Increase in Streptococcus pneumoniae serotype 3 associated parapneumonic pleural effusion/empyema after the introduction of PCV13 in Germany

IntroductionPediatric pneumococcal pneumonia complicated by parapneumonic pleural effusion/empyema (PPE/PE) remains a major concern despite general immunization with pneumococcal conjugate vaccines (PCVs).MethodsIn a nationwide pediatric hospital surveillance study in Germany we identified 584 children <18 years of age with bacteriologically confirmed PPE/PE from October 2010 to June 2018. Streptococcus pneumoniae was identified by culture and/or PCR of blood samples and/or pleural fluid and serotyped.ResultsS. pneumoniae was identified in 256 of 584 (43.8%) children by culture (n = 122) and/or PCR (n = 207). The following pneumococcal serotypes were detected in 114 children: serotype 3 (42.1%), 1 (25.4%), 7F (12.3%), 19A (7.9%), other PCV13 serotypes (4.4%) and non-PCV13 serotypes (7.9%). Between October 2010 and June 2014 serotype 1 (38.1%) and serotype 3 (25.4%) were most prevalent, whereas between July 2014 and June 2018 serotype 3 (62.7%) and non-PCV13 serotypes (15.7%) were dominant. Compared to children with other pneumococcal serotypes, children with serotype 3 associated PPE/PE were younger (median 3.2 years [IQR 2.1–4.3 years] vs. median 5.6 years [IQR 3.8–8.2 years]; p < 0.001) and more frequently admitted to intensive care (43 [89.6%] vs. 48 [73.8%]; p = 0.04). Seventy-six of 114 (66.7%) children with pneumococcal PPE/PE had been vaccinated with pneumococcal vaccines. Thirty-nine of 76 (51.3%) had received a vaccine covering the serotype detected. Thirty of these 39 breakthrough cases were age-appropriately vaccinated with PCV13 and considered vaccine failures, including 26 children with serotype 3, three children with serotype 19A and one child with serotype 1.ConclusionFollowing the introduction of PCV13 in general childhood vaccination we observed a strong emergence of serotype 3 associated PPE/PE in the German pediatric population, including a considerable number of younger children with serotype 3 vaccine breakthrough cases and failures. Future PCVs should not only cover newly emerging serotypes, but also include a more effective component against serotype 3.     

Depression and risk of hospitalization for pneumonia in a cohort study of older Americans

ObjectiveThe aim of this study is to determine if depression is independently associated with risk of hospitalization for pneumonia after adjusting for demographics, medical comorbidity, health-risk behaviors, baseline cognition and functional impairments.MethodsThis secondary analysis of prospectively collected data examined a population-based sample of 6704 Health and Retirement Study (HRS) (1998–2008) participants > 50 years old who consented to have their interviews linked to their Medicare claims and were without a dementia diagnosis. The eight-item Center for Epidemiologic Studies Depression Scale and/or International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) depression diagnoses were used to identify baseline depression. ICD-9-CM diagnoses were used to identify hospitalizations for which the principal discharge diagnosis was for bacterial or viral pneumonia. The odds of hospitalization for pneumonia for participants with depression relative to those without depression were estimated using logistic regression models. Population attributable fractions were calculated to determine the extent that hospitalizations for pneumonia could be attributable to depression.ResultsAfter adjusting for demographic characteristics, clinical factors, and health-risk behaviors, depression was independently associated with increased odds of hospitalization for pneumonia (odds ratio [OR]: 1.28, 95% confidence interval [95%CI]: 1.08, 1.53). This association persisted after adjusting for baseline cognition and functional impairments (OR: 1.24, 95%CI: 1.03, 1.50). In this cohort, 6% (95%CI: 2%, 10%) of hospitalizations for pneumonia were potentially attributable to depression.ConclusionDepression is independently associated with increased odds of hospitalization for pneumonia. This study provides additional rationale for integrating mental health care into medical settings in order to improve outcomes for older adults.     

Treatment Satisfaction of Men and Partners Following Switch from On‐Demand Phosphodiesterase Type 5 Inhibitor Therapy to Tadalafil 5 mg Once Daily

IntroductionTreatment satisfaction of men receiving phosphodiesterase 5 inhibitors (PDE5) for erectile dysfunction (ED) and their partners is essential to successful long‐term therapy.AimThis study aims to assess treatment satisfaction, in men with a partial response to on‐demand (PRN) PDE5 and their female partners, following tadalafil 5 mg once daily or placebo.MethodsThe study was randomized, double‐blind, parallel, and placebo‐controlled in men primarily with mild to moderate ED. Treatment satisfaction was assessed following a 4‐week maximum dose PRN lead‐in, 4‐week nondrug washout, and treatment through 12 weeks. Men were ≥18 years old with ED for ≥3 months and International Index of Erectile Function Erectile Function score of ≥17 and <26 at screening and <26 following PRN lead‐in.Main Outcome MeasuresTreatment satisfaction was assessed using the Treatment Satisfaction Scale (TSS) for patients and partners. TSS domain scores range from 0 to 100, with higher values indicating greater satisfaction. Statistical comparisons were made using analysis of covariance.ResultsTreatment satisfaction was significantly greater with tadalafil once daily vs. placebo across all TSS domains for both patients and their partners (all P < 0.001). For patients, mean scores for the TSS domains Confidence to Complete Sexual Activity and Satisfaction with Orgasm ranged from 53.7 to 57.8 after the PRN lead‐in and 26.7 to 31.9 following the nondrug washout. Following randomized treatment, scores for tadalafil and placebo were 55.4 and 32.6, respectively, for Confidence to Complete Sexual Activity and 57.5 and 37.9, respectively, for Satisfaction with Orgasm. Results were comparable for other TSS domains and between men and their partners.ConclusionsTreatment satisfaction was comparable for tadalafil 5 mg once daily and PRN PDE5 for both patients and female partners, suggesting that tadalafil once daily is a viable therapy option for men with ED who had a partial response to PRN PDE5 therapy. Burns PR, Rosen RC, Dunn M, Baygani SK, and Perelman MA. Treatment satisfaction of men and partners following switch from on‐demand phosphodiesterase type 5 inhibitor therapy to tadalafil 5 mg once daily. J Sex Med 2015;12:720–727.     

Colon and rectal cancer risk after bariatric surgery in a multicountry Nordic cohort study

Obesity is a risk factor for colorectal cancer. Yet, some research indicates that weight-reducing bariatric surgery also increases colorectal cancer risk. Our study was undertaken because current evidence examining bariatric surgery and risk of colorectal cancer is limited and inconsistent. This population-based cohort study included adults with a documented obesity diagnosis in Denmark, Finland, Iceland, Norway or Sweden in 1980–2015. The incidence of colorectal cancer in participants with obesity who had and had not undergone bariatric surgery was compared to the incidence in the corresponding background population by calculating standardized incidence ratios (SIR) with 95% confidence intervals (CI). Additionally, operated and nonoperated participants with obesity were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs adjusted for confounders. Among 502,772 cohort participants with an obesity diagnosis, 49,931(9.9%) underwent bariatric surgery. The overall SIR of colon cancer was increased after bariatric surgery (SIR 1.56; 95% CI 1.28–1.88), with higher SIRs ≥10 years postsurgery. The overall HR of colon cancer in operated compared to nonoperated participants was 1.13 (95% CI 0.92–1.39) and 1.55 (95% CI 1.04–2.31) 10–14 years after bariatric surgery. Bariatric surgery did not significantly increase the risk of rectal cancer (SIR 1.14, 95% CI 0.83–1.52; HR 1.08, 95% CI 0.79–1.49), but the risk estimates increased with longer follow-up periods. Our study suggests that bariatric surgery is associated with an increased risk of colon cancer, while the support for an increased risk of rectal cancer was weaker.     

Magnesium intake and primary liver cancer incidence and mortality in the Prostate,Lung, Colorectal and Ovarian Cancer Screening Trial

Epidemiological studies on magnesium intake and primary liver cancer (PLC) are scarce, and no prospective studies have examined the associations of magnesium intake with PLC incidence and mortality. We sought to clarify whether higher magnesium intake from diet and supplements was associated with lower risks of PLC incidence and mortality in the US population. Magnesium intake from diet and supplements was evaluated through a food frequency questionnaire in a cohort of 104,025 participants. Cox regression was employed to calculate hazard ratios for PLC incidence and competing risk regression was employed to calculate subdistribution hazard ratios for PLC mortality. Restricted cubic spline regression was employed to test nonlinearity. We documented 116 PLC cases during 1,193,513.5 person-years of follow-up and 100 PLC deaths during 1,198,021.3 person-years of follow-up. Total (diet + supplements) magnesium intake was found to be inversely associated with risks of PLC incidence (hazard ratio_{tertile 3 vs. 1}: 0.44; 95% confidence interval: 0.24, 0.80; p_trend = 0.0065) and mortality (subdistribution hazard ratio_{tertile 3 vs. 1}: 0.37; 95% confidence interval: 0.19, 0.71; p_trend = 0.0008). Similar results were obtained for dietary magnesium intake. Nonlinear inverse dose–response associations with PLC incidence and mortality were observed for both total and dietary magnesium intakes (all p_nonlinearity < 0.05). In summary, in the US population, a high magnesium intake is associated with decreased risks of PLC incidence and mortality in a nonlinear dose–response manner. These findings support that increasing the consumption of foods rich in magnesium may be beneficial in reducing PLC incidence and mortality.     

Improvisation and harm avoidance: An ethnographic study of adherence to postnatal care protocols in two hospitals in Southern Ghana

Providers’ adherence to case management protocols can affect quality of care. However, how and why protocols are adhered to by frontline health workers in low- and middle-income countries is not always clear. This study explored midwives’ adherence to national postnatal care protocols in two public hospitals in Southern Ghana using an ethnographic study design. Ninety participant observations and 88 conversations were conducted over a 20-months period, and two group interviews held with the midwives in the two hospitals. Data was analysed using a grounded theory approach.Findings: Midwives collectively decided when to adhere, modify or totally ignore postnatal care protocols. Adherence often occurred if required resources (equipment, tools, supplies) were available. Modification occurred when midwives felt that strict adherence could have negative implications for patients and they could be seen as acting ‘unprofessionally’. Ignoring or modifying protocols also occurred when midwives were uncertain of the patient's health condition; basic supplies, logistics and infrastructure needed for adherence were unavailable or inappropriate; or midwives felt they might expose themselves or their clients to physical, psychological, emotional, financial or social harm. Regardless of the reasons that midwives felt justified to ignore or modify postnatal care protocols, it appeared in many instances to lead to the provision of care of suboptimal quality.Conclusion and recommendations: Providing clinical decision-making protocols is not enough to improve mother and new born care quality and outcomes. Faced with constraining conditions of work, providers are likely to modify guidelines as part of coping behaviour. Addressing constraining conditions of work must accompany guidelines. This includes adequate risks protection for health workers and clients; and resolution of deficits in essential equipment, infrastructure, supplies and staffing.     

High dose trivalent influenza vaccine compared to standard dose vaccine in patients with rheumatoid arthritis receiving TNF-alpha inhibitor therapy and healthy controls: Results of the DMID 10-0076 randomized clinical trial

IntroductionSubjects with rheumatoid arthritis (RA) receiving tumor necrosis factor-inhibiting (TNFi) therapies are at risk for severe influenza, and may respond less well to influenza vaccine. We examined the safety and immunogenicity of high dose influenza vaccine (HD) compared to standard dose vaccine (SD) in participants with RA receiving stable TNFi.MethodsA randomized, double-blinded, Phase II study was conducted in adults with RA receiving TNFi, and healthy, gender and age-matched control subjects. Participants were immunized with HD (Sanofi Pasteur Fluzone High Dose [60 mcg × 3 strains]) or SD (Sanofi Pasteur Fluzone® [15 mcg × 3 strains]) intramuscularly (IM). A self-administered memory aid recorded temperature and systemic and local adverse events (AEs) for 8 days, and safety was evaluated and serum obtained to measure HAI activity on days 7, 21 and 180 days following vaccination.ResultsA greater proportion of RA subjects who received HD seroconverted at day 21 compared to SD, although this was not statistically significant. GMT antibody responses in RA subjects who received HD compared to SD were greater for all strains on day 21, and this was significant for H1N1. Seroconversion rates and GMT values were not different between RA subjects and control subjects. There were no safety concerns for HD or SD in RA subjects, and RA-related symptoms did not differ between SD and HD recipients by a RA-symptom questionnaire (RAPID 3).ConclusionsTNF-inhibitor therapy in people with RA did not appear to influence the immunogenicity of either SD or HD. Influenza seroconversion and GMT values were higher among RA subjects receiving HD compared to SD; however, differences were small and a larger study is needed to validate these findings. Given the apparent risk of increased influenza-related morbidity and mortality among immune compromised subjects, the higher GMT values generated by HD may be beneficial.