Observable characteristics coincident with internal cracks in teeth: Findings from The National Dental Practice-Based Research Network.

BACKGROUND: This study determined if there are observable patient-, tooth- and crack-level characteristics markedly associated with whether a tooth with an external crack also has an internal crack. METHODS: Two hundred nine dentists in The National Dental Practice-Based Research Network enrolled 2,858 adults with a vital permanent posterior tooth having at least 1 observed external crack. Presence and characteristics of internal cracks were recorded for 435 cracked teeth that were treated. Generalized estimating equations were used to identify significant (P < .05) independent odds ratios associated with the tooth having internal cracks. RESULTS: Overall, 389 teeth (89%) had at least 1 internal crack, with 46% of these teeth having 2 or more internal cracks. Sixty-nine percent of treated cracked teeth were associated with 1 or more types of pain assessed before treatment; 53% were associated with cold testing, 37% with bite testing, and 26% with spontaneous pain. In the final model, biting pain, having an external crack that connected with a restoration, or an external crack that extended onto the root was each associated with more than a 2-fold increased odds of having an internal crack. CONCLUSIONS: Essentially 9 of 10 teeth that had at least 1 external crack also had at least 1 internal crack. PRACTICAL IMPLICATIONS: The external cracks that a dental practitioner should be most concerned about, because they are most likely to be associated with internal cracks in the tooth, are those in which the patient experiences biting pain, is connected with a restoration of some type, or extends onto the root.

A phase I study of paclitaxel and continuous daily CAI in patients with refractory solid tumors.

BACKGROUND: Carboxyamido-triazole (CAI) is a calcium influx inhibitor with anti-angiogenic and anti-invasive properties and stabilizes tumor progression in patients. We hypothesized daily oral micronized CAI with q3 week paclitaxel would be well-tolerated and active. RESULTS: Twenty-nine heavily pretreated patients [median 3 [0-7]] were enrolled on five dose levels. No additive or cumulative toxicity was observed, and grade III nonhematological toxicity was rare. Neutropenia was the most common hematologic toxicity, seen in 79% of patients, with a trend towards increasing grade with higher paclitaxel doses. The recommended phase II dose defined by the maximum tolerated dose (MTD) was CAI 250 mg daily and paclitaxel 200 mg/m(2) q3weeks. Pharmacokinetic analysis revealed paclitaxel increases CAI trough concentration at all dose levels by over 100% (p < 0.0001). A trend towards higher steady-state CAI trough concentrations was found in patients with a partial response (PR; p = 0.09). Six patients had confirmed PR (24%; 4-67 cycles, median 10); two patients had minor responses. PATIENTS AND METHODS: Eligible patients with solid tumors received micronized CAI daily (150-250 mg PO) and paclitaxel intravenously q3weeks (175-250 mg/m(2)), sequentially escalating each drug. CAI preceded paclitaxel by one week to permit pharmacokinetic analysis. Patients were assessed for toxicity, pharmacokinetics and disease outcome. CONCLUSIONS: The MTD of the combination of CAI and paclitaxel is 250 mg daily and 200 mg/m(2) q3weeks, respectively. The combination is tolerable and has potential antitumor activity.

The devil is in the details: the pharmaceutical industry's use of gifts to physicians as marketing strategy.

Marketing costs exceed 30% of revenues for the pharmaceutical industry, with over 90% of the effort aimed at physicians. Although there are currently unprecedented numbers of regulatory activities focusing on relationships between the pharmaceutical industry and the medical profession, such legislation is often unrecognized or flouted. The potential influence, although minimized by both parties, must not be ignored. Physicians and drug companies will need to re-evaluate their responsibilities to their patients and their shareholders, and both groups should assume proactive and guidance roles in the transformation.