Overview of thyroid gland characteristics in pregnancy using ultrasonography as an assessment tool

Thyroid gland is one of the most common gland affected during pregnancy as it responds to the increased physiological demands of iodine and energy during pregnancy. Any thyroid dysfunction can result in abortion, preterm labor or affects fetal neurodevelopment. Various anthropometric factors or genetic factors apart from iodine intake are known to affect the size of thyroid gland. Changes in thyroid gland morphology can be easily measured using ultrasonography as clinically the enlargement can be labelled as goiter. In this review, we aimed to evaluate the changes in thyroid gland during pregnancy and assess the different factors affecting its size across the various studies as the literature data concerning the thyroid gland enlargement during pregnancy is controversial. Various articles on thyroid volume changes during pregnancy from literature were reviewed along with a cross-sectional observation done in a government hospital setup in India, on 240 patients who were divided into 4 groups of 60 patients each which included non-pregnant females in group 1 and pregnant females in all three trimesters respectively in the rest 3 groups. Thyroid gland morphology and its characteristics such as volume, nodularity, echogenicity and vascularity were measured using high frequency ultrasonography in each group and then compared. Thyroid volume in the third trimester group (7.24±1.16 ml) was found to be significantly greater (p<0.001) than in the non-pregnant group (5.44±0.82 ml). BMI was found to be the highest in third trimester group as expected. Even in iodine sufficient areas we found thyroid gland volume to increase during pregnancy from non-pregnant group along with thyroid gland nodularity. Vascularity assessed based on CDFS pattern shows pattern I to be most common. Variation in thyroid gland characteristics between pregnant and non-pregnant controls was found

Effect of maternal anaemia on foetal Doppler indices during third trimester of pregnancy

Background: Anaemia is amongst the most common medical disorders encountered during pregnancy all over the world. India has a high rate of anaemia in pregnant women. Anaemia has a recognizable effect on both maternal and foetal health during pregnancy and on perinatal outcome, contributing remarkably to maternal morbidity and mortality. Routine foetal monitoring is an essential investigation for such females with special emphasis on obstetrics Doppler ultrasonography. Various changes due to foetal hypoxia due to maternal anaemia can be remarkably appreciated on Doppler helping in timely management. The objective of this study was to evaluate the effect of maternal anaemia on foetal Doppler indices.Methods: 400 pregnant women were assessed in a cross-section observational study done in the department of Radiodiagnosis in MYH, Indore, India. These women were divided into three groups of mild, moderate and severe anaemia based on the level of haemoglobin.Results: Umbilical artery resistive and pulsatility indices were found to be increased with the increasing severity of anaemia while middle cerebral artery indices and CPR showed a decreasing trend with the increasing severity of anaemia.Conclusions: We found that severe maternal anaemia is associated with marked adaption in foetal haemodynamics. Obstetrics Doppler can be used as an accurate measure of surveillance for foetal monitoring and will help in appropriate management

Recent Advances in Heat Transfer Augmentation by using Twisted Tapes: A Review

In the past decade several studies on the passive techniques of heat transfer augmentation have been reported. The present paper is a review on progress with the passive augmentation techniques in the recent past and will be useful to designers implementing passive augmentation techniques in heat exchanger. In passive technique twisted tape insert is playing an important method to enhance the heat transfer characteristics of a heat exchanger without affecting much the overall performance of the system. The present review is organized in two different sections: augmentation of heat transfer in laminar flow and augmentation of heat transfer in turbulent flow. Key words: Heat transfer augmentation, Passive methods, Twisted Tape inserts, Reynolds number, Friction facto

A Comparative Study of Active and Passive Adverse Drug Reaction Monitoring Methods in Category I Tuberculosis Patients at a Tertiary Care Hospital in India

Background & Aims:  Adverse Drug Reactions (ADRs) are common with drug treatment. They can be collected by active and passive methods. The aim of the study was to compare active and passive ADR monitoring methods in terms of yield and lag period in category I tuberculosis patients. Materials & Methods: A prospective observational analytical study was done in a directly observed therapy short-course (DOTS) center and pharmacovigilance center of SMS hospital, Jaipur, Rajasthan, India from 1.1.2019 to 31.12.2019. A total of 303 category I tubercular patients on DOTS were divided into groups A (150) and B (153). Group A (active) patients were interviewed personally or telephonically for ADRs on 0,3,7,15,30, 90,180 days of therapy as per pre-structured & pre-validated questionnaire. Group B (passive) patients were asked to report ADRs themselves to pharmacovigilance center directly or through a drop box. Collected ADRs were compared statistically using software Minitab 14, Pennsylvania, USA. Results: The yield of ADRs in active method was 4.5 times higher than the passive method. GIT related ADRs were similar in both groups, cutaneous were higher in active and CNS concerned were higher in passive method. However, consistency of ADR reporting was more in passive method. Mean lag period between onset and reporting of ADRs by active and passive methods were 5.72 and 22.4 days, respectively. Conclusion: Active method initially and numerically facilitates ADR  reporting together with decreased lag period  but passive method gives consistent yield in chronic diseases like TB, hence, an integrated approach to identify and manage ADRs will be most beneficial for patients

Baseline Expression of Immune Gene Modules in Blood is Associated With Primary Response to Anti-TNF Therapy in Crohn’s Disease Patients

Background and Aims: Anti-tumour necrosis factor [anti-TNF] therapy is widely used for the treatment of inflammatory bowel disease, yet many patients are primary non-responders, failing to respond to induction therapy. We aimed to identify blood gene expression differences between primary responders and primary non-responders to anti-TNF monoclonal antibodies [infliximab and adalimumab], and to predict response status from blood gene expression and clinical data. Methods: The Personalised Anti-TNF Therapy in Crohn’s Disease [PANTS] study is a UK-wide prospective observational cohort study of anti-TNF therapy outcome in anti-TNF-naive Crohn’s disease patients [ClinicalTrials.gov identifier: NCT03088449]. Blood gene expression in 324 unique patients was measured by RNA-sequencing at baseline [week 0], and at weeks 14, 30, and 54 after treatment initiation [total sample size = 814]. Results: After adjusting for clinical covariates and estimated blood cell composition, baseline expression of major histocompatibility complex, antigen presentation, myeloid cell enriched receptor, and other innate immune gene modules was significantly higher in anti-TNF responders vs non-responders. Expression changes from baseline to week 14 were generally of consistent direction but greater magnitude [i.e. amplified] in responders, but interferon-related genes were upregulated uniquely in non-responders. Expression differences between responders and non-responders observed at week 14 were maintained at weeks 30 and 54. Prediction of response status from baseline clinical data, cell composition, and module expression was poor. Conclusions: Baseline gene module expression was associated with primary response to anti-TNF therapy in PANTS patients. However, these baseline expression differences did not predict response with sufficient sensitivity for clinical use.</p

Mechanisms and management of loss of response to anti-TNF therapy for patients with Crohn's disease:3-year data from the prospective, multicentre PANTS cohort study

Background: We sought to report the effectiveness of infliximab and adalimumab over the first 3 years of treatment and to define the factors that predict anti-TNF treatment failure and the strategies that prevent or mitigate loss of response. Methods: Personalised Anti-TNF therapy in Crohn's disease (PANTS) is a UK-wide, multicentre, prospective observational cohort study reporting the rates of effectiveness of infliximab and adalimumab in anti-TNF-naive patients with active luminal Crohn's disease aged 6 years and older. At the end of the first year, sites were invited to enrol participants still receiving study drug into the 2-year PANTS-extension study. We estimated rates of remission across the whole cohort at the end of years 1, 2, and 3 of the study using a modified survival technique with permutation testing. Multivariable regression and survival analyses were used to identify factors associated with loss of response in patients who had initially responded to anti-TNF therapy and with immunogenicity. Loss of response was defined in patients who initially responded to anti-TNF therapy at the end of induction and who subsequently developed symptomatic activity that warranted an escalation of steroid, immunomodulatory, or anti-TNF therapy, resectional surgery, or exit from study due to treatment failure. This study was registered with ClinicalTrials.gov, NCT03088449, and is now complete. Findings: Between March 19, 2014, and Sept 21, 2017, 389 (41%) of 955 patients treated with infliximab and 209 (32%) of 655 treated with adalimumab in the PANTS study entered the PANTS-extension study (median age 32·5 years [IQR 22·1–46·8], 307 [51%] of 598 were female, and 291 [49%] were male). The estimated proportion of patients in remission at the end of years 1, 2, and 3 were, for infliximab 40·2% (95% CI 36·7–43·7), 34·4% (29·9–39·0), and 34·7% (29·8–39·5), and for adalimumab 35·9% (95% CI 31·2–40·5), 32·9% (26·8–39·2), and 28·9% (21·9–36·3), respectively. Optimal drug concentrations at week 14 to predict remission at any later timepoints were 6·1–10·0 mg/L for infliximab and 10·1–12·0 mg/L for adalimumab. After excluding patients who had primary non-response, the estimated proportions of patients who had loss of response by years 1, 2, and 3 were, for infliximab 34·4% (95% CI 30·4–38·2), 54·5% (49·4–59·0), and 60·0% (54·1–65·2), and for adalimumab 32·1% (26·7–37·1), 47·2% (40·2–53·4), and 68·4% (50·9–79·7), respectively. In multivariable analysis, loss of response at year 2 and 3 for patients treated with infliximab and adalimumab was predicted by low anti-TNF drug concentrations at week 14 (infliximab: hazard ratio [HR] for each ten-fold increase in drug concentration 0·45 [95% CI 0·30–0·67], adalimumab: 0·39 [0·22–0·70]). For patients treated with infliximab, loss of response was also associated with female sex (vs male sex; HR 1·47 [95% CI 1·11–1·95]), obesity (vs not obese 1·62 [1·08–2·42]), baseline white cell count (1·06 [1·02–1·11) per 1 × 109 increase in cells per L), and thiopurine dose quartile. Among patients treated with adalimumab, carriage of the HLA-DQA1*05 risk variant was associated with loss of response (HR 1·95 [95% CI 1·17–3·25]). By the end of year 3, the estimated proportion of patients who developed anti-drug antibodies associated with undetectable drug concentrations was 44·0% (95% CI 38·1–49·4) among patients treated with infliximab and 20·3% (13·8–26·2) among those treated with adalimumab. The development of anti-drug antibodies associated with undetectable drug concentrations was significantly associated with treatment without concomitant immunomodulator use for both groups (HR for immunomodulator use: infliximab 0·40 [95% CI 0·31–0·52], adalimumab 0·42 [95% CI 0·24–0·75]), and with carriage of HLA-DQA1*05 risk variant for infliximab (HR for carriage of risk variant: infliximab 1·46 [1·13–1·88]) but not for adalimumab (HR 1·60 [0·92–2·77]). Concomitant use of an immunomodulator before or on the day of starting infliximab was associated with increased time without the development of anti-drug antibodies associated with undetectable drug concentrations compared with use of infliximab alone (HR 2·87 [95% CI 2·20–3·74]) or introduction of an immunomodulator after anti-TNF initiation (1·70 [1·11–2·59]). In years 2 and 3, 16 (4%) of 389 patients treated with infliximab and 11 (5%) of 209 treated with adalimumab had adverse events leading to treatment withdrawal. Nine (2%) patients treated with infliximab and two (1%) of those treated with adalimumab had serious infections in years 2 and 3. Interpretation: Only around a third of patients with active luminal Crohn's disease treated with an anti-TNF drug were in remission at the end of 3 years of treatment. Low drug concentrations at the end of the induction period predict loss of response by year 3 of treatment, suggesting higher drug concentrations during the first year of treatment, particularly during induction, might lead to better long-term outcomes. Anti-drug antibodies associated with undetectable drug concentrations of infliximab, but not adalimumab, can be predicted by carriage of HLA-DQA1*05 and mitigated by concomitant immunomodulator use for both drugs. Funding: Guts UK, Crohn's and Colitis UK, Cure Crohn's Colitis, AbbVie, Merck Sharp and Dohme, Napp Pharmaceuticals, Pfizer, and Celltrion Healthcare.</p

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text