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Introduction: Prolactin-adjusted adrenocorticotropic hormone (ACTH) ratio is used to improve the diagnostic accuracy of bilateral inferior petrosal sinus sampling (BIPSS) for lateralization of pituitary adenoma. Objective: To study the use of prolactin for successful catheterization during BIPSS, the role of prolactin-normalized ACTH ratio for confirmation of Cushing's disease (CD) and prolactin-adjusted ACTH ratio in predicting the lateralization. Patients and Methods: BIPSS was done in patients with CD; prolactin-adjusted ACTH ratio was compared with intersinus ACTH ratio, magnetic resonance imaging, and intraoperative findings for localization of pituitary adenoma. Histopathology was taken as “gold standard” for the diagnosis of CD. Results: Eight patients underwent BIPSS. All the patients underwent transsphenoidal surgery. All these patients had proper venous sampling during BIPSS as determined by inferior petrosal sinus (IPS):Peripheral prolactin ratio of ≥1.8. Prolactin-normalized ACTH ratio of ≥1.3 was achieved in all the eight patients, which was consistent with the diagnosis of CD. Concordance of intersinus ACTH ratio ≥1.4 with the intraoperative findings was found in five of eight (62.5%) patients depicting correct lateralization. Concordance of prolactin-adjusted ACTH ratio with intraoperative findings was found in four of eight (50%) patients. Seven of eight patients had concordance of intersinus ACTH ratio with prolactin-adjusted ACTH ratio. Conclusion: Prolactin is a useful marker for successful catheterization, confirming the diagnosis of CD during BIPSS, and prolactin-adjusted ACTH ratio does not add to the accuracy of lateralization of pituitary adenoma compared with intersinus ACTH ratio.

Context: Bilateral inferior petrosal sinus sampling (BIPSS) using hCRH is currently considered the ‘gold standard’ test for the differential diagnosis of ACTH-dependent Cushing’s syndrome (CS). Vasopressin is more potent than CRH to stimulate ACTH secretion as shown in animal studies; however, no comparative data of its use are available during BIPSS. Objective: To study the diagnostic accuracy and comparison of hCRH and lysine vasopressin (LVP) stimulation during BIPSS. Patients and methods: 29 patients (27-Cushing’s disease, 2-ectopic CS; confirmed on histopathology) underwent BIPSS and were included for the study. Patients were randomized to receive hCRH, 5 U LVP or 10 U LVP during BIPSS for ACTH stimulation. BIPSS and contrast-enhanced magnetic resonance imaging (CEMRI) were compared with intra-operative findings of trans-sphenoidal surgery (TSS) for localization and lateralization of the ACTH source. Results: BIPSS correctly localized the source of ACTH excess in 29/29 of the patients with accuracy of 26/26 patients, using any of the agent, whereas sensitivity and PPV for lateralization with hCRH, 5 U LVP and 10 U LVP was seen in 10/10, 6/10; 10/10,8/10 and 7/7,6/7 patients respectively. Concordance of BIPSS with TSS was seen in 20/27, CEMRI with BIPSS in 16/24 and CEMRI with TSS in 18/24 of patients for lateralizing the adenoma. Most of the side effects were transient and were comparable in all the three groups. Conclusion: BIPSS using either hCRH or LVP (5 U or 10 U) confirmed the source of ACTH excess in all the patients, while 10 U LVP correctly lateralized the pituitary adenoma in three fourth of the patients.

Abstract Non-functioning pituitary tumours (NF-PitNETs) are common intracranial benign neoplasms that can exhibit aggressive behaviour by invading neighbouring structures and, in some cases, have multiple recurrences. Despite resulting in severe co-morbidities, no predictive biomarkers of recurrence have been identified for NF-PitNETs. In this study we have used high-throughput mass spectrometry-based analysis to examine the phosphorylation pattern of different subsets of NF-PitNETs. Based on histopathological, radiological, surgical and clinical features, we have grouped NF-PitNETs into non-invasive, invasive, and recurrent disease groups. Tumour recurrence was determined based on regular clinical and radiological data of patients for a mean follow-up of 10 years (SD ± 5.4 years). Phosphoproteomic analyses identified a unique phosphopeptide enrichment pattern which correlates with disease recurrence. Candidate phosphorylated proteins were validated in a large cohort of NF-PitNET patients by western blot and immunohistochemistry. We identified a cluster of 22 phosphopeptides upregulated in recurrent NF-PitNETs compared to non-invasive and invasive subgroups. We reveal significant phosphorylation of the β-catenin at Ser552 in recurrent and invasive NF-PitNETs, compared to non-invasive/non-recurrent NF-PitNET subgroup. Moreover, β-catenin pSer552 correlates with the recurrence free survival among 200 patients with NF-PitNET. Together, our results suggest that the phosphorylation status of β-catenin at Ser552 could act as potential biomarker of tumour recurrence in NF-PitNETs.

PurposeNon-functioning pituitary adenomas (NFPAs) exhibit high recurrence rates after surgery. However, the determinants of recurrence are inconsistent in the available literature. The present study sought to investigate the association between nuclear phosphorylated EGFR (pEGFR) levels and recurrence of NFPAs.MethodsTissue microarrays from patients undergoing adenomectomy for NFPAs at our tertiary care center from 2003 to 2015 and having a minimum of 60 months of follow-up (n=102) were accessed. Immunohistochemical analysis (IHC) was performed to determine the expression of nuclear pEGFR T693. h-score was calculated as the product of staining intensity and the number of positively staining cells. Radiological surveillance (MRI) was performed to categorize NFPAs as recurrent or non-recurrent on follow-up.ResultsThe mean age of the cohort was 50 ± 11 years with a male preponderance (61.1%). Recurrence was observed in 46.1% of the patients at a median of 123 months (IQR 72-159) of follow-up. pEGFR T693 positivity was higher in a significantly greater number of recurrent NFPAs as compared to non-recurrent NFPAs (95.7% vs 81%, p=0.02). h-scores were also significantly higher in recurrent NFPAs (122.1 ± 6 vs 81.54 ± 3.3, p

Background Microscopic transsphenoidal excision of pituitary gland, though considered safe from neurosurgical point of view, produces marked cardiovascular and stress responses despite adequate depth of anesthesia. The aim of this study was to evaluate the effect of dexmedetomidine bolus and infusion in microscopic transsphenoidal pituitary surgery on hemodynamics, bleeding in surgical field, and recovery parameters. Materials and Methods A prospective randomized double-blind study was conducted in 40 American Society of Anesthesiologists (ASA) I-II patients between 18 and 65 years, who underwent elective transsphenoidal excision of pituitary tumor. Two groups were constituted: one group received dexmedetomidine 1 μg/kg loading dose followed by 0.5 μg/kg/h infusion, the other received placebo bolus and infusion. A standard anesthesia protocol including isoflurane and fentanyl was used in both groups. The hemodynamic profile, intraoperative bleeding, and recovery profile were studied. Results The heart rate (HR) did not vary significantly from the baseline during surgery and recovery in the dexmedetomidine group. The systolic, diastolic, and mean blood pressures decreased significantly with dexmedetomidine in statistical terms, though they were within the clinically acceptable range and did not require intervention. On comparing the groups, dexmedetomidine group had better perioperative blood pressure profile and decreased isoflurane requirement. Bleeding scores during surgery and recovery were similar in both groups. Conclusions Intraoperative use of dexmedetomidine in transsphenoidal pituitary surgery provided stable perioperative hemodynamics comprising reduced cardiovascular response to intubation and surgical noxious stimuli along with a similar recovery compared with the control group. Therefore, dexmedetomidine appears as a useful adjunct to control hemodynamics in neurosurgical patients undergoing transsphenoidal surgery.

There has been tremendous technological innovation in the healthcare sector, but it has also raised serious ethical and social concerns. The COVID-19 pandemic has only magnified these existing challenges. Hence, addressing these challenges becomes imperative in the "new normal." In this context, this article uses a narrative synthesis approach to discuss the linkages of health technology, innovation, and policy to identify the challenges of this complex interaction by applying the principles of pragmatism and historicity to the existing literature. Moreover, the existing scientific mechanisms in the form of health technology assessment (HTA) and responsible innovation in health (RIH) are described to address these challenges. Using inductive epistemology, the linkages between HTA and RIH within a health innovation ecosystem framework are discussed for the future application of an integrated approach to address societal challenges. The proposed integrated approach of HTA and RIH is a work in progress and conceptualized as transdisciplinary, flexible, and adaptive, which is expected to facilitate future discussion, research, and policy action.

Competing Interests: There are no conflicts of interest.

Achieving persistence in household behavior modification has been a central but elusive goal of environmental conservation attempts that rely on behavioral interventions. We implemented a habit change intervention, designed to achieve persistent change in household water conservation behavior in an affluent residential community in urban India. We found a 15 to 25% reduction in household water consumption in the absence of any volumetric pricing. Most importantly, the effects of our 5-wk intervention persisted for more than a year, after which marginal pricing was introduced. The treatment gap was not bridged even after a year under the marginal price regime., Competing Interests: The authors declare no competing interest.

Background: Mumbai is facing the full brunt of the COVID-19 pandemic epidemiologically and economically., Objectives: The objective was to understand the spatial distribution and trends of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in Mumbai during the lockdown period and draw insights for effective actions., Methods: Spatial and trend analysis was conducted to trace the spread of the virus during the lockdown period in April 2020. The administrative divisions of Mumbai, in the form of wards and zones, have been used as units of analysis., Results: Greater Mumbai area occupies only 0.015% of the landmass of India, but is contributing to over 20% of the SARS-CoV-2 cases in India. Cases of SARS-CoV-2 infections have increased over 375 times within 50 days of the lockdown. An analysis of trends across the wards during the 3-week period (April 4 to April 25) shows a skewed pattern, with three zones out of six contributing to the vast majority of cases in Mumbai. The wards with higher formal economic activity are relatively less affected than the other wards. The test positivity rate in Mumbai is much higher than the rest of India., Conclusion: The study suggests that the virus had already spread to the community in Mumbai before the lockdown started., Competing Interests: None

Methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T, A1298C) has been implicated in increased plasma homocysteine (Hcy) levels. The present study was designed to investigate the association between MTHFR polymorphism and increased Hcy levels in subarachnoid haemorrhage (SAH) patients. A total of 150 subjects from North India were included in the study, comprising of 100 SAH patients and 50 healthy controls. Plasma Hcy levels was determined and MTHFR polymorphism (C677T, A1298C) was screened by High resolution melting (HRM) analysis. Plasma Hcy levels were found to be significantly higher (p < 0.001) in SAH patients than in healthy controls. No significant difference in the genotype and allele frequency of MTHFR A1298C was observed. However, frequency of MTHFR C677T genotype, CT (53% vs. 20%; p < 0.001) and TT (15% vs. 2%; p < 0.05) was significantly higher in SAH group as compared to healthy controls. The frequency of T allele (41.5% vs. 12%; p < 0.001) was also found to be higher in SAH patients in comparison to healthy controls. Furthermore, Hcy levels were higher in SAH patients with TT genotype than in patients having CT genotype, whereas CC genotype had lower Hcy levels. The study suggests that higher frequency of MTHFR C677T allele may contribute to etiopathology of SAH through increase in Hcy levels.

Competing Interests: Compliance with Ethical StandardsThere is no conflict of interest between the authors.Informed signed written consent was taken from the patient involved.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.No animals were involved in the study.

Medicines constitute a substantial proportion of out-of-pocket (OOP) expenses in Indian households. In order to address this issue, the Government of India launched the Jan Aushadhi (Medicine for the Masses) Scheme (JAS) to provide cheap generic medicines to the patients (http://janaushadhi.gov.in/about&#95;jan&#95;aushadhi.html). These medicines are provided through the Jan Aushadhi stores established across the country. The objective of this study was to do a quick assessment for policy-makers regarding the objective of the JAS. Implications on cost savings for patients and policy implications of the scheme were analyzed. Secondary data sources were used to obtain prices of medicines under the JAS and prices of branded medicines of the same formulations. A cost analysis design was used. There are substantial differences between the JAS price and the cheapest branded medicine available in the market. However, not all JAS prices are lower than branded medicines. For example, the cheapest branded cefuroxime axetil (500 mg) (antibiotic) in the market is almost three times cheaper than its JAS price. Hence, there are cheaper brands available for some commonly prescribed medicines. From the policy perspective, it raises serious questions regarding the pricing of medicines in the JAS and its overarching goal. Since patients are dependent on physicians for medicine prescriptions and have little knowledge of the price variations among branded and generic medicines, the JAS may not provide the cheapest alternative for the patients. Hence, the government should urgently review the JAS prices to achieve its goal of providing low-cost affordable medicines., (© 2017 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Hemophilia is a genetic disorder with high health care burden. In India, most patients with hemophilia seek care through self-purchasing factor concentrate and incur huge out-of-pocket (OOP) expenditure. In March 2013, the government of India launched a pilot hematology program through the National Rural Health Mission for providing free treatment services to patients with hemophilia in the state of Maharashtra., Objectives: To estimate the benefit-cost ratio of the program from a patient perspective, to estimate reduction in OOP expenditure of the patients and their families, and to assess the quality of care delivered and the barriers to access care among patients with hemophilia., Methods: This cross-sectional study evaluated the intervention of free treatment to patients with hemophilia at four district civil hospitals of Maharashtra. The study sample included 232 people with hemophilia (193 with hemophilia A, 31 with hemophilia B, 6 with von Willebrand disease, and 2 others) under four study arms over a 1-year study period. Cost-benefit analysis was performed for patients undergoing treatment at government hospitals and through nongovernmental organizations., Results: The benefit-cost ratio for the government program was 1.89. There was reduction in OOP expenditure by 21% per patient annually for the families. About 98% patients were highly satisfied with the services, whereas a major barrier to access was difficulty in commuting during active bleeding episodes., Conclusions: The government intervention through the National Rural Health Mission was cost-beneficial to the patients with hemophilia. It helped in reducing the OOP expenditure by 21%., (Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objective: To understand the knowledge and services of informal providers and to explore their role in addressing the human resource gap in Uttar Pradesh, India, within the context of maternal health., Materials and Methods: The study is exploratory in nature, conducted in four blocks of four districts of Uttar Pradesh state, India. Semi-structured interviews were conducted with 114 informal providers., Results: More than one-third (38%) providers have some formal education and unrecognized degrees. Approximately three-fourths (74%) of them have more than 5 years of work experience. They also provide delivery and in-patient services and have basic equipment available. However, they lack essential knowledge about maternal health. They have mixed opinion about their contribution towards maternal health but the only ones available. Therefore, despite lacking requisite knowledge, training and services, they become indispensable due to lack of emergency and timely public health services, and being the only ones existing in the community., Conclusion: Informal sector practitioners are a critical link in reaching out to population for health services in developing countries. As opposed to the general notion, they possess years of formal education, experience, informal trainings along with trust of communities. Thus, it becomes important to accept their presence and manage them to the best of their abilities even for specialized care like maternal health.

The recent series of ad interim orders issued by the Bombay High Court under ordinary original civil jurisdiction following public interest litigation (PIL) on the provision of free clotting factor concentrates for persons living with haemophilia, especially those below the poverty line and emergency cases, highlights the need to think about the ethicality of various aspects of access to medicine and the rights of patients suffering from rare diseases from the public health perspective. The PIL (number 82/2012) [Vinay Vijay Nair and Ors vs. Department of Health, State of Maharashtra and Ors), which calls for free treatment for all haemophiliacs who go to the designated hospitals, was followed by the issuance of five ad interim orders (July 19, 2012, October 22, 2012, November 6, 2012, January 24, 2013, and March 19, 2013).

Functional neurological disorders (FND) have been a challenge to treat both for neurologists and neurosurgeons. Various ablative as well as non-ablative techniques have been used to treat these disorders. Gamma knife radiosurgery (GKRS) is also being practised to treat refractory obsessive- compulsive disorder (OCD). The subsequent complications of GKRS reported have been variable, with headache being the most common. We discuss here a rare complication of 'late onset radiation necrosis in bilateral caudate nuclei' in a patient after receiving GKRS three years back. This case highlights the need to be more cautious before administering ablative procedures in patients suffering with functional disorders.

Additive integration of information is ubiquitous in judgment and has been shown to be effective even when multiplicative rules of probability theory are prescribed. We explore the generality of these findings in the context of estimating probabilities of success in contests. We first define a normative model of these probabilities that takes account of relative skill levels in contests where only a limited number of entrants can win. We then report 4 experiments using a scenario about a competition. Experiments 1 and 2 both elicited judgments of probabilities, and, although participants' responses demonstrated considerable variability, their mean judgments provide a good fit to a simple linear model. Experiment 3 explored choices. Most participants entered most contests and showed little awareness of appropriate probabilities. Experiment 4 investigated effects of providing aids to calculate probabilities, specifically, access to expert advice and 2 simulation tools. With these aids, estimates were accurate and decisions varied appropriately with economic consequences. We discuss implications by considering when additive decision rules are dysfunctional, the interpretation of overconfidence based on contest-entry behavior, and the use of aids to help people make better decisions.

Lymphomas occur with an increased frequency in patients with Human Immunodeficiency Virus (HIV) infection. These are usually high-grade immunoblastic lymphomas and primary central nervous system lymphomas. Anaplastic large cell lymphoma (ALCL) is a distinct type of non-Hodgkin's lymphoma. It is uncommon in HIV infected individuals. We describe here an uncommon presentation of this relatively rare lymphoma in the form of spinal cord compression syndrome in a young HIV infected individual.

This article presents a dual system model (DSM) of decision making under risk and uncertainty according to which the value of a gamble is a combination of the values assigned to it independently by the affective and deliberative systems. On the basis of research on dual process theories and empirical research in Hsee and Rottenstreich (2004) and Rottenstreich and Hsee (2001) among others, the DSM incorporates (a) individual differences in disposition to rational versus emotional decision making, (b) the affective nature of outcomes, and (c) different task construals within its framework. The model has good descriptive validity and accounts for (a) violation of nontransparent stochastic dominance, (b) fourfold pattern of risk attitudes, (c) ambiguity aversion, (d) common consequence effect, (e) common ratio effect, (f) isolation effect, and (g) coalescing and event-splitting effects. The DSM is also used to make several novel predictions of conditions under which specific behavior patterns may or may not occur.

Background: Mother-to-child transmission of HIV is an important mode of spread of HIV in India. With strategies like caesarian section and nevirapine therapy, this spread has been reduced. However, they have costs attached. In this context, this paper attempts to compare the cost-effectiveness of alternative childbirth strategies among HIV-positive mothers receiving nevirapine., Materials and Methods: Using sentinel surveillance data from three districts in Tamil Nadu, a model was created to test the cost-effectiveness of vaginal delivery against elective caesarian section among mothers receiving nevirapine. Sensitivity analysis was applied to evaluate cost per HIV infection prevented., Results: Vaginal delivery is not only cheaper in HIV-infected mothers receiving nevirapine but also cost-effective as compared to elective caesarian section. The incremental cost for preventing an additional HIV infection through caesarian section was Rs. 76,000. Sensitivity analysis reveals that the findings are robust over a range of HIV transmission probabilities, 0.04-0.14 for vaginal delivery and 0.00-0.02 for caesarian section., Conclusions: From a clinical perspective, the findings suggest that pregnant HIV-infected women receiving nevirapine should consider the benefits of a cheaper and safer vaginal delivery. From an economic perspective, the findings support the strategy of vaginal delivery in mothers receiving nevirapine.

Quality Problem or Issue: One of the prime goals of any health system is to deliver good and competent quality of healthcare. Through World Bank-assisted Maharashtra Health Systems Development Project, Government of Maharashtra in India developed and implemented clinical indicators to improve quality., Initial Assessment: During this, clinical areas eligible for monitoring quality of care and roles of health staff working at various levels were identified., Choice of Solution: Brainstorming discussion sessions were conducted to refine list of potential clinical indicators and to identify implementation problems., Implementation: It was implemented in four stages. (a) Self-explanatory tool of record, standard operating procedures and training manual were prepared during tools preparation stage. (b) Pilot implementation was done to monitor the usefulness of indicators, document the experiences and standardize the system accordingly. (c) The final selection of indicators was done taking into consideration points like data reliability, indicator usefulness etc. For final implementation, 15 indicators for district and 6 indicators for rural hospitals were selected. (d) Transfer of skills was done through training of various hospital functionaries., Evaluation and Lessons Learned: Selection and prioritization of clinical indicators is the most crucial part. Active participation of local employees is essential for sustainability of the scheme. It is also important to ensure that data recorded/reported is both reliable and valid, to conduct monthly review of the scheme at various levels and to link it with the quality improvement programme.

The present study investigated the changes in ultrastructural features of dermal collagen fibrils of mice following exposure to different cumulative chronic low-dose X-irradiation through digital image analysis-based statistical modeling. Pubertal mice were X-irradiated and dorsal skin biopsies were collected and processed for transmission electron microscopic (TEM) analysis. TEM features of collagen fibrils showed alteration in the cross-sectional area, population density and in the axial periodic pattern of light and dark bands. The mathematical analysis of histogram data from TEM images revealed some adaptive behavior in collagen structures of the X-irradiated group. This finding indicated that exposure to chronic low-dose X-radiation induced an altered steady state with adaptive variation in dermal collagen fibrils in irradiated mice.

This paper presents an automatic method for classification of progressive stages of oral precancerous conditions like oral submucous fibrosis (OSF). The classifier used is a three-layered feed-forward neural network and the feature vector, is formed by calculating the wavelet coefficients. Four wavelet decomposition functions, namely GABOR, HAAR, DB2 and DB4 have been used to extract the feature vector set and their performance has been compared. The samples used are transmission electron microscopic (TEM) images of collagen fibers from oral subepithelial region of normal and OSF patients. The trained network could classify normal fibers from less advanced and advanced stages of OSF successfully.

Background: Distal anterior cerebral artery (DACA) aneurysms are uncommon. Most authors have reported technical difficulties during surgery for these aneurysms, and a variety of surgical approaches have been advocated., Methods: Over a period of 5 years (1999-2003), 67 patients with DACA aneurysms were operated. Twenty-eight of these were operated on through the bifrontal basal anterior interhemispheric approach. Of the 28 patients, 68% were in poor clinical grade (Hunt and Hess grade III-V) and 89.3% had a Fisher grade III and IV on computed tomography scan. A surgical trajectory about 2 to 3 cm superior to the anterior cranial fossa floor led directly to the aneurysm. Proximal control was achieved before aneurysm dissection and parallel clipping., Results: Good outcome (Glasgow Outcome Scale V and IV) was seen in 57.19 of the patients, 14.3% had a poor outcome, and 28.6% died. The cause of death in most patients was found to be a poor clinical grade, postoperative infarct, or presence of multiple aneurysms., Conclusions: The advantages of the bifrontal basal anterior interhemispheric approach were the following: (a) It provided the shortest and a direct trajectory to the aneurysm. (b) Proximal control of the parent A(2) vessels could be easily achieved. (c) Release of cerebrospinal fluid from basal cisterns could be done, if necessary. (d) There was a minimal distortion of or traction over the aneurysm.

The effect of blood transfusion on DNA profiles of an individual is a significant issue in the forensic context. In the present study, the effects of blood transfusion in 5 recipients were studied by performing restriction fragment length polymorphism and polymerase chain reaction HLA-DQA1 and Polymarker (LDLR, GYPA, HBGG, D7S8, and GC) assays (Roche Molecular Systems, Branchburg, NJ) on serial posttransfusion blood samples. Pretransfusion and posttransfusion DNA profiles of all 5 recipients were consistent with no evidence of the donor genetic material. Currently used DNA profiling techniques in forensic science are reliable and informative for paternity and identity purposes in situations involving transfusion of 1 or 2 U of blood up to 24 hours posttransfusion.