Discontinuation of surgical versus nonsurgical clinical trials: an analysis of 88,498 trials.

BACKGROUND: It has been previously reported that over 20% of surgical trials will be discontinued prematurely raising ethical and financial concerns. Previous studies have been limited in scope owing to the need for manual review of selected trials. To date, there has been no broad analysis comparing surgical and nonsurgical registered clinical trials. MATERIALS AND METHODS: ClinicalTrials.gov was queried October 7, 2017 for all US trials from 2005 to 2017. Trials were assigned to surgical or nonsurgical groups by automated sorting. The sorting algorithm was validated by comparison with manual assignments made by blinded investigators. Comparisons were made between trial status, funding sources, and trial design. The reasons for discontinuation were examined and tabulated. RESULTS: The database search yielded 82,719 nonsurgical and 5779 surgical trials after automatic assignment. The algorithm for assignments had an overall accuracy of 87.99% and a positive likelihood ratio of 6.09 and negative likelihood ratio of 0.093. Significant differences existed in trial status (nonsurgical versus surgical: completed: 55.51% versus 39.49%, P < 0.001 and discontinued: 11.07% versus 15.97%, P < 0.001). Discontinuation due to poor recruitment was more commonly cited by surgical trials (44.65% versus 34.74% P < 0.001). Industry funding predicted discontinuation for all trials (odds ratio 1.63 P < 0.001) and surgical trials independently (OR 1.25 P = 0.041). Patient enrollment, reporting results, and NIH funding were all protective against discontinuation. CONCLUSIONS: Surgical trials are more likely to prematurely discontinue than nonsurgical trials. Industry funding independently predicts trial discontinuation. Poor recruitment is a major cause of early trial discontinuation for all trials and is more pronounced in surgical trials.

Guillain-Barré syndrome.

Guillain-Barré syndrome consists of a group of neuropathic conditions characterized by progressive weakness and diminished or absent myotatic reflexes. The estimated annual incidence in the United States is 1.65 to 1.79 per 100,000 persons. Guillain-Barré syndrome is believed to result from an aberrant immune response that attacks nerve tissue. This response may be triggered by surgery, immunizations, or infections. The most common form of the disease, acute inflammatory demyelinating polyradiculoneuropathy, presents as progressive motor weakness, usually beginning in the legs and advancing proximally. Symptoms typically peak within four weeks, then plateau before resolving. More than one-half of patients experience severe pain, and about two-thirds have autonomic symptoms, such as cardiac arrhythmias, blood pressure instability, or urinary retention. Advancing symptoms may compromise respiration and vital functions. Diagnosis is based on clinical features, cerebrospinal fluid testing, and nerve conduction studies. Cerebrospinal fluid testing shows increased protein levels but a normal white blood cell count. Nerve conduction studies show a slowing, or possible blockage, of conduction. Patients should be hospitalized for multidisciplinary supportive care and disease-modifying therapy. Supportive therapy includes controlling pain with nonsteroidal anti-inflammatory drugs, carbamazepine, or gabapentin; monitoring for respiratory and autonomic complications; and preventing venous thrombosis, skin breakdown, and deconditioning. Plasma exchange therapy has been shown to improve short-term and long-term outcomes, and intravenous immune globulin has been shown to hasten recovery in adults and children. Other therapies, including corticosteroids, have not demonstrated benefit. About 3 percent of patients with Guillain-Barré syndrome die. Neurologic problems persist in up to 20 percent of patients with the disease, and one-half of these patients are severely disabled.

Hearing loss in older adults.

Hearing loss affects approximately one-third of adults 61 to 70 years of age and more than 80 percent of those older than 85 years. Men usually experience greater hearing loss and have earlier onset compared with women. The most common type is age-related hearing loss; however, many conditions can interfere with the conduction of sound vibrations to the inner ear and their conversion to electrical impulses for conduction to the brain. Screening for hearing loss is recommended in adults older than 50 to 60 years. Office screening tests include the whispered voice test and audioscopy. Older patients who admit to having difficulty hearing may be referred directly for audiometry. The history can identify risk factors for hearing loss, especially noise exposure and use of ototoxic medications. Examination of the auditory canal and tympanic membrane can identify causes of conductive hearing loss. Audiometric testing is required to confirm hearing loss. Adults presenting with idiopathic sudden sensorineural hearing loss should be referred for urgent assessment. Management of hearing loss is based on addressing underlying causes, especially obstructions (including cerumen) and ototoxic medications. Residual hearing should be optimized by use of hearing aids, assistive listening devices, and rehabilitation programs. Surgical implants are indicated for selected patients. Major barriers to improved hearing in older adults include lack of recognition of hearing loss; perception that hearing loss is a normal part of aging or is not amenable to treatment; and patient nonadherence with hearing aids because of stigma, cost, inconvenience, disappointing initial results, or other factors.

Clinical outcome and echocardiographic predictors of aortic valve replacement in patients with bicuspid aortic valve.

BACKGROUND: Clinical outcomes and echocardiographic parameters associated with aortic valve replacement (AVR) for bicuspid aortic valve are scarce. METHODS: We conducted retrospective analysis of 208 adults with bicuspid aortic valve referred for transthoracic echocardiograms. RESULTS: The Kaplan-Meier survival free of death or need for cardiac surgery was 72% at 5 years. Cardiac surgery was performed in 19%, the majority (68%) for symptomatic aortic stenosis. Peak gradient 80 mm Hg or greater (hazard ratio 11.8, 95% confidence interval 3.7-37.8, P < .0001) and aortic valve area less than or equal to 0.75 cm(2) (hazard ratio 2.9, 95% confidence interval 1.0-8.5, P = .05) predicted the need for AVR. Patients with a large (54%) versus normal left ventricular outflow tract dimension underwent AVR for symptomatic aortic stenosis at a larger calculated aortic valve area (1.07 +/- 0.21 vs 0.75 +/- 0.18 cm(2), P < .0001) but at a similar peak gradient and velocity ratio (76 +/- 19 vs 76 +/- 22 mm Hg, P = not significant; 0.23 +/- 0.06 vs 0.26 +/- 0.12, P = not significant, respectively). CONCLUSIONS: Clinical events are common among patients with bicuspid aortic valve. Peak gradient 80 mm Hg or more and aortic valve area less than or equal to 0.75 cm(2) predicts the need for AVR. Gradients and velocity ratio better reflect the hemodynamic burden of aortic stenosis in patients with a large left ventricular outflow tract.

Dementia with Lewy bodies: an emerging disease.

Dementia with Lewy bodies appears to be the second most common form of dementia, accounting for about one in five cases. The condition is characterized by dementia accompanied by delirium, visual hallucinations, and parkinsonism. Other common symptoms include syncope, falls, sleep disorders, and depression. The presence of both Lewy bodies and amyloidplaques with deficiencies in both acetylcholine and dopamine neurotransmitters suggests that dementia with Lewy bodies represents the middle of a disease spectrum ranging from Alzheimer's disease to Parkinson's disease. The diagnosis of dementia with Lewy bodies is based on clinical features and exclusion of other diagnoses. Individualized behavioral, environmental, and pharmacologic therapies are used to alleviate symptoms and support patients and their families. Cholinesterase inhibitors are more effective in patients who have dementia with Lewy bodies than in those with Alzheimer's disease. Conversely, patients who have dementia with Lewy bodies do not respond as well to antiparkinsonian medications. Anticholinergic medications should be avoided because they exacerbate the symptoms of dementia. Traditional antipsychotic medications can precipitate severe reactions and may double or triple the rate of mortality in patients who have dementia with Lewy bodies.

Pancreatic cancer: diagnosis and management.

Although only 32,000 new cases of adenocarcinoma of the pancreas occur in the United States each year, it is the fourth leading cause of cancer deaths in this country. The overall five-year survival rate is 4 percent, and localized, resectable disease has only a 17 percent survival rate. Risk factors include smoking, certain familial cancer syndromes, and familial chronic pancreatitis. The link between risk of pancreatic cancer and other factors (e.g., diabetes, obesity) is less clear. Most patients present with obstructive jaundice caused by compression of the bile duct in the head of the pancreas. Epigastric or back pain, vague abdominal symptoms, and weight loss also are characteristic of pancreatic cancer. More than one half of cases have distant metastasis at diagnosis. Computed tomography is the most useful diagnostic and staging tool. Ultrasonography, magnetic resonance imaging, and endoscopic retrograde cholangiopancreatography may provide additional information. The majority of tumors are not surgically resectable because of metastasis and invasion of the major vessels posterior to the pancreas. Resectable tumors are treated with the Whipple procedure or the pylorus-preserving Whipple procedure. Adjuvant fluorouracil-based chemotherapy may prolong survival. For nonresectable tumors, chemotherapy with gemcitabine prolongs survival. Other agents are being studied. Radiation combined with chemotherapy has slowed progression in locally advanced cancers. Throughout the illness and during end-of-life care, patients need comprehensive symptom control.

Patient satisfaction with migraine management by family physicians.

Over 70% of the estimated 5 million office visits per year for migraine headache are to family physicians. Both the number of visits and proportion of migraine patients seeking medical care are increasing rapidly. Patient satisfaction with migraine care by primary care physicians is reported to be low but most data are obtained from patients referred to subspecialists or entered in clinical trials. We surveyed patients who consulted family physicians in 10 Kansas practices during 2002 to assess patient satisfaction and investigate any differences between satisfied and unsatisfied migraine patients. Of our 447 respondents, 74% were "satisfied" or "very satisfied" with migraine care by family physicians. Dissatisfied patients were significantly more likely to report moderate or severe migraine-related disability and less likely to use triptans or to have most medications paid by insurance. Dissatisfied patients were twice as likely to have discontinued taking triptans than satisfied patients. Patient satisfaction with migraine treatment in family practice is substantially higher than generally reported. Statistically significant differences exist between satisfied and dissatisfied patients.

Tuberous sclerosis complex in a young woman diagnosed incidentally on the basis of pregnancy ultrasonography.

Tuberous sclerosis complex (TSC) is more prevalent than previously believed and most cases result from new mutations and, hence, do not have affected relatives. Many patients who meet the new diagnostic criteria have unrecognized skin lesions and/or occult lesions in internal organs. As early diagnosis and appropriate intervention can reduce morbidity and mortality from the neurologic. renal, and pulmonary complications of TSC, physicians should be alert for the dermatological signs of the condition and for the incidental finding of TSC lesions during diagnostic testing. Patients with TSC may be asymptomatic and of normal intelligence. We report a case of TSC diagnosed by the incidental finding of renal lesions in a young woman during pregnancy ultrasonic examination.

Addisonian crisis precipitated by thyroxine therapy: a complication of type 2 autoimmune polyglandular syndrome.

Hypothyroidism is a common condition. Rarely, it may occur in combination with autoimmune failure of other endocrine glands (autoimmune polyendocrinopathy syndrome type 2, previously known as Schmidt's syndrome). In such cases, restoring normal thyroid function may precipitate adrenal failure. Clinicians should have a high index of suspicion for this condition in patients with Addison's disease, those with a family history of autoimmune endocrine gland failure, patients with one autoimmune endocrine disease who develop nonspecific or serious illness, and patients with type 1 diabetes mellitus whose insulin requirements drop without obvious explanation.

Diagnosing pericarditis.

Pericarditis, or inflammation of the pericardium, is most often caused by viral infection. It can also develop as a result of bacterial or other infection, autoimmune disease, renal failure, injury to the mediastinal area, and the effects of certain drugs (notably hydralazine and procainamide). The clinical features of pericarditis depend on its cause, as well as the volume and type of effusion. Patients with uncomplicated pericarditis have pleuritic-type chest pain that radiates to the left shoulder and may be relieved by leaning forward. Chest radiographs, Doppler studies, and laboratory tests confirm the diagnosis and provide information about the degree of effusion. In most patients, pericarditis is mild and resolves spontaneously, although treatment with a nonsteroidal anti-inflammatory drug or a short course of a corticosteroid may be helpful. When a large pericardial effusion is produced, cardiac function may be compromised, and cardiac tamponade can occur. In patients with longstanding inflammation, the pericardium becomes fibrous or calcified, resulting in constriction of the heart. Drainage or surgical intervention may be necessary in patients with complicated pericarditis.

A thematic approach to enhance clinical content in a cell and tissue biology course.

OBJECTIVE: (1) To integrate clinical problem solving into freshman cell and tissue biology (CTB) and (2) to enhance understanding of diabetes using CTB principles to explain the etiology, management, and development of complications in terms of cell, tissue, and organ structure and function. DESCRIPTION: First-year medical students often question the need to learn detailed basic science material. Although clinical content has increased throughout basic science courses, little attempt has been made to link clinical correlations to one another or to enhance use of basic science material in clinical problem solving. The CTB course applies pertinent cell biology concepts such as cell proliferation, differentiation, migration, adhesion, and morphogenesis to tissue and organ function. Diabetes mellitus was chosen as a theme for CTB as diabetes has devastating effects on multiple tissues, and the disease has reached epidemic proportions in the United States, affecting individuals of every age and population group. Type I diabetes, presenting as ketoacidosis in a ten-year-old boy, was introduced by generalist physicians using a "grand rounds" approach. This format challenged students on the first day of medical school to diagnose a patient's problem and to explain the clinical findings in terms of anatomic, biochemical, and physiologic changes. The role of the blood/bicarbonate buffering system was the main focus of faculty-led discussion. The patient was then presented at age 25 with many diabetic complications. This stimulated discussion of the etiology of diabetes (type I versus type II), glycation, and the use of hemoglobin (Hb) A1c to monitor blood sugar control. Compliance and other aspects of diabetes management were added to the discussion. Faculty provided scientific information as necessary, and summary materials were distributed after the sessions. The interaction of a cell biologist with two generalist physicians optimized the integration of basic science with clinical problem solving. During the two semesters of CTB, the diabetes case is frequently referenced. Insulin synthesis provides the model for protein synthesis. Glycation, advanced glycation end products (AGE), and receptors (RAGE) are discussed. Other diabetes-related topics include wound healing (epithelium), basement membrane thickening (connective tissue), insulin regulation of muscle metabolism, diabetic neuropathy (neurohistology), platelet adhesiveness, glycation and HbA1c (blood), osteoporosis and Charcot joints (skeletal system), autoimmune mechanisms (cellular immunology), atherosclerosis and high blood pressure (blood vessels), diabetic nephropathy (renal), altered hepatic and gastrointestinal function, impotence (male reproductive system), and a comparison of type I and type II diabetes (endocrine system). DISCUSSION: Students have provided very positive feedback. The initial case enhanced interest in CTB, established clinical relevance, and has motivated learning and integration of materials from different parts of CTB and other courses. Other courses are now formally linking to the theme. For example, neuroscience will revisit diabetic neuropathy and retinopathy, physiology will relate ketoacidosis to acid-base balance, a human anatomy clinical correlation is being designed for transplantation surgeons to "cure" our diabetic patient with a renal-pancreas transplant. Uses of the case for introduction to clinical medicine, aspects of medical ethics, preventive medicine, and courses in pharmacology and pathology are contemplated.

Lactose intolerance.

Persons with lactose intolerance are unable to digest significant amounts of lactose because of a genetically inadequate amount of the enzyme lactase. Common symptoms include abdominal pain and bloating, excessive flatus, and watery stool following the ingestion of foods containing lactose. Lactase deficiency is present in up to 15 percent of persons of northern European descent, up to 80 percent of blacks and Latinos, and up to 100 percent of American Indians and Asians. A sizable number of adults believe they are lactose intolerant but do not actually have impaired lactose digestion, and some persons with lactase deficiency can tolerate moderate amounts of ingested lactose. A diagnosis of lactose intolerance can usually be made with a careful history supported by dietary manipulation. If necessary, diagnosis can be confirmed by using a breath hydrogen or lactose tolerance test. Treatment consists primarily of avoiding lactose-containing foods. Lactase enzyme supplements may be helpful. The degree of lactose malabsorption varies greatly among patients with lactose intolerance, but most of them can ingest up to 12 oz of milk daily without symptoms. Lactose-intolerant patients must ensure adequate calcium intake.

Headache during pregnancy.

Headache in pregnancy is a common problem but diagnosis and management can be challenging. Most headaches in pregnant women are either migraine or tension types and can be easily treated. Rarely, the headache in a pregnant patient signals a life-threatening condition. Obstetricians should be able to effectively manage the common causes of headache as well as recognize the warning signs of potentially serious conditions. Diagnosis and management should be systematic yet individualized.