Median Conversion Time Research Articles

Extensively Drug‐Resistant Tuberculosis in California, 1993–2006

Extensively drug-resistant (XDR) tuberculosis (TB) is a global public health emergency. We investigated the characteristics and extent of XDR TB in California to inform public health interventions. XDR TB was defined as TB with resistance to at least isoniazid, rifampin, a fluoroquinolone, and 1 of 3 injectable second-line drugs (amikacin, kanamycin, or capreomycin). Pre-XDR TB was defined as TB with resistance to isoniazid and rifampin and either a fluoroquinolone or second-line injectable agent but not both. We analyzed TB case reports submitted to the state TB registry for the period 1993-2006. Local health departments and the state TB laboratory were queried to ensure complete drug susceptibility reporting. Among 424 multidrug-resistant (MDR) TB cases with complete drug susceptibility reporting, 18 (4.2%) were extensively drug resistant, and 77 (18%) were pre-extensively drug resistant. The proportion of pre-XDR TB cases increased over time, from 7% in 1993 to 32% in 2005 (P = .02)). Among XDR TB cases, 83% of cases involved foreign-born patients, and 43% were diagnosed in patients within 6 months after arrival in the United States. Mexico was the most common country of origin. Five cases (29%) of XDR TB were acquired during therapy in California. All patients with XDR TB had pulmonary disease, and most had prolonged infectious periods; the median time for conversion of sputum culture results was 195 days. Among 17 patients with known outcomes, 7 (41.2%) completed therapy, 5 (29.4%) moved, and 5 (29.4%) died. One patient continues to receive treatment. XDR TB and pre-XDR TB cases comprise a substantial fraction of MDR TB cases in California, indicating the need for interventions that improve surveillance, directly observed therapy, and rapid drug susceptibility testing and reporting.

Management of Extensively Drug-Resistant Tuberculosis in Peru: Cure Is Possible

AimTo describe the incidence of extensive drug-resistant tuberculosis (XDR-TB) reported in the Peruvian National multidrug-resistant tuberculosis (MDR-TB) registry over a period of more than ten years and present the treatment outcomes for a cohort of these patients.MethodsFrom the Peruvian MDR-TB registry we extracted all entries that were approved for second-line anti-TB treatment between January 1997 and June of 2007 and that had Drug Susceptibility Test (DST) results indicating resistance to both rifampicin and isoniazid (i.e. MDR-TB) in addition to results for at least one fluoroquinolone and one second-line injectable (amikacin, capreomycin and kanamycin).ResultsOf 1,989 confirmed MDR-TB cases with second-line DSTs, 119(6.0%) XDR-TB cases were detected between January 1997 and June of 2007. Lima and its metropolitan area account for 91% of cases, a distribution statistically similar to that of MDR-TB. A total of 43 XDR-TB cases were included in the cohort analysis, 37 of them received ITR. Of these, 17(46%) were cured, 8(22%) died and 11(30%) either failed or defaulted treatment. Of the 14 XDR-TB patients diagnosed as such before ITR treatment initiation, 10 (71%) were cured and the median conversion time was 2 months.ConclusionIn the Peruvian context, with long experience in treating MDR-TB and low HIV burden, although the overall cure rate was poor, a large proportion of XDR-TB patients can be cured if DST to second-line drugs is performed early and treatment is delivered according to the WHO Guidelines.

An Empirical Examination of the Timing of Land Conversions in the Presence of Farmland Preservation Programs

AbstractUsing a panel of parcel‐level data we estimate a hazard model and find strong evidence that the mere existence of an option to preserve farmland delays decisions to convert farmland to developed uses by about six years, a reduction in median conversion time of 12 to 43% depending on parcel size. Where such delays allow local governments to improve infrastructure or implement stricter growth control measures, benefits of a preservation option may be even more long term. Also, increases in the variance of returns to development tended to slow conversion for parcels with all but the highest lot capacities.

Efficacy of Magnesium-Amiodarone Step-Up Scheme in Critically Ill Patients With New-Onset Atrial Fibrillation: A Prospective Observational Study

Amiodarone is considered a first-choice antiarrhythmic drug in critically ill patients with new-onset atrial fibrillation (AF). However, evidence supporting the use of this potentially toxic drug in critically ill patients is scarce. Magnesium sulphate (MgSO4) has shown to be effective for both rate and rhythm control, to act synergistically with antiarrhythmic drugs, and to prevent proarrhythmia. Treatment with MgSO4 may reduce the need for antiarrhythmic drugs such as amiodarone in critically ill patients with new-onset atrial fibrillation. The efficacy of a new institutional protocol was evaluated. Patients were treated with a new institutional protocol for new-onset atrial fibrillation in critically ill patients. An MgSO4 bolus (0.037 g/kg body weight in 15 minutes) was followed by continuous infusion (0.025 g/kg body weight/h). Intravenous amiodarone (loading dose 300 mg, followed by continuous infusion of 1200 mg/24 h) was given to those not responding to MgSO4 within 1 hour. Clinical response was defined as conversion to sinus rhythm or decrease in heart rate <110 beats/min. Sixteen of the 29 patients responded to MgSO4 monotherapy, whereas the addition of amiodarone was needed in 13 patients. Median (range) time until conversion to sinus rhythm after MgSO4 was 2 (1-45) hours. Median (range) conversion time in patients requiring amiodarone was 4 (2-78) hours, and median (range) conversion time in all patients was 3 (1-78) hours. The 24-hour conversion rate was 90%. Relapse atrial fibrillation was seen in 7 patients. The magnesium-amiodarone step-up scheme reduces the need for amiodarone, effectively converts new-onset atrial fibrillation into a sinus rhythm within 24 hours, and seems to be safe in critically ill patients.

Comparison of outcomes after transplantation of peripheral blood stem cells versus bone marrow following an identical nonmyeloablative conditioning regimen

This is the first study to examine the outcomes in 54 patients with hematologic malignancies who received an HLA-matched related donor bone marrow (BM, n = 42) or GCSF-mobilized peripheral blood stem cells (PBSC, n = 12) following identical nonmyeloablative conditioning with the intention of induction of mixed chimerism (MC) followed by prophylactic donor leukocyte infusion (pDLI) to convert MC to full donor chimerism (FDC) and capture a graft-versus-tumor effect without clinical graft-versus-host disease (GVHD). Neutrophil and platelet recovery were faster and transfusion requirement was less in PBSC recipients (P < 0.05). A total of 48% of BMT recipients achieved FDC with a median conversion time of 84 days, including 13 following pDLI. In contrast, 83% (P = 0.04) in the PBSC group had spontaneous FDC at a median of 14 days, precluding the administration of pDLI. There was no significant difference in the incidences of acute or chronic GVHD, though the rates of chronic GVHD were considerably higher in PBSC group than in the BM group (6/7, 86% vs 10/24, 42%). CD4 and CD8 T-cell recovery was faster in PBSC recipients. In PBSC recipients, a higher number of CD34+ cells was associated with increased rates of severe, grade III-IV acute GVHD.

Clinical Comparison of Ibutilide and Propafenone for Converting Atrial Flutter

To evaluate the efficacy and safety of intravenous ibutilide and propafenone for immediate treatment of atrial flutter. Forty patients with atrial flutter with an arrhythmia duration of three hours to 90 days were randomized to receive up to two 10-minute infusions of ibutilide (1 and 1 mg) or propafenone (70 and 70 mg) with a 10-minute interval. Ibutilide was superior to propafenone for treating atrial flutter (90% vs. 30%, p < 0.01). The median conversion time in the ibutilide group was 11 min (the 25th and 75th percentile was 10 and 45 min), and the median conversion time in the propafenone group was 35 min (range 20-55 min). In all patients, the duration of arrhythmia before treatment was a predictor of arrhythmia termination, although this was more obvious in the group that received ibutilide. Conversion of atrial flutter by ibutilide was characterized mainly by increased cycle length variability. Bradycardia (2/20) and hypotension (4/20) were more common side effects with propafenone. Of 20 patients given ibutilide, 8 (40%) who developed monomorphic ventricular extrasystoles or repetitive atrial flutter with aberrant conduction tachycardia, no one required any specific treatment except for the interruption of ibutilide infusion. Ibutilide is highly effective for rapidly terminating atrial flutter. This new class III drug, under monitored conditions, is a potential alternative to currently available cardioversion options.

The Role Treatment for Cervical Intraepithelial Neoplasia Plays in the Disappearance of Human Papilloma Virus

To explore the role played by excision of the transformation zone in women diagnosed with cervical intraepithelial neoplasia (CIN) in the disappearance of human papillomavirus (HPV). In a retrospective, cohort study, women with CIN who were treated by loop electrosurgical excision procedure of the transformation zone were compared with another group of women with CIN who were managed expectantly. The decision to treat or manage expectantly was made by one of the authors on clinical grounds. All patients were evaluated with cervical cytologic analysis, pathologic examination of excised tissue, and HPV DNA testing, which was considered positive when high-risk HPV types were detected. Among women treated with loop electrosurgical excision procedure, the median lag time was calculated from diagnosis of CIN to treatment. The median time for conversion from HPV-positive to HPV-negative status in both groups was compared, as well as the 1- and 2-year cure rates (defined as converting to HPV-negative status) in the treated and untreated groups. In the treated group, 12% had CIN 1, 83% had CIN 2,3, 2% had cancer, and 3% had normal pathologic results. In the untreated group, 82% had CIN 1, 16% had CIN 2,3, and 2% had normal pathologic results (p < 0.0001). The lag time from the initial diagnosis of CIN to treatment was less than 1 month. The median follow-up time was 7 months (range, 1-121 months) in the treated group and 13 months (range, 1-70 months) in the untreated group. The 1-year rates of conversion to HPV-negative status, defined as the cure rates in the treated and untreated groups, were 65% (+/- 6%) and 23% (+/- 7%), respectively, and the 2-year cure rates in the treated and untreated groups were 90% (+/- 4%) and 56% (+/- 11%), respectively (p < 0.0001). Median time to conversion to a negative HPV status was 7.7 months for the treated patients compared with 19.4 months in the untreated patients (p < 0.0001). Women treated by loop electrosurgical excision procedure are more likely convert to HPV-negative status at 1 and 2 years and do so significantly sooner than those managed expectantly.

Pulmonary Resection Combined with Isoniazid-and Rifampin-based Drug Therapy for Patients with Multidrug-resistant Tuberculosis

Background : To evaluate the clinical efficacy of pulmonary resection combined with first-line antituberculous drug therapy in patients with well-localized, cavities-containing pulmonary multidrug-resistant tuberculosis (MDR-TB). Method : From February 1998, seventeen patients with well-localized, cavities-containing pulmonary MDR-TB were enrolled and followed prospectively up to December 2004. After radical pulmonary resection, the patients were treated with antituberculous drugs comprising of isoniazid (H), rifampin (R), pyrazinamide (Z), ethambutol (E), and streptomycin (S) (3HERZS/3HERS/6HER). Results : All recovered isolates of M. tuberculosis were resistant to both isoniazid and rifampin, and to a mean of 4.8 antituberculous drugs (range, 2 to 7 drugs). Surgical procedures included lobectomy (13 patients), lobectomy plus segmentectomy (3 patients), and pneumonectomy (1 patient). The median time for postoperative sputum smear and culture conversion was 2 days (range, 1 to 23 days). Fifteen (94%) patients had durable cures (mean follow-up period, 39.0 months). One patient failed to convert her sputum and was successfully switched to second-line therapy; one patient developed active disease again almost 7 years later, likely due to re-infection with a new M. tuberculosis strain. Conclusion : Radical resection combined with administration of first-line antituberculous agents was effective in patients with well-localized, cavities-containing pulmonary MDR-TB.

Age-specific incidence rates of Alzheimer's disease: the Baltimore Longitudinal Study of Aging.

To estimate age-specific incidence rates of AD in the Baltimore Longitudinal Study of Aging (BLSA). The BLSA is a volunteer cohort of normal subjects followed longitudinally with biennial evaluations at the Gerontology Research Center of the National Institute on Aging. Subjects are 1236 participants (802 men, 434 women) in the BLSA with longitudinal follow-up between January 1985 and May 1998. The average length of follow-up was 7.5 years, with participants evaluated every 2 years by physical, neurologic, and neuropsychological examinations. Using Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, the authors diagnosed dementia and AD. The authors diagnosed 155 cases of dementia, of which 114 (74%) were AD. Incidence rates of AD increased with age from an estimated 0.08% per year (95% CI 0.00 to 0.43) in the 60 to 65 age group to an estimated 6.48% per year (95% CI 5.01 to 8.38) in the 85+ age group for men and women combined. The doubling time of incidence rates was estimated to be approximately 4.4 years and the median time of conversion from mild cognitive impairment to diagnosis of AD was estimated to be 4.4 years. There was a trend for women to have higher incidence rates than men and for fewer years of education to be associated with higher incidence rates; however, these effects were not significant. Incidence rates for AD in the BLSA are consistent with published rates in other studies. The longitudinally followed subjects of the BLSA offer a unique opportunity to prospectively investigate the antecedents of AD.

Effectiveness of amiodarone as a single oral dose for recent-onset atrial fibrillation

The efficacy of amiodarone has been proved in long-term maintenance of sinus rhythm (SR) in patients with paroxysmal atrial fibrillation (AF). The present study evaluates the efficacy and safety of a single oral dose of amiodarone in patients with recent-onset AF (<48 hours). Seventy-two patients were randomized to receive 30 mg/kg of either amiodarone or placebo. Conversion to SR was verified by 24-hour Holter monitoring. Ten patients were excluded because of SR in the beginning of monitoring or technical failure during Holter monitoring. The remaining study groups were comparable (n = 31 for each), except that in the placebo group β blockers were more common. The patients receiving amiodarone converted to SR more effectively than those receiving placebo (p <0.0001). At 8 hours, approximately 50% of patients in the amiodarone group and 20% in the placebo group (Holter successful) had converted to SR, whereas after 24 hours the corresponding figures were 87% and 35%, respectively. The median time for conversion (8.7 hours for amiodarone and 7.9 hours for placebo) did not differ in the groups. Amiodarone was hemodynamically well tolerated, and the number of adverse events in the study groups was similar. Amiodarone as a single oral dose of 30 mg/kg appears to be effective and safe in patients with recent-onset AF.

Papillomas at high risk for malignant progression arising both early and late during two-stage carcinogenesis in SENCAR mice.

The current study was designed to further establish that most papillomas produced in SENCAR mice during two-stage skin carcinogenesis are, in fact, premalignant lesions and to specifically determine the malignant conversion potential of papillomas that arise at different times during the carcinogenesis process. A method was established to physically map and monitor the lifespan of all papillomas produced in SENCAR mice during the course of an initiation-promotion experiment using DMBA as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. The results from these experiments showed that in groups of mice initiated with either 0.5 or 2.0 microg DMBA, long-term (60 weeks) treatment with TPA yielded a significantly higher number of SCCs compared to short-term treatment (7 weeks). Papillomas that emerged after 11 weeks and thereafter in all treatment groups had the ability to progress to SCCs. The median conversion time for all papillomas in all groups was 26 weeks. When corrected for median conversion time, papillomas that emerged in week 11 and thereafter in all treatment groups had similar or greater conversion ratios compared to those that emerged within the first 10 weeks. Interestingly, the median conversion time was significantly shorter (18 versus 27 weeks, respectively; P<0.0002) for papillomas that emerged in week 11 and thereafter compared to those that emerged at or prior to 10 weeks for all groups. The data in this study demonstrate that papillomas arising throughout a two-stage carcinogenesis protocol in SENCAR mice progress to SCCs. Many papillomas that arise later in two-stage carcinogenesis protocols do not have sufficient time to allow for conversion and should be excluded from the analyses. Furthermore, another novel finding of the current study was the observation that papillomas arising later in the two-stage protocol (>11 weeks) progressed to SCCs at a faster rate than those that arose earliest in the protocol.

Propafenone versus amiodarone in field treatment of primary atrial tachydysrhythmias

Thirty-nine patients with paroxysmal atrial fibrillation or supraventricular tachycardia randomly received amiodarone or propafenone intravenously at home. Fifteen patients received amiodarone and 24 received propafenone; 87.5% of the patients who received propafenone and 40% of the patients who received amiodarone were converted at home to sinus rhythm (P less than .005). The median time of conversion was 10 minutes (range 5 to 35) for propafenone and 60 minutes (range 20 to 130) for amiodarone (P less than 0.005). When either drug failed to terminate atrial tachydysrhythmias at home, the same drug always restored sinus rhythm with subsequent oral treatment during hospitalization. No major side effects were observed after the infusion of either drug. The incidence of minor side effects was not significantly different between the two drugs. Both the drugs are efficacious and safe in the acute management of primary supraventricular tachydysrhythmias. Propafenone showed a greater rapidity of action.

Digoxin Therapy in the Fetus-Reply

In Reply .—Drs De Lia and Emery raise some questions about the conclusions drawn from our study. I would agree that there is a lack of pharmacokinetic data on the use of digoxin during pregnancy. However, we cited the article by Saarikoski 1 because it provides valuable data on the equilibration of intravenous digoxin in the human fetus. De Lia and Emery cite the article by Fouron, which describes the dynamics of the placental transfer of digoxin in a dog model. Saarikoski 1 shows that equilibration appears to begin within a few minutes of infusion in the mother and is attained in fetal blood within 30 minutes, far less time than that cited by De Lia and Emery. In addition, the traditional treatment of choice of supraventricular tachycardia in infants and children is intravenous digoxin with a median time of conversion to sinus rhythm of six hours. 2 This supports

Conversion to problem-oriented records in an established practice. A timed study.

A change to problem-oriented records was initiated in a 21-year-old solo primary practice generally limited to nonsurgical adult medical patients. The change was valuable because it produced a critical review of patients' problems. Important but neglected clinical data were unearthed. Three hundred charts were reviewed in depth, and complete problem sheets were constructed. An average of 6.4 minutes was necessary for each chart, but the median time for conversion of charts was slightly less than 5 minutes. An average of two charts were reviewed in each half-day office session. A change to problem-oriented records can be accomplished with a modest expenditure of time and effort, even in a busy established practice.