How I treat sickle cell disease in pregnancy.

ABSTRACT: Fifty years ago, people with sickle cell disease (SCD) were discouraged from becoming pregnant, but now, most should be supported if they choose to pursue a pregnancy. They and their providers, however, should be aware of the physiological changes of pregnancy that aggravate SCD and pregnancy's unique maternal and fetal challenges. Maternal problems can arise from chronic underlying organ dysfunction such as renal disease or pulmonary hypertension; from acute complications of SCD such as acute anemia, vaso-occlusive crises, and acute chest syndrome; and/or from pregnancy-related complications such as preeclampsia, sepsis, severe anemia, thromboembolism, and the need for cesarean delivery. Fetal problems include alloimmunization, opioid exposure, fetal growth restriction, preterm delivery, and stillbirth. Before and during pregnancy, in addition to the assessment and care that every pregnant patient should receive, patients with SCD should be evaluated and treated by a multidisciplinary team with respect to their unique maternal and fetal issues.

Trapped O2 and the origin of voltage fade in layered Li-rich cathodes.

Oxygen redox cathodes, such as Li1.2Ni0.13Co0.13Mn0.54O2, deliver higher energy densities than those based on transition metal redox alone. However, they commonly exhibit voltage fade, a gradually diminishing discharge voltage on extended cycling. Recent research has shown that, on the first charge, oxidation of O2- ions forms O2 molecules trapped in nano-sized voids within the structure, which can be fully reduced to O2- on the subsequent discharge. Here we show that the loss of O-redox capacity on cycling and therefore voltage fade arises from a combination of a reduction in the reversibility of the O2-/O2 redox process and O2 loss. The closed voids that trap O2 grow on cycling, rendering more of the trapped O2 electrochemically inactive. The size and density of voids leads to cracking of the particles and open voids at the surfaces, releasing O2. Our findings implicate the thermodynamic driving force to form O2 as the root cause of transition metal migration, void formation and consequently voltage fade in Li-rich cathodes.

Rescue of Familial Lecithin:Cholesterol Acyltranferase Deficiency Mutations with an Allosteric Activator.

Lecithin:cholesterol acyltransferase (LCAT) deficiencies represent severe disorders characterized by aberrant cholesterol esterification in plasma, leading to life-threatening conditions. This study investigates the efficacy of Compound 2, a piperidinyl pyrazolopyridine allosteric activator that binds the membrane-binding domain of LCAT, in rescuing the activity of LCAT variants associated with disease. The variants K218N, N228K, and G230R, all located in the cap and lid domains of LCAT, demonstrated notable activity restoration in response to Compound 2. Molecular dynamics simulations and structural modeling indicate that these mutations disrupt the lid and membrane binding domain, with Compound 2 potentially dampening these structural alterations. Conversely, variants such as M252K and F382V in the cap and α/ß-hydrolase domain, respectively, exhibited limited or no rescue by Compound 2. Future research should prioritize in vivo investigations that would validate the therapeutic potential of Compound 2 and related activators in familial LCAT deficiency patients with mutations in the cap and lid of the enzyme. SIGNIFICANCE STATEMENT: Lecithin:cholesterol acyltranferase (LCAT) catalyzes the first step of reverse cholesterol transport, namely the esterification of cholesterol in high density lipoprotein particles. Somatic mutations in LCAT lead to excess cholesterol in blood plasma and, in severe cases, kidney failure. In this study, we show that recently discovered small molecule activators can rescue function in LCAT-deficient variants when the mutations occur in the lid and cap domains of the enzyme.

Visualization of Tetrahedral Li in the Alkali Layers of Li-Rich Layered Metal Oxides.

Understanding Li+ ion diffusion pathways in Li-rich layered transition metal (TM) oxides is crucial for understanding the sluggish kinetics in anionic O2- redox. Although Li diffusion within the alkali layers undergoes a low-barrier octahedral-tetrahedral-octahedral pathway, it is less clear how Li diffuses in and out of the TM layers, particularly given the complex structural rearrangements that take place during the oxidation of O2-. Here, we develop simultaneous electron ptychography and annular dark field imaging methods to unlock the Li migration pathways in Li1.2Ni0.13Mn0.54Co0.13O2 associated with structural changes in the charge-discharge cycle. At the end of TM oxidation and before the high-voltage O oxidation plateau, we show that the Li migrating out of the TM layers occupies the alkali-layer tetrahedral sites on opposite sides of the TM layers, forming Li-Li dumbbell configurations, consistent with the density functional theory calculations. Also occurring are the TM migration and phase transition from O3 to O1 stacking, leading to unstable tetrahedral Li and the absence of Li contrast in imaging. Upon further Li deintercalation to 4.8 V, most of the tetrahedral Li are removed. After discharging to 2 V, we did not identify the reformation of tetrahedral Li but observed permanently migrated TMs at the alkali-layer sites, disfavoring the Li occupying the tetrahedral sites for diffusion. Our findings suggest a landscape of Li diffusion pathways in Li-rich layered oxides and strategies for minimizing the disruption of Li diffusion.

Analytical and clinical validation of direct detection of antimicrobial resistance markers by plasma microbial cell-free DNA sequencing.

Sequencing of plasma microbial cell-free DNA (mcfDNA) has gained increased acceptance as a valuable adjunct to standard-of-care testing for diagnosis of infections throughout the body. Here, we report the analytical and clinical validation of a novel application of mcfDNA sequencing, the non-invasive detection of seven common antimicrobial resistance (AMR) genetic markers in 18 important pathogens. The AMR markers include SCCmec, mecA, mecC, vanA, vanB, blaCTX-M, and blaKPC. The AMR markers were computationally linked to the pathogens detected. Analytical validation showed high reproducibility (100%), inclusivity (54 to 100%), and exclusivity (100%). Clinical accuracy was assessed with 114 unique plasma samples from patients at seven study sites with concordant culture results for target bacteria from a variety of specimen types and correlated with available phenotypic antimicrobial susceptibility test results and genotypic results. The positive percent agreement (PPA), negative percent agreement (NPA), and diagnostic yield (DY) were estimated for each AMR marker. DY was defined as the percentage of tests that yielded an actionable result of either detected or not detected. The results for the combination of SCCmec and mecA for staphylococci were PPA 19/20 (95.0%), NPA 21/22 (95.4%), DY 42/60 (70.0%); vanA for enterococci were PPA 3/3 (100%), NPA 2/2 (100%), DY 5/6 (83.3%); blaCTX-M for gram-negative bacilli were PPA 5/6 (83.3%), NPA 29/29 (100%), DY 35/49 (71.4%); and blaKPC for gram-negative bacilli were PPA 0/2 (0%), NPA: 23/23 (100%), DY 25/44 (56.8%). The addition of AMR capability to plasma mcfDNA sequencing should provide clinicians with an effective new culture-independent tool for optimization of therapy. IMPORTANCE: This manuscript is ideally suited for the Innovative Diagnostic Methods sections as it reports the analytical and clinical validation of a novel application of plasma microbial cell-free DNA sequencing for direct detection of seven selected antimicrobial resistance markers in 18 target pathogens. Clearly, it has potential clinical utility in optimizing therapy and was incorporated into the Karius test workflow in September 2023. In addition, the workflow could readily be adapted to expand the number of target bacteria and antimicrobial resistance markers as needed.

The Effect of Reactive Oxygen Species on Respiratory Complex I Activity in Liposomes.

Respiratory complex I (R-CI) is an essential enzyme in the mitochondrial electron transport chain but also a major source of reactive oxygen species (ROS), which are implicated in neurodegenerative diseases and ageing. While the mechanism of ROS production by R-CI is well-established, the feedback of ROS on R-CI activity is poorly understood. Here, we perform EPR spectroscopy on R-CI incorporated in artificial membrane vesicles to reveal that ROS (particularly hydroxyl radicals) reduce R-CI activity by making the membrane more polar and by increasing its hydrogen bonding capability. Moreover, the mechanism that we have uncovered reveals that the feedback of ROS on R-CI activity via the membrane is transient and not permanent; lipid peroxidation is negligible for the levels of ROS generated under these conditions. Our successful use of modular proteoliposome systems in conjunction with EPR spectroscopy and other biophysical techniques is a powerful approach for investigating ROS effects on other membrane proteins.

Trends in day-case bladder outflow obstruction surgery: a study using Hospital Episode Statistics.

OBJECTIVES: To describe the contemporary evolution of day-case bladder outflow obstruction (BOO) surgery in England and to profile day-case BOO surgery practices across England in terms of the types of operation performed and their safety profiles. MATERIALS AND METHODS: This was a retrospective observational analysis of Hospital Episode Statistics and UK Office for National Statistics data. All 111 043 recorded operations across 117 hospital trusts over 66 months, from 1 January 2017 to 30 June 2022, were obtained. Operations were identified as one of: transurethral resection of prostate (TURP); laser ablation or enucleation; vapour therapy; prostatic urethral lift (PUL); or bladder neck incision. Monthly day-case rate trends were plotted across the study period. Descriptive data, day-case rates and 30-day hospital readmissions were analysed for each operation type. Multilevel regression modelling with mixed effects was performed to determine whether day-case surgery was associated with higher 30-day hospital readmissions. RESULTS: Day-case patients were younger, with fewer comorbidities. Time series analysis showed a linear day-case rate increase from 8.3% (January 2017) to 21.0% (June 2022). Day-case rates improved for 92/117 trusts in 2021/2022 compared with 2017. Three of the six trusts with the highest day-case rates performed predominantly day-case TURP, and the other three laser surgery. Nationally, PUL and vapour surgery had the highest day-case rates (80.9% and 38.1%). Most inpatient operations were TURP. Multilevel regression modelling found reduced odds of 30-day readmission after day-case BOO surgery (all operations pooled), no difference for day-case vs inpatient TURP, and reduced odds following day-case LASER operations. CONCLUSIONS: The day-case rates for BOO surgery have linearly increased. Minimally invasive surgical technologies are commonly performed as day cases, whereas high day-case rates for TURP and for laser ablation operations are seen in a minority of hospitals. Day-case pathways to treat BOO can be safely developed irrespective of operative modality.

The Getting It right First Time (GIRFT) programme in urology; rationale and methodology.

The Getting It Right First Time (GIRFT) programme is a quality improvement initiative covering the National Health Service in England. The programme aims to standardise clinical practices and improve patient and system level outcomes by utilising data-driven insights and clinically-led recommendations. There are GIRFT workstreams for every medical and surgical specialty, including urology. Defining features of the GIRFT methodology are that it is clinically led by experienced clinicians, data-driven, and specialty specific. Each specialty workstream conducts deep-dive visits to every hospital, analysing performance data and engaging with clinicians and management to identify and share improvement priorities. For urology, GIRFT has completed deep-dive visits and published reports outlining priority areas for development. Reports include recommendations pertaining to streamlining care pathways, reducing the acuity of care environments, enhancing emergency services, optimising utilisation of outpatient services, and workforce training and utilisation. The GIRFT academy provides guides for implementing best practices specific to priority areas of care. These include important disease pathways, and GIRFT-advocated innovations such as urology investigation units and urology area networks. GIRFT offers clinical transformation, cost reduction, equity in access to care, and leaner models of care that are often more environmentally sustainable. Evaluation efforts of the programme have focussed on assessing the adoption of GIRFT recommendations, understanding barriers to change, and modelling the climate impact of advocated practices.

The carbon footprint of the perioperative transurethral resection of bladder tumour pathway.

OBJECTIVES: To evaluate the carbon footprint of the perioperative transurethral resection of bladder tumour (TURBT) pathway from decision to treat to postoperative discharge, and model potential greenhouse gas (GHG) emissions reduction strategies. MATERIALS AND METHODS: This process-based attributional cradle-to-grave life-cycle assessment (LCA) of GHG emissions modelled the perioperative TURBT pathway at a hospital in Southwest England. We included travel, energy and water use, all reusable and consumable items, and laundry and equipment sterilisation. Resource use for 30 patients undergoing surgery was recorded to understand average GHG emissions and the inter-case variability. Sensitivity analysis was performed for manufacturing location, pharmaceutical manufacturing carbon-intensity, and theatre list utilisation. RESULTS: The median (interquartile range) perioperative TURBT carbon footprint was 131.8 (119.8-153.6) kg of carbon dioxide equivalent. Major pathway categories contributing to GHG emissions were surgical equipment (22.2%), travel (18.6%), gas and electricity (13.3%), and anaesthesia/drugs and associated adjuncts (27.0%), primarily due to consumable items and processes. Readily modifiable GHG emissions hotspots included patient travel for preoperative assessment, glove use, catheter use, irrigation delivery and extraction, and mitomycin C disposal. GHG emissions were higher for those admitted as inpatients after surgery. CONCLUSIONS: This cradle-to-grave LCA found multiple modifiable GHG emissions hotspots. Key mitigation themes include minimising avoidable patient travel, rationalising equipment use, optimally filling operating theatre lists, and safely avoiding postoperative catheterisation and hospital admission where possible. A crucial next step is to design and deliver an implementation strategy for the environmentally sustainable changes demonstrated herein.

Nivolumab Safety in Renal Cell Carcinoma: A Case Report.

Nivolumab is used to treat several different types of cancers. Although it is generally considered to be effective and well-tolerated, it has been associated with adverse effects requiring discontinuation of treatment, like many other drugs used for cancer. A 70-year-old male was switched from sunitinib to nivolumab for renal cell carcinoma. The patient developed persistent hypothyroidism, onycholysis, and pneumonitis at nivolumab cycle 6, 10, and 11, respectively. Using the Naranjo causality method, the likelihood of causality was deemed "probable" for pneumonitis and hypothyroidism and "possible" for onycholysis. Nivolumab was eventually discontinued due to disease progression, rather than safety concerns. Eudravigilance, the European pharmacovigilance database, was searched for all nivolumab-related individual case safety reports from Malta, up to September 4, 2023. Six reports were identified in Malta, although the 3 events identified in this case report were not reported, suggesting under-reporting in Malta. This case report identified an uncommon nivolumab adverse drug reaction (ADR), onycholysis and showed how, despite the occurrence of 3 ADRs, it was its lack of efficacy rather than its safety which led to its discontinuation in this particular patient.

Calpain Promotes LPS-induced Lung Endothelial Barrier Dysfunction via Cleavage of Talin.

Acute lung injury (ALI) is characterized by lung vascular endothelial cell (EC) barrier compromise resulting in increased endothelial permeability and pulmonary edema. The infection of gram-negative bacteria that produce toxins like LPS is one of the major causes of ALI. LPS activates Toll-like receptor 4, leading to cytoskeleton reorganization, resulting in lung endothelial barrier disruption and pulmonary edema in ALI. However, the signaling pathways that lead to the cytoskeleton reorganization and lung microvascular EC barrier disruption remain largely unexplored. Here we show that LPS induces calpain activation and talin cleavage into head and rod domains and that inhibition of calpain attenuates talin cleavage, RhoA activation, and pulmonary EC barrier disruption in LPS-treated human lung microvascular ECs in vitro and lung EC barrier disruption and pulmonary edema induced by LPS in ALI in vivo. Moreover, overexpression of calpain causes talin cleavage and RhoA activation, myosin light chain (MLC) phosphorylation, and increases in actin stress fiber formation. Furthermore, knockdown of talin attenuates LPS-induced RhoA activation and MLC phosphorylation and increased stress fiber formation and mitigates LPS-induced lung microvascular endothelial barrier disruption. Additionally, overexpression of talin head and rod domains increases RhoA activation, MLC phosphorylation, and stress fiber formation and enhances lung endothelial barrier disruption. Finally, overexpression of cleavage-resistant talin mutant reduces LPS-induced increases in MLC phosphorylation in human lung microvascular ECs and attenuates LPS-induced lung microvascular endothelial barrier disruption. These results provide the first evidence that calpain mediates LPS-induced lung microvascular endothelial barrier disruption in ALI via cleavage of talin.

Color-Dual Fates of F

We find that the duality between color and kinematics can be used to inform the high energy behavior of effective field theories. Namely, we demonstrate that the massless gauge theory of Yang-Mills deformed by a higher-derivative F^{3} operator cannot be tree level color dual while consistently factorizing without a tower of additional four-point counterterms with rigidly fixed Wilson coefficients that reaches to the ultraviolet (UV). We find through explicit calculation a suggestive resummation, namely that their amplitudes are consistent with the α^{'} expansion of those generated by the (DF)^{2}+YM theory, a known color-dual theory where the F^{2} term has been given a mass squared proportional to 1/α^{'}. As a result, considering consistent double-copy construction as a physical principle implies that an F^{3}-based color-dual resolution of the UV divergence in N=4 supergravity comes at the cost of field-theoretic locality. Similarly, when double copying F^{3} with itself, double-copy consistency lifts R^{3} gravity to a family of gravity theories with an all-order tower of higher-derivative corrections, which includes the closed bosonic string as a standard adjoint-type double copy.

Sentiment analysis of the Twitter response to Netflix's Our Planet documentary.

The role of nature documentaries in shaping public attitudes and behavior toward conservation and wildlife issues is unclear. We analyzed the emotional content of over 2 million tweets related to Our Planet, a major nature documentary released on Netflix, with dictionary and rule-based automatic sentiment analysis. We also compared the sentiment associated with species mentioned in Our Planet and a set of control species with similar features but not mentioned in the documentary. Tweets were largely negative in sentiment at the time of release of the series. This effect was primarily linked to the highly skewed distributions of retweets and, in particular, to a single negatively valenced and massively retweeted tweet (>150,000 retweets). Species mentioned in Our Planet were associated with more negative sentiment than the control species, and this effect coincided with a short period following the airing of the series. Our results are consistent with a general negativity bias in cultural transmission and document the difficulty of evoking positive sentiment, on social media and elsewhere, in response to environmental problems.

Análisis de sentimientos de la respuesta en Twitter al documental Nuestro Planeta de Netflix Resumen No está claro el papel que tienen los documentales sobre naturaleza en la formación de actitudes públicas y respuestas a los temas de conservación y vida silvestre. Aplicamos un análisis automático de sentimientos basado en reglas y el diccionario al contenido emocional de más de dos millones de tuits relacionados a Nuestro Planeta, un importante documental estrenado en Netflix. También comparamos entre los sentimientos asociados a las especies mencionadas en el documental y un conjunto de especies control con características similares pero que no mencionan en el documental. En general, los tuits contenían sentimientos negativos cuando se estrenó la serie. Relacionamos este efecto a la distribución sesgada de retuits particularmente de un solo tuit negativo con retuits masivos (>150,000). Las especies mencionadas estuvieron asociadas con más sentimientos negativos que las especies control. Este efecto coincidió con un periodo corto después de la emisión de la serie. Nuestros resultados son coherentes con un sesgo generalizado de negatividad en la transmisión cultural y documentan lo difícil que es provocar sentimientos positivos, en redes sociales o en demás sitios, como respuesta a los problemas ambientales.

Accelerated and personalized therapy for heart failure with reduced ejection fraction.

AIMS: Previously, guidelines recommended initiating therapy in patients with heart failure and reduced ejection fraction (HFrEF) in a sequence that follows the chronological order in which trials were conducted, with cautious up-titration of each treatment. It remains unclear whether this historical approach is optimal and alternative approaches may improve patient outcomes. METHODS AND RESULTS: The potential reductions in events that might result from (i) more rapid up-titration of therapies used in the conventional order (based on the chronology of the trials), and (ii) accelerated up-titration and using treatments in different orders than is conventional were modelled using data from six pivotal trials in HFrEF. Over the first 12 months from starting therapy, using a rapid up-titration schedule led to 23 fewer patients per 1000 patients experiencing the composite of heart failure hospitalization or cardiovascular death and seven fewer deaths from any cause. In addition to accelerating up-titration of treatments, optimized alternative ordering of the drugs used resulted in a further reduction of 24 patients experiencing the composite outcome and six fewer deaths at 12 months. The optimal alternative sequences included sodium-glucose cotransporter 2 inhibition and a mineralocorticoid receptor antagonist as the first two therapies. CONCLUSION: Modelling of accelerated up-titration schedule and optimized ordering of treatment suggested that at least 14 deaths and 47 patients experiencing the composite outcome per 1000 treated might be prevented over the first 12 months after starting therapy. Standard treatment guidance may not lead to the best patient outcomes in HFrEF, though these findings should be tested in clinical trials.

Performance of Tuberculosis Molecular Bacterial Load Assay Compared to Alere TB-LAM in Urine of Pulmonary Tuberculosis Patients with HIV Co-Infections.

Alternative tools are needed to improve the detection of M. tuberculosis (M. tb) in HIV co-infections. We evaluated the utility of Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) compared to lipoarabinomannan (LAM) to detect M. tb in urine. Sputum Xpert MTB/RIF-positive patients were consented to provide urine at baseline, weeks 2, 8, 16, and 24 of treatment for TB-MBLA, culture, and LAM. Results were compared with sputum cultures and microscopy. Initial M. tb. H37Rv spiking experiments were performed to validate the tests. A total of 63 urine samples from 47 patients were analyzed. The median age (IQR) was 38 (30-41) years; 25 (53.2%) were male, 3 (6.5%) had urine for all visits, 45 (95.7%) were HIV positive, of whom 18 (40%) had CD4 cell counts below 200 cells/µL, and 33 (73.3%) were on ART at enrollment. Overall urine LAM positivity was 14.3% compared to 4.8% with TB-MBLA. Culture and microscopy of their sputum counterparts were positive in 20.6% and 12.7% of patients, respectively. Of the three patients with urine and sputum at baseline, one (33.33%) had urine TB-MBLA and LAM positive compared to 100% with sputum MGIT culture positive. Spearman's rank correction coefficient (r) between TB-MBLA and MGIT was -0.85 and 0.89 with a solid culture, p > 0.05. TB-MBLA has the promising potential to improve M. tb detection in urine of HIV-co-infected patients and complement current TB diagnostics.

Psychological distress and risk of diabetes among medical students: A cross sectional study.

Background: Medical students are affected both psychologically and physically due to the change in environment for most from home to the hostel and the extensive undergraduate curriculum. This study was undertaken to assess psychological distress and measure surrogate markers of the physical health risk score in a medical college in South India. Methods: The study group included three batches of medical students, from first to third year. Along with anthropometric measurements and a questionnaire on personal history, the Indian Diabetic Risk Score (IDRS), and the Kessler's psychological distress scale based on K10 questions were applied and assessed for each participant. Results: There were gender differences in the association of IDRS with physical activity, Body Mass Index (BMI), Waist Hip Ratio (WHR), and sleep. More than one-third of medical students had various psychological distress grades (40%) and were at risk of developing diabetes (36.7%). There was a significant difference in the K10 scores (p = 0.000) among the three groups, with the first-year students showing maximum psychological distress. Conclusions: A large number of medical students undergo psychological distress and also are at risk for developing Diabetes Mellitus. Long-term cohort studies are needed to assess the effect of such stress on medical students.

Impact of a quality improvement program: Early initiation of breastfeeding after cesarean section in a tertiary care hospital, in Eastern India.

Background: Early initiation of breastfeeding (EIBF) within 1 h of birth is crucial in preventing newborn deaths and plays a vital role in early infant nutrition. Promoting and supporting breastfeeding is an integral part of midwifery. The objective of the study was to improve the EIBF rate in neonates born through a Cesarean Section (CS) from 0% to 50% within six months through a quality improvement (QI) process and to assess the maternal experience of EIBF in operation theatre (OT). Methods: Six Plan-Do-Study-Act (PDSA) cycles were conducted to test the change ideas proposed by the team members for a month to improve EIBF. Participants of the study were the stable term newborns delivered by CS under spinal anesthesia. Results: The EIBF rate improved from 0% to 88% after the sixth PDSA cycle. The effect was sustained for six months. Mothers of 51 neonates (98%) who received EIBF reported that their newborns were breastfed successfully, and it was not physically tiring to feed immediately in the OT. Conclusions: A quality improvement (QI) initiative was able to improve and sustain the improved EIBF rate after CS. Early skin-to-skin contact to be initiated with EIBF for better neonatal outcomes.

Prevalence and novel risk factors for vitamin D insufficiency in elite athletes: systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Vitamin D insufficiency may be common among elite athletes, but prevalence is unclear, and some potentially important risk factors are uncertain. The present study aimed to (a) estimate the prevalence of vitamin D insufficiency in elite athletes, and (b) examine differences in prevalence between the sexes, and between adults and adolescents, from recent studies which used a contemporary definition of insufficiency. METHODS: Four databases (Web of Science, SPORTDiscus, PubMed, and Sports Medicine and Education Index) were searched for studies in elite athletes. Literature selection, data extraction, and risk of bias assessment were conducted independently by two researchers. Vitamin D insufficiency was defined as 25(OH)D < 50 nmol/L. Meta-analysis was conducted, using R software x64 4.0.2, to provide estimates of prevalence of insufficiency for adults and adolescents, and to examine between-sex differences in risk of insufficiency. RESULTS: From the initial 943 literature search hits, 51 studies were eligible with 5456 participants, 33 studies in adults (12/33 in winter and spring), 15 studies in adolescents (6/15 in winter and spring) and 3 studies with age of study participants not given. Prevalence of vitamin D insufficiency from meta-analysis was 30% (95% CI 22-39%) in adults and prevalence was higher, though not significantly so, at 39% (95% CI 25-55%) in adolescents. Differences in the prevalence of insufficiency between the sexes for the eight studies which provided within-study comparisons was not significant (RR = 1.0; 95% CI 0.79-1.26). Evidence quality was moderate. CONCLUSIONS: Prevalence of vitamin D insufficiency (≤ 50 nmol/L) in elite athletes is high, suggesting a need for greater attention to prevention and treatment. Prevalence estimates in the present study are conservative due to a relative lack of studies in winter. While there was no evidence of higher risk among women than men in the present study, there was less evidence on women.

Investigating Investigation (Ab)Use: Thyroid Function Test Audit in a Tertiary Care Teaching Institute in Eastern India.

An essential component of contemporary health care is laboratory testing. As the utilization of diagnostic tests grow, there is also an increase in the scrutiny of such tests for its effectiveness, balance of cost and over- utilization. Thyroid dysfunction is common across all age groups and is associated with a number of comorbid states. The thyroid function tests (TFTs) are very important for the diagnosis and monitoring of such patients. The guidelines recommend serum thyroid stimulating hormone (TSH) as the single most reliable test to diagnose all common forms of hypothyroidism and hyperthyroidism, except in few cases. This study was conducted to study the investigation requesting pattern of TFTs. Our results showed that TFT panel was ordered in almost equal numbers (35.58%) as single test of TSH (41.27%). Subclinical thyroid disease was diagnosed in 22.1% of cases and the rest were excluded as having any thyroid dysfunction. Over 2/3rd of all requests were for women. An important conclusion from our study was that, the essentiality of lab tests is a decision entirely in the hands of the treating physician keeping in mind the cost and best outcome for patients. Hospitals can develop strategic protocols for ordering laboratory tests keeping resources, need and patient satisfaction and outcomes optimal.

Estimation of 24 h Urine Protein Versus Spot Urine Protein Creatinine Ratio in Patients with Kidney Disease.

This cross-sectional study was undertaken to compare 24-h urine protein estimation with spot urine protein-creatinine ratio (PCR). 72 patients having proteinuria of > 150 mg/day were included in this study. 24-h urine total protein (UTP) test were also asked to give their mid-morning spot urine sample the following day for urine protein-creatinine ratio. The subjects were grouped according to their UTP into Groups as described follows: Group A < 1 g/day, Group B 1-3.5 g/day and Group C > 3.5 g/day. Pearson's correlation (r) and paired Student's T test were done. The paired T test showed no difference in the UTP and PCR in the subgroup having qualitative protein of zero and in group A. There was no agreement between the two methods used for quantitation. In the overtly proteinuric patients, the correlation between the UTP and PCR was positive in group A which was statistically significant (p = 0.05) whereas it was not significant (p = 0.07) in group B. Though there was a negative correlation in the massive proteinuria group C it was not significant (p = 0.65). Our study demonstrates that spot PCR can be reliable parameter for initial diagnostic criterion of proteinuria but for follow-up measurements and for proteinuria > 0.5 gm/day, 24-h UTP is the single most accurate measurement of protein excretion.