Slipping through the cracks: a qualitative study to explore pathways of HIV care and treatment amongst hospitalised patients with advanced HIV in Kenya and the Democratic Republic of the Congo

Advanced HIV causes substantial mortality in sub-Saharan Africa despite widespread antiretroviral therapy coverage. This paper explores pathways of care amongst hospitalised patients with advanced HIV in rural Kenya and urban Democratic Republic of the Congo, with a view to understanding their care-seeking trajectories and poor health outcomes. Thirty in-depth interviews were conducted with hospitalised patients with advanced HIV who had previously initiated first-line antiretroviral therapy, covering their experiences of living with HIV and care-seeking. Interviews were audio-recorded, transcribed and translated before being coded inductively and analysed thematically. In both settings, participants' health journeys were defined by recurrent, severe symptoms and complex pathways of care before hospitalisation. Patients were often hospitalised after multiple failed attempts to obtain adequate care at health centres. Most participants managed their ill-health with limited support networks, lived in fragile economic situations and often experienced stress and other mental health concerns. Treatment-taking was sometimes undermined by strict messaging around adherence that was delivered in health facilities. These findings reveal a group of patients who had "slipped through the cracks" of health systems and social support structures, indicating both missed opportunities for timely management of advanced HIV and the need for interventions beyond hospital and clinical settings

Pregabalin Dispensing Patterns in Amman-Jordan: an Observational Study from Community Pharmacies

Objectives Pregabalin is currently approved for the treatment of epilepsy, generalized anxiety disorder, neuropathic pain and fibromyalgia. Rising attention to the abuse liability of pregabalin causing addictive behaviors is partially based on case reports and published literature of pregabalin used in dosages that override the approved therapeutic range. This study was conducted to provide background data regarding the abuse/misuse of pregabalin from community pharmacy in Jordan. Methods A prospective cross-sectional observational study design was used, which was conducted at different community pharmacies in Amman-Jordan. During the study period (November 2016-January 2017), a total 77 requests for pregabalin were observed from 14 pharmacies. A structured interview was conducted with all customers to gather information regarding their demographic and their request of pregabalin. Results A total of 77 pregabalin requests form 77 customers in a community pharmacy setting were observed in this study. Spinal disc herniation was the most common complaint for which the customer asked for the medication (n= 27, 35.1%). Self-medication was the most frequent method of requesting pregabalin (n= 44, 57.1%), while a total of 33 customers (42.9%) asked for the product using a prescription. During the observation period the number of customers suspected of abusing pregabalin for non-medical reason was 35 (45.5%). A total of 33 out of the 35 suspected customers (94.3%) asked for the product without a prescription, and 19/35 weren‘t sold due to suspicion of abuse (54.3%). Conclusion The study underscores the need for regulatory efforts to manage pregabalin abuse, through the addition of pregabalin containing products to the controlled drug list which can’t be purchased without a prescription. Also, pharmacists and customers must be educated at a community pharmacy level regarding potential hazards of pregabalin abuse

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Customer satisfaction--a competitive edge in the apparel industry

Thesis (M.S.)--Massachusetts Institute of Technology, Sloan School of Management, 1994.Includes bibliographical references (leaves 86-87).by Laurent Bossard and Anne-Claire Monod.M.S

Thyroid cancer: is the incidence rise abating?

OBJECTIVE: The aim of the present study was to determine recent trends in thyroid cancer incidence rates and to analyze histopathological characteristics and geographical distribution. METHODS: Histologically proven 5367 cases were collected over the period 1998-2006 in France from the Rhône-Alpes thyroid cancer registry. Geographical variations of incidence were analyzed using a mixed Poisson model. RESULTS: The average incidence rates, age standardized to the world population, were 3.9/100,000 in men and 12.3/100,000 in women, higher than those previously reported in France. After an initial increase during the first 3 years, a steady level of incidence was observed for the period 2001-2006. The annual incidence rate of microcarcinomas was correlated with that of all cancers in men and women (r=0.78 and 0.89; P<0.01) respectively. Papillary microcarcinomas represented 38% of tumors and two-thirds of them measured less than 5 mm in diameter. They were fortuitously discovered after thyroidectomy for benign diseases in 64% of cases. Histological marks of aggressiveness differed according to the size of the tumor. Despite recent advances in diagnosis, 13% of tumors were diagnosed at advanced stage especially in men. Geographical distribution of incidence based on subregional administrative entities showed lower incidence rates in rural than in urban zones in men (relative rate: 0.72; 95% CI: 0.62-0.84) and women (relative rate: 0.85; 95% CI: 0.73-0.93). CONCLUSION: The present study suggests that the rise in thyroid cancer incidence is now abating. It could reflect standardization in diagnostic procedures. Further studies, performed on a more prolonged period, are necessary to confirm these data

Assessing accuracy of heat detection in dairy herds

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PD-L1 and PD-1 expression profile depending on the microsatellite status and the histological subtype in colorectal carcinomas.

International audienceBackground: PD-1/PD-L1 blockade showed therapeutic efficacy in only microsatellite (MSI) colorectal carcinomas (CRC), however, the profile of PD-L1 and PD-1 expression in CRC is only partially described. Methods: We thus analyzed on FFPE whole-tissue sections of 80 CRC, the expression profile of PD-L1 by tumor and/or immune cells by immunohistochemistry (clone E1L3N) depending on the MSI status and the histological subtype, and correlated to the density of PD-1+ and Tbet+ (able to secrete IFNg known to induce PD-L1) tumor-infiltrating lymphocytes (TIL). Results: 78% of MSI CRC (32/41) overexpressed PD-L1 either by tumor or immune cells versus 46% of MSS CRC (18/39) (p 0.005). This overexpression was heterogeneous within the same tumor in most of cases. Among MSI CRC, PD-L1 was preferentially overexpressed in medullary carcinomas (MC, 19/21, 90%) compared with 65% (13/20) in non-medullary adenocarcinomas (p 0.06). PD-L1 expression by tumor cells was only observed in MSI CRC (19/41, 46% with PD-L1 expression in more than 5% of tumor cells – score 1), and preferentially in MC (57% vs 5% in no medullary adenocarcinomas, with PD-L1 expression in more than 50% of tumor cells – score 3, p 0.0005). Conversely, PD-L1 expression by immune cells was observed in MSI CRC (23/41, 56% with PD-L1 expression by more than 5 sheets of 50 positive cells) but also in MSS CRC (18/39, 43%) (p 0.5). The density of PD-1+ cells was significantly correlated to the PD-L1 expression, as well as the density of Tbet+ TIL. Conclusions: PD-L1 expression is 1) heterogeneous in CRC, among CRC but also within the same tumor, 2) preferentially observed in MSI CRC (78%), especially in MC (90%), where PD-L1 is expressed by tumor cells, 3) correlated with the density of PD-1+ or T-bet+ TIL, and 4) observed in a significant proportion of MSS CRC (46%) by immune cells only. From a clinical point of view, PD-L1 expression has to be determined at best in full tissue section and besides its preferential expression in MSI CRC, its significant frequency and expression profile (only by immune cells) in MSS CRC should be taken into account in the future clinical trials testing the efficacy of anti-PD-1/PD-L1 antibodies

Potential therapeutic target for PD1/PDL1 blockade in microsatellite medullary carcinomas based on PDL1 expression by tumor cells and infiltration by numerous PD1+ T lymphocytes.

International audienceBackground: PD1/PDL1 blockade showed therapeutic efficacy in only microsatellite (MSI) colorectal carcinomas (CRC), however, the profile of PDL1 and PD1 expression in CRC is only partially described. Methods: We thus analyzed on FFPE whole-tissue sections of 80 CRC, the expression profile of PDL1 by tumor and/or immune cells by immunohistochemistry (clone E1L3N) depending on the MSI status and the histological subtype, and correlated to the density of PD1+ and Tbet+ (able to secrete IFNg known to induce PDL1) tumor-infiltrating lymphocytes (TIL). Results: 78% of MSI CRC (32/41) overexpressed PDL1 either by tumor or immune cells versus 46% of MSS CRC (18/39) (p 0.005). This overexpression was heterogeneous within the same tumor in most of cases. Among MSI CRC, PDL1 was preferentially overexpressed in medullary carcinomas (MC, 19/21, 90%) compared with 65% (13/20) in non medullary adenocarcinomas (p 0.06). PDL1 expression by tumor cells was only observed in MSI CRC (19/41, 46% with PDL1 expression in more than 5% of tumor cells – score 1), and preferentially in MC (57% vs 5% in no medullary adenocarcinomas, with PDL1 expression in more than 50% of tumor cells – score 3, p 0.0005). Conversely, PDL1 expression by immune cells was observed in MSI CRC (23/41, 56% with PDL1 expression by more than 5 sheets of 50 positive cells) but also in MSS CRC (18/39, 43%) (p 0.5). The density of PD1+ cells was significantly correlated to the PDL1 expression, as well as the density of Tbet+ TIL. Conclusions: PDL1 expression is 1) heterogeneous in CRC, among CRC but also within the same tumor, 2) preferentially observed in MSI CRC (78%), especially in MC (90%), where PDL1 is expressed by tumor cells, 3) correlated with the density of PD1+ or Tbet+ TIL, and 4) observed in a significant proportion of MSS CRC (46%) by immune cells only. From a clinical point of view, PDL1 expression has to be determined at best in full tissue section and besides its preferential expression in MSI CRC, its significant frequency and expression profil (only by immune cells) in MSS CRC should be taken into account in the future clinical trials testing the efficacy of anti-PD1/PDL1 antibodies