New oral anticoagulants

The new oral anticoagulants may prove to be one of the most significant innovations in clinical practice in the past 60 years. Apixaban and rivaroxaban are specific inhibitors of Factor Xa while dabigatran inhibits Factor IIa. The predictable pharmacological profile of these new agents will allow physicians to use these drugs without the need for routine coagulation monitoring which is the mainstay of warfarin therapy. In addition, these new agents have not been shown to have any food interactions and limited drug–drug interactions due to their minimal metabolism through the CYP450 system. This unique pharmacokinetic profile may usher in for clinicians a new era of managing thromboembolic disorders. In this paper, the pharmacology of these new oral anticoagulants are reviewed along with the major clinical trials in venous thromboembolism prevention in total hip and knee replacement orthopedic surgery, the treatment of venous thromboembolic disorders and stroke prevention in atrial fibrillation.     

Drug-induced oral ulcerations

Different side effects of drugs have been described in the oral cavity, including oral ulcerations. Direct contact between drugs and oral mucosa may induce chemical burn or local hypersensitivity. Less frequently, these drug-induced oral ulcerations are part of a complex reaction with cutaneous or systemic manifestations. Sometimes, one or more oral ulcerations appear as the main side-effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations usually appear after few weeks of treatment. In most of cases, these lesions resist to conventional treatments, with a rapid healing following the suppression of the responsible drug. This diagnosis is usually difficult, particularly with patients receiving multiple drug therapy. Besides, special attention must be paid to new drugs. Oral ulcerations following symptoms of burning mouth, metallic taste, dysgueusia or agueusia are strongly suggestive of a pharmacological origin. Most of the molecules able to induce solitary oral ulcerations are commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen, indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine, methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology: angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2-receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry: antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).     

Randomized comparison of two nystatin oral gels with miconazole oral gel for treatment of oral thrush in infants

Summary Recently, two commercial oral nystatin gels have been marketed in Germany (Candio-Hermal®, Hermal; Lederlind®, Lederle). In a prospective open randomized multicentre study involving 12 paediatricians in private practice, Candio-Hermal® and Lederlind® were compared with miconazole oral gel (Daktar®, Janssen) in 95 infants with oral thrush (candidosis). Oral and rectal swabs were taken on days 0 and 14. Treatment duration varied according to the amount of drug contained in one tube (Candio-Hermal® 10 days; Lederlind® 14 days; Daktar® 8 days). On day 14, clinical cure was observed in 23 of 27 infants treated with Daktar® (85.1%), in 15 of 35 infants treated with Candio-Hermal® (42.8%; p<0.0007); and in 16 of 33 infants treated with Lederlind® (48.5%; p<0.004). Clinical relapses were observed in 15 patients (Candio-Hermal®: n=9; Lederlind®: n=6). The overall oral mycologic cure rate was significantly higher with Daktar® (29.6%) and Candio-Hermal® (20.0%) than with Lederlind® (3.0%; p<0.005 and <0.03, respectively). It can be concluded that Daktar® oral gel is significantly more effective than Candio-Hermal® and Lederlind® in curing oral thrush in infants.

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Randomisierter Vergleich zweier Nystatin-Mundgele mit Miconazol-Mundgel für die Mundsoorbehandlung bei Säuglingen

Zusammenfassung Kürzlich sind in Deutschland zwei kommerzielle Nystatin-Mundgele in den Handel gekommen (Candio-Hermal®, Hermal, Lederlind®, Lederle). In einer prospektiven offenen randomisierten multizentrischen Studie mit 12 niedergelassenen Kinderärzten verglichen wir Candio-Hermal® und Lederlind® mit Miconazol-Mundgel (Daktar®, Janssen) bei 95 Säuglingen mit Mundsoor. Mundhöhlen- und Rektalabstriche wurden an den Tagen 0 und 14 entnommen. Die Behandlungsdauer variierte je nach der Gelmenge, die in einer Originalpackung enthalten ist (Candio-Hermal®: 10 Tage; Lederlind®: 14 Tage; Daktar®: 8 Tage). Wir sahen eine klinische Heilung des Mundsoors an Tag 14 bei 23 von 27 mit Daktar® behandelten Patienten (85,1%), bei 15 von 35 mit Candio-Hermal® behandelten Patienten (42,8%, p<0,0007) und bei 16 von 33 mit Lederlind® behandelten Patienten (48,5%, p<0,004). Klinische Rezidive wurden bei 15 Patienten beobachtet (Candio-Hermal®: n=9; Lederlind®: n=6). Die mykologische Gesamtheilungsrate war signifikant höher bei Daktar® (29,6%) und Candio-Hermal® (20,0%) als bei Lederlind® (3,0%, p<0,005 bzw. <0,03). Wir folgern, daß Daktar®-Mundgel signifikant effektiver einen Mundsoor bei Säuglingen heilt als Candio-Hermal® und Lederlind®.

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The study group consisted of the following paediatricians in private practice: Drs.K.-F. Bruchhaus, Holzgerlingen;R. Burr, Hirrlingen;H. Ebeling, Mössingen;C. Harter, Blaustein;H. Lange, Lingen;K. Moosmann, Albstadt;K. von Puttkamer, Tübingen;G. Schauerhammer, Korntal-Münchingen;P. Schlunk, Sigmaringen;U. Schmidt-Riese, Tübingen;R. Wartha, Oberndorf; andJ. Zimmer, Ehingen, Germany.     

Risk indicators for HIV-associated jointly occurring oral candidiasis and oral hairy leukoplakia

Joint occurrence of two or more diseases may impact their transmission, clinical presentation, management approaches, and treatment efficacy. Although oral candidiasis (OC) and oral hairy leukoplakia (OHL) are the most commonly occurring opportunistic oral diseases of HIV-infected patients, literature describing their joint occurrence is sparse. The purpose of this project was to develop an explanatory multivariable model for joint occurrence of OC and OHL (OC-OHL). This cross-sectional study examined 631 adult dentate HIV-1 seropositive persons for OC and OHL from 1995-2000 at the University of North Carolina Hospitals in Chapel Hill, NC. Data collected from medical record review, interviews and clinical examinations were analyzed using chi(2) tests, t itests, and nonparametric tests. Multivariable proportional odds models were developed, using the likelihood ratio test and adjusting for several demographic, behavioral, and biological factors. Thirteen percent of participants had OC only; 12.8% had OHL only; 4.6% had OC-OHL; whereas 69.7% had neither. Occurrence of OC-OHL was independently associated with CD4+ counts less than 200 cells per microliter (adjusted odds ratio [OR] (95% confidence interval {CI}) = 13.4 (6.6, 27.2) and CD4+ counts 200-499 cells per microliter (OR = 3.9 [1.9, 8.1]); current smokers (OR = 2.3 [1.4, 3.8]); and whites (OR = 1.7 [1.1, 2.5]). Combination antiretroviral therapy was protective (OR = 0.5 [0.3, 0.9]). In an HIV-1-infected population, lower CD4+ cell counts and smoking were important independent risk indicators for joint occurrence of OC and OHL.     

Anaphylaxis to oral furosemide

Furosemide, one of the most used diuretic drugs, rarely induces type-1 allergic reactions It is included in the non-aromatic sulfonamides but a cross-reactivity mechanism between this group and the sulfonamides antibiotics, has not been clearly demonstrated. A 24-year-old woman, 10 minutes after the intake of one pill of Seguril 40mg experienced oral itching, generalized urticaria, facial angioedema, dyspnea and hypotension. She recovered after the administration of parental adrenaline, methyl-prednisolone and dyphenhydramine. An skin prick test with furosemide (10 mg/ml) was negative. The intradermal skin tests were positive to furosemide (1 %) as well as sulfamethoxazole (0.03 mg/ml), with 10 atopic and non-atopic negative controls. The patient rejected the performance of an oral challenge test with sulfamethoxazole. IgE-mediated reactions to furosemide are infrequent, but it could be the cause of life-threatening reactions. We have reported a case of anaphylaxis after the oral administration of furosemide with a demonstrated hypersensitivity mechanism through the positive intradermal skin test. The previous administration of the drug could probably the mechanism of sensitization, but the positive intradermal test to sulfamethoxazole would open the hypothesis of a cross-reactivity between non-aromatic and antimicrobial sulfonamides. It could be necessary an oral challenge test with furosemide in allergic patients to sulfamides.     

Electrophysiology of oral encainide

The electrophysiologic effects of oral encainide were assessed in 15 patients. Electrophysiologic studies were performed before and after 3 or more days of oral encainide therapy, 100 to 300 mg/day (mean 242 ± 66). Patients received no other cardioactive drugs during this time. Encainide significantly (p < 0.005) lengthened the following: A-H interval (74.5 ± 21.5 to 105.5 ± 39.1 ms, mean ± standard deviation), the shortest atrial pacing cycle length maintaining 1:1 atrioventricular (A-V) nodal conduction (339.0 ± 71.3 to 417.0 ± 88.6 ms), H-V interval (47.5 ± 7.8 to 67.1 ± 12.9 ms), QRS interval (103.5 ± 30.9 to 132.3 ± 35.7 ms), right atrial (233.8 ± 27.2 ms to 282.9 ± 38.6 ms) and right ventricular (235.7 ± 15.6 to 267.1 ± 36.9 ms) effective refractory periods and Q-T interval (364.4 ± 38.0 to 416.9 ± 55.3 ms). The spontaneous sinus cycle length did not change significantly. In four patients who had accessory A-V muscle connections (two manifest, two concealed) encainide abolished anterograde conduction over the accessory pathway in two patients, and increased the retrograde effective refractory period and/or lengthened retrograde conduction time or blocked retrograde conduction in the accessory pathway, or all three variables, in all four patients. There was no correlation between the plasma encainide concentration obtained at the time of study and the magnitude of change in any electrophysiologic variable.It is concluded that (1) encainide depresses conduction in the A-V node, His-Purkinje system and accessory pathway, and increases refractoriness of the atrium, ventricle and accessory pathway, and (2) differences between these results and those of earlier studies using encainide in a single intravenous dose (which found no significant effects on A-V nodal conduction or atrial and ventricular refractoriness) may be explained in part by the effects of an active metabolite of encainide.     

New oral antidiabetic agents

The pathophysiology of hyperglycemia in type 2 diabetes (T2DM) involves 3 main defects: insulin deficiency, excess hepatic glucose output, and insulin resistance. Oral anti-diabetic agents act in a variety of ways. These include agents that stimulate insulin secretion, reduce hepatic glucose production, delay digestion and absorption of intestinal carbohydrate or improve insulin action. Because of improved knowledge of pathophysiology, new drugs with mechanisms of action focussed on specific pathophysiological alterations have appeared, in order to utilize all the possibilities of treating this condition. Here, we focus on the new agents used in the latest years and the overcoming ones in future, in particular incretin-based therapies, drugs inhibiting kidney glucose reabsorption (SGLT2 inhibitors), and glucokinase activators. The strategy for new drug development advocated here is to establish a broad range of anti-diabetic medicines with different mechanisms of action and potential opportunities for effective combination therapies.     

Nutrition and oral health

Reduced chewing function in community-dwelling older people with adequate general health is linked to having fewer than 20 teeth present or to wearing removable dentures. By chewing for longer periods of time or swallowing larger food particles they are normally able to compensate for the impaired function. The masticatory function can be restored by adequate prosthetic therapy, which results in increased activity of the masticatory muscles during chewing and reduces the chewing time and the number of chewing strokes until swallowing. In frail or dependent elderly people undernutrition is prevalent because of health problems, reduced appetite and poor quality of life. Poor oral health and xerostomia are often associated with a reduced body mass index and serum albumin level and the avoidance of difficult-to-chew foods. Maintenance or re-establishment of masticatory function is an integral part of the medical health care of these patients, with the aim of improving their nutritional status and quality of life.