Pneumococcal carriage and disease in adults in England 2011-2019: the importance of adults as a reservoir for pneumococcus in communities.

BACKGROUND: Pneumococcal carriage in children has been extensively studied, but carriage in healthy adults and its relationship to invasive pneumococcal disease (IPD) is less understood. METHODS: Nasal wash samples from adults without close contact with young children (Liverpool, UK), 2011-2019, were cultured, and culture-negative samples tested by PCR. Pneumococcal carriage in adults 18-44 years was compared with carriage among PCV-vaccinated children 13-48 months (nasopharyngeal swabs, Thames Valley, UK) and IPD data for England for the same ages for 2014-2019. Age-group specific serotype invasiveness was calculated and used with national IPD data to estimate carriage serotype distributions for adults aged 65+ years. RESULTS: In total 98 isolates (97 carriers) were identified from 1,631 adults aged 18+ years (age and sex standardized carriage prevalence 6.4%), with only three identified solely by PCR. Despite different carriage and IPD serotype distributions between adults and children, serotype invasiveness was highly correlated (R=0.9). Serotypes 3, 37 and 8 represented a higher proportion of adult carriage than expected from direct low-level transmission from children to adults. The predicted carriage serotype distributions for 65+ years aligned more closely with the carriage serotype distribution for young adults than young children. CONCLUSIONS: The nasal wash technique is highly sensitive; additional benefit of PCR is limited. Comparison of carriage serotype distributions suggests some serotypes may be circulating preferentially within these specific young adults. Our data suggest that for some serotypes carried by adults 65+ years, other adults may be an important reservoir for transmission. Age groups such as older children should also be considered.

Corrigendum for health-related quality of life and hospitalizations in chronic thromboembolic pulmonary hypertension versus idiopathic pulmonary arterial hypertension: And analysis from the Pulmonary Hypertension Association Registry.

[This corrects the article DOI: 10.1177/20458940211053196.].

High 3He/4He ratios in lower East Rift Zone steaming vents precede a new phase of Kilauea 2018 eruption by 8 months.

On May 1, 2018, a magnitude 5.0 earthquake heralded the collapse of the Pu'u O'o Vent on the middle East Rift Zone (ERZ) of Kilauea Volcano, active since 1983. Increased seismicity was recorded on the middle to lower ERZ from April 30 until May 2, 2018. The active lava lakes within both Pu'u O'o Vent and Halema'uma'u Crater began to drain and the summit caldera began to deflate, with the summit collapse ending on August 2, 2018 and lower ERZ eruptive lava activity ending by 4 September 2018. Herein we report on elevated 3He/4He ratios in steaming vents in the lower ERZ from samples collected in early September 2017. Gas isotopic measurements were made with a new, field-portable He isotope detector capable of sub-daily monitoring of the 3He/4He ratio. When corrected for air contamination, these values exceed those previously reported for Kilauea by nearly twofold, resembling a purer hotspot plume signature, such as those measured directly over the mantle plume at Loihi Seamount to the SE of Hawaii Island, and in older basalt flows when Kilauea and its sister Hawaiian shield volcanoes were located more directly over the plume. The discovery, which presages the eruption there by more than eight months, suggests that we either sampled a 3He/4He rich magma already in place in the lower ERZ or a shallow groundwater reservoir in the lower ERZ (Puna district) with anomalously low values of 4He relative to their 3He/4He ratio, similar to previous findings there and suggestive of a previously unknown He isotopic fractionation.

Can teacher-child relationships alter the effects of early socioeconomic status on achievement in middle childhood?

Using data from the NICHD SECCYD (N=1053), we used two-level hierarchical linear models with site fixed effects to examine whether teacher-child closeness and conflict moderated associations between two indicators of early socioeconomic status (maternal education and family income) and standardized measures of children's math and reading achievement at 54months, 1st, 3rd, and 5th grades. Children whose mothers had lower levels of education and conflictual relationships with teachers exhibited lower reading achievement, on average, across elementary school. At the same time, children with less educated mothers who experienced increases in teacher-child closeness and decreases in teacher-child conflict exhibited improvements in reading achievement across elementary school. Finally, low teacher-child closeness elevated the risk for poor math achievement posed by low family income. Implications for intervention design and development are discussed.

[Prevention of perioperative hypothermia : Implementation of the S3 guideline]. / Vermeidung perioperativer Hypothermie : Umsetzung der S3-Leitlinie.

To improve perioperative quality and patient safety, the German S3 guideline should be consistently implemented to avoid perioperative hypothermia. Perioperative normothermia is a quality indicator and should be achieved by anesthesiologists and surgeons. To detect hypothermia early during the perioperative process, measuring body temperature should be started 1-2 h preoperatively. Patients should be actively warmed for 20-30 min before starting anesthesia. Prewarming is most effective and should be included in the preoperative process. Patients should be informed about the risks of perioperative hypothermia and members of the perioperative team should be educated. A standard operating procedure (SOP) to avoid hypothermia should be introduced in every operative unit. The incidence of postoperative hypothermia should be evaluated in operative patients every 3-6 months. The goals should be to measure body temperature in >80% of patients undergoing surgery and for >70% to exhibit a core temperature >36 °C at the end of surgery.

Neighborhood deprivation and depression in adult twins: genetics and gene×environment interaction.

BACKGROUND: Depression is a significant problem and it is vital to understand its underlying causes and related policy implications. Neighborhood characteristics are implicated in depression but the nature of this association is unclear. Unobserved or unmeasured factors may confound the relationship. This study addresses confounding in a twin study investigating neighborhood-level effects on depression controlling for genetics, common environment, and gene×environment (G × E) interactions. METHOD: Data on neighborhood deprivation and depression were gathered from 3155 monozygotic twin pairs and 1275 dizygotic pairs (65.7% female) between 2006 and 2013. The variance for both depression and neighborhood deprivation was decomposed into three components: additive genetic variance (A); shared environmental variance (C); and non-shared environmental variance (E). Depression was then regressed on neighborhood deprivation to test the direct association and whether that association was confounded. We also tested for a G × E interaction in which the heritability of depression was modified by the level of neighborhood deprivation. RESULTS: Depression and neighborhood deprivation showed evidence of significant A (21.8% and 15.9%, respectively) and C (13.9% and 32.7%, respectively) variance. Depression increased with increasing neighborhood deprivation across all twins (p = 0.009), but this regression was not significant after controlling for A and C variance common to both phenotypes (p = 0.615). The G × E model showed genetic influences on depression increasing with increasing neighborhood deprivation (p < 0.001). CONCLUSIONS: Neighborhood deprivation is an important contributor to depression via increasing the genetic risk. Modifiable pathways that link neighborhoods to depression have been proposed and should serve as targets for intervention and research.

[Collaborative care for co-morbid major depressive disorder in chronically ill outpatients in a general hospital]. / Collaborative care voor de behandeling van comorbide depressieve stoornis bij chronisch lichamelijk zieke patiënten op een polikliniek van een algemeen ziekenhuis.

BACKGROUND: Depression is highly prevalent in patients with chronic physical illnesses. A promising intervention for this group of patients is the collaborative care treatment as developed in the us. AIM: To demonstrate the prevalence of depression and the risk factors of depression in diabetes patients, to describe how the screening for depression can be carried out and to assess whether the collaborative care treatment in the Netherlands is effective. METHOD: A questionnaire was completed every three months in order to determine whether there was an improvement in patients' depression and physical symptoms. The outcomes were analysed by means of the multilevel logistic regression analyses. RESULTS: On the basis of the Patient Health Questionnaire, about 26% of the diabetes patients were found to have a depression. This questionnaire was validated for the measurement of depression in diabetes patients, the best results being found at a cut-off point of 12. In cases of fairly severe depression, collaborative care had no effect on depressive symptoms but did reduce severe physical complications. In cases of more severe depression, collaborative care only had an effect on depressive symptoms, but was not found to have any effect on physical complications. CONCLUSION: There is evidence that collaborative care can reduce depression and physical complications in chronically ill patients. However, more research is needed to find out whether collaborative care can become more effective if it is supplemented with digital methods and group therapy.

Adoptive and Nonadoptive Mother-Child Behavioral Interaction: A Comparative Study at 4 Years of Age.

Comparable samples of low-risk adopted and nonadopted children and mothers were observed during 3 tasks at age 4 years. Quality of mother-child interactions, child level of functioning in 4 domains, and maternal parenting satisfaction and social support were assessed. Adopted children were as competent as nonadopted children on measures of developmental functioning. Both groups of mothers expressed high satisfaction and support as parents. However, ratings of child, maternal, and dyadic behavior when interacting were all lower for adoptive dyads than for nonadoptive dyads, and adoptive dyads with boys accounted for the maternal and dyadic group differences.

A phase II trial of high-dose chemotherapy (HDCT) supported by hematopoietic stem-cell transplantation (HSCT) in germ-cell tumors (GCTs) patients failing cisplatin-based chemotherapy: the Multicentric TAXIF II study.

BACKGROUND: High-dose chemotherapy (HDCT) is an effective salvage treatment of germ-cell tumors (GCTs) patients. In the first salvage setting, 30%-70% of patients may achieve durable remissions. Even when HDCT is administered as subsequent salvage treatment, up to 20% of patients may still be definitively cured. However, patients with refractory/relapsed disease still have a very poor long-term prognosis, requiring earlier intervention of HDCT. PATIENTS AND METHODS: This phase II trial was addressed to nonrefractory patients failing Cisplatin-based chemotherapy. Inclusion criteria included seminomatous GCT in relapse after two lines of chemotherapy, nonseminomatous GCT in relapse after first or second lines, partial remission after first line, primary mediastinal GCT in first relapse. Patients received two cycles combining Epirubicin and Paclitaxel (Epi-Tax), followed by three consecutive HDCT, one using a Paclitaxel/Thiotepa (Thio-Tax) association and two using the 5-day Ifosfamide-Carboplatin-Etoposide regimen. The main objective was to determine the complete response rate. RESULTS: Forty-five patients were included between September 2004 and December 2007: 44 received the first HDCT cycle, 39 two HDCT cycles, 29 could receive the whole protocol. Sixteen patients did not receive the entire protocol, including eight (17.7%) for toxic side-effects. Two patients (4.4%) died of toxicities, and 17 (37.7%) of disease progression. With a median follow-up time of 26 months (range, 4-51), the final overall response rate was 48.8% (including a complete response rate of 15.5% and a partial response/negative serum markers rate of 26.6%) in an intent-to-treat analysis. The median progression-free survival (PFS) and overall survival (OS) times were 22 months [95% confidence interval (CI) 2-not reached] and 32 months (95% CI 4-49), respectively. The 2-year PFS was a plateau setup at 50% (95% CI 32-67) and the 2-year OS was 66% (95% CI 44-81). CONCLUSION: The TAXIF II protocol was effective in nonrefractory GCT patients failing Cisplatin-based chemotherapy. The toxic death rate remained acceptable in the field of HDCT regimens. TRIAL REGISTRATION NUMBER: NCT00231582.

Targeting of preexisting and induced breast cancer stem cells with trastuzumab and trastuzumab emtansine (T-DM1).

The antibody trastuzumab (Herceptin) has substantially improved overall survival for patients with aggressive HER2-positive breast cancer. However, about 70% of all treated patients will experience relapse or disease progression. This may be related to an insufficient targeting of the CD44(high)CD24(low) breast cancer stem cell subset, which is not only highly resistant to chemotherapy and radiotherapy but also a poor target for trastuzumab due to low HER2 surface expression. Hence, we explored whether the new antibody-drug conjugate T-DM1, which consists of the potent chemotherapeutic DM1 coupled to trastuzumab, could improve the targeting of these tumor-initiating or metastasis-initiating cells. To this aim, primary HER2-overexpressing tumor cells as well as HER2-positive and HER2-negative breast cancer cell lines were treated with T-DM1, and effects on survival, colony formation, gene and protein expression as well as antibody internalization were assessed. This revealed that CD44(high)CD24(low)HER2(low) stem cell-like breast cancer cells show high endocytic activity and are thus particularly sensitive towards the antibody-drug conjugate T-DM1. Consequently, preexisting CD44(high)CD24(low) cancer stem cells were depleted by concentrations of T-DM1 that did not affect the bulk of the tumor cells. Likewise, colony formation was efficiently suppressed. Moreover, when tumor cells were cocultured with natural killer cells, antibody-dependent cell-mediated cytotoxicity was enhanced, and EMT-mediated induction of stem cell-like properties was prevented in differentiated tumor cells. Thus our study reveals an unanticipated targeting of stem cell-like breast cancer cells by T-DM1 that may contribute to the clinical efficacy of this recently approved antibody-drug conjugate.

Prison prescribing practice: practitioners' perspectives on why prison is different.

The current prison population in England and Wales has multiple, complex healthcare needs, presenting unique challenges to those caring for prisoners. Prison numbers have increased dramatically in the last 10 years. There are now approximately 84,000 prisoners in England and Wales and 120,000 new episodes of imprisonment each year . The authors all contribute to prison healthcare. Below, we discuss a key issue arising from first-hand experience of prisoners' health and social care needs, the prescription of psycho-active drugs by primary and secondary care practitioners. This is a core medical task, but beset with difficulties. These difficulties are not necessarily encountered in other areas of prison healthcare. However, they do illustrate how providing healthcare to prisoners is complex, often lacking a research base and can have pitfalls that are not obvious to the outsider.

The effect of short time periods of pre-operative warming in the prevention of peri-operative hypothermia.

The aim of our study was to evaluate the performance of different durations of active pre-operative skin-surface warming (pre-warming) to prevent peri-operative hypothermia and postoperative shivering. We randomly assigned 200 patients, scheduled for surgery of 30-90 min under general anaesthesia, to receive passive insulation or forced-air skin surface warming for 10, 20 or 30 min. Body temperature was measured at the tympanic membrane. Shivering was graded by visual inspection. There were significant differences in changes of core temperature between the non-pre-warmed group and all the pre-warmed groups (p < 0.00001), but none between the three pre-warmed groups (p = 0.54). Without pre-warming, 38/55 (69%) patients became hypothermic (< 36 °C) at the end of anaesthesia, whereas only 7/52 (13%), 3/43 (7%) and 3/50 (6%) patients following 10, 20 or 30 min pre-warming, respectively, became hypothermic (p < 0.001 vs no pre-warming). Shivering was observed in 10 patients without, and in three, three and one patients with pre-warming in the respective groups (p = 0.02). Pre-warming of patients for only 10 or 20 min before general anaesthesia mostly prevents hypothermia and reduces shivering.

[Biological experiments in microgravity: equilibrium function].

The review deals with the investigations of structural and functional modifications in the equilibrium organ (EO) in invertebrates (coelenterates, shells, crustaceans and insects) and vertebrates (fishes, amphibians, rats, primates) on different ontogenetic stages in the condition of microgravity and during readaptation to the Earth's gravity. Results of the investigations detail the adaptive strategy of terrestrial organism in the environment lacking the gravitational components that leads to the discrepancy of an inner model of the body-environment schema constructed by the central nervous system at 1 g and the novel reality. It is manifested by ataxic behavior and increased graviceptors' afferentation against efferent system inactivation. The new condition is defined as a sensibilization phase ensued by the eluding phase: behavior obeys the innate motion strategy, whereas graviceptors' afferentation decreases due to activation of the efferent system. Readaptation to 1 G takes several to 50 days and proceeds as a sequence of slow in motion behavior, ataxia and vestibular sensitization. Reactivity of the gravitosensory system to microgravity was found to be age-dependent. Gain in the EO inertial mass in microgravity and reduction with return to 1 g indicates gravity relevance to EO genesis.

Assessment and management of methotrexate hepatotoxicity in psoriasis patients: report from a consensus conference to evaluate current practice and identify key questions toward optimizing methotrexate use in the clinic.

Experts in psoriasis, hepatology, pharmacokinetics and pharmacogenetics convened to discuss the safety and monitoring of methotrexate with respect to hepatotoxicity when used in the treatment of psoriasis. Methotrexate is an efficacious and cost-effective treatment for psoriasis, but is associated with significant safety issues, particularly relating to hepatotoxicity. Current British, Dutch, German, EU and US guidelines for baseline evaluations, monitoring and prevention of hepatotoxicity in patients with psoriasis receiving methotrexate were evaluated. Liver safety monitoring is currently reliant upon multiple methods, including biopsy, serological tests for biomarkers such as type III procollagen amino terminal propeptide (PIIINP), and liver function tests based on liver enzymes. Monitoring of patients receiving long-term therapy is expected to be improved by the utilization of serum biomarkers currently in development such as the Enhanced Liver Fibrosis (ELF) panel and other non-invasive tests of hepatic architecture, such as fibroelastography, microbubbles and magnetic resonance imaging. Appropriate studies to determine optimal dosing to maximize efficacy and minimize toxicity, potentially utilizing pharmacogenetic principles, are clearly needed. Key questions for future research are identified including needs for optimal screening and monitoring, identification of appropriate biomarkers, assessment of relationships between dosing and safety, utility of liver biopsy, optimal dosing regimens (including route of administration), methods to measure methotrexate levels in blood, and use of methotrexate as a standardized active comparator in trials of experimental drugs used to treat psoriasis.

More co-morbid depression in patients with Type 2 diabetes with multiple complications. An observational study at a specialized outpatient clinic.

AIMS: The impact of depression on patients with chronic medical illnesses such as diabetes is well documented. Depression is relatively common in diabetes patients with diabetes-related complications and they are more likely to be referred to specialized outpatient facilities. Only a few studies have addressed the association between depression and multiple diabetes-related complications at these specialized outpatient facilities. The aim of this study was to determine the association between diabetes with multiple complications and depression in patients with Type 2 diabetes at a specialized outpatient clinic. METHODS: After giving informed consent, 1194 patients were screened for depression using the Patient Health Questionnaire (PHQ-9). Additional data on the type of diabetes and complications were taken from the medical records. Logistic regression analysis was conducted, with complications as the predictor variable and the probability of depression as the dependent variable. RESULTS: A total of 596 (63%) patients with Type 2 diabetes participated in the study. The presence of two or more complications (OR 2.23, 95% CI 1.02­2.94) was significantly associated with depression. Neuropathy (OR 1.7, 95% CI 1.10­2.77) and nephropathy (OR 1.68, 95% CI 1.00­2.48) were especially related to depression. CONCLUSIONS: Patients with Type 2 diabetes with two or more complications, especially neuropathy or nephropathy, are at high risk of depression. Knowing this can help clinicians identify patients at risk for depression and facilitate timely and adequate treatment.

Exploring the association between cardiovascular and other disease-related risk factors in the psoriasis population: the need for increased understanding across the medical community.

There is abundant and accumulating evidence on the classification of psoriasis as a systemic disease that exhibits a host of co-morbidities. As a consequence, the second Interdisciplinary Conference on Co-morbidities and Lifestyle Modification, convened by the International Psoriasis Council, has concluded that specialist physicians, primary care physicians and dermatologists are faced with an opportunity to impact, not just psoriasis disease understanding and management, but overall patient well-being. The conference panel was represented by the disciplines of dermatology, cardiology, rheumatology, epidemiology, endocrinology, hepatology and gastroenterology, and medical specialists with particular expertise in obesity, diabetes mellitus, inflammation and genetics. The multiple co-morbidities associated with psoriasis were reviewed with a view to identify possible mechanisms linking psoriatic disease with obesity, metabolic syndrome, diabetes, cardiovascular disease and non-alcoholic fatty liver disease. Consensus was established on the association of psoriasis with other co-morbidities and disease states. Consequently, there is a significant opportunity for specialist and primary care physicians to collaborate with dermatologists in the management of the overall health of psoriasis patients. First, there is an important need for physicians to routinely screen psoriasis patients for the multiple susceptibility risk factors and co-morbidities associated with psoriasis. Second, the design and implementation of lifestyle modification plans including exercise, diet and the limitation of alcohol and tobacco intake, will not only benefit their general medical health but also their psoriasis.

Topical corticosteroids in psoriasis: strategies for improving safety.

Corticosteroids are a mainstay of topical therapy for psoriasis. While efficacious and relatively safe when used carefully, the potential for side effects, notably skin atrophy and adrenal suppression, have been associated with excesses in potency, prolonged or widespread use. The International Psoriasis Council Working Group on Topical Therapy has reviewed the efficacy and safety of topical corticosteroids and recommends strategies for safe, long-term use of these agents.

Altered gravity affects ventral root activity during fictive swimming and the static vestibuloocular reflex in young tadpoles (Xenopus laevis).

During early periods of life, modifications of the gravitational environment affect the development of sensory, neuronal and motor systems. The vestibular system exerts significant effects on motor networks that control eye and body posture as well as swimming. The objective of the present study was to study whether altered gravity (AG) affects vestibuloocular and spinal motor systems in a correlated manner. During the French Soyuz taxi flight Andromède to the International Space Station ISS (launch: October 21, 2001; landing: October 31, 2001) Xenopus laevis embryos were exposed for 10 days to microgravity (microg). In addition, a similar experiment with 3g-hypergravity (3g) was performed in the laboratory. At onset of AG, embryos had reached developmental stages 24 to 27. After exposure to AG, each tadpole was tested for its roll-induced vestibuloocular reflex (rVOR) and 3 hours later it was tested for the neuronal activity recorded from the ventral roots (VR) during fictive swimming. During the post-AG recording periods tadpoles had reached developmental stages 45 to 47. It was observed that microgravity affected VR activity during fictive swimming and rVOR. In particular, VR activity changes included a significant decrease of the rostrocaudal delay and a significant increase of episode duration. The rVOR-amplitude was transiently depressed. Hypergravity was less effective on the locomotor pattern; occurring effects on fictive swimming were the opposite of microg effects. As after microgravity, the rVOR was depressed after 3g-exposure. All modifications of the rVOR and VR-activity recovered to normal levels within 4 to 7 days after termination of AG. Significant correlations between the rVOR amplitude and VR activity of respective tadpoles during the recording period have been observed in both tadpoles with or without AG experience. The data are consistent with the assumptions that during this period of life which is characterized by a progressive development of vestibuloocular and vestibulospinal projections (i) microgravity retards the development of VR activity while hypergravity weakly accelerates it; (ii) that microgravity retards the rVOR development while hypergravity caused a sensitization, and that (iii) AG-induced changes of VR activity during fictive swimming have a vestibular origin.