No evidence of resistance to itraconazole in a prospective real-world trial of dermatomycosis in India.

BACKGROUND: The prevalence of superficial fungal infections in India is believed to have increased substantially in the past decade. We evaluated the treatment outcomes and risk factors associated with clinical response to a treatment course of itraconazole for the management of dermatomycosis in India. METHODS: In this real-world, prospective pilot study (August 2019 to March 2020), adult participants (18-60 years), diagnosed with T. cruris or T. corporis, received itraconazole 200 mg/day (any formulation) orally for 7 days, and were followed for an additional 7 days. RESULTS: The study was terminated early due to the COVID-19 pandemic. Of 40 enrolled participants (mean [SD] age, 35.5 [12.73] years; {62.5%}] male; 37 received itraconazole and 20 (50%) completed the study. The median (range) Clinical Evaluation Tool Signs and Symptoms total score at baseline was 5.5 (2-10). Clinical response of "healed" or "markedly improved" based on the Investigator Global Evaluation Tool at day 7 (primary objective) was 42.9% (12/28; 95% CI: 24.53%, 61.19%). Itraconazole minimum inhibitory concentration for identified microorganisms, T. mentagrophytes species complex (91.7%) and T. rubrum (8.3%), was within the susceptibility range (0.015-0.25 mcg/mL). At day 14, 8/13 (61.5%) participants achieved a mycological response, 2/13 participants (15.4%) had a mycological failure and 90% showed a clinical response. CONCLUSION: COVID-19 pandemic affected patient recruitment and follow-up, so the findings call for a careful interpretation. Nevertheless, this real-world study reconfirmed the clinical efficacy and microbial susceptibility to itraconazole for the fungi causing dermatophytosis in India. TRIAL REGISTRATION: Trial registration number: Clinicaltrials.gov NCT03923010.

Etanercept as prophylactic psoriatic therapy before interferon-alpha and ribavirin treatment for active hepatitis C infection.

Patients with psoriasis and chronic hepatitis C virus (HCV) infection are a therapeutic challenge. Systemic psoriasis treatment with methotrexate and acitretin can be hepatotoxic, and interferon (IFN)-alpha for treatment of HCV can worsen psoriasis. Etanercept can be successfully used in patients with psoriasis and HCV. To our knowledge, this is the first case report of etanercept used prophylactically to prevent a psoriatic flare in a patient with HCV treated with IFN-alpha and ribavirin.

Retranslocation of foliar nutrients in evergreen tree species planted in a Mediterranean environment.

Internal nutrient recycling through retranslocation (resorption) is important for meeting the nutrient demands of new tissue production in trees. We conducted a comparative study of nutrient retranslocation from leaves of five tree species from three genera grown in plantation forests for commercial or environmental purposes in southern Australia--Acacia mearnsii De Wild., Eucalyptus globulus Labill., E. fraxinoides H. Deane & Maiden, E. grandis W. Hill ex Maiden and Pinus radiata D. Don. Significant amounts of nitrogen, phosphorus and potassium were retranslocated during three phases of leaf life. In the first phase, retranslocation occurred from young leaves beginning 6 months after leaf initiation, even when leaves were physiologically most active. In the second phase, retranslocation occurred from mature green leaves during their second year, and in the third phase, retranslocation occurred during senescence before leaf fall. Nutrient retranslocation occurred mainly in response to new shoot production. The pattern of retranslocation was remarkably similar in the leaves of all study species (and in the phyllodes of Casuarina glauca Sieber ex Spreng.), despite their diverse genetics, leaf forms and growth rates. There was no net retranslocation of calcium in any of the species. The amounts of nutrients at the start of each pre-retranslocation phase had a strong positive relationship with the amounts subsequently retranslocated, and all species fitted a common relationship. The percentage reduction in concentration or content (retranslocation efficiency) at a particular growth phase is subject to many variables, even within a species, and is therefore not a meaningful measure of interspecific variation. It is proposed that the pattern of retranslocation and its governing factors are similar among species in the absence of interspecies competition for growth and crown structure which occurs in mixed species stands.

Cyclic fatigue testing of ProTaper NiTi rotary instruments after clinical use.

PURPOSE: The purpose of this study was to evaluate the cyclic fatigue of ProTaper nickel-titanium (NiTi) rotary instruments (Tulsa Dental, Tulsa, Okla) after multiple clinical uses. STUDY DESIGN: Two hundred twenty-five ProTaper instruments were divided into 3 groups: A = 75 used as controls, B = 75 used in 2 molars (6-8 canals), and C = 75 used in 4 molars (12-16 canals). The number of rotations to breakage and the fractured tip length were recorded for each file and the mean was calculated by ANOVA. RESULTS: No S1-2 or F1-2-3 instrument separated during intracanal use, even if they were reused for a number of cases (x 4 molar cases). CONCLUSION: It is clear that prolonged reuse of NiTi rotary instruments strongly affects instruments' fatigue, but our data suggest the hypothesis that other factors (primarily errors and misuse) may be more accountable for intracanal instrument separation. Further studies could assess the cyclic fatigue of each instrument at different levels of the shaft by altering the radius of curvature.

Shanxi Province cervical cancer screening study II: self-sampling for high-risk human papillomavirus compared to direct sampling for human papillomavirus and liquid based cervical cytology.

The objective of this study was to compare the sensitivity and specificity of a new method for self-sampling for high risk human papillomavirus (HPV) with direct sampling and liquid based cervical cytology. In Shanxi Province, China, 8,497 women (ages 27-56) underwent a self-sample for HPV using a conical-shaped brush placed into the upper vagina and rotated. Three to sixteen months later the women were screened with liquid-based cytology and direct HPV tests. Subjects with any abnormal test underwent colposcopy and multiple biopsies. Mean age was 40.9 years. 4.4 percent of subjects had >or=CIN II, 26% a positive self-sample and 24% a positive direct test for HPV. The sensitivity for detection of >or=CIN II was 87.5% for self-sampling, and 96.8% for the direct test (P < 0.001). The specificity was 77.2% for the self-sample and 79.7% for the direct test. With an abnormal Pap defined as ASCUS or greater the sensitivity of the Pap for the detection of >CIN II was 88.3% and the specificity was 81.2%. We conclude that self-sampling for HPV is less sensitive for >CIN II than the direct test, but similar to liquid based cytology.

Patient acceptance of self-sampling for human papillomavirus in rural china.

OBJECTIVE.: To test a new survey instrument and determine the acceptance and potential barriers of cervicovaginal self-sampling for high-risk human papillomavirus in rural Chinese women. MATERIALS AND METHODS.: Data from thirteen survey questions assessed acceptance of the self-sampling procedure. Pain, comprehension, and cultural beliefs were potential barriers evaluated by the survey. RESULTS.: A total of 1,560 women were surveyed. The average and mode number of steps of the self-sampling procedure recalled was 5 (out of 7). Ninety-one percent preferred performing the test at a clinic versus their home. The major barrier encountered was related to the educational level of the women. CONCLUSIONS.: The measure performed well in this population. The self-collection brush was well accepted by these women. Education is the largest hurdle to overcome in implementing a self-sampling screening program.

Bilateral simultaneous facial nerve palsy.

Bilateral simultaneous facial nerve palsy is an extremely rare clinical entity with Bell's palsy responsible for a mere 20 per cent of cases. It is, therefore, important that clinicians are aware of the differential diagnosis when evaluating a case.

Coprescribing and codispensing of cisapride and contraindicated drugs.

CONTEXT: Cisapride, an oral prokinetic drug indicated for the symptomatic treatment of nocturnal heartburn due to gastroesophageal reflux disease, was approved by the US Food and Drug Administration in July 1993. After reports of serious cardiac arrhythmias and deaths during administration of cisapride, most involving concomitant exposure to another drug, a series of label changes and warnings were issued in February 1995, October 1995, June 1998, and June 1999. Cisapride was removed from general distribution in July 2000. OBJECTIVE: To determine the frequency of contraindicted coprescribing and codispensings, in which cisapride and a contraindicated drug were prescribed or dispensed to the same patient for overlapping periods, and the proportion of contraindicated coprescribing by the same physicians and codispensing by the same pharmacies. DESIGN AND SETTING: Retrospective study of prescription claims from a managed care organization database for all patients with cisapride prescriptions between July 1993 and December 1998. PARTICIPANTS: A total of 38 757 adult and pediatric patients who had a cisapride prescription immediately preceded by at least 60 days of insurance eligibility. MAIN OUTCOME MEASURE: Proportion of cisapride prescriptions or dispensing occurring during the same treatment period as a drug contraindicated at that time prescribed by the same physicians or dispensed by the same pharmacies. RESULTS: Of 131 485 cisapride prescriptions dispensed after the warnings began, 4414 (3.4%) overlapped with at least 1 drug contraindicated in the labeling at the time of the prescription. Of all overlapping prescription pairs, 2190 (50%) were by the same physicians, 3908 (89%) were by the same pharmacies, and 765 (17%) were dispensed on the same day. CONCLUSION: Prescriptions dispensed by the same pharmacies accounted for a far higher proportion of contraindicated medication pairs than prescriptions from the same physicians. The pharmacy may be an important and underutilized intervention point to prevent contraindicated drugs from being used together.

Contraindicated medications dispensed with cisapride: temporal trends in relation to the sending of 'Dear Doctor' letters.

PURPOSE: 'Dear Doctor' letters alert the prescribing community of drug labeling changes that contain new contraindications, warnings, adverse reactions, and precautions. There has been little assessment of the impact of these letters. We quantified the impact of two 'Dear Doctor' letters concerning interactions between cisapride and a series of drugs. A letter in 1995 described a risk of prolonged QT intervals and serious ventricular arrhythmia in patients who received macrolide antibiotics and imidazole antifungals in conjunction with cisapride. A June 1998 letter that expanded the list of contraindicated comedications had wider distribution than an earlier one, was accompanied by substantial Internet and media coverage, and was complemented by an effort to inform large pharmacy dispensing information organizations of the warnings against concurrent use of the named drugs. METHODS: Health plan members with one or more outpatient pharmacy claims for cisapride during the period 1 January 1995 through 31 May 1999 were identified among members of a large New England health insurer. A retrospective review of concurrent and nearly concurrent dispensings of cisapride and contraindicated comedications was undertaken in the automated pharmacy claims data using both graphical and statistical time-series analysis. We tabulated by month the fraction of cisapride dispensings that occurred in close temporal relation to dispensings of contraindicated comedications. Codispensings that occurred on the same day were taken as the most direct measure of prescriber responsiveness to the letters. Codispensings that occurred in windows of plus or minus 2 weeks (29 day window) and plus or minus 4 weeks (57 day window) were taken as measures of possible simultaneous consumption. Among overlapping dispensings, we counted the proportion dispensed by the same pharmacy. Time series regression analysis of secular, seasonal, and step-effects was conducted. RESULTS: There was a steady decline in codispensing of cisapride and contraindicated medicines, and a pronounced seasonal effect, arising principally from the seasonal use of macrolide antibiotics. Against this background, the isolated Dear Doctor letter of October 1995 had no discernible effect on prescribing practices. The 1998 letter and surrounding activity, by contrast, were followed by a 66% decline in same-day dispensings and a smaller, but still pronounced decline in dispensings in the wider time windows. For most codispensings of contraindicated medications with cisapride, both medications came from the same pharmacy. CONCLUSIONS: Publicity and direct intervention with dispensing pharmacies may be an important supplement to Dear Doctor letters when the goal is to eliminate the codispensing of drugs that should not be taken together.

Temporal patterns of NSAID spontaneous adverse event reports: the Weber effect revisited.

OBJECTIVES: Determine whether recent US adverse event reports for several non-steroidal anti-inflammatory drugs (NSAIDs) conform to the temporal pattern observed by Dr JCP Weber in the UK in the early 1980s, i.e. a rising count in the first few years after launch presumably reflecting increased exposure, followed by a decline, presumably reflecting decreased enthusiasm for reporting as adverse events become well known. STUDY SETTING: US adverse event report data available from the US Food and Drug Administration, reformatted by a commercial vendor. METHODS: For the 5 NSAIDs launched in the US between 1987 and 1993 that had data suitable for this study, we tabulated by year from launch the number of reports and the reporting rate (number of reports per 1000 prescriptions). RESULTS: The number of reports for 3 of the 5 NSAIDs showed a temporal pattern approximating that described by Weber. The number of reports for the other 2 NSAIDs showed temporal patterns markedly different from that described by Weber. For 4 of the 5 NSAIDs, reporting rates did not decline consistently with time from launch. DISCUSSION: The temporal patterns of adverse event reports are more complex than those described in Weber's classic report. The number of reports does not reliably rise and then fall after launch and the reporting rate does not reliably decrease with time from launch.

Fractionation and characterization of phenolic resins by high-performance liquid chromatography and gel-permeation chromatography combined with ultraviolet, refractive index, mass spectrometry and light-scattering detection.

HPLC and gel permeation chromatographic (GPC) characterization of complex phenol-formaldehyde resins is described. Reversed-phase HPLC fingerprints the phenolic monomers, dimers and some oligomers. The molecular masses of these phenolic compounds were determined using an ion trap mass spectrometer. GPC analyzes tetrahydrofuran-soluble phenolic polymers beyond HPLC capability. The molecular mass distribution and structural information of the phenolics was determined by both conventional and laser light-scattering calibration methods. GPC with both UV and refractive index detection provides weight concentration of phenolic resin and the molar concentration of the phenol unit in the oligomers or polymers.

Evaluation of a fluorescent lectin-based staining technique for some acidophilic mining bacteria.

A fluorescence-labeled wheat germ agglutinin staining technique (R. K. Sizemore et al., Appl. Environ. Microbiol. 56:2245-2247, 1990) was modified and found to be effective for staining gram-positive, acidophilic mining bacteria. Bacteria identified by others as being gram positive through 16S rRNA sequence analyses, yet clustering near the divergence of that group, stained weakly. Gram-negative bacteria did not stain. Background staining of environmental samples was negligible, and pyrite and soil particles in the samples did not interfere with the staining procedure.

Foliar nutrient retranslocation in Eucalyptus globulus.

We measured patterns of change in concentrations and contents of nitrogen, phosphorus, potassium, magnesium and calcium in fully expanded leaves of young Eucalyptus globulus (Labill.) trees growing in a plantation in southeastern Australia, over a 12-month period beginning at the onset of spring. There was significant net retranslocation of mobile nutrients on a seasonal basis from green leaves, coinciding with continued growth and production of foliage. There was a close positive relationship between initial nutrient content (N, P and K) of the leaf and amount retranslocated, and a tight coupling between N and P retranslocated from leaves. Net retranslocation was significantly correlated with basal area growth increments. Artificial shading of leaves resulted in senescence and reduction in leaf mass. It also induced retranslocation of N, P and K from leaves of different ages and from different position in the canopy. Although the mechanisms underlying the effects of shading intensity on these changes were not elucidated, shading provided an experimental tool for studying retranslocation. Comparison of the results with published data for Pinus radiata (D. Don) grown in the same environment indicated a similarity between the species in patterns of change in foliar nutrient contents and in factors governing foliar nutrient retranslocation, giving rise to unifying principles.

Endoscopic sinus surgery: are junior doctors being properly trained?

Endoscopic sinus surgery (ESS) is a technique which carries great potential benefits for the treatment of many nasal conditions. However, it also carries substantial risks. The key to safe surgery lies with adequate training. A survey carried out as part of a North (East) Thames Region audit of higher surgical trainees revealed large discrepancies in their training and in their subsequent clinical practice. Almost half the trainees had started ESS without having been on a training course or performed any cadaver dissections. Despite the potential hazards of ESS, audit of complications and outcome received a low priority. The trainees made several suggestions for improving training, including better provision of courses, regional training programmes and improved access to cadavers for dissection. Other surgical specialties are being forced to examine the prospect of specific accreditation for minimally invasive techniques and otorhinolaryngology may have to follow suit.

The risk of seizures associated with tramadol.

We conducted a study of the risk of idiopathic incident seizures among users of tramadol derived from data present in the General Practice Research Database based in the United Kingdom for 1994-1996. We used a nested case-control study design, comparing risks of idiopathic incident seizures during exposed and unexposed times among patients who had ever taken tramadol using a 90-day follow-up. Among the 10,916 subjects, we identified 17 cases of idiopathic seizures, 11 of which were definite and 6 possible. None of the patients was exposed to tramadol alone in the prior 90 days. Eight patients were exposed to opiates, five to both tramadol and opiates, three to other analgesics, and one to no analgesics. We found no increased risk of idiopathic incident seizures associated with exposure to tramadol alone. Thus seizures seem rarely attributable to the agent.

The management of lumps in the neck.

The many diagnostic problems associated with neck lumps demand a systematized and team approach to their management. Use of current imaging technology, effective examination of the upper aerodigestive tract and minimal surgical techniques for tissue diagnosis are discussed.

Effects of brain injury on college academic performance.

Brain injury, a leading cause of mortality, morbidity and disability in the United States, has serious consequences and substantial costs. Although previous studies have assessed a variety of outcomes subsequent to brain injury, documentation of performance prior to brain injury using a case-control approach has not been included; preinjury performance differences may confound the estimate of the effects of brain injury on performance. The primary objective of this study was to compare academic performance before and after brain injury in a population of university undergraduate students to determine the extent to which the academic career of the brain-injured person was altered from what would have been expected in the absence of such an injury. Cases included all undergraduate students in a major university, between the ages of 17 and 27, who incurred a brain injury requiring hospitalization between 1980 and 1984 (n = 99). Two comparison groups were used to determine whether changes in academic performance were specifically related to brain injuries or injuries in general: (1) injured controls, i.e. 121 students between the ages of 17 and 27 years, hospitalized for injuries other than to the central nervous system, and (2) uninjured academic controls, i.e. 198 students with out injuries requiring hospitalization during the study period, matched 2:1 to the brain-injured students by age, gender, and completed course credits categorized as < 90, > or = 90. Although there were no differences when the total groups, including both males and females, were compared, there was a significant pre- to postinjury decrease in the grade point average for female cases when compared to their uninjured academic controls (p < 0.02). This difference was related to the effects of brain injury, and not to the effects of injury in general. No such difference was observed for the males. There were also no differences when the total groups, including males and females, were compared relevant to return to school. However, a significantly higher proportion of the female cases, compared with their uninjured academic controls, did not return to school after their injury; similar findings were identified for the injured controls as well. Thus, these differences were not specific to brain injury but rather to injury in general. In spite of this observation, the difference between female cases who returned and those who did not return was associated with neurological deficits, especially upper left limb motor deficits, as the time of hospital discharge. The findings from this effort are suggestive of gender differences in the consequences of brain injury and serve as a basis for further studies to evaluate the magnitude of this problem.

Mortality in a cohort of homeless adults in Philadelphia.

BACKGROUND: Homeless people are at high risk for death from many causes, but age-adjusted death rates for well-defined homeless populations have not been determined. METHODS: We identified 6308 homeless persons 15 to 74 years of age who were served by one or both of two agencies for the homeless in Philadelphia between January 1, 1985, and December 31, 1988. Using a data base that contained all deaths in Philadelphia and listings of all Philadelphia residents during the same period, we compared the mortality rate for this homeless population with the rate in the general population of Philadelphia. RESULTS: The age-adjusted mortality rate among the homeless was 3.5 times that of Philadelphia's general population (95 percent confidence interval, 2.8 to 4.5). The age-adjusted number of years of potential life lost before the age of 75 years was 3.6 times higher for the homeless people than for the general population (345 vs. 97 years lost per 1000 person-years of observation). Fifty-one of the 96 deaths of homeless persons (53 percent) occurred during the summer months. Mortality rates were higher among the homeless than in the general population for nonwhites, whites, women, and men. Within the homeless cohort, white men and substance abusers had higher mortality rates than other subgroups, but even homeless people not known to be substance abusers had a threefold higher risk of death than members of the general population. Injuries, heart disease, liver disease, poisoning, and ill-defined conditions accounted for 73 percent of all the deaths among the homeless. CONCLUSIONS: Homeless adults in Philadelphia have an age-adjusted mortality rate nearly four times that of Philadelphia's general population. White men and substance abusers are at particularly high risk. Matching cohorts of homeless people to death records is a useful way to monitor mortality rates over time, evaluate interventions, and identify subgroups with an increased risk of death.

Laboratory-based reporting of AIDS.

To improve the speed and completeness of AIDS reporting, the Philadelphia Board of Health adopted regulations requiring medical laboratories to report directly to the Department of Public Health all results indicative of AIDS-defining diagnoses. Reports were used to focus active AIDS surveillance on physicians who had requested laboratory reports whose results were likely to have diagnosed AIDS recently. One year after implementation, laboratories provided the first lead to 20% of all AIDS reports. Reports originating with laboratories reach our data base sooner after diagnosis and ascertain a slightly higher proportion of women than do other reports. Laboratory-based reporting offers a practical way to focus the limited resources available for active surveillance on health providers likely to have an AIDS diagnosis to report.