Adrenocorticotropic Hormone-Dependent Cushing’s Syndrome : Use of an octreotide trial to distinguish between pituitary or ectopic sources

Objectives: Adrenocorticotropic hormone (ACTH) overproduction is usually due to a pituitary tumour which is often not visible on magnetic resonance imaging (MRI). However, ACTH overproduction may be due to an ectopic source. This study aimed to develop a simple non-invasive technique to differentiate these sources. Methods: This study took place in King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia, and Sultan Qaboos University Hospital, Muscat, Oman, between 1988 and 2012. Serum cortisol levels were measured in nine patients with ACTH-dependent Cushing’s syndrome before and during a 72-hour trial of octreotide. All patients underwent computed tomography (CT) scans. MRI scans were performed on six patients. Results: CT scans were abnormal in three patients with ectopic ACTH production. MRI scans showed that three patients had pituitary microadenomas. Serum cortisol levels returned to normal in those with confirmed ectopic ACTH production. No response was found in the other six patients. Conclusion: A 72-hour trial of octreotide is recommended for patients with ACTH-dependent Cushing’s syndrome and a normal pituitary MRI. This trial will be a useful alternative to petrosal sinus sampling

Influence of gender roles and responsibilities on family planning decisions in adults, in Karachi, Pakistan: A qualitative analysis of open-ended interviews

Background: In Pakistan, the slow pace of declining fertility rate accounts for troubling consequences like multiple pregnancies, induced abortions, the low 34% contraceptive prevalence rate, and overpopulation. This coupled with the lack of literature on this topic in the country makes it pivotal to explore the gender roles and responsibilities of adults in marital life and within the family and their influence on Family Planning decisions in adults, in Karachi, Pakistan.Methods: The study design involved purposive selection of 12 consenting married adults belonging to Gulberg Town, from whom detailed qualitative data was collected using open-ended, semi-structured interviews, supported by field notes. For the sake of anonymity, participants were assigned codes. Furthermore, all discussions were conducted in English or Urdu language by the female investigator herself and were audio recorded after obtaining participants’ consent. Thereafter, a rigorous thematic analysis of the interviews was carried out, with the results being double-checked before being securely stored in soft or hard copy.Results: The study observations identified that gender roles and responsibilities do affect Family Planning decisions in Pakistan. The results were broadly categorized into two themes: superficial reasons and deeper reasons affecting FP decisions. The first theme has three main categories; interpretation of FP, awareness about FP, and couple as representative of FP decision making whereas the second theme has five categories; roles and responsibilities of men in the family, roles and responsibilities of women in the family, women autonomy, mind the gap or taming the women, and way forward.Conclusions: Our study findings suggest that while superficial reasons must be resolved, it is primarily crucial to eliminate the subtler, tap root factors influencing FP decisions by strongly addressing school curricula, nurses and other Health Care Workers (HCWs) to positively impact the society. Further qualitative and quantitative research is ultimately necessary for assessing the viewpoint of important stakeholders and how, using a multiprong approach, the stringent perceptions pertaining to Family Planning can be altered to benefit the society

Synthesis and styrene copolymerization of novel difluoro and chlorofluoro ring-disubstituted isobutyl phenylcyanoacrylates

Novel difluoro and chlorofluoro ring-disubstituted isobutyl phenylcyanoacrylates, RPhCH=C(CN)CO2CH2CH(CH3)2 (where R is 2,3-difluoro, 2,4-difluoro, 2,6-difluoro, 3,4-difluoro, 3,5-difluoro, 2-chloro-4-fluoro, 2-chloro-6-fluoro, 3-chloro-2-fluoro, 3-chloro-4-fluoro, 4-chloro-3-fluoro) were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-disubstituted benzaldehydes and isobutyl cyanoacetate and characterized by CHN analysis, IR, 1H and 13C NMR. The acrylates were copolymerized with styrene in solution with radical initiation at 70C. The compositions of the copolymers were calculated from nitrogen analysis

Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINE-ACT study: a prospective test validation study.

BACKGROUND Cross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC. METHODS We did a prospective multicentre study in adult participants (age ≥18 years) with newly diagnosed adrenal masses. We assessed the accuracy of diagnostic imaging strategies based on maximum tumour diameter (≥4 cm vs <4 cm), imaging characteristics (positive vs negative), and urine steroid metabolomics (low, medium, or high risk of ACC), separately and in combination, using a reference standard of histopathology and follow-up investigations. With respect to imaging characteristics, we also assessed the diagnostic utility of increasing the unenhanced CT tumour attenuation threshold from the recommended 10 Hounsfield units (HU) to 20 HU. FINDINGS Of 2169 participants recruited between Jan 17, 2011, and July 15, 2016, we included 2017 from 14 specialist centres in 11 countries in the final analysis. 98 (4·9%) had histopathologically or clinically and biochemically confirmed ACC. Tumours with diameters of 4 cm or larger were identified in 488 participants (24·2%), including 96 of the 98 with ACC (positive predictive value [PPV] 19·7%, 95% CI 16·2-23·5). For imaging characteristics, increasing the unenhanced CT tumour attenuation threshold to 20 HU from the recommended 10 HU increased specificity for ACC (80·0% [95% CI 77·9-82·0] vs 64·0% [61·4-66.4]) while maintaining sensitivity (99·0% [94·4-100·0] vs 100·0% [96·3-100·0]; PPV 19·7%, 16·3-23·5). A urine steroid metabolomics result indicating high risk of ACC had a PPV of 34·6% (95% CI 28·6-41·0). When the three tests were combined, in the order of tumour diameter, positive imaging characteristics, and urine steroid metabolomics, 106 (5·3%) participants had the result maximum tumour diameter of 4 cm or larger, positive imaging characteristics (with the 20 HU cutoff), and urine steroid metabolomics indicating high risk of ACC, for which the PPV was 76·4% (95% CI 67·2-84·1). 70 (3·5%) were classified as being at moderate risk of ACC and 1841 (91·3%) at low risk (negative predictive value 99·7%, 99·4-100·0). INTERPRETATION An unenhanced CT tumour attenuation cutoff of 20 HU should replace that of 10 HU for exclusion of ACC. A triple test strategy of tumour diameter, imaging characteristics, and urine steroid metabolomics improves detection of ACC, which could shorten time to surgery for patients with ACC and help to avoid unnecessary surgery in patients with benign tumours. FUNDING European Commission, UK Medical Research Council, Wellcome Trust, and UK National Institute for Health Research, US National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research

Enhanced infection prophylaxis reduces mortality in severely immunosuppressed HIV-infected adults and older children initiating antiretroviral therapy in Kenya, Malawi, Uganda and Zimbabwe: the REALITY trial

Meeting abstract FRAB0101LB from 21st International AIDS Conference 18–22 July 2016, Durban, South Africa. Introduction: Mortality from infections is high in the first 6 months of antiretroviral therapy (ART) among HIV‐infected adults and children with advanced disease in sub‐Saharan Africa. Whether an enhanced package of infection prophylaxis at ART initiation would reduce mortality is unknown. Methods: The REALITY 2×2×2 factorial open‐label trial (ISRCTN43622374) randomized ART‐naïve HIV‐infected adults and children >5 years with CD4 <100 cells/mm3. This randomization compared initiating ART with enhanced prophylaxis (continuous cotrimoxazole plus 12 weeks isoniazid/pyridoxine (anti‐tuberculosis) and fluconazole (anti‐cryptococcal/candida), 5 days azithromycin (anti‐bacterial/protozoal) and single‐dose albendazole (anti‐helminth)), versus standard‐of‐care cotrimoxazole. Isoniazid/pyridoxine/cotrimoxazole was formulated as a scored fixed‐dose combination. Two other randomizations investigated 12‐week adjunctive raltegravir or supplementary food. The primary endpoint was 24‐week mortality. Results: 1805 eligible adults (n = 1733; 96.0%) and children/adolescents (n = 72; 4.0%) (median 36 years; 53.2% male) were randomized to enhanced (n = 906) or standard prophylaxis (n = 899) and followed for 48 weeks (3.8% loss‐to‐follow‐up). Median baseline CD4 was 36 cells/mm3 (IQR: 16–62) but 47.3% were WHO Stage 1/2. 80 (8.9%) enhanced versus 108(12.2%) standard prophylaxis died before 24 weeks (adjusted hazard ratio (aHR) = 0.73 (95% CI: 0.54–0.97) p = 0.03; Figure 1) and 98(11.0%) versus 127(14.4%) respectively died before 48 weeks (aHR = 0.75 (0.58–0.98) p = 0.04), with no evidence of interaction with the two other randomizations (p > 0.8). Enhanced prophylaxis significantly reduced incidence of tuberculosis (p = 0.02), cryptococcal disease (p = 0.01), oral/oesophageal candidiasis (p = 0.02), deaths of unknown cause (p = 0.02) and (marginally) hospitalisations (p = 0.06) but not presumed severe bacterial infections (p = 0.38). Serious and grade 4 adverse events were marginally less common with enhanced prophylaxis (p = 0.06). CD4 increases and VL suppression were similar between groups (p > 0.2). Conclusions: Enhanced infection prophylaxis at ART initiation reduces early mortality by 25% among HIV‐infected adults and children with advanced disease. The pill burden did not adversely affect VL suppression. Policy makers should consider adopting and implementing this low‐cost broad infection prevention package which could save 3.3 lives for every 100 individuals treated