Clinical Profile and Knowledge, Attitude and Practice of Patients Presenting with Headache.

Background Headache disorders are among the most prevalent and disabling conditions worldwide. People, however, do not seek early advice in developing countries. Objective To study clinical profile of patients with headache and their existing knowledge, attitude, and practice regarding primary headaches. Method Descriptive cross-sectional study conducted among 196 patients. Patients were selected using purposive sampling technique fulfilling inclusion criteria. Patients were interviewed based on semi-structural headache questionnaire and data was collected from 4th October to 21st December 2021. Descriptive statistics was used for analysis and interpretation. Result Among 196 participants, 74% were females, 29.6% of patients were between (31 to 40) years of age. The majority were Hindu and belongs to province 3; 36.7% were homemakers, and 32.2% were literate. Migraine headache was the most common type with 14.3% reporting aura. Most reported headache within 1 to 5 years. The commonest triggers were sunlight 64.8%, crowd 54.7%, stress 39.8%, fasting state 31.7%, cold 26.3%. Almost 39% believed that headache could be a chronic neurologic disorder. Majority had knowledge of the causes, triggers, and the relieving factors. Fifty-five percent seek help of a doctor for first time, and the rest seek help of a pharmacist or self-medication. Only 19% tried to manage the headache triggers; 66.8% felt that lifestyle modification is the best treatment for headache comparing drugs. Conclusion Migraine headache was the commonest headache occurring at middle age group with sunlight being the most common trigger factor. Lifestyle modification was perceived to be the best for headache management.

Effects of acetate, propionate, and pH on volatile fatty acid thermodynamics in continuous cultures of ruminal contents.

To investigate the effects of acetate, propionate, and pH on thermodynamics of volatile fatty acids (VFA) in the rumen, a dual-flow continuous culture study was conducted to quantify production of major VFA, interconversions among the VFA, and H2 and CH4 emissions in a 4 × 4 Latin square design. The 4 treatments were (1) control: pH buffered to an average of 6.75; (2) control plus 20 mmol/d of infused acetate (InfAc); (3) control plus 7 mmol/d of infused propionate (InfPr); and (4) a 0.5-unit decline in pH elicited by adjustment of the buffer (LowpH). All fermentors were fed 40 g of a pelleted diet containing whole alfalfa pellets and concentrate mix pellets (50:50) once daily. After 7 d of treatment, sequential, continuous infusions of [2-13C] sodium acetate (3.5 mmol/d), [U-13C] sodium propionate (2.9 mmol/d), and [1-13C] sodium butyrate (0.22 mmol/d) were carried out from 12 h before feeding for 36 h. Filtered liquid effluent (4 mL) was sampled at 0, 2, 4, 6, 8, 12, 16, and 22 h after feeding, and assessed for VFA concentrations, with another filtered sample (20 mL) used to quantify aqueous concentrations of CH4 and H2. Headspace CH4 and H2 gases were monitored continuously. Ruminal microbes were isolated from the mixed effluent samples, and the microbial community structure was analyzed using the 16S rRNA amplicon sequencing technique. The digestibility of neutral detergent fiber, acid detergent fiber, and starch and microbial C sequestrated from VFA were not affected by treatments. The LowpH treatment increased net propionate production and decreased H2 and CH4 headspace emissions, primarily due to shifts in metabolic pathways of VFA formation, likely due to the observed changes in bacterial community structure. Significant interconversions occurred between acetate and butyrate, whereas interconversions of other VFA with propionate were relatively small. The InfAc and InfPr treatments increased net acetate and propionate production, respectively; however, interconversions among VFA were not affected by pH, acetate, or propionate treatments, suggesting that thermodynamics might not be a primary influencer of metabolic pathways used for VFA formation.

Cervical cancer screening utilization, and associated factors, in Nepal: a systematic review and meta-analysis.

OBJECTIVE: To systematically appraise the existing published literature on cervical cancer screening utilization, and associated barriers and facilitators, in Nepal. STUDY DESIGN: Systematic literature review and meta-analysis. METHODS: PubMed/MEDLINE, CINAHL, Scopus, Embase, and, Google Scholar were systematically searched using Preferred Reporting Items for Systematic Review and Meta-Analysis guideline. All quantitative and qualitative studies reporting cervical cancer screening (using the Pap smear test or visual inspection with acetic acid or human papillomavirus test) utilization, barriers, and facilitators for screening were identified. A meta-analysis was performed to estimate Nepal's pooled cervical cancer screening utilization proportion. RESULTS: The search yielded 97 records, of which 17 studies were included. Fifteen studies were quantitative and two were qualitative. Of the 17 studies, six were hospital-based and six were community-based. The pooled cervical cancer screening utilization proportion (using Pap smear test) among Nepalese women was 17% from the studies in the hospital settings, and 16% in the community. Six studies reported barriers to cervical cancer screening, of which four reported embarrassments related to the gynecological examination and a low level of knowledge on cervical cancer. Three (of four) studies reported health personnel, and two studies reported screening services-related facilitators for cervical cancer screening. CONCLUSION: Our review reported that cervical cancer screening utilization (16%) is more than four times lower than the national target (70%) in Nepal. Multiple barriers such as low levels of knowledge and embarrassment are associated with cervical cancer screening utilization. Health personnel's gender, counseling, and privacy of screening services were commonly reported facilitators. These findings could help to inform future research, and policy efforts to increase cervical cancer screening utilization in Nepal.

Profile of Women receiving Second-trimester Safe Abortion Service at Paropakar Maternity and Women's Hospital.

Background Second trimester abortions account for a small percentage of abortions globally. Abortion is one of the safest medical procedures. Accessibility of safe and high quality second-trimester abortion care can decrease severe complications associated with it. Objective The profile of women undergoing second-trimester abortion was assessed during the study. The profile includes demographic and clinical aspects. The study also aims to find out the rate of surgical and medical methods of abortion and to understand its indications. Method It is a study based on retrospective data collected from charts available at the comprehensive abortion care center at the Paropakar Maternity and Women's Hospital. The data from Shrawan to Magh 2077 B.S. was collected and calculations were done on MS Excel. Result Higher proportion of women receiving second-trimester abortion were of the age between 21-25 years (n=31; 31%). Most women were literate (n=69; 69%) and n=38(38%) were nulliparous. The most common indication for abortion was maternal mental issues (n=32; 32%). The rate of medical abortion was higher (n=71; 71%) than surgical method of abortion (n=29; 29%). Conclusion There exists both demographic and clinical variations in women undergoing secondtrimester abortion. Though few women undergo second trimester abortion than first-trimester the variation in profile is significant with most women referring to second trimester abortion due to later diagnosis of pregnancy, women facing financial and logistic barriers to health care, victims of violence and women with pregnancy complications or fetal anomalies.

First-Generation SARS-CoV-2 Vaccines: A Comparative Analysis between Vaccinated and Unvaccinated Hospitalized Patients Infected with SARS-CoV-2.

Background Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) variants, which have emerged due to several mutations in spike protein, have a potential to escape immune protection provided by the first-generation vaccines, thereby resulting in breakthrough infections. Objective To identify the socio-demographic factors, clinical features, and outcomes in both vaccinated and unvaccinated hospitalized patients infected with SARS-CoV-2. Method Socio-demographic details, clinical features, and the outcomes among fully vaccinated (double for Covishield/AstraZeneca and BBIBP-CorV and single for Janssen), partially vaccinated, and unvaccinated hospitalized patients with coronavirus disease of 2019 (COVID-19) were collected and analyzed using SPSS version 17. Result Among the hospitalized COVID-19 patients (n=299), 175 (58.5%) patients received a single-dose, 82 (27.4%) double-dose, and 124 (41.5%) did not receive any dose of the COVID-19 vaccines. The risk of SARS-CoV-2 infection when compared between vaccinated and unvaccinated patients was found to be associated among professional degree holders (23.4% versus 9.7%) (p<0.05), professional workers (43.4% vs. 25.0%) (p<0.05), hospitalization to general ward (76.6% vs. 72.6%) (p<0.05), and presence of multiple symptoms (> or equel 3) (86.8% vs. 75.0%) (p>0.05) and comorbidities (> or equal 2) (15.5% vs. 13.7%) (p>0.05). Despite such approximate incidences, the risk of in-hospital mortality among the vaccinated patients was reduced (0.6% vs. 3.2%) (p>0.05), when compared to the unvaccinated patients. The risk of in-hospital mortality was associated with the older age and the presence of multiple comorbidities including bronchial asthma, diabetes, and hypertension. Conclusion Full or partial vaccination against the SARS-CoV-2 variants of concerns might be effective in preventing in-hospital mortality among COVID-19 patients.

COVID-19 Booster Vaccine: is it an absolute need?

Booster vaccine doses are meant to revive the fading immunity created by prior exposure to an immunizing antigen. They stabilize the antibody response ultimately leading to longer and higher protection against pathogens. Immunological studies done for COVID-19 vaccines have documented a steady decrease in antibody levels among vaccinated individuals and evidence of breakthrough infections over a course of time. With an emerging science behind the need for COVID-19 vaccine booster shots, there equally is a contrasting idea regarding its absolute necessity.

Awareness of Thyroid Disorders among Nepalese Women: A Cross-Sectional Study.

Background Thyroid disorders are emerging public health issues. Clients' awareness is crucial for prevention, early diagnosis, and treatment of the thyroid disorders. Studies, assessing knowledge on thyroid disorders among Nepalese population, is lacking. Objective To assess the awareness of thyroid disorders among women, a susceptible subgroup, and find the correlates of poor knowledge. Method A cross-sectional study was conducted among 423 women at the gynecological outpatient department of Tribhuvan University Teaching Hospital. Eighteen-item scale, with a Cronbach's Alpha of 0.913, was developed to assess participant's knowledge on various constructs of thyroid disorder. A linear regression model with Bootstrap approach was used to identify the predictors of the total knowledge score. Result The mean (±SD) age of the participant was 29.2 ± 7.0 years. About 49% of the women had inadequate knowledge, defined at or below the mean cumulative knowledge score. In linear regression, the total knowledge score was significantly lower among participants who were Janajati (ß=-2.87, BCa 95%CI=-4.61, -1.11), illiterate (ß=- 6.37, BCa 95%CI =-9.14, -3.21), and low income (ß=-3.76, BCa 95%CI=-5.68, -1.83). Likewise, a university education (ß=5.94, BCa 95%CI=3.50, 8.26), working status (ß=4.04, BCa 95%CI=2.19, 5.81), urban residence (ß=2.06, BCa 95%CI=0.02, 3.96) and family history (ß=2.20, BCa 95%CI=0.71, 3.63) of thyroid disorder predicted higher knowledge score. Conclusion This study identified a poor level of knowledge on thyroid disorders among Nepali women and thus proposes them to be an important subgroup for an intervention or policy aimed at promoting awarenessof thyroid disorders. The findings also warrant increased awareness among these population through hospital and communitybased behavior change communication campaigns.

Pharmacokinetics of 2,000 Milligram Ertapenem in Tuberculosis Patients.

Ertapenem is a carbapenem antibiotic with activity against Mycobacterium tuberculosis Dose simulations in a hollow-fiber infection model showed that 2,000 mg once daily is an appropriate dose to be tested in clinical studies. Before using this dose in a phase II study, the aim of this prospective pharmacokinetic study was to confirm the pharmacokinetics of 2,000 mg once daily in tuberculosis (TB) patients. Twelve TB patients received a single intravenous dose of 2,000 mg ertapenem as a 30-min infusion. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 8, 12, and 24 h postadministration. Drug concentrations were measured using a validated liquid chromatography-tandem mass spectrometry assay. A large interindividual variation in the pharmacokinetics of ertapenem was observed. The median (interquartile range) area under the plasma concentration-time curve to infinity (AUC0-∞) was 2,032 (1,751 to 2,346) mg · h/liter, the intercompartmental clearance (CL12) was 1.941 (0.979 to 2.817) liters/h, and the volume of distribution in the central compartment (V1) was 1.514 (1.064 to 2.210) liters. A more than dose-proportional increase in AUC was observed compared to results reported for 1,000 mg ertapenem in multidrug-resistant TB patients. Based on a MIC of 1.0 mg/liter, 11 out of 12 patients would have reached the target value of unbound drug exceeding the MIC over 40% of the time (f40% T>MIC). In conclusion, this study shows that 2,000 mg ertapenem once daily in TB patients reached the expected f40% T>MIC for most of the patients, and exploration in a phase 2 study can be advocated.

Observation of backward high-harmonic emission from solids.

We experimentally demonstrate backward emission of high-harmonics of a near-infrared laser from MgO and Si crystals in the direction of specular reflection. We show that the variation of the high-harmonic power with the angle of incidence can be predicted with nonlinear reflection coefficients derived originally for perturbative nonlinearities. A comparison of transmission and reflection geometries suggests that backward-propagating high-harmonics are an excellent reference to study nonlinear propagation of intense light in solids. Backward emission will enable phase matching of the high-harmonic beam and the integration of the functionalities of extended gas-phase high-harmonic beamlines into a single optical element. The potential to achieve phase matching paves the way to solid-state based high-harmonic sources with higher flux than the best transmission-based sources, where high-harmonics are strongly absorbed by the crystal itself.

X-ray and optical wave mixing.

Light-matter interactions are ubiquitous, and underpin a wide range of basic research fields and applied technologies. Although optical interactions have been intensively studied, their microscopic details are often poorly understood and have so far not been directly measurable. X-ray and optical wave mixing was proposed nearly half a century ago as an atomic-scale probe of optical interactions but has not yet been observed owing to a lack of sufficiently intense X-ray sources. Here we use an X-ray laser to demonstrate X-ray and optical sum-frequency generation. The underlying nonlinearity is a reciprocal-space probe of the optically induced charges and associated microscopic fields that arise in an illuminated material. To within the experimental errors, the measured efficiency is consistent with first-principles calculations of microscopic optical polarization in diamond. The ability to probe optical interactions on the atomic scale offers new opportunities in both basic and applied areas of science.

Uterine Rupture: Shifting Paradigm in Etiology.

Background Rupture uterus is associated with significant maternal and perinatal mortality and morbidity. Etiologies of uterine rupture are changing with time. There has been shift in etiology from an obstructed labour and multiparity towards rupture of a caesarean section scar. There is paucity of studies regarding this changing paradigm. Objective To study the changing etiological pattern of rupture uterus. Method We retrospectively analysed details of all patients with ruptured gravid uterus from Medical records of Nobel Medical College from 2013 July 1 to 2015 June 30. Sociodemographic predisposing risk factors and feto-maternal outcomes were recorded in a structured proforma. Result Of the 11,571 deliveries, total of 52 (0.45%) had ruptured uterus. Caesarean Section were 3,218 (28%) of total deliveries. Among 52 rupture cases, 41 (78.84%) were because of previous Caesarean scar followed by obstructed labor, prostaglandin and oxytocin. The occurrence of rupture in previously scarred uterus was 1.27%. 82.9% of the uterine rupture occurred in women with one previous LSCS. Most women were primipara of 25-29 years. It was seen more commonly in unbooked cases 49 (~95%). Laparotomy with repairment of rupture and bilateral tubal ligation was the commonest mode of management. Majority were anemic. Perinatal mortality was 41 (79%) with 5 (9.6%) maternal deaths. Conclusion Previously scarred uterus is the commonest cause of uterine rupture. Early diagnosis and management is needed to prevent poor outcomes. Avoidance of injudicious cesarean deliveries reduces number of future scars. Awareness generation regarding antenatal care and timely referral are vital.

Developing tool and Measuring Integration Characteristics of Basic Science Curriculum to Improve Curriculum Integration.

Background Integrated curriculum enhances students' learning and the retention of knowledge. At Patan Academy of Health Sciences, integrated organ system based curriculum is used with Problem Based Learning as the principle teaching learning method to foster students' learning. In addition, other approaches of integration were under taken such as integrated assessment; logical arrangement teaching learning methods (lectures and practicals); joint effort of faculty in curriculum planning and delivery; conducive environment to foster hidden curriculum. This study describes the perception of faculty and students on integration characteristics of Basic Science curriculum. Objective To measure the integration characteristics of Basic Science Curriculum. Method Tool was developed to measure integration characteristics of Basic Science Curriculum and ensure whether such planned integration has been achieved. Mixed method was used to measure the perception of the integration characteristics i) quantitatively by questionnaire survey to faculty and students ii) qualitatively by in-depth interview of students. Result Both faculty and students perceived that all the blocks in Basic Science was well integrated in the quantitative questionnaire survey. But, in the in-depth interview, students perceived integration of curriculum in organ system blocks were better integrated compared to Principle of Human Biology blocks where fundamentals of basic science disciplines were delivered. Students reflected that Problem Based Learning not only integrated Basic Science disciplines but also with clinical sciences and the social context. But, students perceived that Community Health Sciences curriculum was not so well integrated with Basic Science subjects. Conclusion Overall, this study showed that planned integration in Basic Science curriculum was successfully executed during curriculum implementation.

Representing interconversions among volatile fatty acids in the Molly cow model.

The Molly cow model uses fixed stoichiometric coefficients for predicting volatile fatty acid (VFA) production from the fermented individual dietary nutrient fractions of forage and concentrate. We previously showed that predictions of VFA production had large errors and hypothesized that it was due to a lack of representation of carbon exchange among VFA. The objectives of the present study were to add VFA interconversion equations based on thermodynamics to the Molly cow model and evaluate the effect of these additions on model accuracy and precision of VFA predictions. Previously described thermodynamic equations were introduced to represent interconversions among VFA. The model was further modified to predict de novo acetate, propionate, and butyrate production coefficients based on forage-to-concentrate ratios rather than discrete, fixed sets of coefficients for forage-based, concentrate-based, and mixed diets. Both the original model and the modified one were reparameterized and evaluated against a common data set containing 8 studies reporting pH, VFA concentration, and VFA production rates using isotope dilution techniques and 62 studies reporting VFA concentrations and pH. Evaluations after parameter estimation revealed that predictions of VFA production rates were not improved, with root mean squared prediction errors (RMSPE) of 77, 60, and 51% for acetate, propionate, and butyrate, respectively, for the revised model versus 75, 63, and 55, respectively, for the original model. The RMSPE for predictions of VFA concentrations were reduced from 28, 46, and 40% to 22, 31, and 26% for acetate, propionate, and butyrate, respectively, simply by rederiving the VFA coefficients, but minimal further improvement was achieved with the addition of thermodynamically driven interconversion equations (RMSPE of 21, 32, and 27% for acetate, propionate, and butyrate, respectively). Thus, the results indicate that thermodynamically driven interchanges among VFA, as represented in this study, may not be a primary determinant for the accuracy of predictions of net production rates. Including the effect of pH on VFA absorption reduced the mean bias of propionate production and slope bias of acetate production, but not the overall RMSPE. The larger prediction errors for VFA production as compared with concentrations suggest the data quality may not be high, or that our representation of VFA production and absorption as well as ruminal digestion is inadequate. Additional data are required to discriminate among these hypotheses.

Emerging drugs and alternative possibilities in the treatment of tuberculosis.

INTRODUCTION: Tuberculosis (TB) remains a global health problem. Drug resistance, treatment duration, complexity, and adverse drug reactions associated with anti-TB regimens are associated with treatment failure, prolonged infectiousness and relapse. With the current set of anti-TB drugs the goal to end TB has not been met. New drugs and new treatment regimens are needed to eradicate TB. AREAS COVERED: Literature was explored to select publications on drugs currently in phase II and phase III trials. These include new chemical entities, immunotherapy, established drugs in new treatment regimens and vaccines for the prophylaxis of TB. EXPERT OPINION: Well designed trials, with detailed pharmacokinetic/pharmacodynamic analysis, in which information on drug exposure and drug susceptibility of the entire anti-TB regimen is included, in combination with long-term follow-up will provide relevant data to optimize TB treatment. The new multi arm multistage trial design could be used to test new combinations of compounds, immunotherapy and therapeutic vaccines. This new approach will both reduce the number of patients exposed to inferior treatment and the financial burden. Moreover, it will speed up drug evaluation. Considering the investments involved in development of new drugs it is worthwhile to thoroughly investigate existing, non-TB drugs in new regimens.

Femtosecond electronic response of atoms to ultra-intense X-rays.

An era of exploring the interactions of high-intensity, hard X-rays with matter has begun with the start-up of a hard-X-ray free-electron laser, the Linac Coherent Light Source (LCLS). Understanding how electrons in matter respond to ultra-intense X-ray radiation is essential for all applications. Here we reveal the nature of the electronic response in a free atom to unprecedented high-intensity, short-wavelength, high-fluence radiation (respectively 10(18) W cm(-2), 1.5-0.6 nm, approximately 10(5) X-ray photons per A(2)). At this fluence, the neon target inevitably changes during the course of a single femtosecond-duration X-ray pulse-by sequentially ejecting electrons-to produce fully-stripped neon through absorption of six photons. Rapid photoejection of inner-shell electrons produces 'hollow' atoms and an intensity-induced X-ray transparency. Such transparency, due to the presence of inner-shell vacancies, can be induced in all atomic, molecular and condensed matter systems at high intensity. Quantitative comparison with theory allows us to extract LCLS fluence and pulse duration. Our successful modelling of X-ray/atom interactions using a straightforward rate equation approach augurs favourably for extension to complex systems.

Prevalence of Sensory Neuropathy in Type 2 Diabetes Mellitus and Its Correlation with Duration of Disease.

Background Peripheral neuropathy is one of the most common and distressing late complication of diabetes mellitus. Ignorance of the complications may develop foot ulcers and gangrene requiring amputation. Objective The main objective of this study is to find out the prevalence of sensory neuropathy in type 2 diabetes mellitus and to compare it with the duration of disease. Method Two hundred seventy one patients with type 2 diabetes mellitus of both gender age 30 years and above willing to participate were included in this study. Patients having hypothyroidism, rheumatoid arthritis, B12 deficiency, cerebrovascular disease, chronic musculoskeletal disease, Parkinson's disease, alcohol abuse, chronic renal or liver failure and cancer were excluded from the study. Touch, pin prick and vibration sensation were tested. Vibration perception threshold was recorded from six different sites of the sole of each foot using Biothesiometer. Result Two hundreds seventy one type 2 diabetic outpatients were studied. The mean age was 59.81±22.85 years. The overall prevalence of diabetic sensory neuropathy in the study population was 58.70%. A rising trend of diabetic sensory neuropathy with increasing age and duration of diabetes was observed. Neuropathy was found more in patients having urinary microalbuminuria. Burning and pins and needles sensation were most common symptoms. Conclusion The overall prevalence of diabetic sensory neuropathy in the study population was 58.70% (mean age 59.81±22.85 yrs), and its prevalence increased with duration of diabetes and increasing age. Its prevalence was found more in patients having microalbuminuria.

Below gap optical absorption in GaAs driven by intense, single-cycle coherent transition radiation.

Single-cycle terahertz fields generated by coherent transition radiation from a relativistic electron beam are used to study the high field optical response of single crystal GaAs. Large amplitude changes in the sub-band-gap optical absorption are induced and probed dynamically by measuring the absorption of a broad-band optical beam generated by transition radiation from the same electron bunch, providing an absolutely synchronized pump and probe geometry. This modification of the optical properties is consistent with strong-field-induced electroabsorption. These processes are pertinent to a wide range of nonlinear terahertz-driven light-matter interactions anticipated at accelerator-based sources.

Evaluation of predictions of volatile fatty acid production rates by the Molly cow model.

Predicting ruminal volatile fatty acid (VFA) production is important, as VFA are an energy source to the animal, affect nutrient partitioning, and dictate methane production. The VFA production submodel in the Molly cow model was evaluated using data from 8 publications that reported VFA production rates for cattle. Evaluations were conducted with ruminal water balance predictions enabled and the ruminal VFA stoichiometry coefficients set to "mixed" for all diets, or "mixed" when forage represented between 20 and 80% of the diet, "concentrate" when <20% forage, or "forage" when >80% forage. Prediction errors were relatively insensitive to changes in VFA coefficients by diet type. Root mean square prediction errors (RMSPE) were 63, 63, and 49% for acetate, propionate, and butyrate production rates, respectively. A large proportion of the error was slope bias for acetate and butyrate, and a modest proportion for propionate. Because interconversions between acetate and propionate represent approximately 15% of the variation in net production rates, lack of such consideration in the model may contribute to the substantial model prediction errors. The potential of using thermodynamic equations to predict interconversions was assessed using observed ruminal pH and VFA concentrations from 2 studies and assuming constant hydrogen pressure and concentrations of CO2, H2O, adenosine diphosphate, ATP, and inorganic P. Rate constants for conversion of acetate to propionate and propionate to acetate were derived independently from the control treatments and used to predict the fluxes for the other treatment. The observed changes in VFA concentrations and pH explained the observed changes in conversion of acetate to propionate, but overpredicted the change in the propionate to acetate flux in one study. When applied to the other study, the equations predicted the increase in propionate to acetate flux, but failed to predict the observed reduction in acetate to propionate flux. The inability to predict responses accurately may be due to a lack of data for controlling factors other than pH and VFA concentrations.

Measurement of isoniazid in tuberculosis patients using finger sweat with creatinine normalisation: A controlled administration study.

BACKGROUND: Insufficient exposure and poor compliance with anti-tuberculosis (TB) medications are risk factors for treatment failure and the development of drug resistance. Measurement of drugs in biological samples, such as blood and saliva, can be used to assess adherence and make dose adjustments by therapeutic drug monitoring (TDM). Finger sweat testing is a convenient and non-invasive method to monitor patients. OBJECTIVES: To assess the feasibility of finger sweat testing for medication adherence and as a semi-quantitative tool for TDM analysis. METHODS: Ten patients provided finger sweat, blood and saliva samples following a controlled dose of isoniazid. Samples were analysed by liquid chromatography-mass spectrometry. RESULTS: Isoniazid can be detected in finger sweat 1-6 h following administration at typically prescribed dosages. The normalisation of isoniazid to creatinine increases the correlation between finger sweat and serum isoniazid concentration and provides a means to account for inconsistent sample volumes. CONCLUSION: We describe the time-course measurement of isoniazid (or drug-to-creatinine ratio) in finger sweat compared to the pharmacokinetic profile in blood for the first time. This technique, adaptable for other drugs, could reduce the burden on clinics and improve patient experience.

An evidence-based approach for providing cautionary recommendations to sulfonamide-allergic patients and determining cross-reactivity among sulfonamide-containing medications.

WHAT IS KNOWN AND OBJECTIVE: Prescribing sulfonamide-containing medications for patients with sulfonamide allergy continues to complicate medical decisions. We examined the cautionary recommendations in the approved drug monographs and primary literature, and formulated an evidence-based grading of cautionary recommendations for sulfonamide allergy and cross-reactivity among sulfonamide-containing medications. METHODS: Drug monographs were collected from six countries and three drug compendia. Two reviewers independently extracted the data from the contraindication, warning and/or precaution sections of drug monographs. Evidence for cross-reactivity was examined in the primary literature and compared with drug monograph recommendations. Consequently, medications were categorized based on the strength of recommendation and level of evidence by consensus. RESULTS AND DISCUSSION: We identified wide variability in cautionary recommendations ranging from no warning or precaution to contraindication among the sources reviewed. The recommendations were located mainly in the contraindication section of monographs for France (65·2%), United Kingdom (51·9%), Italy (50·0%), South Korea (43·5%), United States (38·2%) and Canada (37·0%), whereas in drug compendia, the recommendations were found in the precaution section for Martindale (51·4%) and Micromedex-Drugdex (33·3%), and contraindication and precaution section for the American Hospital Formulary Service Drug Information 2010 (30·8%). Evidence from the primary literature varied with recommendation included in drug monographs. Evidence-based categorization was carried out for 16 medications. Two sulfonamide-moiety-containing drugs were considered safe, six non-sulfonylarylamines required precaution, and eight medications from all three sulfonamide chemical classes were considered mostly unsafe. WHAT IS NEW AND CONCLUSION: There are significant discrepancies in cautionary recommendations included in drug-labels and drug compendia. Statements concerning cross-reactive hypersensitivity with other sulfonamides generally suggest theoretical possibilities. The consensus evidence-based grading instrument developed may be useful for deriving cautionary recommendations for sulfonamide-allergic patients.