Outpatient management of biliary colic: A prospective observational study of prescribing habits and analgesia effectiveness

AbstractBackgroundUncomplicated biliary colic presents a significant health and financial burden to hospitals and primary care services alike. There is little guidance on the correct analgesia to use on an outpatient basis. This study aimed to evaluate the effectiveness of oral analgesics on biliary colic pain and to explore the prescribing habits of community doctors.MethodsConsecutive patients with ultrasound proven symptomatic gallstones completed a questionnaire recording demographics and symptomatology. Pain was assessed using a visual analogue scale (VAS) based on the Biliary Symptom Score (BSS) to evaluate the effectiveness of various analgesic agents. Local General Practitioners were also surveyed to establish prescribing practices.ResultsCo-Codamol had the highest mean effectiveness VAS score (6.5/10). Patients with increased BMI, short symptom duration and a BSS >70 were most likely to suffer from severe pain. Patients in a subgroup with severe pain were most likely to have their pain reduced by NSAID analgesia compared to no NSAID (OR 2.20, p = 0.027). This effect remained significant upon multivariable regression (OR 2.52, p = 0.018) in a model containing age and NSAIDs. There was wide variation in the prescribing practice of GPs and hospital doctors.ConclusionsThe range of drugs prescribed for biliary colic is extensive with little evidence base. In this study NSAIDs were the most effective analgesia for patients with severe pain. In the absence of contraindications to their use, physician education or guidance emphasizing the benefits of NSAIDs may potentially reduce symptomatic hospital presentation and admissions for biliary colic

Natural abundance 14N and 15N solid-state NMR of pharmaceuticals and their polymorphs

14N ultra-wideline (UW), 1H{15N} indirectly-detected HETCOR (idHETCOR) and 15N dynamic nuclear polarization (DNP) solid-state NMR (SSNMR) experiments, in combination with plane-wave density functional theory (DFT) calculations of 14N EFG tensors, were utilized to characterize a series of nitrogen-containing active pharmaceutical ingredients (APIs), including HCl salts of scopolamine, alprenolol, isoprenaline, acebutolol, dibucaine, nicardipine, and ranitidine. A case study applying these methods for the differentiation of polymorphs of bupivacaine HCl is also presented. All experiments were conducted upon samples with naturally-abundant nitrogen isotopes. For most of the APIs, it was possible to acquire frequency-stepped UW 14N SSNMR spectra of stationary samples, which display powder patterns corresponding to pseudo-tetrahedral (i.e., RR′R′′NH+ and RR′NH2+) or other (i.e., RNH2 and RNO2) nitrogen environments. Directly-excited 14N NMR spectra were acquired using the WURST-CPMG pulse sequence, which incorporates WURST (wideband, uniform rate, and smooth truncation) pulses and a CPMG (Carr-Purcell Meiboom-Gill) refocusing protocol. In certain cases, spectra were acquired using 1H → 14N broadband cross-polarization, via the BRAIN-CP (broadband adiabatic inversion – cross polarization) pulse sequence. These spectra provide 14N electric field gradient (EFG) tensor parameters and orientations that are particularly sensitive to variations in local structure and intermolecular hydrogen-bonding interactions. The 1H{15N} idHETCOR spectra, acquired under conditions of fast magic-angle spinning (MAS), used CP transfers to provide 1H–15N chemical shift correlations for all nitrogen environments, except for two sites in acebutolol and nicardipine. One of these two sites (RR′NH2+ in acebutolol) was successfully detected using the DNP-enhanced 15N{1H} CP/MAS measurement, and one (RNO2 in nicardipine) remained elusive due to the absence of nearby protons. This exploratory study suggests that this combination of techniques has great potential for the characterization of solid APIs and numerous other organic, biological, and inorganic systems

Determinants of species richness in the Park Grass experiment

The Park Grass Experiment at Rothamsted in southeast England was started in 1856, making it the longest-running experiment in plant ecology anywhere in the world. Experimental inputs include a range of fertilizers (nitrogen, phosphorus, potassium, and organic manures) applied annually, with lime applied occasionally, and these have led to an increase in biomass and, where nitrogen was applied in the form of ammonium sulfate, to substantial decreases in soil pH. The number of species per plot varies from three to 44 per 200 m2, affording a unique opportunity to study the determinants of plant species richness and to estimate the effect sizes attributable to different factors. The response of species richness to biomass depends on the amount and type of nitrogen applied; richness declined monotonically with increasing biomass on plots receiving no nitrogen or receiving nitrogen in the form of sodium nitrate, but there was no relationship between species richness and biomass on plots acidified by ammonium sulfate application. The response to lime also depended on the type of nitrogen applied; there was no relationship between lime treatment and species richness, except in plots receiving nitrogen in the form of ammonium sulfate, where species richness increased sharply with increasing soil pH. The addition of phosphorus reduced species richness, and application of potassium along with phosphorus reduced species richness further, but the biggest negative effects were when nitrogen and phosphorus were applied together. The analysis demonstrates how multiple factors contribute to the observed diversity patterns and how environmental regulation of species pools can operate at the same spatial and temporal scale as biomass effects

Interpreting multiple sulfur isotope signals in modern anoxic sediments using a full diagenetic model (California-Mexico margin: Alfonso basin)

Recent studies targeting the metabolic, physiological, and biochemical controls of sulfur isotope fractionation in microbial systems have drawn linkages between results from culture experiments and the sulfur isotope signatures observed in natural environments. Several of those studies have used newer techniques to explore the minor isotope (33S and 36S) variability in those systems, and also have attempted to place them in an ecophysiological context. Sparingly few have incorporated this newfound understanding of minor isotope behavior into natural systems (sediment pore waters, water columns) and none of them have refined existing isotope-dependent reaction-transport models to explicitly include 33S. In this study, we construct a three-isotope (32S, 33S, and 34S) reaction-transport model of pore water sulfate for a well-characterized sedimentary system within the California-Mexico Margin (Alfonso Basin). An additional goal is placing recent laboratory culture work into a natural, physical context. The model first reproduces the measured bulk geochemical characteristics of the pore water profiles of [SO4 2], [CH4], dissolved inorganic carbon ([DIC]), and [Ca2]—and predicts bulk (non-isotope-specific but depth-dependent) rates of sulfate reduction. Next, the model uses those depth-dependent bulk rates, in combination with empirically calibrated fractionation factors, to explain the minor isotope characteristics (34S and 33S values) of the 0 to 40 cm pore water SO4 2. The down core, isotopic evolution of pore water sulfate requires a large fractionation associated with sulfate reduction (34 SR 70 5) that appears to be independent of bulk rate, but in line with low temperature thermodynamic predictions. The minor isotope characteristics (33 SR 0.5130) are also independent of rate and fall within the range expected from microbial calibrations, but differ from minor isotope predictions of thermodynamic equilibrium. The high value of 34 SR raises key questions in relating the physiological state of marine microorganisms relative to their laboratory counterparts, as well as point toward exceedingly low metabolic rates in natural marine sediments

Operationalizing Human Immunodeficiency Virus Cure-related Trials with Analytic Treatment Interruptions During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pandemic: A Collaborative Approach

Efforts to recognize and minimize the risk to study participants will be necessary to safely and ethically resume scientific research in the context of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. These efforts are uniquely challenging in the context of human immunodeficiency virus (HIV) cure clinical trials, which often involve complex experimental therapy regimens and perhaps analytic treatment interruption, in which participants pause antiretroviral therapy. In this viewpoint, we discuss our approach to reopening an HIV cure trial in this context, with a focus on key considerations regarding study design, informed consent and participant education, and study implementation. These recommendations might be informative to other groups seeking to resume HIV cure research in settings similar to ours

Coexistence of double alternating antiferromagnetic chains in (VO)_2P_2O_7 : NMR study

Nuclear magnetic resonance (NMR) of 31P and 51V nuclei has been measured in a spin-1/2 alternating-chain compound (VO)_2P_2O_7. By analyzing the temperature variation of the 31P NMR spectra, we have found that (VO)_2P_2O_7 has two independent spin components with different spin-gap energies. The spin gaps are determined from the temperature dependence of the shifts at 31P and 51V sites to be 35 K and 68 K, which are in excellent agreement with those observed in the recent inelastic neutron scattering experiments [A.W. Garrett et al., Phys. Rev. Lett. 79, 745 (1997)]. This suggests that (VO)_2P_2O_7 is composed of two magnetic subsystems showing distinct magnetic excitations, which are associated with the two crystallographically-inequivalent V chains running along the b axis. The difference of the spin-gap energies between the chains is attributed to the small differences in the V-V distances, which may result in the different exchange alternation in each magnetic chain. The exchange interactions in each alternating chain are estimated and are discussed based on the empirical relation between the exchange interaction and the interatomic distance.Comment: 10 pages, 11 embedded eps figures, REVTeX, Submitted to Phys. Rev.

Training regimes and recovery monitoring practices of elite British swimmers.

Consistent prescriptions for event-specific training of swimmers are lacking, which points to likely differences in training practices and a potential gap between practice and scientific knowledge. This study aimed to analyze the distance-specific training load of elite swimmers, derive a consistent training sessions' description and reflect on the current recommendations for training and recovery. The individual training regimes of 18 elite British swimmers were documented by surveying four swim and two strength and conditioning (S&C) coaches. The annual and weekly training load and content were compared between swimmers competing in sprint, middle and long-distance events. Thematic analysis of the surveys was conducted to identify key codes and general dimensions and to define a unified classification of the swimming and S&C training sessions. Weekly training loads and content of the swim (ƞ - effect size; p = 0.016, ƞ = 0.423) and S&C (p 0.028, ƞ = 0.38) sessions significantly differed between the groups. Long-distance swimmers swam significantly longer distances (mean ± SD; 58.1 ± 10.2 km . 43.2 ± 5.3 km; p = 0.018) weekly but completed similar number of S&C sessions compared to sprinters. The annual swimming load distribution of middle-distance specialists did not differ from that of long-distance swimmers but consisted of more S&C sessions per week (4.7 ± 0.5 . 2.3 ± 2.3; p = 0.04). Sprinters and middle-distance swimmers swam similar distances per week and completed similar number of S&C sessions but with different proportional content. Whereas all coaches reported monitoring fatigue, only 51% indicated implementing individualized recovery protocols. We propose a consistent terminology for the description of training sessions in elite swimming to facilitate good practice exchanges. While the training prescription of elite British swimmers conforms to the scientific training principles, recommendations for recovery protocols to reduce the risk of injury and overtraining are warranted

Orthorhombic versus monoclinic symmetry of the charge-ordered state of NaV2O5

High-resolution X-ray diffraction data show that the low-temperature superstructure of alpha-NaV2O5 has an F-centered orthorhombic 2a x 2b x 4c superlattice. A structure model is proposed, that is characterized by layers with zigzag charge order on all ladders and stacking disorder, such that the averaged structure has space group Fmm2. This model is in accordance with both X-ray scattering and NMR data. Variations in the stacking order and disorder offer an explanation for the recently observed devils staircase of the superlattice period along c.Comment: REVTEX, 4 pages including 2 figures, shortened, submitted to PR

Incipient Separation in Shock Wave Boundary Layer Interactions as Induced by Sharp Fin

The incipient separation induced by the shock wave turbulent boundary layer interaction at the sharp fin is the subject of present study. Existing theories for the prediction of incipient separation, such as those put forward by McCabe (1966) and Dou and Deng (1992), can have thus far only predicting the direction of surface streamline and tend to over-predict the incipient separation condition based on the Stanbrook's criterion. In this paper, the incipient separation is firstly predicted with Dou and Deng (1992)'s theory and then compared with Lu and Settles (1990)' experimental data. The physical mechanism of the incipient separation as induced by the shock wave/turbulent boundary layer interactions at sharp fin is explained via the surface flow pattern analysis. Furthermore, the reason for the observed discrepancy between the predicted and experimental incipient separation conditions is clarified. It is found that when the wall limiting streamlines behind the shock wave becomes\ aligning with one ray from the virtual origin as the strength of shock wave increases, the incipient separation line is formed at which the wall limiting streamline becomes perpendicular to the local pressure gradient. The formation of this incipient separation line is the beginning of the separation process. The effects of Reynolds number and the Mach number on incipient separation are also discussed. Finally, a correlation for the correction of the incipient separation angle as predicted by the theory is also given.Comment: 34 pages; 9 figure