New and emerging therapies might provide benefit in patients with pulmonary arterial hypertension. Their efficacy and safety will be compared with existing combination therapies in randomized clinical trials. Appropriate end points for these trials need to be identified: these will include exercise testing, the composite end point of time to clinical worsening, and hemodynamic markers, includin...

Phase 3 clinical trials, which evaluate the effect that new interventions have on the clinical outcomes of particular relevance to the patient (such as death, loss of vision, or other major symptomatic event), often require many participants to be followed for a long time.There has recently been great interest in using surrogate end points, such as tumor shrinkage or changes in cholesterol leve...

A careful history, physical examination, and an electrocardiogram (ECG) are the most important components of the evaluation of a syncopal episode. These three components will provide a diagnosis or determine whether diagnostic testing is necessary in most patients. The potential cost savings made by avoiding unnecessary and expensive investigations are obvious when one considers that good clini...

Acute heart failure syndromes (AHFS) remain a major cause of morbidity and mortality, in part because the development of new therapies for these disorders has been marked by frequent failure and little success. The heterogeneity of current approaches to AHFS drug development, particularly with regard to end points, remains a major potential barrier to progress in the field. End points involving...

Surrogate end points in clinical research pose real danger. A surrogate end point is an outcome measure, commonly a laboratory test, that substitutes for a clinical event of true importance. Resistance to activated protein C, for example, has been used as a surrogate for venous thrombosis in women using oral contraceptives. Other examples of inappropriate surrogate end points in contraception i...

There are four fundamental atomic particles-the proton, the neutron, the electron, and the positron. The proton has mass and a unit positive electrical charge. The neutron has mass and no charge. The electron has very small mass compared with the proton and neutron, and has unit negative electrical charge. The positron is the positively charged counterpart of the electron, having equal mass and...

The objective response rate is the initial method to assess the activity of a novel anticancer agent. Response rates may not characterize a new agent's clinical benefit, however, especially if moderate to severe toxicity may be associated with treatment. Clinical end points, such as improvement in survival or relief of disease-related symptoms, provide clinicians with a more rational basis for ...

C hronic kidney disease (CKD) worsens over time by transitions through a sequence of stages, regardless of the specific cause of kidney damage or rate of progression (Figure 1). Recent guidelines and public health campaigns have focused on early detection and treatment of CKD on the basis of the rationale that treatments that are initiated early in the disease course will have a greater effect ...

This cross-sectional study clinically assesses the tightness of proximal contact points of fixed dental prosthesis with natural teeth. Sixty nine (69) patients visiting the Department of Prosthodontics, Armed Forces Institute of Dentists (AFID), Rawalpindi, were included. The crowns, as a single unit or terminal abutment of bridge, prepared and fabricated at the same institute were included. A ...

This paper reports results of a meta-analysis of construct reliability measures reported in MIS research. Based on 418 measures from 63 articles published in four major journals, it is observed that although scales developed more recently are no more reliable than those developed in the 1980s, the reliability of most scales reported in the literature is above generally accepted levels. However,...