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BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P

A 68-year-old man was seen in the rheumatology clinic because of increasing skin tightness, joint pain, and edema of the hands and feet. Nine months earlier, he had received a diagnosis of multiple myeloma and had undergone autologous stem-cell transplantation.

BACKGROUND We conducted a double-blind, randomized, placebo-controlled trial to determine the effects of oral cyclophosphamide on lung function and health-related symptoms in patients with evidence of active alveolitis and scleroderma-related interstitial lung disease. METHODS At 13 clinical centers throughout the United States, we enrolled 158 patients with scleroderma, restrictive lung physiology, dyspnea, and evidence of inflammatory interstitial lung disease on examination of bronchoalveolar-lavage fluid, thoracic highresolution computed tomography, or both. Patients received oral cyclophosphamide (≤2 mg per kilogram of body weight per day) or matching placebo for one year and were followed for an additional year. Pulmonary function was assessed every three months during the first year, and the primary end point was the forced vital capacity (FVC, expressed as a percentage of the predicted value) at 12 months, after adjustment for the baseline FVC. RESULTS Of 158 patients, 145 completed at least six months of treatment and were included in the analysis. The mean absolute difference in adjusted 12-month FVC percent predicted between the cyclophosphamide and placebo groups was 2.53 percent (95 percent confidence interval, 0.28 to 4.79 percent), favoring cyclophosphamide (P

Background and Methods To define better the bacteria responsible for infections of dog and cat bites, we conducted a prospective study at 18 emergency departments. To be eligible for enrollment, patients had to meet one of three major criteria for infection of a bite wound (fever, abscess, and lymphangitis) or four of five minor criteria (wound-associated erythema, tenderness at the wound site, swelling at the site, purulent drainage, and leukocytosis). Wound specimens were cultured for aerobic and anaerobic bacteria at a research microbiology laboratory and, in some cases, at local hospital laboratories. Results The infected wounds of 50 patients with dog bites and 57 patients with cat bites yielded a median of 5 bacterial isolates per culture (range, 0 to 16) at the reference laboratory. Significantly more isolates grew at the reference laboratory than at the local laboratories (median, 1; range, 0 to 5; P

To the Editor: In his review of skin and softtissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA), Daum (July 26 issue)1 cites a study2 indicating that intravenous trimethoprim–sulfamethoxazole (TMP-SMX) is significantly less effective than vancomycin for the treatment of serious S. aureus infections. However, in this randomized, double-blind, comparative trial of TMP-SMX and vancomycin, therapeutic failures occurred only in patients with methicillin-susceptible S. aureus (MSSA) infections. TMP-SMX was successful in treating all MRSA infections, including tricuspid-valve endocarditis. Clinical failures commonly occurred with MSSA tricuspid-valve endocarditis; otherwise, the cure rates with TMPSMX and with vancomycin were similar. On the basis of the results of this study, vancomycin may be superior for MSSA infections; however, the same cannot be concluded for MRSA infections. Although the currently available clinical data for community-associated MRSA skin infections are sparse, in this era of an increasing incidence of MRSA infection and concern about the variable efficacy of vancomycin, TMP-SMX may be a useful alternative in selected cases.

In a prospective epidemiologic study of 1001 middle-aged men, we examined the relation between dietary information collected approximately 20 years ago and subsequent mortality from coronary heart disease. The men were initially enrolled in three cohorts: one of men born and living in Ireland, another of those born in Ireland who had emigrated to Boston, and the third of those born in the Boston area of Irish immigrants. There were no differences in mortality from coronary heart disease among the three cohorts. In within-population analyses, those who died of coronary heart disease had higher Keys (P = 0.06) and modified Hegsted (P = 0.02) dietary scores than did those who did not (a high score indicates a high intake of saturated fatty acids and cholesterol and a relatively low intake of polyunsaturated fatty acids). These associations were significant (P = 0.03 for the Keys and P = 0.04 for the modified Hegsted scores) after adjustment for other risk factors for coronary heart disease. Fiber intake (P = 0.04) and a vegetable-foods score, which rose with increased intake of fiber, vegetable protein, and starch (P = 0.02), were lower among those who died from coronary heart disease, though not significantly so after adjustment for other risk factors. A higher Keys score carried an increased risk of coronary heart disease (relative risk, 1.60), and a higher fiber intake carried a decreased risk (relative risk, 0.57). Overall, these results tend to support the hypothesis that diet is related, albeit weakly, to the development of coronary heart disease.

OPTIONS for the treatment of thoracoabdominally conjoined twins are largely dependent on the anatomy of the cardiovascular system.1 2 3 The extent of the conjunction of the heart and the severity of the associated cardiac defects primarily determine the feasibility of successful separation of the infants. Typically, the cardiovascular system is investigated first in the evaluation of thoracoabdominally conjoined twins. Only if the condition of the heart and associated structures is suitable for separation are the other organ systems, such as the gastrointestinal and urinary tracts, investigated. Definition of the cardiovascular anatomy in utero would facilitate prenatal counseling and perinatal management. Recent . . .

Raynaud's phenomenon may cause severe digital pain and functional disability, particularly in patients with underlying connective-tissue disease. The treatment of this condition is difficult.1 Nife...

Limited data are available on the relation between physical fitness and mortality from cardiovascular disease. We examined this question in a study of 4276 men, 30 to 69 years of age, whom we followed for an average of 8.5 years. Examinations at base line included assessment of conventional coronary risk factors and treadmill exercise testing. The heart rate during submaximal exercise (stage 2 of the exercise test) and the duration of exercise were used as measures of physical fitness. Men with incomplete data (n = 308) or who were using cardiovascular drugs (n = 213) were excluded from the analysis. Men who had clinical evidence of cardiovascular disease at base line (n = 649) were analyzed separately. Forty-five deaths from cardiovascular causes occurred among the remaining 3106 men. A lower level of physical fitness was associated with a higher risk of death from cardiovascular and coronary heart disease, after adjustment for age and cardiovascular risk factors. The relative risk of death from...

PROTEIN is an essential component of protoplasm. Both structure and function of bodytissues are dependent on specific proteins, such as enzymes and hormones. Fluid balance, hemostasis, many hormone and lipoprotein complexes and certain immune mechanisms are related to protein nutrition. Recent observations derived from many sources have re-emphasized and extended the clinical significance of plasma proteins, protein metabolites and protein degradation products. The concept of constant interchange or "dynamic equilibrium" between the proteins of blood and other tissues,1 , 2 the elucidation of indispensable amino acids,3 , 4 the application of heavy nitrogen and marked carbon to problems of nitrogen metabolism and immunology5 6 7 and . . .

NUTRITION in clinical medicine has come to have several different connotations depending on whether one is thinking of diagnosis and specific treatment or of patient management. Under the first hea...

MOST general practitioners, internists and neuropsychiatrists with a sufficiently large and varied practice sooner or later have the distressing experience of mistaking a brain tumor for a psychoneurosis or of unnecessarily delaying the correct diagnosis. As in other disorders involving behavior, the opinions of family and friends, as well as of other lay people in the community, often contribute to confuse the opinions of the physician, particularly of the general practitioner. Such considerations stimulated the present investigation of diagnostic errors made in 100 proved cases of brain tumor. It is impossible to extract a bibliography on diagnostic errors from the . . .

BACKGROUND: The next-generation cystic fibrosis transmembrane conductance regulator (CFTR) corrector VX-659, in triple combination with tezacaftor and ivacaftor (VX-659–tezacaftor–ivacaftor), was developed to restore the function of Phe508del CFTR protein in patients with cystic fibrosis. METHODS: We evaluated the effects of VX-659–tezacaftor–ivacaftor on the processing, trafficking, and function of Phe508del CFTR protein using human bronchial epithelial cells. A range of oral VX-659–tezacaftor–ivacaftor doses in triple combination were then evaluated in randomized, controlled, double-blind, multicenter trials involving patients with cystic fibrosis who were heterozygous for the Phe508del CFTR mutation and a minimal-function CFTR mutation (Phe508del–MF genotypes) or homozygous for the Phe508del CFTR mutation (Phe508del–Phe508del genotype). The primary end points were safety and the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV1). RESULTS: VX-659–tezacaftor–ivacaftor significantly improved the processing and trafficking of Phe508del CFTR protein as well as chloride transport in vitro. In patients, VX-659–tezacaftor–ivacaftor had an acceptable safety and side-effect profile. Most adverse events were mild or moderate. VX-659–tezacaftor–ivacaftor resulted in significant mean increases in the percentage of predicted FEV1 through day 29 (P

The fact that they have M.D.'s backing up the product is the biggest plus they have. . . . For decades the multilevel field [of marketing] has been the province of snake-oil salesmen, so the credib...