 110) or usual care (N = 104) group. In the intervention group 93% started treatment, using on average 40.5 sessions (SD 15.1). At 52 weeks, the difference in change in PSC1 between groups favored the intervention group (mean difference [95% CI]; -1.8 [-2.4 to -1.2]). additionally, all secondary outcomes, except the SF-36 MSC, showed significantly greater improvements in the intervention group with effect sizes ranging from 0.4-0.7. CONCLUSION: Long-term, supervised exercise therapy proved more effective than usual care in improving functional disability and physical quality of life in people with axSpA and severe functional limitations. CLINICAL TRIAL REGISTER NUMBER: Netherlands Trial Register NL8238, included in the International Clinical Trial Registry Platform (ICTRP) (https://trialsearch.who.int/Trial2.aspx?TrialID=NL8238).

Quality of reporting and nature of harms in clinical trials on supervised exercise in patients with rheumatoid arthritis or axial spondyloarthritis.

To describe the quality of reporting and the nature of reported harms in clinical studies on the effectiveness of supervised exercises in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA). We performed a systematic review, searching eight databases up to February 2023. Randomized controlled trials (RCTs) evaluating supervised exercises in adults with RA or axSpA were considered eligible. Data on harms were extracted according to the CONSORT Harms 2022 Checklist. Among others, it was recorded if harms were prespecified or non-prespecified. Moreover, the nature of reported harms was listed. Forty RCTs were included for RA and 25 for axSpA, of which 29 (73%) and 13 (52%) reported information on harms. In 13 (33%) RCTs in RA and four (16%) in axSpA, the collection of harms outcomes was described in the methods section. Prespecified outcomes were reported by eight (RA) and two (axSpA) RCTs. Non-specified harms outcomes were reported by six (RA) and four (axSpA) RCTs. Prespecified harms outcomes included measures of pain, disease activity, inflammation, and structural joint changes. The nature of non-prespecified harms outcomes varied largely, with pain being most common. A considerable proportion of trials on supervised exercise in RA or axSpA does not or inadequately report harms outcomes. Pain was the most commonly reported prespecified or non-specified harm. For a considerate interpretation of the balance between benefits and harms of supervised exercise in RA or axSpA, use of the CONSORT Harms 2022 Checklist for the design, conduct and reporting of trials is advocated.

Functional limitations of people with rheumatoid arthritis or axial spondyloarthritis and severe functional disability: a cross-sectional descriptive study.

The objective of the study is to describe the nature of functional limitations in activities and participation in people with Rheumatoid Arthritis (RA) or axial SpondyloArthritis (axSpA) with severe functional disability. Baseline data from people with RA (n = 206) or axSpA (n = 155) and severe functional disability participating in an exercise trial were used. Their three most limited activities were derived from the Patient Specific Complaint (PSC) instrument and linked to the International Classification of Functioning and Health (ICF). The frequencies of ICF categories were calculated and compared with Activities and Participation items of the ICF Core Sets for RA (32 second-level categories) and Ankylosing Spondylitis (AS) (24 second-level categories). In total 618 and 465 PSC activities were linked to 909 (72 unique in total; 25 unique second-level) and 759 (57 unique in total; 23 unique second-level) ICF categories in RA and axSpA. Taking into account all three prioritized activities, the five most frequent limited activities concerned the ICF chapter "Mobility", and included "Walking" (RA and axSpA 2 categories), "Changing basic body position" (RA and axSpA 1 category), "Stair climbing"(RA) and "Grasping" (RA),"Lifting" (axSpA) and "Maintaining a standing position" (axSpA). In RA, 21/32 (66%) and in axSpA 14/24 (58%) unique second-level categories identified in the prioritized activities are present in the Comprehensive Core Sets. Most limitations of people with RA or axSpA and severe functional disability were seen in the ICF chapter "Mobility". Most of the identified ICF categories were covered by the corresponding items of the ICF RA and AS Core Sets.

The Extent and Nature of Functional Limitations According to the Health Assessment Questionnaire Disability Index in Patients with Rheumatoid Arthritis and Severe Functional Disability.

BACKGROUND: For a subgroup of people with rheumatoid arthritis (RA) and severe disability, insight into their limitations is crucial for adequate treatment. AIM: To describe the extent and nature of functional limitations in people with RA and severe disability and to explore the associations of the extent of the functional limitations with patient characteristics, disease characteristics, and outcome measures. METHODS: Baseline data of 215 participants in an RCT on the (cost-)effectiveness of longstanding physiotherapy were used. Functional limitations were assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI). The total HAQ-DI including eight domain scores were calculated. Associations between high HAQ-DI scores (≥2, yes/no) and other variables were examined using the Student's t-test or Chi-squared test where appropriate. RESULTS: The participants (90% women, age 58.8 ± 12.8 years) had a mean HAQ-DI score of 1.7 ± 0.5. The majority (56%) showed a moderate-to-severe disability in all domains. Higher HAQ-DI scores seemed to be associated with advanced age, longer disease duration, unemployment, joint replacements, and outcomes for daily functioning and physical quality of life, but not with measures of disease activity. CONCLUSIONS: Our findings indicate that a comprehensive assessment of all areas of daily activities in this subgroup is necessary in order to provide appropriate (non-)pharmacological care.

Effectiveness and cost-effectiveness of longstanding exercise therapy versus usual care in patients with axial spondyloarthritis or rheumatoid arthritis and severe limitations: The protocols of two parallel randomized controlled trials.

OBJECTIVES: Research on effectiveness and cost-effectiveness of longstanding exercise therapy in patients with axial SpondyloArthritis (axSpA) or Rheumatoid Arthritis (RA) is scarce, and mainly concerned patients with a relatively favorable health status. We aim to evaluate the effectiveness and cost-effectiveness of longstanding exercise therapy compared to usual care in the subgroup of patients with axSpA or RA and severe limitations in functioning. METHODS: In two separate, parallel randomized controlled trials the effectiveness and cost-effectiveness of longstanding, active exercise therapy (52 weeks) compared with usual care (1:1) will be evaluated. The longstanding, active exercise therapy will focus on improving individual limitations in daily activities and participation and will be given by a trained physical therapist in the vicinity of the participant. For each diagnosis, 215 patients with severe limitations in activities and participation will be included. Assessments are performed at baseline, 12, 26, and 52 weeks. The primary outcome measure of effectiveness is the individual level of functioning (activities and participation), as measured with the Patient-Specific Complaints instrument at 52 weeks. For cost-effectiveness analyses, the EuroQol (EQ-5D-5L) and questionnaires on healthcare use and productivity will be administered. The economic evaluation will be a cost-utility analysis from a societal perspective. After 52 weeks, the patients in the usual care group are offered longstanding, active exercise therapy as well. Follow-up assessments are done at 104, 156, and 208 weeks. CONCLUSION: The results of these studies will provide insights in the effectiveness and cost-effectiveness of longstanding exercise therapy in the subgroup of axSpA and RA patients with severe functional limitations.

Routine preoperative upper gastrointestinal series (UGIS) in patients with biliary tract disease: a plea for more selectivity.

Preoperative upper gastrointestinal x-ray series (UGIS) in patients with documented biliary tract disease commonly is carried out before cholecystectomy. Of 250 patients who had consecutive cholecystectomies performed in a 400-bed private hospital, 105 patients did not have UGIS prior to operation and no gastroduodenal disease was discovered at operation. Thirty-nine positive x-ray examinations were obtained among the 145 patients who had preoperative UGIS. In only three of these patients was a gastric procedure added at operation; no unexpected cancers were found. In the other 36, "positive" findings consisted of small hiatal hernias, diverticula of the esophagus, stomach, or duodenum not clinically significant or postgastrectomy anatomic abnormalities. This review suggests that routine preoperative UGIS may not be warranted in such patients and urges greater selectivity of patients having this procedure.

Failure of gastric pH control by antacids or cimetidine in the critically ill: a valid sign of sepsis.

To compare the ability of antacids and cimetidine to control gastric pH and potential hemorrhage, 77 critically ill patients were randomized into two groups initially receiving either antacids (37 patients) or cimetidine (40 patients). Gastric pH was monitored hourly and the dosage of medication adjusted as required to maintain gastric pH above 4. Forty-nine patients maintained a pH above 4 while receiving a standard dose of antacids (29 patients) or cimetidine (20 patients). Only 8 of these 49 patients proved to be septic, compared to 20 of the 28 patients who required additional medication to maintain pH above 4 (P less than 0.001). There were five episodes of gastrointestinal hemorrhage occurring in septic patients who had a gastric pH consistently below 4 despite treatment. Excluding septic patients, 8 of 23 failed to maintain a gastric pH of 4 on cimetidine compared to 0 of 26 receiving antacids (P less than 0.005). The data suggest that (1) persistent failure of antacids and/or cimetidine to maintain gastric pH above 4 is yet another indicator of often unappreciated infection, (2) maintaining gastric pH above 4 largely prevents gastrointestinal hemorrhage, and (3) cimetidine is not as consistently effective as antacids in maintaining gastric pH above 4.

The use of computerized axial tomography versus peritoneal lavage in the evaluation of blunt abdominal trauma: a prospective study.

Computerized axial tomography (CAT) of the abdomen was prospectively compared with peritoneal lavage (PL) in 19 patients who sustained acute blunt abdominal trauma. All were selected carefully and were deemed stable, never having been in shock, and all required diagnostic PL. Seven patients underwent exploratory laparotomy on the basis of CAT and PL findings. There were no negative findings at laparotomy. Three significant splenic injuries, one hepatic laceration, and two hemoperitoneums were undetected by CAT. All seven cases explored were preceded by a grossly positive PL. Thus no major injury would have been missed if PL had been used alone. There were no complications of PL but one patient aspirated oral contrast medium and one patient developed hypotension during CAT. Open PL required one half the time (20.6 minutes) as CAT (47.4 minutes). The total cost of CAT was approximately eight times that of PL ($900.01 versus $116.38). In our hands, PL would seem to be significantly more sensitive with fewer false negative results than CAT of the abdomen in acute blunt abdominal trauma, a deviation from results of earlier reported series. CAT alone would have added cost, time, some risk, and very little information of use that would not be obtained by PL followed by surgery. Therefore before CAT replaces PL in the evaluation of adult patients with blunt abdominal trauma, we feel that additional prospective studies are needed to better define the accuracy and sensitivity of CAT as compared with PL with regard to intraperitoneal injuries.

Bleeding vascular malformations of the intestine.

Thirty-nine patients with bleeding vascular malformations were evaluated. The age range was from 3 to 78 years, with a bimodal age distribution. The younger patients had no associated diseases, while those in the older category invariably had an associated cardiac lesion (aortic stenosis in 12 patients and severe atherosclerotic disease in 11 patients). With experience, colonoscopy has become a valuable adjunct to arteriography with the lesion visualized in 12 patients. Arteriography is the most useful study being diagnostic in 35 of 38 cases. Exploration alone was diagnostic in only one of 39 patients. The most common site of bleeding was the cecum (21 patients) followed by the proximal small intestine (eight patients), terminal ileum (seven patients), and ascending colon (five patients). The lesions in the proximal small bowel were much more common in the younger patients and were believed to be congenital. Resection controlled the bleeding in the majority of patients, although four recurrences have been noted. All have been documented angiographically to have been from a new lesion and two were controlled with reoperation. The key elements to control of these patient's bleeding include: (1) systematic work-up with a team approach emphasizing careful visceral angiography, and (2) the avoidance of a premature laparotomy prior to complete evaluation.

Diagnostic and therapeutic colonoscopy. A critical review of 662 examinations.

The results of 662 therapeutic and diagnostic colonoscopic examinations were reviewed to assess the morbidity, clinical benefit, diagnostic accuracy, and indications for the procedure, with special emphasis on detection and endoscopic excision of small, occult, invasive cancers. Overall, the frequency of detecting occult lesions (19%), the (89%) ability to clarify questionable radiographic findings, and a substantial reduction in laparotomy-colotomy procedures required for removal of colonic polyps (88%), coupled with a low morbidity (3%) and low false-negative examination rate (1%) established colonoscopy as one of the most important advances in the management of colon disease in recent years. Although early experience suggests that small, occult, invasive carcinomas, when properly selected, could be adequately treated by endoscopic excision, larger series and longer follow-up periods are necessary to validate any conclusions regarding the decision to manage these lesions conservatively.

Cholate sodium infusion for retained common bile duct stones.

Eight patients with stones retained in the extrahepatic biliary tract underwent cholate sodium infusion for dissolution of the stones. In six patients, the stones disappeared. However, in two of the patients, the stones did not disappear, and they were removed with the ureteral basket. Infusion of cholate sodium was well tolerated by six patients, but was accompanied by nausea, vomiting, and abdominal pain in two patients. In one case, mucosal deformity of the common bile duct was noticed during the infusion, but it was not apparent on a subsequent cholangiogram. As a result of our experience, we conclude that cholate sodium infusion is a safe procedure for the attempted dissolution of retained common bile duct stones.

Breast tumor incidence in rats after partial mammary resection.

The use of subcutaneous mastectomy in women at high risk for breast cancer is based on the assumption that surgical reduction of the tissue at risk results in a corresponding reduction in risk. To assess the validity of this assumption in an animal model, we subjected 120 female Sprague-Dawley rats to the mammary carcinogen 7,12-dimethylbenz(alpha)anthracene and a 20% fat diet. Two days later, one mammary ridge was excised in half of the animals (mastectomy group), and a midline incision was made without excision of tissue in the other half (control group). Seventy-nine rats survived dosing and operation and were observed for 77 weeks. After 15 weeks, 17 of 39 controls and seven of 40 animals with mastectomies had histologically confirmed neoplastic tumors of the breast. However, after 77 weeks, 32 of 39 controls and 35 of 40 animals in the mastectomy group had neoplastic tumors. The incidence of carcinogen-induced mammary neoplasms in rats progressed with time; whereas surgical reduction of breast tissue was followed by early reduction in neoplasias, the difference was not maintained.

Familial papillary carcinoma of the thyroid.

Although the number of reported cases of papillary carcinoma of the thyroid in families is few, a review of the literature and the three cases presented here strongly suggest the characteristics of hereditary cancer. Further study and reportage of similar cases is indicated to confirm whether this is indeed a familial cancer.

Failure of cimetidine prophylaxis in the critically ill.

Stress ulcers with subsequent hemorrhage are a well-recognized cause of morbidity and mortality in patients hospitalized for other serious illnesses. In 39 critically ill patients, cimetidine was used as a prophylaxis against stress ulcers with the intent to keep the gastric pH level above 4. In 11 of the 39 patients, cimetidine alone did not effect consistent elevation of the gastric pH level above 4. Of the 11 patients, nine had positive blood cultures or clinical infection and five also developed renal failure. Five comatose patients never had pH greater than 4 on cimetidine alone. The mortality for those whose conditions failed to respond to cimetidine was five times greater than for those whose conditions responded to cimetidine. These data imply that a high-risk group of patients can be identified whose conditions may not respond to cimetidine treatment and whose gastric pH must be regularly monitored.

Diversion of duodenal contents: its effect on the production of experimental gastric cancer.

Diversion of duodenal contents after gastroenterostomy and vagotomy did not protect 240 laboratory rats from increased risk of gastric carcinoma. They were divided into three groups of 80: group 1 received 0.9 mg of 3-methylcholanthrene injected submucosally into the gastric antrum; groups 2 and 3 had bilateral truncal vagotomy and gastroenterostomy, with carcinogen injected into the gastric submucosa near the anastomosis; group 3 also had total duodenoenteric diversion. Blind histopathologic examination of surviving rats during necropsy eight months later disclosed that cancer had developed in six of 60 (10%) group 1 rats, in 23 of 71 (33%) group 2 rats, and in seven of 27 (22%) group 3 rats. Compared with group 1, groups 2 and 3 had an increased incidence of gastric cancer but did not differ from one another in this regard.

Value of colonoscopy in patients with rectal blood loss unexplained by rigid proctosigmoidoscopy and barium contrast enema examinations.

Total colonoscopy is the procedure of choice for patients with any amount of rectal blood loss unexplained by proctosigmoidoscopy and barium contrast enema examinations. In 168 endoscopic examinations, 46 unsuspected lesions in 39 patients (23 percent) were detected, 50 percent of which were 1 cm or greater in diameter. Considering that 30 percent of all unsuspected lesions, 100 percent of angiodysplastic abnormalities and 40 percent of unsuspected carcinomas were located proximal to the splenic flexure, emphasis is placed on the importance of examining the entire colon to the cecum.

Feeding jejunostomy: a small bowel stress test?

A review of 143 patients with 144 feeding jejunostomies was carried out. In the 129 patients in whom catheters were utilized, only 48 (45 percent) had no complications. Seventy-one patients (55 percent) suffered one or more catheter-related complications. Ten of these complications were life-threatening or fatal, including five cases of fatal small bowel necrosis. There was a significant increase in risk factors for decreased mesenteric blood flow in those patients with small bowel necrosis compared with those without this complication. In addition, the other 17 patients with abdominal distention (a manifestation of tube feeding intolerance) had a significantly increased number of risk factors for decreased mesenteric blood flow. Documented low-flow states should prompt discontinuation of tube feedings even in the patient without gastrointestinal symptoms and signs. Distention is a nonspecific but ominous finding and should prompt discontinuation of tube feedings permanently unless a reversible cause for distention is determined.

Recurrent gastric bezoars. A new approach to treatment and prevention.

A recurrent gastric phytobezoar was successfully dispersed using an endoscopically directed intermittent jet of dilute papain. Dissolution analysis of a retrieved bezoar fragment showed pancrelipase and Adolph's Meat Tenderizer to be effective specific solvents. The patient remained free of symptoms while on a prophylactic regimen of pancrelipase taken daily. However, when the patient discontinued his medication, the bezoar recurred. The dissolution process was successfully repeated. Selecting a reagent on the basis of demonstrated effectiveness should enhance the chance of successful dissolution of a phytobezoar, whereas prophylactic doses of the reagent may prevent its recurrence.

Perceived needs for gastrointestinal endoscopic training in surgical residencies.

Questionnaires sent to directors of 126 university surgical residency programs analyzed the availability and quality of fiberoptic gastrointestinal endoscopic training. Seventy percent responded: 59 percent of their programs included some endoscopy training. Only half of the respondents believed their residents were adequately trained in endoscopic techniques. Although 67 percent of institutions had at least one surgeon performing endoscopy, many did not involve surgical residents in their cases. Insufficient caseloads were the rule, with fewer than 30 patients available to each resident for gastroscopy in 63 percent of the programs and for colonoscopy in 89 percent. Only half of all directors were satisfied with their relation with gastroenterology with respect to endoscopy. Gastroenterology service monopolized the performance of endoscopy at 41 percent of the universities. Since endoscopy is helpful in the management of many gastrointestinal disorders treated by surgeons, training surgical residents in such techniques is advisable. To do so properly, program directors must recruit skilled faculty and provide more concentrated endoscopic rotations with adequate caseloads or develop truly sharp educational experiences with their colleagues in gastroenterology.