Intermittent Prophylaxis Research Articles

Management of Menstrual Migraine: A Review of Current Abortive and Prophylactic Therapies

After menarche, women have an increased prevalence of migraine compared to men. There is significant variability in the frequency and severity of migraine throughout the menstrual cycle. Women report migraines occur more frequently during menses, and that those are more severe than other migraines. This creates a unique challenge of effectively treating menstrually related and pure menstrual migraines. As with treatment of other migraines, both abortive and prophylactic treatment regimens are used. Triptans demonstrate efficacy in the abortive management of menstrually related and pure menstrual migraines. For migraines that occur primarily during menses or that are particularly resistant to other therapies, intermittent prophylactic therapies can be used. Naproxen and estrogens have been studied for this use. More recently, triptans have been examined and have shown efficacy for intermittent prophylaxis of menstrual migraine.

Intermittent prophylaxis in febrile convulsions: diazepam or valproic acid?

In an open, prospective, randomized, and hospital-based study, comprising 219 consecutive children, 169 were given intermittent prophylaxis for one year, receiving either diazepam or valproic acid after their first febrile convulsion. Children admitted on odd dates (n = 89) were given rectal diazepam in solution every 12 h, whenever the temperature was 38.5 degrees C or more. Children admitted on even dates (n = 80) were given valproic acid as suppositories at times of fever. Twenty-three children in the diazepam group had a recurrence within 1 year versus 14 in the valproic acid group. On an intention-to-treat basis the 12-month recurrence rates in the 2 groups were similar, 27% vs 20%. The latter is well below figures for untreated controls from Denmark (32%), suggesting that intermittent valproic acid at times of fever may be effective, but further studies are needed. The number of complex recurrences, however, were significantly higher in the valproic acid group than in the diazepam group. Parental non-compliance was a major problem, and in the 2 study groups only 5 and 12 children, respectively, with recurrences were treated adequately. Sixty-nine children receiving diazepam had side-effects vs 37 receiving valproic acid. None were serious.

First Census of Patients with Hemophilia a/B and Von Willebrand Disease Type 3 in the Eastern Part of Germany since 1988

Diagnostics and treatment of severe forms of haemorrhagic diatheses (HD), such as haemophilia A, B or type 3 von Willebrand disease (VWD) need high standards in haemophilia treatment centers (HTCs). Due to their generally low incidence, a close cooperation of haemophilia treaters is needed to optimize treatment strategies. For this purpose, the “Kompetenznetz Hämorrhagische Diathesen Ost” was founded. The first project was the conduction of a survey of epidemiological data of patients with HA, HB and type 3 VWD in all HTCs in the eastern part of Germany. The study assessed the data regarding numbers of patients treated with HA, HB or type 3 VWD, disease severity, regime of coagulation factor replacement (CFR) and the frequency of factor VIII and IX inhibitors. Data of 838 patients (a prevalence of 52.38 per 1 million citizen) from 27 HTCs were evaluated (5–151 per HTCs). Among the included patients, 201 (prevalence: 12.56/million) were children or adolescents (< 18 years). 81 children suffered from severe HA (prevalence: 5.06/million), 20 from severe HB (prevalence: 1.25/million) and 10 from type 3 VWD (prevalence: 0.63/million). In 637 adults (prevalence: 39.82/million) we found 246 with severe HA (prevalence: 15.38/million), 51 severe HB (prevalence: 3.19/million) and 28 VWD of type 3 (prevalence: 1.75/million). The most commonly used treatment of CFR in patients with severe disease was prophylactic modality. 90% of the children received prophylaxis, but also in 64% of the adults an intermittent or longterm secondary prophylaxis was the preferred treatment. At the time of survey conduction, a factor VIII or IX inhibitor was present in 1.9% of the children and in 1.6% of the adults with haemophilia. Our data allow an overview of the number of patients and treatment strategies in the eastern part of Germany.

Safety and efficacy of lower-dose unfractionated heparin for prophylaxis of deep vein thrombosis and pulmonary embolism in an Asian population

The objective of this study is to analyze the tolerance and efficacy of the subcutaneous administration of a reduced 2,500-unit low-dose unfractionated heparin given for an efficacious, yet Asian population-sensitive, prophylaxis for deep vein thrombosis and fatal pulmonary embolism. Eighty-seven Japanese patients were operated on either for abdominal or pelvic complications or both, as well as for gynecologic conditions including ovarian, cervical, and corpus cancers. Thirty-two of the patients were administered the experimental low dose of unfractionated calcium heparin for prophylaxis. The 2,500 units of low-dose unfractionated heparin were given subcutaneously 2 h preoperatively and again 12 h postoperatively. Other standard methods of mechanical prophylaxis, including graduated compression stockings and intermittent pneumatic compression, were performed. Fifty-five of the patients were not administered heparin, but did receive the same standard mechanical graduated compression stockings and intermittent pneumatic compression prophylaxis. We compared the surgical and postsurgical complications noted for low-dose unfractionated heparin patients with the results of those who received no heparin prophylaxis and analyzed this data using the Mann-Whitney U-test. There was no significant difference in the mean of the blood loss volumes. There were also no significant differences found in the perioperative bleeding complications between the two groups. However, three (3/55; 6%) of the patients in the no-heparin group suffered a symptomatic pulmonary embolism, although none were fatal. There were no pulmonary embolism onsets in the heparin prophylaxis group. We feel that we have provided evidence that several serious complications, such as perisurgical hemorrhage, deep vein thrombosis, fatal pulmonary embolism, and increased postoperative recovery times, can be prevented by prophylaxis with 2,500-unit low-dose unfractionated heparin.

Menstrual-Related Pain Conditions: Dysmenorrhea and Migraine

Menstrual disorders affect millions of women in the United States and represent an important health burden. The most common menstrual disorders are dysmenorrhea and headache; these conditions are leading causes of work or school absenteeism and substantially impact quality of life. Headache associated with menses is often migraine and referred to as menstrual migraine. Although the pathogenesis of menstrual-related pain conditions is not fully understood, menstrual-related overproduction of prostaglandins is implicated in the pathophysiology of both menstrual migraine and dysmenorrhea. In clinical practice, nonsteroidal anti-inflammatory drugs (NSAIDs) are considered the first-line therapeutic option for managing pain associated with dysmenorrhea. NSAIDs also play a role in the acute treatment and intermittent prophylaxis of migraine. Triptans, a class of highly selective serotonin receptor agonists, represent the gold standard for acute treatment of migraine. In addition, hormone therapy is effective in many cases for treating dysmenorrhea and may be beneficial in the management of menstrual migraine. Thus, overlapping treatment regimens may be advantageous in treating the coexisting menstrual-related pain conditions of dysmenorrhea and migraine.

New recommendations for the prevention of infective endocarditis

A revision of the American Heart Association guidelines for the prevention of infective endocarditis was recently published in their journal Circulation. Pediatric practitioners as well as other primary care specialists and dentists will need to advise patients as to whether they require antibiotic prophylaxis prior to invasive procedures. Some patients who formerly received prophylaxis for certain procedures may need an explanation when they are told that antibiotic prophylaxis is no longer recommended for them. New research casts doubt on whether dental, surgical and invasive diagnostic procedures really are the cause of infective endocarditis. Events of daily life are more likely to cause bacteremia than planned procedures. Neither constant nor intermittent antibiotic prophylaxis has been proven to prevent endocarditis. The authors of the revised American Heart Association guidelines made significant changes from past guidelines restricting prophylaxis to only those individuals with cardiac conditions that pose the highest risk for bad outcome should infective endocarditis occur and only for dental procedures causing the highest bacteremia rates.

Patienten mit Hämophilie A, B oder von-Willebrand-Syndrom Typ 3

Diagnostics and treatment of severe forms of haemorrhagic diatheses (HD), such as haemophilia A, B or type 3 von Willebrand disease (VWD) need high standards in haemophilia treatment centers (HTCs). Due to their generally low incidence, a close cooperation of haemophilia treaters is needed to optimize treatment strategies. For this purpose, the Kompetenznetz Hämorrhagische Diathesen Ost was founded. The first project was the conduction of a survey of epidemiological data of patients with HA, HB and type 3 VWD in all HTCs in the eastern part of Germany. The study assessed the data regarding numbers of patients treated with HA, HB or type 3 VWD, disease severity, regime of coagulation factor replacement (CFR) and the frequency of factor VIII and IX inhibitors. Up to now, data of 838 patients from 27 HTCs were evaluated (5-151 per HTCs). Among the included patients, 201 were children or adolescents (<18 years). 81 children suffered from severe HA, 20 from severe HB and 10 from type 3 VWD. In 637 adults we found 246 with severe HA, 51 severe HB and 28 VWD of type 3. The most commonly used treatment of CFR in patients with severe disease was prophylactic modality. 90% of the children received prophylaxis, but also in 64% of the adults an intermittent or long-term secondary prophylaxis was the preferred treatment. At the time of survey conduction, a factor VIII or IX inhibitor was present in 1.9% of the children and in 1.6% of the adults with haemophilia. Our data allow an overview of the number of patients and treatment strategies in the eastern part of Germany.

Comment on Childhood Febrile Seizures: Overview and Implications by Tonia Jones and Steven J. Jacobsen

Reading the review article “Childhood Febrile Seizures: Overview and Implications” by Jones and Jacobsen that was recently published in International Journal of Medical Sciences (Int J Med Sci 2007; 4:110-114, http://www.medsci.org/v04p0110.htm), we noticed some points which we believe are worth mentioning. Additionally, we would like to report our own data from a large prospective study with a long-term follow up. The authors make a brief reference to the predictors of febrile seizure (FS) recurrence; however they do not distinguish between the first recurrence and further ones. In our recently published study we identified not only the prognostic factors for the first recurrence but also for further ones. Statistical analysis showed as significant prognostic factors for the first recurrence of FS: low age at onset (< 18 months), low duration of fever (< 12 hours), height of fever up to 38.5oC, recurrence within the same febrile illness, neurological abnormalities, family history of FS and particularly maternal preponderance. The latter one is an extremely strong prognostic marker, for the first time mentioned in literature. Prognostic factors for the second or further recurrences revealed that the factors retaining their prognostic value were: family history of FS and low age at onset. The rest factors lost their power for the prognosis of multiple recurrences 3. As far as the issue of management of FS is concerned, intermittent rectal diazepam prophylaxis is found in our study to be effective and safe for the prevention of FS recurrence only in high-risk population 4. Others have evaluated the use of oral diazepam prophylaxis at times of fever and demonstrated significant reduction in the percentage of febrile seizure recurrence 5, 6 who also report minor and reversible side effects. Many are concerned that the side effects of diazepam may delay the diagnosis of an underlying illness (e.g. meningitis or encephalitis). Infection of central nervous system must always be considered in case of a seizure with fever, especially in infants less than 18 months of age. When the clinician is uncertain, a lumbar puncture should be performed. In our opinion, parental education is essential and optimal management of febrile seizures involves preventing their recurrence only in those populations that are at high risk. This can be done most effectively with intermittent rectal diazepam provided that it is given at the onset of fever. The authors do not refer at all to the prognostic factors for the subsequent development of epilepsy after FS, which would have been a valuable additional parameter to be included in their review article. Major risk factors for the occurrence of epilepsy after FS are: age at onset of FS older than 3 years old, family history of epilepsy, complex FS and principally multiple episodes of FS (more than four). Rational thought is that since multiple febrile seizures lead to epilepsy and short duration seizures beget new seizures 1, 2, then the prevention of febrile seizures may reduce the risk of subsequent epilepsy. However, studies have shown no difference in the occurrence of epilepsy among children who received prophylaxis for FS and those without prophylaxis. It is possible that a common genetic predisposition is responsible for the development of epilepsy after FS, rather than an underlying lesion caused by recurrent seizures. However, large prospective studies are needed in order to verify that prevention of FS does not also prevent subsequent epilepsy.

Effectiveness of Intermittent Diazepam Prophylaxis in Febrile Seizures: Long-Term Prospective Controlled Study

The efficacy of intermittent rectal diazepam prophylaxis is assessed in the prevention of febrile seizures. In a prospective randomized cohort trial, 139 children (77 girls, 62 boys) who experienced a first febrile seizure were allocated to two groups: group A, which received intermittent diazepam (n = 68), and group B, which received no prophylaxis (n = 71). All children had a 3-year follow-up. The inclusion criteria were no personal history of afebrile seizures, normal neurodevelopment, no previous anticonvulsant therapy, and age between 6 months and 3 years. Each group was stratified to low, intermediate, and high risk according to the available clinical data. The 36-month recurrence rates in the no-prophylaxis group were 83% in high-risk patients, 55% in intermediate-risk patients, and 46% in low-risk patients. In the prophylaxis group, the recurrence rates were reduced in all risk groups: 38%, 35%, and 33%, respectively. Intermittent diazepam prophylaxis reduces the recurrence rate mainly in high-risk children provided that sufficient doses are given on time and adequately.

Early Start to Therapy Preserves Kidney Function in Spina Bifida Patients

ObjectiveRenal scarring and renal failure remain life-threatening for children born with spinal dysraphism. We reviewed our data of spina bifida patients to evaluate whether optimal treatment of the neurogenic bladder from birth onwards can preserve kidney function. MethodsWe reviewed data on all newborns with spinal dysraphism who were referred to our hospital between January 1988 and June 2001. We looked at their situations at referral and at follow-up: the type of treatment, antimuscarinic agents, clean intermittent catheterisation (CIC), antibiotic prophylaxis, and operations (sling procedures, bladder augmentations, antireflux procedures). Renal function (ultrasound, DMSA scan, serum creatinin, creatinin clearance) and bladder function (urodynamic studies) were evaluated over time. ResultsData of 144 children of 176 could be evaluated by the end of the study: 5 patients had pre-existing renal abnormalities, 69 had an overactive sphincter, 27 had reflux, and six had renal scarring. None are currently developing end-stage renal disease. All patients with spina bifida aperta started CIC and antimuscarinic therapy shortly after birth. Five of the six patients with renal scarring were started on therapy with intermittent catheterisation and antimuscarinic therapy several months after birth. Sixty-three of 82 children with spina bifida were dry at school age (age six), although 37 of these had not had an operation. ConclusionWe show that an early start to therapy helps to safeguard renal function for children born with spina bifida. Our data support other recent reports that children born with spina bifida can probably use their own kidneys for a lifetime, if they are given adequate urological treatment. To protect the upper urinary tract, we need to ensure low intravesical pressure by starting children early on CIC (the preferred treatment); antimuscarinic agents to counteract detrusor instability are indispensable in most cases. Proactive treatment of risks for upper tract deterioration results in a negligible loss of renal function, even when early urinary continence is included in the treatment protocol.

A RANDOMIZED CONTROLLED TRIAL TO COMPARE EFFICACY OF ORAL CLOBAZAM WITH ORAL DIAZEPAM FOR PROPHYLAXIS OF FEBRILE SEIZURES

Objectives: Objectives: To compare the efficacy of intermittent prophylaxis with oral clobazam versus oral diazepam in children with febrile seizures.

Frovatriptan: a review of pharmacology, pharmacokinetics and clinical potential in the treatment of menstrual migraine

Frovatriptan is an orally active 5-hydroxytryptamine (5-HT) receptor agonist which binds with high affinity to 5-HT(1B) and 5-HT(1D) receptors. Earlier clinical trials demonstrated that frovatriptan 2.5 mg is significantly more effective than placebo in the acute management of migraine and its associated symptoms. More recently, frovatriptan was shown to be effective in the management of menstrual migraine. The incidence of menstrual migraine in subjects receiving frovatriptan 2.5 mg twice daily during the six day perimenstrual period was 41% compared with 67% with placebo. Frovatriptan treatment is generally well tolerated. The most commonly reported adverse effects were dizziness, paresthesia, dry mouth, and fatigue. Pharmacologic studies demonstrated that frovatriptan is cerebroselective. Its selectivity for cerebral vessels lessens the potential for undesirable peripheral effects. Frovatriptan has a terminal deposition half-life of approximately 26 hours, which appears to be independent of age, gender, and renal function. This imparts that frovatriptan may be particularly well suited to patients with prolonged migraines and those who suffer migraine recurrence. Frovatriptan does not alter cytochrome P450 (CYP450) isoenzymes, as such it is unlikely to affect the metabolism of other drugs. No dosage adjustments are necessary based on age, renal, or mild to moderate hepatic impairment. Apart from its efficacy in the acute management of migraine, frovatriptan is an effective agent when used as either acute therapy or as intermittent prophylaxis therapy of menstrual migraines, particularly in women who do not respond to conventional therapies.

Indikation der intermittierenden Diazepamprophylaxe bei Fieberkrämpfen

In a prospective controlled study we evaluated the efficacy of intermittent diazepam prophylaxis in the recurrence rate of febrile seizures (FS). A total of 139 children aged between 6 and 36 months, who had a first FS, were enrolled in the study and were randomly allocated to two groups: group (A) that received diazepam prophylaxis and group (B) without prophylaxis. All children were followed up for at least 3 years after their first FS. The prophylaxis group (n = 68) received rectal diazepam the first two days of a febrile illness, whenever the temperature was > 38 degrees C (0.33 mg/kg every 8 h on the first day, and 0.33 mg/kg every 12 h on the second day of fever, max. dosage 7.5 mg). The no-prophylaxis group (n = 71) did not receive any prophylaxis at all. Each group was stratified to low, intermediate and high risk subgroups according to the following clinical data: age at the first febrile seizure </= 15 months, positive family history of febrile seizure or epilepsy in first degree relatives, complex first febrile seizure and frequent febrile illness. The 3-year recurrence rates in the no-prophylaxis group were 83 % in high- risk, 55 % in intermediate-risk and 46 % in low-risk patients. In the prophylaxis group we established a reduction of febrile seizure recurrence at 38 %, 35 % and 33 % in the three risk subgroups respectively. The intermittent prophylaxis with rectal diazepam during febrile episodes lead to a reduction of febrile seizure recurrence, especially in high-risk patients. The results of our study set the indication for the use of intermittent diazepam prophylaxis in this subgroup.

Early diagnosis of the urofacial syndrome is essential to prevent irreversible renal failure

The urofacial or Ochoa syndrome is a rare disease characterized by the presence of functional obstructive uropathy associated with peculiar facial features when patients attempt to smile or laugh. Unfortunately, many of these patients remain without proper diagnosis or adequate treatment due to lack of recognition of the disease. This can ultimately result in upper tract deterioration and eventual renal failure. We present our experience with this rare syndrome. We identified 3 patients who presented initially with acute renal failure, urinary tract infection (UTI) and severe dysfunctional elimination. All patients were thoroughly evaluated, including screening for spinal cord anomalies, and were subsequently diagnosed with urofacial syndrome. At the outset, the two older patients (aged 4 and 9 years) presented with the typical facial features when attempting to smile or laugh. One patient in the newborn period presented with urinary and fecal retention and septicemia and, to our knowledge, represents the youngest case of urofacial syndrome reported so far. All patients were evaluated with ultrasonography, renal scan, voiding cystourethrogram (VCUG) and urodynamics. Findings included hydronephrosis and a thick-walled, trabeculated bladder with poor compliance and detrusor hypereflexia respectively in each patient. All were subsequently treated with clean intermittent catheterization (CIC), antibiotic prophylaxis and anticholinergic therapy. One patient required appendicovesicostomy for CIC due to discomfort secondary to a sensate urethra. Our series demonstrates that early recognition of this rare syndrome is necessary to adequately treat and prevent upper tract deterioration in these unique individuals. Although the urofacial is difficult to diagnose in infants, cognizance must be maintained in order to prevent severe subsequent sequalae.

Recurrent Antiviral‐Resistant Genital Herpes in an Immunocompetent Patient

Herpes simplex virus type 2 (HSV-2) resistance to antiviral drugs has been described primarily in immunocompromised patients. We report an apparently immunocompetent, human immunodeficiency virus-negative male patient who has experienced repeated HSV-2 genital outbreaks despite receiving antiviral prophylaxis with several different drugs. Several of the HSV-2 genital isolates from this patient have been confirmed as resistant to acyclovir and penciclovir. Antiviral resistance occurred in the setting of long-term prednisone treatment and intermittent acyclovir prophylaxis at suboptimal doses and persisted despite the cessation of oral steroid treatment. The patient's genital herpes outbreaks were not controlled by high-dose prophylaxis with acyclovir, valacyclovir, and famciclovir. Cessation of antiviral prophylaxis resulted in reversion of this patient's HSV-2 isolates to acyclovir and penciclovir sensitivity, although resistant virus reappeared when antiviral prophylaxis was resumed. Transmission of a sensitive HSV-2 strain from this patient to a female sex partner was observed. These observations confirm previous reports that resistance to acyclovir may develop during prophylactic therapy in an otherwise well, immunocompetent patient. These findings support the conclusion that both drug-sensitive and drug-resistant HSV-2 strains established latency in this patient and that both strains are capable of frequent reactivation.

Advanced strategies of short-term prophylaxis in menstrual migraine: state of the art and prospects

Patients suffering from menstrual migraine (MM) may be ideal candidates for an intermittent prophylaxis, usually termed short-term or mini-prophylaxis. It covers the whole period of vulnerability, e. g., the perimenstrual period, starting some days before the expected onset of MM attack. Theoretically MM attacks are an optimal target for drugs specifically developed for acute head pain. Unfortunately, due to their particular tendency to be longer, more intense and less responsive to analgesics, symptomatic approaches alone are not often able to completely control pain and its correlates. Many drugs have been proposed for short-term prophylaxis of MM. In this paper we analyse only non-steroidal anti-inflammatory drugs, coxibs and triptans (especially those with longer half-life, naratriptan and frovatriptan). Moreover, MM can be prevented by a variety of hormonal manipulations, including oral contraceptives, which may be administered with an extended-dosing strategy; oestrogen replacement therapy; antioestrogen agents (danazol, tamoxifen); gonadotropin-releasing hormone agonists followed by oestrogen add-back therapy. Finally, the use of some products, such as magnesium and phytoestrogens, that probably meet the requirements of those patients that appreciate a more "natural" approach, is discussed.

Deep Venous Thrombosis and Pulmonary Embolism in Neurosurgery: A Review of the Risks and Benefits of Prophylaxis

Background : In neurosurgery and spine surgery in particular, the unique risks and benefits of utilizing different prophylaxis regimens against deep venous thrombosis (DVT) and pulmonary embolism (PE) must be carefully weighed. Our aim was to comprehensively review the safety and efficacy of different regimens of prophylaxis against DVT and PE in neurosurgical cranial and spinal studies.Methods : Patients undergoing cranial or spinal procedures may receive one or more types of prophylaxis; elastic stockings (ES), intermittent pneumatic compression stockings (IPC), low dose unfractionated subcutaneous heparin (typically 5000 U q12h), and/or low dose low molecular weight heparin alternatives. The incidence of DVT, PE, and hemorrhage, particularly for those receiving low dose fractionated or low molecular weight heparin, were reviewed.Results : IPC stockings appeared to be very effective, particularly in spinal surgical series where the frequency of DVT/PE remained lower than in cranial studies. Although the addition of low dose unfractionated subcutaneous or low dose low molecular weight heparin regimens further decreased the frequency of DVT and PE, it carried a 2%-4% risk of major postoperative hemorrhage.Conclusions : Intermittent compression stocking prophylaxis (IPC) alone provide adequate prophylaxis against DVT and PE in most patients undergoing spinal procedures. The “value added” of low dose unfractionated subcutaneous or low dose low molecular weight heparin regimens regarding further reduction in the incidence of DVT and PE, poses the significant risk of major postoperative hemorrhage.

Pathogens in acute otitis media—impact of intermittent penicillin V prophylaxis on infant nasopharyngeal flora

Objective: To investigate whether intermittent short-term courses of penicillin V (PcV) administered as intermittent prophylaxis against acute otitis media (AOM) during upper respiratory tract infections altered the nasopharyngeal bacterial flora and/or its susceptibility to penicillin. Methods: In a double blind, placebo controlled study 70 children (30 in the PcV group and 40 in the placebo group) were followed for 1 year. At episodes of upper respiratory tract infection the children were given PcV or placebo and then seen by one of the investigators within 3 days. The tympanic membranes were examined by otomicroscopy and a culture from the nasopharynx was obtained. If AOM was found PcV was given (25 mg/kg bw b.i.d) for 5 days. If the child presented normal eardrums or signs of secretory otitis media (SOM) the study treatment was continued for a total of 5 days. All children were also examined bimonthly throughout the study irrespective of episodes of URTI or AOM. Results: No increase in the number of isolates of S. pneumoniae with reduced susceptibility to penicillin (MIC≥0.125 mg/l) was noted in either group compared with the incidence in the population in Sweden at the time of the study (when ca. 10% of pneumococci had a reduced susceptibility to penicillin). The number of cultures positive for S. pneumoniae were statistically reduced in children during treatment with PcV compared with children receiving placebo, while the number of cultures positive for H. influenzae and M. catarrhalis were unaffected. No increase in the number of cultures positive for β-lactamase producing H. influenzae was noted (ca. 10%). Conclusion: Repetitive short term PcV courses during URTI in infants did not increase the number of cultures positive for S. pneumoniae with reduced susceptibility to penicillin or β-lactamase producing H. influenzae.

Venous thromboembolism prophylaxis: patients at high risk to fail intermittent pneumatic compression

Objective To identify patients who fail intermittent pneumatic compression and who might be considered for other more intense thromboembolic prophylaxis. Methods We conducted a retrospective review of consecutive gynecologic surgery patients treated with intermittent pneumatic compression. Risk factors associated with thromboemboli and demographic data were reviewed. Clinical suspicion of thromboemboli was confirmed by established diagnostic techniques such as duplex Doppler ultrasound and ventilation perfusion scanning. The association between individual risk factors and the incidence of thromboemboli was identified. To control for confounding of variables, multivariable stepwise logistic regression analysis was performed. Results A total of 1862 patients undergoing gynecologic surgery between 1996 and 1997 were treated perioperatively with intermittent pneumatic compression. The overall incidence of postoperative thromboemboli was 1.3% (15 cases of clinically significant postoperative pulmonary emboli and nine deep venous thrombosis). Risk factors associated with the occurrence of thromboemboli were: cancer ( P = .001), history of deep venous thrombosis ( P = .03), hypertension ( P = .05), use of antihypertensives ( P = .04), and age at least 60 years ( P = .002). Intraoperative risk factors included duration of anesthesia more than 3 hours ( P = .05). The multivariable regression analysis found that the diagnosis of cancer ( P = .001), history of deep venous thrombosis ( P = .006), and age greater than 60 years ( P = .04) were independent prognostic factors. Patients with two or three of these variables had a 3.2% incidence of developing thromboemboli as compared with a 0.6% incidence of thromboemboli if the patient had none or one risk factor. Conclusion Patients most likely to fail intermittent pneumatic compression prophylaxis include those with cancer, a past history of deep venous thrombosis, or who are 60 years or older. This information identifies a “higher-risk” group of patients who should be considered for more intense prophylaxis programs.

Treatment of Febrile Seizures: The Influence of Treatment Efficacy and Side-Effect Profile on Value to Parents

We examined parents' perception of the value of treatments designed to reduce the risk of febrile seizure recurrence. The families of 42 children with febrile seizures were recruited after pediatric or neuropediatric consultation. A mail questionnaire addressed the family's willingness to pay for a hypothetical treatment for febrile seizures with risk reductions for future febrile seizures of 25%, 50%, 75%, and 100%. The hypothetical clinical scenario was then modified to include the side- effect profiles of either daily phenobarbital or valproic acid, or intermittent diazepam prophylaxis. Covariates included the nature of the child's febrile seizure(s), parents' familiarity with febrile seizures, experiences at the time of febrile seizures or with medication side effects, education and income, and mastery and trait anxiety. Thirty-eight parents, representing 22 of 42 families, completed questionnaires. There was a dramatic inflection in parents' willingness to pay for 100% risk reduction as opposed to 75% or lower risk reductions. Introduction of side effects dramatically reduced the value attached to each level of treatment benefit. Nevertheless, a few parents (3/38) would pay "as much as it takes" to be rid of their child's recurrence risk. Given the range of value assigned to prophylactic medication for febrile seizures, management strategies for children with febrile seizures must be responsive to the needs and values of individual families.