Evidence for contrasting roles for prolactin in eusocial naked mole-rats, Heterocephalus glaber and Damaraland mole-rats, Fukomys damarensis

Elevated prolactin (PRL) has been associated with the expression of social and cooperative behaviours in a number of vertebrate species, as well as suppression of reproduction. As social mole-rats exhibit both of these traits, PRL is a prime candidate in mediating their social phenotype. While naked and Damaraland mole-rats (NMRs and DMRs) have evolved eusociality independently within their family, both species exhibit an extreme skew in lifetime reproductive success, with breeding restricted to a single female and one or two males. Non-breeding NMRs of both sexes are physiologically inhibited from reproducing, while in DMRs only the non-breeding females are physiologically suppressed. Newly emerging work has implicated the dopamine system and PRL as a component in socially induced reproductive suppression and eusociality in NMR, but the DMR remains unstudied in this context. To investigate evolutionary convergence in the role of PRL in shaping African mole-rat eusociality, we determined plasma PRL concentrations in breeders and non-breeders of both sexes, comparing DMRs with NMRs. Among samples from non-breeding NMRs 80% had detectable plasma PRL concentrations. As a benchmark, these often (37%) exceeding those considered clinically hyperprolactinaemic (25 ng ml−1) in humans: mean ± s.e.m.: 34.81 ± 5.87 ngml−1; range 0.00–330.30 ng ml−1. Conversely, 85% of non-breeding DMR samples had undetectable values and none had concentrations above 25 ng ml−1: 0.71 ± 0.38 ng ml−1; 0.00–23.87 ngml−1. Breeders in both species had the expected variance in plasma PRL concentrations as part of normal reproductive function, with lactating queens having significantly higher values. These results suggest that while elevated PRL in non-breeders is implicated in NMR eusociality, this may not be the case in DMRs, and suggests a lack of evolutionary convergence in the proximate control of the social phenotype in these mole-rats.SARCHI Chair to NCB (Grant N64756)http://rsbl.royalsocietypublishing2019-05-01hj2018Anatomy and PhysiologyMammal Research InstituteZoology and Entomolog

The high mental health burden of "Long COVID" and its association with on-going physical and respiratory symptoms in all adults discharged from hospital

Adults discharged from hospital with COVID-19 may experience 'Long COVID', where mental health symptoms are significant and linked to physical symptoms such as breathlessness. Clinicians should use brief screening questionnaires to support their recovery

A Prospective Longitudinal Study of the Clinical Outcomes from Cryptococcal Meningitis following Treatment Induction with 800 mg Oral Fluconazole in Blantyre, Malawi

Introduction: Cryptococcal meningitis is the most common neurological infection in HIV infected patients in Sub Saharan Africa, where gold standard treatment with intravenous amphotericin B and 5 flucytosine is often unavailable or difficult to administer. Fluconazole monotherapy is frequently recommended in national guidelines but is a fungistatic drug compromised by uncertainty over optimal dosing and a paucity of clinical end-point outcome data. Methods: From July 2010 until March 2011, HIV infected adults with a first episode of cryptococcal meningitis were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients were treated with oral fluconazole monotherapy 800 mg daily, as per national guidelines. ART was started at 4 weeks. Outcomes and factors associated with treatment failure were assessed 4, 10 and 52 weeks after fluconazole initiation. Results: Sixty patients were recruited. 26/60 (43%) died by 4 weeks. 35/60 (58.0%) and 43/56 (77%) died or failed treatment by 10 or 52 weeks respectively. Reduced consciousness (Glasgow Coma Score ,14 of 15), moderate/severe neurological disability (modified Rankin Score .3 of 5) and confusion (Abbreviated Mental Test Score ,8 of 10) were all common at baseline and associated with death or treatment failure. ART prior to recruitment was not associated with better outcomes. Conclusions: Mortality and treatment failure from cryptococcal meningitis following initiation of treatment with 800 mg oral fluconazole is unacceptably high. To improve outcomes, there is an urgent need for better therapeutic strategies and point-of-care diagnostics, allowing earlier diagnosis before development of neurological deficit

The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.

Background Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. Purpose We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. Data source We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Study selection Two authors independently reviewed the studies for eligibility. Data extraction Data about studies characteristics, adjusted effect estimates and quality were extracted. Data synthesis Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). Conclusion In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics

Adult meningitis in a setting of high HIV and TB prevalence: findings from 4961 suspected cases

BACKGROUND: The presentation and causes of adult meningitis in South Africa have changed substantially as a result of HIV. Knowledge of aetiology and laboratory findings in patients presenting with meningitis are important in guiding management. We performed a retrospective study to determine these findings in a setting of high HIV and TB prevalence in Cape Town. METHODS: Patients undergoing lumbar punctures between 1st January 2006 and 31st December 2008 at a public sector referral hospital were studied. Cases were classified by microbiological diagnosis, or in the absence of definitive microbiology as 1) normal CSF (neutrophils or =1.5 mmol/L), 2) minor abnormalities (neutrophils 2-5, lymphocytes 6-20, protein 0.51-1.0, glucose 1.0-1.49) or 3) markedly abnormal (neutrophils>5, lymphocytes>20, protein>1.0, glucose<1.0). RESULTS: 5578 LPs were performed on 4549 patients, representing 4961 clinical episodes. Of these, 2293 had normal CSF and 931 had minor abnormalities and no aetiology identified. Of the remaining 1737, microbiological diagnoses were obtained in 820 (47%). Cryptococcus accounted for 63% (514) of microbiological diagnoses, TB for 28% (227), bacterial meningitis for 8% (68). Of the remaining 917 who had marked abnormalities, the majority (59%) had a sterile lymphocytic CSF. Of note 16% (81) patients with confirmed Cryptococcus, 5% (12) with TB and 4% (3) with bacterial meningitis had normal CSF cell-counts and biochemistry. CONCLUSIONS: Cryptococcal and tuberculous meningitis are now the commonest causes of adult meningitis in this setting. TB meningitis is probably underdiagnosed by laboratory investigation, as evidence by the large numbers presenting with sterile lymphocytic markedly abnormal CSFs

Acting on Reflection: the Effect of Reflection on Students’ Clinical Performance on a Standardized Patient Examination

BACKGROUND: Little evidence exists to support the value of reflection in the clinical setting. OBJECTIVE: To determine whether reflecting and revisiting the “patient” during a standardized patient (SP) examination improves junior medical students’ performance and to analyze students’ perceptions of its value. DESIGN: Students completed a six-encounter clinical skills examination, writing a guided assessment after each encounter to trigger reflection. SPs evaluated the students with Medical Skills and Patient Satisfaction checklists. During the last three encounters, students could opt to revisit the SP and be reevaluated with identical checklists. PARTICIPANTS: One hundred and forty-nine third year medical students. MEASUREMENTS: Changes in scores in the Medical Skills and Patient Satisfaction checklists between first visit and revisit were tested separately per case as well as across cases. RESULTS: On the medical skills and patient satisfaction checklists, mean revisit scores across cases were significantly higher than mean first visit scores [12.6 vs 12.2 (pooled SD = 2.4), P = .0001; 31.2 vs 31.0 (pooled SD = 3.5), P = .0001)]. Sixty-five percent of the time, students rated “reflect–revisit” positively, 34% neutrally, and 0.4% negatively. Five themes were identified in the positive comments: enhancement of (1) medical decision making, (2) patient education/counseling, (3) student satisfaction/confidence, (4) patient satisfaction/confidence, and (5) clinical realism. CONCLUSIONS: Offering third year medical students the option to reflect and revisit an SP during a clinical skills examination produced a small but nontrivial increase in clinical performance. Students perceived the reflect–revisit experience as enhancing patient-centered practices (counseling, education) as well as their own medical decision making and clinical confidence

Presentation and Outcome of Tuberculous Meningitis in a High HIV Prevalence Setting

Mycobacterium tuberculosis is a common, devastating cause of meningitis in HIV-infected persons. Due to international rollout programs, access to antiretroviral therapy (ART) is increasing globally. Starting patients with HIV-associated tuberculous meningitis (TBM) on ART during tuberculosis (TB) treatment may increase survival in these patients. We undertook this study to describe causes of meningitis at a secondary-level hospital in a high HIV/TB co-infection setting and to determine predictors of mortality in patients with TBM.A retrospective review of cerebrospinal fluid findings and clinical records over a six-month period (March 2009-August 2009). Definite, probable and possible TBM were diagnosed according to published case definitions.TBM was diagnosed in 120/211 patients (57%) with meningitis. In 106 HIV-infected patients with TBM, six-month all-cause mortality was lower in those who received antiretroviral therapy (ART) during TB treatment; hazard ratio = 0.30 (95% CI = 0.08-0.82). Factors associated with inpatient mortality in HIV-infected patients were 1) low CD4(+) count at presentation; adjusted odds ratio (AOR) = 1.4 (95% confidence interval [CI] = 1.03-1.96) per 50 cells/µL drop in CD4(+) count and, 2) higher British Medical Research Council TBM disease grade (2 or 3 versus 1); AOR = 4.8 (95% CI = 1.45-15.87).Starting ART prior to or during TB treatment may be associated with lower mortality in patients with HIV-associated TBM. Advanced HIV and worse stage of TBM disease predict in-hospital mortality in patients presenting with TBM

Risk factors for fatal candidemia caused by Candida albicans and non-albicans Candida species

BACKGROUND: Invasive fungal infections, such as candidemia, caused by Candida species have been increasing. Candidemia is not only associated with a high mortality (30% to 40%) but also extends the length of hospital stay and increases the costs of medical care. Sepsis caused by Candida species is clinically indistinguishable from bacterial infections. Although, the clinical presentations of the patients with candidemia caused by Candida albicans and non-albicans Candida species (NAC) are indistinguishable, the susceptibilities to antifungal agents of these species are different. In this study, we attempted to identify the risk factors for candidemia caused by C. albicans and NAC in the hope that this may guide initial empiric therapy. METHODS: A retrospective chart review was conducted during 1996 to 1999 at the Veterans General Hospital-Taipei. RESULTS: There were 130 fatal cases of candidemia, including 68 patients with C. albicans and 62 with NAC. Candidemia was the most likely cause of death in 55 of the 130 patients (42.3 %). There was no significant difference in the distribution of Candida species between those died of candidemia and those died of underlying conditions. Patients who had one of the following conditions were more likely to have C. albicans, age ≧ 65 years, immunosuppression accounted to prior use of steroids, leukocytosis, in the intensive care unit (ICU), and intravascular and urinary catheters. Patients who had undergone cancer chemotherapy often appeared less critically ill and were more likely to have NAC. CONCLUSION: Clinical and epidemiological differences in the risk factors between candidemia caused by C. albicans and NAC may provide helpful clues to initiate empiric therapy for patients infected with C. albicans versus NAC