Antibiotics Not Associated with Shorter Duration or Reduced Severity of Acute Lower Respiratory Tract Infection.

BACKGROUND: Antibiotic use remains common for the treatment of lower respiratory tract infections. The objective of this study was to evaluate the impact of antibiotic use on the duration and severity of acute lower respiratory tract infection (LRTI). PARTICIPANTS: Adult patients presenting to US primary or urgent care sites with a chief complaint of cough and symptoms consistent with LRTI. MAIN MEASURES: Collected data included demographics, comorbidities, symptoms, and 48 viral and bacterial respiratory pathogens by PCR. Severity of signs/symptoms was reported for up to 28 days using diaries and text messages. Interpolation was used where data were missing. KEY RESULTS: Of 718 patients with baseline data, 29% had an antibiotic prescribed at baseline. The most common antibiotics were amoxicillin-clavulanate, azithromycin, doxycycline, and amoxicillin in 85% of patients. Provision of an antibiotic had no effect on the duration or overall severity of cough, including in patients with viral, bacterial, and mixed infections. Receipt of an antibiotic did reduce the likelihood of a follow-up visit (14.1% vs 8.2%, aOR 0.47, 95% CI 0.26-0.84), perhaps by removing the motivation of getting an antibiotic at a follow-up visit. However, they were also more likely to receive a systemic corticosteroid (31.9% vs 4.5%, p < 0.001) and were also more likely to receive an albuterol inhaler (22.7% vs 7.6%, p < 0.001). Patients believed that receiving an antibiotic would reduce the duration of their illness by nearly 4 days. CONCLUSIONS: In this large prospective study in the US primary and urgent care setting, antibiotics had no measurable impact on the severity or duration of cough due to acute LRTI. Patients had unrealistic expectations regarding the duration of LRTI and the effect of antibiotics which should be the target of antibiotic stewardship efforts.

Prevalence, Comorbidity, and Correlates of Psychiatric and Substance Use Disorders and Associations with HIV Risk Behaviors in a Multisite Cohort of Women Living with HIV.

We used the World Health Organization's Composite International Diagnostic Interview to determine the prevalence, comorbidity, and correlates of lifetime and 12-month behavioral health disorders in a multisite cohort of 1027 women living with HIV in the United States. Most (82.6%) had one or more lifetime disorders including 34.2% with mood disorders, 61.6% with anxiety disorders, and 58.3% with substance use disorders. Over half (53.9%) had at least one 12-month disorder, including 22.1% with mood disorders, 45.4% with anxiety disorders, and 11.1% with substance use disorders. Behavioral health disorder onset preceded HIV diagnosis by an average of 19 years. In multivariable models, likelihood of disorders was associated with women's race/ethnicity, employment status, and income. Women with 12-month behavioral health disorders were significantly more likely than their counterparts to engage in subsequent sexual and substance use HIV risk behaviors. We discuss the complex physical and behavioral health needs of women living with HIV.

Evidence-based HMO care for prostate specific antigen testing.

BACKGROUND: There is pressure in the U.S. system to move away from fee-for-service models to a more pre-paid system, which may result in decreased costs, but the impact on evidence-based care is unclear. We examined a large pre-paid Health Maintenance Organizations (HMO) in Israel to see if evidence-based guidelines are followed for prostate specific antigen (PSA) testing. METHODS: A retrospective cohort of ambulatory visits from 2002 to 2011 of patients age >75 receiving care from Clalit Health Services was conducted. Historically reported U.S. cohorts were used for comparison. The main measure was the percent of patients who had at least one PSA after age 75. RESULTS: In each of the 10 years of follow-up, 22% of the yearly Israeli cohort, with no known malignancy or benign prostatic hyperplasia, had at least one PSA, while for the total 10 years, 30% of the men had at least one PSA. These rates are considerably lower than previously reported U.S. rates. CONCLUSIONS: In a pre-paid system in which physicians have no incentive to order tests, they appear to order PSA tests at a lower rate than has been observed in the U.S. system. Additional quality of measures should continue to be examined as the U.S. shifts away from a fee-for-service model. Copyright © 2016 John Wiley & Sons, Ltd.

Safety of Bifidobacterium animalis Subsp. Lactis (B. lactis) Strain BB-12-Supplemented Yogurt in Healthy Children.

OBJECTIVES: Probiotics are live microorganisms that may provide health benefits to the individual when consumed in sufficient quantities. For studies conducted on health or disease endpoints on probiotics in the United States, the Food and Administration has required those studies to be conducted as investigational new drugs. This phase I, double-blinded, randomized, controlled safety study represents the first requirement of this pathway. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp. lactis (B lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of children. The secondary aim was to assess the effect of BB-12-supplemented yogurt on the gut microbiota of the children. METHODS: Sixty children ages 1 to 5 years were randomly assigned to consume 4 ounces of either BB-12-supplemented yogurt or nonsupplemented control yogurt daily for 10 days. The primary outcome was to assess safety and tolerability, as determined by the number of reported adverse events. RESULTS: A total of 186 nonserious adverse events were reported, with no significant differences between the control and BB-12 groups. No significant changes due to probiotic treatment were observed in the gut microbiota of the study cohort. CONCLUSIONS: BB-12-supplemented yogurt is safe and well-tolerated when consumed by healthy children. The present study will form the basis for future randomized clinical trials investigating the potential effects of BB-12-supplemented yogurt in different disease states.

Evaluating the lifestyles of physicians and PAs in orthopedics.

OBJECTIVE: Limited current research is available comparing job satisfaction and lifestyles of physicians and physician assistants (PAs). Given the professional similarities and the upward trend in employment for both professions, this research is important in educating future professionals and employers. This study examined job contentment among orthopedic physicians and PAs. METHODS: A cross-sectional survey was designed to assess career and lifestyle satisfaction. The survey was e-mailed to orthopedic clinics across the United States. RESULTS: 27 PAs and 50 physicians completed the survey. Compared with physicians, PAs were more likely to recommend their career and to desire to switch specialties. Physicians reported a higher level of agreement that the professional schedule overshadows personal life, and that the stress and demand of the profession impair personal health. CONCLUSION: PAs in orthopedics self-reported a higher lifestyle satisfaction than physicians. One specialty was examined and larger, more diverse studies should be conducted.

Probiotic use in at-risk populations.

OBJECTIVE: To inform health care providers about quality standards for manufacture of probiotic products being recommended for at-risk patient populations. SUMMARY: Probiotics are used in a variety of clinical settings, sometimes in at-risk populations for therapeutic endpoints. Although probiotics might not be approved as drugs, they are sometimes used for the prevention or treatment of disease. In the United States, and many regions of the world, probiotic products are marketed as dietary supplements (not drugs) and are therefore subject to different manufacturing and quality control standards than approved drugs are. Health care providers need to be assured that probiotic products used in at-risk populations are safe for this use. Pharmacists should require certificates of analysis, which document quality standards, from manufacturers of products stocked in hospital formularies or other pharmacies dispensing to at-risk people. Although responsible manufacturers use stringent quality standards on their processes and finished products, using a third party to verify compliance with manufacturing and accuracy of product labeling adds assurance to end users that the product is of high quality. CONCLUSION: It is in patients' best interest to use probiotics in the prevention and treatment of conditions when the evidence is convincing. To protect high-risk patients, probiotic products should meet stringent microbiological standards. Product testing results should be available for review before recommending probiotic products to at-risk individuals. For products used in at-risk populations, manufacturers should provide this information or participate in a third-party verification program that certifies compliance.

Short-term, daily intake of yogurt containing Bifidobacterium animalis ssp. lactis Bf-6 (LMG 24384) does not affect colonic transit time in women.

The present study investigated the effect of Bifidobacterium animalis ssp. lactis Bf-6 (LMG 24 384) (Bf-6)-supplemented yogurt on colonic transit time (CTT). A triple-blinded, randomised, placebo-controlled, two-period cross-over trial was conducted with sixty-eight women with a self-reported history of straining during bowel movements or hard or lumpy stools in the past 2 years. As per regulatory requirements for probiotic studies, eligible women were generally healthy and not actively constipated at the time of enrolment. Participants consumed both Bf-6 and placebo yogurts for 14 d each in a randomised order, with a 6-week washout period between the treatments. The primary outcome, CTT, was assessed via Sitz marker X-rays. The average CTT was 42·1 h for the active period and 43·3 h for the control period (mean difference 1·2 h, 95 % CI - 4·9, 7·4). Since the statistical tests for the cross-over study implied that the mean CTT for the active and control periods in period 2 were biased, the standard protocol suggests examining the results of only period 1 as a traditional randomised controlled trial. This showed that the mean CTT was 35·2 h for the active period v. 52·9 h for the control period (P= 0·015). Bootstrapping demonstrated that both the mean and median differences remained significant (P= 0·016 and P= 0·045, respectively). Few adverse events were noted, with no differences among the active and control periods. The paired analysis showed no differences between the active and control periods during the cross-over trial. Further trials should be conducted in populations with underlying problems associated with disordered transit to determine the potential value of probiotic supplementation more accurately.

Is There Evidence to Support Probiotic Use for Healthy People?

Probiotics are typically marketed as foods and dietary supplements, categories for products intended to maintain health in generally healthy populations and which, unlike drugs, cannot claim to treat or cure disease. This review addresses the existing evidence that probiotics are beneficial to healthy people. Our approach was to perform a descriptive review of efficacy evidence that probiotics can prevent urinary, vaginal, gastrointestinal, and respiratory infections, and improve risk factors associated with cardiovascular health or reduce antibiotic use. Other endpoints such as mental, dental, or immune health were not specifically addressed. We concluded that there is sufficient evidence of efficacy and safety for clinicians and consumers to consider using specific probiotics for some indications - such as the use of probiotics to support gut function during antibiotic use or to reduce the risk of respiratory tract infections - for certain people. However, we did not find a sufficiently high level of evidence to support unconditional, population-wide recommendations for other preventive endpoints we reviewed for healthy people. Although evidence for some indications is suggestive of the preventive benefits of probiotics, additional research is needed.

Impact of eating probiotic yogurt on colonization by Candida species of the oral and vaginal mucosa in HIV-infected and HIV-uninfected women.

BACKGROUND: Candidiasis in HIV/AIDS patients continues to be a public health problem. Antifungal therapies are not always effective and may result in complications, such as the development of drug-resistant strains of Candida species. OBJECTIVES: This study evaluated the impact of probiotic consumption on Candida colonization of the oral and vaginal mucosa. PATIENTS/METHODS: A pilot study was conducted in 24 women (17 HIV-infected, 7 HIV-uninfected) from the Women's Interagency HIV Study. The women underwent a 60-day initiation period with no probiotic consumption, followed by two 15-day consumption periods, with a different probiotic yogurt (DanActive™ or YoPlus™ yogurt) during each interval. There was a 30-day washout period between the two yogurt consumption periods. Oral and vaginal culture swabs were collected on days 0, 60, 74, and 120. Candida was detected by inoculating each swab in both Sabouraud's dextrose agar with or without chloramphenicol and CHROMagar. RESULTS: Less fungal colonization among women was observed when the women consumed probiotic yogurts (54 % of the women had vaginal fungal colonization during the non-probiotic yogurt consumption period, 29 % during the DanActive™ period, and 38 % during YoPlus™ yogurt consumption period), and HIV-infected women had significantly lower vaginal fungal colonization after they consumed DanActive™ yogurt compared to the non-intervention periods (54 vs 29 %, p = 0.03). CONCLUSIONS: These data are promising, but as expected in a small pilot study, there were some significant changes but also some areas where colonization was not changed. This type of conflicting data is supportive of the need for a larger trial to further elucidate the role of probiotic yogurts in fungal growth in HIV-infected women.

Kombucha tea as an anti-hyperglycemic agent in humans with diabetes - a randomized controlled pilot investigation.

Introduction: Kombucha is a popular fermented tea that has attracted considerable attention due, in part, to its suggested health benefits. Previous results from animal models led us to hypothesize kombucha may reduce blood sugar levels in humans with diabetes. The objective of this pilot clinical study was to evaluate kombucha for its anti-hyperglycemic activities in adults with diabetes mellitus type II. Methods: The study was organized as a prospective randomized double-blinded crossover study at a single-center urban hospital system. Participants (n = 12) were instructed to consume either a kombucha product or a placebo control (each 240 mL) for 4 weeks. After an 8-week washout period, participants consumed the alternate product. Fasting blood glucose levels were self-determined at baseline and at 1 and 4 weeks during each treatment period. Secondary health outcomes, including overall health, insulin requirement, gut health, skin health, mental health, and vulvovaginal health were measured by questionnaire at the same time points. The kombucha microbiota was assessed by selective culturing and 16S rRNA gene (bacteria) and ITS (fungi) sequencing. Fermentation end products were assessed by HPLC. Statistical significance of changes in fasting blood glucose was determined using paired, two-tailed student's t-tests. Results: Kombucha lowered average fasting blood glucose levels at 4 weeks compared to baseline (164 vs. 116 mg/dL, p = 0.035), whereas the placebo did not (162 vs. 141 mg/dL, p = 0.078). The kombucha microbiota, as assessed by cultural enumeration, was mainly comprised of lactic acid bacteria, acetic acid bacteria, and yeast, with each group present at about 106 colony forming units (CFU)/mL. Likewise, 16S rRNA gene sequencing confirmed that lactic acid and acetic acid bacteria were the most abundant bacteria, and ITS sequencing showed Dekkera was the most abundant yeast. The primary fermentation end products were lactic and acetic acids, both less than 1%. Ethanol was present at 1.5%. Discussion: Although this pilot study was limited by a small sample size, kombucha was associated with reduced blood glucose levels in humans with diabetes. Larger follow-up studies are warranted. Clinical trial registration: ClinicalTrials.gov, identifier NCT04107207.

Administration of Bifidobacterium animalis subsp. lactis Strain BB-12 ® in Healthy Children: Characterization, Functional Composition, and Metabolism of the Gut Microbiome.

The consumption of probiotics may influence children's gut microbiome and metabolome, which may reflect shifts in gut microbial diversity composition and metabolism. These potential changes might have a beneficial impact on health. However, there is a lack of evidence investigating the effect of probiotics on the gut microbiome and metabolome of children. We aimed to examine the potential impact of a two ( Streptococcus thermophilus and Lactobacillus delbrueckii ; S2) vs . three (S2 + Bifidobacterium animalis subsp. lactis strain BB-12) strain-supplemented yogurt. Included in this study were 59 participants, aged one to five years old, recruited to phase I of a double-blinded, randomized controlled trial. Fecal samples were collected at baseline, after the intervention, and at twenty days post-intervention discontinuation, and untargeted metabolomics and shotgun metagenomics were performed. Shotgun metagenomics and metabolomic analyses showed no global changes in either intervention group's gut microbiome alpha or beta diversity indices. The relative abundance of the two and three intervention bacteria increased in the S2 and S2 + BB12 groups, respectively, from Day 0 to Day 10 . In the S2+BB12 group, the abundance of several fecal metabolites was reduced at Day 10 , including alanine, glycine, lysine, phenylalanine, serine, and valine. These fecal metabolite changes did not occur in the S2 group. Future research using longer probiotic intervention durations and in children at risk for gastrointestinal disorders may elucidate if functional metabolite changes confer a protective gastrointestinal effect.

Administration of Bifidobacterium animalis subsp. lactis strain BB-12® in healthy children: characterization, functional composition, and metabolism of the gut microbiome.

Introduction: The consumption of probiotics may influence children's gut microbiome and metabolome, which may reflect shifts in gut microbial diversity composition and metabolism. These potential changes might have a beneficial impact on health. However, there is a lack of evidence investigating the effect of probiotics on the gut microbiome and metabolome of children. We aimed to examine the potential impact of a two (Streptococcus thermophilus and Lactobacillus delbrueckii; S2) vs. three (S2 + Bifidobacterium animalis subsp. lactis strain BB-12) strain-supplemented yogurt. Methods: Included in this study were 59 participants, aged one to five years old, recruited to phase I of a double-blinded, randomized controlled trial. Fecal samples were collected at baseline, after the intervention, and at twenty days post-intervention discontinuation, and untargeted metabolomics and shotgun metagenomics were performed. Results: Shotgun metagenomics and metabolomic analyses showed no global changes in either intervention group's gut microbiome alpha or beta diversity indices, except for a lower microbial diversity in the S2 + BB12 group at Day 30. The relative abundance of the two and three intervention bacteria increased in the S2 and S2 + BB12 groups, respectively, from Day 0 to Day 10. In the S2 + BB12 group, the abundance of several fecal metabolites increased at Day 10, including alanine, glycine, lysine, phenylalanine, serine, and valine. These fecal metabolite changes did not occur in the S2 group. Discussion: In conclusion, there were were no significant differences in the global metagenomic or metabolomic profiles between healthy children receiving two (S2) vs. three (S2 + BB12) probiotic strains for 10 days. Nevertheless, we observed a significant increase (Day 0 to Day 10) in the relative abundance of the two and three probiotics administered in the S2 and S2 + BB12 groups, respectively, indicating the intervention had a measurable impact on the bacteria of interest in the gut microbiome. Future research using longer probiotic intervention durations and in children at risk for gastrointestinal disorders may elucidate if functional metabolite changes confer a protective gastrointestinal effect.

Recommendations to Improve Quality of Probiotic Systematic Reviews With Meta-Analyses.

Importance: Systematic reviews and meta-analyses often report conflicting results when assessing evidence for probiotic efficacy, partially because of the lack of understanding of the unique features of probiotic trials. As a consequence, clinical decisions on the use of probiotics have been confusing. Objective: To provide recommendations to improve the quality and consistency of systematic reviews with meta-analyses on probiotics, so evidence-based clinical decisions can be made with more clarity. Evidence Review: For this consensus statement, an updated literature review was conducted (January 1, 2020, to June 30, 2022) to supplement a previously published 2018 literature search to identify areas where probiotic systematic reviews with meta-analyses might be improved. An expert panel of 21 scientists and physicians with experience on writing and reviewing probiotic reviews and meta-analyses was convened and used a modified Delphi method to develop recommendations for future probiotic reviews. Findings: A total of 206 systematic reviews with meta-analysis components on probiotics were screened and representative examples discussed to determine areas for improvement. The expert panel initially identified 36 items that were inconsistently reported or were considered important to consider in probiotic meta-analyses. Of these, a consensus was reached for 9 recommendations to improve the quality of future probiotic meta-analyses. Conclusions and Relevance: In this study, the expert panel reached a consensus on 9 recommendations that should promote improved reporting of probiotic systematic reviews with meta-analyses and, thereby, assist in clinical decisions regarding the use of probiotics.

Genital herpes evaluation by quantitative TaqMan PCR: correlating single detection and quantity of HSV-2 DNA in cervicovaginal lavage fluids with cross-sectional and longitudinal clinical data.

OBJECTIVE: To evaluate the utility of a single quantitative PCR (qPCR) measurement of HSV (HSV-1&2) DNA in cervicovaginal lavage (CVL) specimens collected from women with predominantly chronic HSV-2 infection in assessing genital HSV shedding and the clinical course of genital herpes (GH) within a cohort with semiannual schedule of follow up and collection of specimens. METHODS: Two previously described methods used for detection of HSV DNA in mucocutaneous swab samples were adapted for quantification of HSV DNA in CVLs. Single CVL specimens from 509 women were tested. Presence and quantity of CVL HSV DNA were explored in relation to observed cross-sectional and longitudinal clinical data. RESULTS: The PCR assay was sensitive and reproducible with a limit of quantification of ~50 copies per milliliter of CVL. Overall, 7% of the samples were positive for HSV-2 DNA with median log10 HSV-2 DNA copy number of 3.9 (IQR: 2.6-5.7). No HSV-1 was detected. Presence and quantity of HSV-2 DNA in CVL directly correlated with the clinical signs and symptoms of presence of active symptomatic disease with frequent recurrences. CONCLUSION: Single qPCR measurement of HSV DNA in CVL fluids of women with chronic HSV-2 infection provided useful information for assessing GH in the setting of infrequent sampling of specimens. Observed positive correlation of the presence and quantity of HSV-2 DNA with the presence of active and more severe course of HSV-2 infection may have clinical significance in the evaluation and management of HSV-2 infected patients.

Probiotics as a Tx resource in primary care.

While probiotics have not been marketed as drugs, clinicians can still recommend them in an evidence-based manner.

Probiotics and prebiotics in intestinal health and disease: from biology to the clinic.

Probiotics and prebiotics are microbiota-management tools for improving host health. They target gastrointestinal effects via the gut, although direct application to other sites such as the oral cavity, vaginal tract and skin is being explored. Here, we describe gut-derived effects in humans. In the past decade, research on the gut microbiome has rapidly accumulated and has been accompanied by increased interest in probiotics and prebiotics as a means to modulate the gut microbiota. Given the importance of these approaches for public health, it is timely to reiterate factual and supporting information on their clinical application and use. In this Review, we discuss scientific evidence on probiotics and prebiotics, including mechanistic insights into health effects. Strains of Lactobacillus, Bifidobacterium and Saccharomyces have a long history of safe and effective use as probiotics, but Roseburia spp., Akkermansia spp., Propionibacterium spp. and Faecalibacterium spp. show promise for the future. For prebiotics, glucans and fructans are well proven, and evidence is building on the prebiotic effects of other substances (for example, oligomers of mannose, glucose, xylose, pectin, starches, human milk and polyphenols).

Author Correction: Probiotics and prebiotics in intestinal health and disease: from biology to the clinic.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Shared mechanisms among probiotic taxa: implications for general probiotic claims.

Strain-specificity of probiotic effects has been a cornerstone principle of probiotic science for decades. Certainly, some important mechanisms are present in only a few probiotic strains. But scientific advances now reveal commonalities among members of certain taxonomic groups of probiotic microbes. Some clinical benefits likely derive from these shared mechanisms, suggesting that sub-species-specific, species-specific or genus-specific probiotic effects exist. Human trials are necessary to confirm specific health benefits. However, a strain that has not been tested in human efficacy trials may meet the minimum definition of the term 'probiotic' if it is a member of a well-studied probiotic species expressing underlying core mechanisms and it is delivered at an effective dose.