The US Food and Drug Administration (FDA) has approved Allergan Inc. product Botox (botulinum toxin type A) to improve the appearance of moderate to severe glabellar lines, or furrows between the eyebrows. The approval applies to men and women 65 or younger.

The FDA approved Botox in 1989 for the treatment of crossed eyes and uncontrollable blinking. In December 2000, the drug won US approval for treating abnormal head position and neck pain associated with cervical dystonia.

Botox, administered by injection, improves the appearance of brow furrow lines by blocking the nerve impulses that lead to contraction of the major muscles in the forehead. Treatment is usually repeated at least every four months to preserve the effect.

FDA approval was based on a 12-month repeated-treatment trial of 537 patients and eight months of open-label follow-up of 373 of those subjects. Maximum response rate was achieved at day 30, with about 80% of Botox-group subjects identified by investigators as responders, compared with 3% of the placebo group.

The preoperative use of Botox to reduce adverse effects of blepharoplasty requires more support – very little literature is available and most of it reports personal surgical experience.

http://www.rcplondon.ac.uk/pubs/books/botox/botox.pdf

Fagien, Steven M.D. Temporal Brow Lift Using Botulinum Toxin A. Plastic & Reconstructive Surgery. 112(5) Supplement:105S-107S, October 2003.

The first study by Monreal and colleagues, was a prospective cohort follow-up study in which the primary goal was to assess the sensitivity of diagnostic work-up for occult malignancy in patients with VTE.  Their extensive work-up included medical history, physical exam (included pelvic, rectal, and breast exams), laboratory tests, or chest X-ray. Cancer was diagnosed in 34 patients (3.9%) which translates into a sensitivity of identifying malignancy by routine examination of 55.7% (95% CI, 43.3-67.5%).. Some patients had  cancer markers (PSA, CA125) and abdomino-pelvic ultrasonography and identified malignancies in 13 additional patients for a sensitivity of 48.1% (95% CI, 30.7-66.0%).

The randomized multicenter clinical trial conducted by Piccioli and colleagues, was designed to compare extensive screening for occult malignancy with no screening in patients with acute idiopathic VTE. The primary outcome evaluated cancer related mortality and the secondary outcome evaluated the cluster of cancer-related mortality, documented residual malignancy, or recurrent malignancy at 24 months.  The study had accrued a total of 201 patients (99 extensive screening, 102 control group) at the time it was terminated. Cancer related mortality occurred in 2% of the extensive screening group compared to 3.9% in the control group, an absolute difference of 1.9% (95% CI, -5.5-10.9%). The secondary outcome event occurred in 5.1% of the patients in the extensive screening group versus 7.9% of the control patients, an absolute difference of 2.8% (95% CI, -6.3-13.4%).

The most recent guideline to address this was by Mandala et al in 2011. It writes:

In conclusion, there is no consensus that any screening for malignancy needs to be performed in DVT. In individual cases of idiopathic DVT in your patients without risk factors, screening may be warranted. The extent of the diagnostic work-up in these patients should include a routine examination and should be performed in accordance with current screening recommendations.

M. Mandalà, A. Falanga and F. Roila Management of Venous Thromboembolism (VTE) in Cancer Patients: ESMO Clinical Practice Guidelines Ann Oncol 2011; 22 (Suppl 6): vi85-vi92.

Otten H-M, Prins MH. Venous Thromboembolism and Occult Malignancy. Thromb Res. 2001;102(6):V187-194.

Monreal M, Lensing AWA, Prins MH, Bonet M, Fernandez-Llamazares J, et al. Screening for occult cancer in patients with acute deep vein thrombosis or pulmonary embolism. J Thromb Haemost. 2004;2:876-881.

Piccioli A, Lensing AWA, Prins MH, Falanga A, Scannapieco GL, et al. Extensive screening for occult malignant disease in idiopathic venous thromboembolism: a prospective randomized clinical trial. J Thromb Haemost. 2004;2:884-9.

McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developedin collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Cardiol. 2009;53:1573.

Galiè N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2009;30:2493–537.