Clinical Impact of the Implementation Strategies Used to Apply the 2013 Pain, Agitation/Sedation, Delirium or 2018 Pain, Agitation/Sedation, Delirium, Immobility, Sleep Disruption Guideline Recommendations: A Systematic Review and Meta-Analysis.

OBJECTIVES: To summarize the effectiveness of implementation strategies for ICU execution of recommendations from the 2013 Pain, Agitation/Sedation, Delirium (PAD) or 2018 PAD, Immobility, Sleep Disruption (PADIS) guidelines. DATA SOURCES: PubMed, CINAHL, Scopus, and Web of Science were searched from January 2012 to August 2023. The protocol was registered with PROSPERO (CRD42020175268). STUDY SELECTION: Articles were included if: 1) design was randomized or cohort, 2) adult population evaluated, 3) employed recommendations from greater than or equal to two PAD/PADIS domains, and 4) evaluated greater than or equal to 1 of the following outcome(s): short-term mortality, delirium occurrence, mechanical ventilation (MV) duration, or ICU length of stay (LOS). DATA EXTRACTION: Two authors independently reviewed articles for eligibility, number of PAD/PADIS domains, quality according to National Heart, Lung, and Blood Institute assessment tools, implementation strategy use (including Assess, prevent, and manage pain; Both SAT and SBT; Choice of analgesia and sedation; Delirium: assess, prevent, and manage; Early mobility and exercise; Family engagement and empowerment [ABCDEF] bundle) by Cochrane Effective Practice and Organization of Care (EPOC) category, and clinical outcomes. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. DATA SYNTHESIS: Among the 25 of 243 (10.3%) full-text articles included ( n = 23,215 patients), risk of bias was high in 13 (52%). Most studies were cohort ( n = 22, 88%). A median of 5 (interquartile range [IQR] 4-7) EPOC strategies were used to implement recommendations from two (IQR 2-3) PAD/PADIS domains. Cohort and randomized studies were pooled separately. In the cohort studies, use of EPOC strategies was not associated with a change in mortality (risk ratio [RR] 1.01; 95% CI, 0.9-1.12), or delirium (RR 0.92; 95% CI, 0.82-1.03), but was associated with a reduction in MV duration (weighted mean difference [WMD] -0.84 d; 95% CI, -1.25 to -0.43) and ICU LOS (WMD -0.77 d; 95% CI, -1.51 to 0.04). For randomized studies, EPOC strategy use was associated with reduced mortality and MV duration but not delirium or ICU LOS. CONCLUSIONS: Using multiple implementation strategies to adopt PAD/PADIS guideline recommendations may reduce mortality, duration of MV, and ICU LOS. Further prospective, controlled studies are needed to identify the most effective strategies to implement PAD/PADIS recommendations.

PubMed's core clinical journals filter: redesigned for contemporary clinical impact and utility.

Objective: The Core Clinical Journals (CCJ) list, produced by the U.S. National Library of Medicine (NLM), has been used by clinicians and librarians for half a century for two main purposes: narrowing a literature search to clinically useful journals and identifying high priority titles for library collections. After documentation of low usage of the existing CCJ, a review was undertaken to assess current validity, followed by an update to current clinical needs. Methods: As the subject coverage of the 50-year-old list had never been evaluated, the CCJ committee began its innovative step-wise approach by analyzing the existing subject scope. To determine whether clinical subjects had changed over the last half-century, the committee collected data on journal usage in hospitals and medical facilities, adding journal usage from Morning Report blogs recording the journal article citations used by physicians and residents in response to clinical questions. Patient-driven high-frequency diagnoses and subjects added contextual data by depicting the clinical environment. Results: The analysis identified a total of 80 subjects and selected 241 journals for the updated Clinical Journals filter, based on actual clinical utility of each journal. Discussion: These data-driven methods created a different framework for evaluating the structure and content of this filter. It is the real-world evidence needed to highlight CCJ clinical impact and push clinically useful journals to first page results. Since the new process resulted in a new product, the name warrants a change from Core Clinical Journals (CCJ) to Clinically Useful Journals (CUJ). Therefore, the redesigned NLM Core Clinical Journals/AIM set from this point forward will be referred to as Clinically Useful Journals (CUJ). The evidence-based process used to reframe evaluation of the clinical impact and utility of biomedical journals is documented in this article.

Indoor and outdoor air pollution and couple fecundability: a systematic review.

BACKGROUND: Air pollution is both a sensory blight and a threat to human health. Inhaled environmental pollutants can be naturally occurring or human-made, and include traffic-related air pollution (TRAP), ozone, particulate matter (PM) and volatile organic compounds, among other substances, including those from secondhand smoking. Studies of air pollution on reproductive and endocrine systems have reported associations of TRAP, secondhand smoke (SHS), organic solvents and biomass fueled-cooking with adverse birth outcomes. While some evidence suggests that air pollution contributes to infertility, the extant literature is mixed, and varying effects of pollutants have been reported. OBJECTIVE AND RATIONALE: Although some reviews have studied the association between common outdoor air pollutants and time to pregnancy (TTP), there are no comprehensive reviews that also include exposure to indoor inhaled pollutants, such as airborne occupational toxicants and SHS. The current systematic review summarizes the strength of evidence for associations of outdoor air pollution, SHS and indoor inhaled air pollution with couple fecundability and identifies gaps and limitations in the literature to inform policy decisions and future research. SEARCH METHODS: We performed an electronic search of six databases for original research articles in English published since 1990 on TTP or fecundability and a number of chemicals in the context of air pollution, inhalation and aerosolization. Standardized forms for screening, data extraction and study quality were developed using DistillerSR software and completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of both air pollution and fecundability studies. OUTCOMES: The search returned 5200 articles, 4994 of which were excluded at the level of title and abstract screening. After full-text screening, 35 papers remained for data extraction and synthesis. An additional 3 papers were identified independently that fit criteria, and 5 papers involving multiple routes of exposure were removed, yielding 33 articles from 28 studies for analysis. There were 8 papers that examined outdoor air quality, while 6 papers examined SHS exposure and 19 papers examined indoor air quality. The results indicated an association between outdoor air pollution and reduced fecundability, including TRAP and specifically nitrogen oxides and PM with a diameter of ≤2.5 µm, as well as exposure to SHS and formaldehyde. However, exposure windows differed greatly between studies as did the method of exposure assessment. There was little evidence that exposure to volatile solvents is associated with reduced fecundability. WIDER IMPLICATIONS: The evidence suggests that exposure to outdoor air pollutants, SHS and some occupational inhaled pollutants may reduce fecundability. Future studies of SHS should use indoor air monitors and biomarkers to improve exposure assessment. Air monitors that capture real-time exposure can provide valuable insight about the role of indoor air pollution and are helpful in assessing the short-term acute effects of pollutants on TTP.

Delphi-endorsed Communication Skills Clinicians Need to Care for Hospitalized Incapacitated Patients.

Background: The National Academy of Medicine recently identified improving clinicians' serious illness communication skills as a necessary step in improving patient and family outcomes near the end of life, but there is not an accepted set of core communication skills for engaging with surrogate decision makers. Objective: To determine the core serious illness communication skills clinicians should acquire to care for incapacitated, hospitalized patients with acute, life-threatening illness, including patients with Alzheimer's disease and related dementias. Methods: From January 2019 to July 2020, we conducted a modified Delphi study with a panel of 79 experts in the field of serious illness communication. We developed a preliminary list of candidate communication skills through a structured literature review. We presented the candidate skills to the panelists in the context of three prototypical serious illness conversations. Over three rounds, panelists first augmented the list of candidate skills, then voted on the skills. The final set included skills deemed "very important" or "essential" by 70% of panelists. For external validation, we engaged 11 practicing clinicians and 7 community stakeholders for their perspectives on the expert-endorsed list of skills. Results: The panelists' ratings indicate the importance of a diverse set of communication skills related to providing clear information exchange as well as emotional and psychological support to surrogates. The final set included 33 skills, 12 of which were endorsed for all three prototypical serious illness conversations. Practicing clinicians and community stakeholders supported the expert-endorsed framework with only minor additions. Conclusion: We generated a stakeholder-endorsed list of skills that can inform the content of communication skills training programs for clinicians who care for incapacitated patients in the inpatient setting. The skills go beyond those required to provide traditional cognitive decision support and suggest the need for a paradigm shift in curricular content for communication training.

A Systematic Review of Palliative Care Content in the Doctor of Pharmacy Curriculum.

Objective. To describe the methods of teaching and evaluating palliative care experiences for pharmacy students.Findings. A literature search retrieved 971 reports, from which 26 studies met all of study criteria. Educational interventions concerning palliative care included didactic courses, flipped classrooms, advanced pharmacy practice experiences (APPEs), workshops, and seminars. Total direct hours of education in palliative care ranged from 1-200. Seven (27%) focused experiences were reported as required, while nine (35%) were reported as elective. The majority (n=14, 54%) of studies measured pharmacy students' confidence, attitudes, or perceptions as the main outcome, and of those most studies reported an improvement. Five (19%) studies reported on interprofessional experiences in palliative care conducted in the United States, and four (15%) studies reported on similar experiences conducted outside the United States. When reported, most experiences were developed for students to complete prior to beginning their APPE year. All of the included studies used a non-randomized design.Summary. This review suggests a palliative care experience for pharmacy students should be interprofessional, occur during the year prior to APPEs, and measure skills-based outcomes.

Dexmedetomidine for Facilitating Mechanical Ventilation Extubation in Difficult-to-Wean ICU Patients: Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND: Agitation and delirium are common in mechanically ventilated adult intensive care unit (ICU) patients and may contribute to delayed extubation times. Difficult-to-wean ICU patients have been associated with an increased risk of longer ICU length of stays and mortality. The purpose of this systematic review and meta-analysis is to evaluate the evidence of dexmedetomidine facilitating successful mechanical ventilation extubation in difficult-to-wean ICU patients and clinical outcomes. METHODS: A literature search was conducted using MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Global Health, Cochrane Central Register of Controlled Trials, Clinical Trial Registries, and the Health Technology Assessment Database from inception to December 5, 2019. Randomized controlled trials evaluating dexmedetomidine with the intended purpose to facilitate mechanical ventilation liberation in adult ICU patients (≥18 years) experiencing extubation failure were included. The primary outcome of time to extubation was evaluated using the weighted mean difference (WMD), with a random effects model. Secondary analyses included hospital and ICU length of stay, in-hospital mortality, hypotension, and bradycardia. RESULTS: A total of 6 trials (n = 306 patients) were included. Dexmedetomidine significantly reduced the time to extubation (WMD: -11.61 hours, 95% CI: -16.5 to -6.7, P = .005) and ICU length of stay (WMD: -3.04 days; 95% CI: -4.66 to -1.43). Hypotension risk was increased with dexmedetomidine (risk ratio [RR]: 1.62, 95% CI: 1.05-2.51), but there was no difference in bradycardia risk (RR: 3.98, 95% CI: 0.70-22.78). No differences were observed in mortality rates (RR: 1.30, 95% CI: 0.45-3.75) or hospital length of stay (WMD: -2.67 days; 95% CI: -7.73 to 2.39). CONCLUSIONS: Dexmedetomidine was associated with a significant reduction in the time to extubation and shorter ICU stay in difficult-to-wean ICU patients. Although hypotension risk was increased with dexmedetomidine, no differences in other clinical outcomes were observed.

Persistent organic pollutants and couple fecundability: a systematic review.

BACKGROUND: Despite increasing regulation, exposure to persistent organic pollutants (POPs) remains a serious public health concern due to their accumulation in the environment and ability to biomagnify up the food chain. POPs are associated with endocrine-disrupting effects including adverse reproductive outcomes that could affect fecundability, i.e. the capacity to conceive a pregnancy, quantified as time to pregnancy (TTP). OBJECTIVE AND RATIONALE: Results of epidemiologic studies that examine the impact of various chemical classes of POPs on TTP have not been synthesised. We undertook a systematic review to summarise the strength of evidence for associations of four common groups of POPs with couple fecundability and to identify gaps and limitations in the literature in order to inform policy decisions and future research. SEARCH METHODS: We performed an electronic search of literature published between 1 January 2007 and 6 August 2019 in MEDLINE, EMBASE.com, Global Health, DART/TOXLINE and POPLINE. We included empirical research papers that examined human exposure to organochlorine (OC) pesticides, brominated flame retardants, polychlorinated organic compounds and/or per- and polyfluoroalkyl substances (PFAS) and considered TTP or fecundability as an outcome. Standardised forms for screening, data extraction and study quality were developed using DistillerSR software, and all reviews were completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of fecundability studies. OUTCOMES: The search returned 4573 articles, and 28 papers from 19 different studies met inclusion criteria. Among them, four studies measured TTP prospectively, three had data on participants' prenatal exposure, three examined associations in both male and female partners and one focused exclusively on males. Analyses varied widely in terms of exposure characterisation, precluding a meta-analytic approach. Evidence was strongest for adverse associations of female exposure to polychlorinated biphenyls with TTP, with some additional support for associations of female exposure to polybrominated diphenyl ethers and PFAS with longer TTP. Our review provided little or no support for associations between female exposure to OC pesticides or male exposure to any of the POP groups and TTP. WIDER IMPLICATIONS: Evidence suggests that female exposure to at least some POPs may reduce fecundability. Although many of these chemicals are no longer in production, they are still detectable in human biosamples because of their persistence in the environment. Replacement chemicals that are being introduced as older ones are restricted may have similar reproductive consequences. Future studies should examine these newer POPs, assess interactions between POPs and other chemical and non-chemical exposures, investigate how POPs are distributed in and metabolised by the human body and focus on populations that may be disproportionately exposed.

Impact of community pharmacist-led interventions in chronic disease management on clinical, utilization, and economic outcomes: An umbrella review.

BACKGROUND: Chronic disease represents a significant burden to the United States (US) health care system, with approximately 50% of all adults in the US having one or more chronic disease conditions. Pharmacist-led chronic disease management interventions are of special interest since 80% of medical treatments involve the use of prescription drugs. Moreover, community pharmacists are among the most accessible health care professionals to provide care for populations with chronic diseases. The impact of care provided by community pharmacists isn't well defined, with interventions taking on diverse forms with varied effects on outcomes. OBJECTIVE: The purpose of this review is to summarize evidence from secondary literature on community pharmacist-led chronic disease management interventions and the impact on clinical, utilization, and economic outcomes. METHODS: We conducted a systematic search of systematic reviews, meta-analyses, and narrative reviews using MEDLINE via PubMed, EMBASE.com and Cochrane Library databases published between January 1, 2007 and October 17, 2017. The following data were extracted: citation details, review type, number of primary studies included, disease state, description of the intervention, outcomes assessed, and results. RESULTS: Our search strategy retrieved 2296 titles and abstracts of which 15 references met our inclusion criteria. Selected articles covered 7 main diseases -diabetes, asthma, chronic obstructive pulmonary disease (COPD), hypertension, heart failure, hyperlipidemia, and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Community pharmacist-led interventions mostly consisted of patient consultations and education. In diabetes, interventions achieved significant reductions in hemoglobin A1c, total cholesterol, and low-density lipoprotein (LDL). Reviews also reported favorable reductions in blood pressure, improved medication adherence and reduced readmission rates in patients with heart failure, improved lung function in patients with respiratory conditions, and increased medication adherence in those with HIV/AIDs. Literature reporting economic and utilization outcomes were limited and mostly focused on pharmacy interventions in diabetes. In some cases, community pharmacy services demonstrated a decrease in medical and health care costs in patients with diabetes. CONCLUSION: We found that community pharmacists can improve clinical outcomes in a wide array of chronic diseases, including diabetes, hyperlipidemia, HIV/AIDS, cardiovascular and respiratory diseases. More robust studies are needed to further assess the impact of specific interventions on economic and utilization outcomes.

Interventions to Improve Patient Comprehension in Informed Consent for Medical and Surgical Procedures: An Updated Systematic Review.

Background. Patient comprehension is fundamental to valid informed consent. Current practices often result in inadequate patient comprehension. Purpose. An updated review to evaluate the characteristics and outcomes of interventions to improve patient comprehension in clinical informed consent. Data Sources. Systematic searches of MEDLINE and EMBASE (2008-2018). Study Selection. We included randomized and nonrandomized controlled trials evaluating interventions to improve patient comprehension in clinical informed consent. Data Extraction. Reviewers independently abstracted data using a standardized form, comparing all results and resolving disagreements by consensus. Data Synthesis. Fifty-two studies of 60 interventions met inclusion criteria. Compared with standard informed consent, a statistically significant improvement in patient comprehension was seen with 43% (6/14) of written interventions, 56% (15/27) of audiovisual interventions, 67% (2/3) of multicomponent interventions, 85% (11/13) of interactive digital interventions, and 100% (3/3) of verbal discussion with test/feedback or teach-back interventions. Eighty-five percent of studies (44/52) evaluated patients' understanding of risks, 69% (41/52) general knowledge about the procedure, 35% (18/52) understanding of benefits, and 31% (16/52) understanding of alternatives. Participants' education level was reported heterogeneously, and only 8% (4/52) of studies examined effects according to health literacy. Most studies (79%, 41/52) did not specify participants' race/ethnicity. Limitations. Variation in interventions and outcome measures precluded conduct of a meta-analysis or calculation of mean effect size. Control group processes were variable and inconsistently characterized. Nearly half of studies (44%, 23/52) had a high risk of bias for the patient comprehension outcome. Conclusions. Interventions to improve patient comprehension in informed consent are heterogeneous. Interactive interventions, particularly with test/feedback or teach-back components, appear superior. Future research should emphasize all key elements of informed consent and explore effects among vulnerable populations.

Comparing Specialty and Primary Palliative Care Interventions: Analysis of a Systematic Review.

Background: Investigators have tested interventions delivered by specialty palliative care (SPC) clinicians, or by clinicians without palliative care specialization (primary palliative care, PPC). Objective: To compare the characteristics and outcomes of randomized clinical trials (RCTs) of SPC and PPC interventions. Design: Systematic review secondary analysis. Setting/Subjects: RCTs of palliative care interventions. Measurements: Interventions were classified SPC if delivered by palliative care board-certified or subspecialty trained clinicians, or those with extensive clinical experience; all others were PPC. We abstracted data for each intervention: delivery setting, delivery clinicians, outcomes measured, trial results, and Cochrane's Risk of Bias. We conducted narrative synthesis for quality of life, symptom burden, and survival. Results: Of 43 RCTs, 27 tested SPC and 16 tested PPC interventions. SPC interventions were more comprehensive (4.2 elements of palliative care vs. 3.1 in PPC, p = 0.02). SPC interventions were delivered in inpatient (44%) or outpatient settings (52%) by specialty physicians (44%) and nurses (44%); PPC interventions were delivered in inpatient (38%) and home settings (38%) by nurses (75%). PPC trials were more often of high risk of bias than SPC trials. Improvements were demonstrated on quality of life by SPC and PPC trials and on physical symptoms by SPC trials. Conclusions: Compared to PPC, SPC interventions were more comprehensive, were more often delivered in clinical settings, and demonstrated stronger evidence for improving physical symptoms. In the face of SPC workforce limitations, PPC interventions should be tested in more trials with low risk of bias, and may effectively meet some palliative care needs.

Does Deprescribing Improve Quality of Life? A Systematic Review of the Literature.

BACKGROUND: Deprescribing has been shown to reduce potentially inappropriate or unnecessary medications; however, whether these benefits translate into improved quality of life (QOL) is uncertain. OBJECTIVE: The objective of this study was to isolate the impact of deprescribing on patient or designated representative reported QOL; satisfaction with care (SWC) and emergency department (ED) visits and hospitalizations were also investigated to further explore this question. METHODS: This systematic review searched the Cochrane Library, Cumulative Index to Nursing and Allied Health (CINAHL), MEDLINE, and EMBASE from database inception until November 2017. Randomized controlled trials and non-randomized prospective studies of older adults (> 65 years or older) and older persons with life-limiting conditions were included. Two reviewers independently assessed the search results and performed risk of bias assessments. Data on QOL, SWC, and ED visits and hospitalizations were extracted from all identified studies. Risk of bias of individual studies was assessed using measures recommended by the Cochrane Collaboration. RESULTS: Screening of 6543 eligible records identified 12 studies within 13 articles. In ten studies investigating the reduction of at least one medication deprescribed, compared with usual care, all but two found no difference in QOL. To date there has only been one study examining the impact of deprescribing on SWC, which was found to be not statistically significant. Four studies exploring the impact of deprescribing on ED visits and hospitalizations also found no significant difference. However, many studies were found to have a higher performance, detection, or other bias. We found considerable heterogeneity in patient populations, targeted medications for deprescribing, and QOL measurements used in these studies. CONCLUSION: Based on a limited number of studies with varying methodological rigor, deprescribing may not significantly improve QOL or SWC; however, it may not contribute to additional ED visits and hospitalizations. Future controlled studies are needed.

Comparison of Palliative Care Interventions for Cancer versus Heart Failure Patients: A Secondary Analysis of a Systematic Review.

Background: In 2016, Kavalieratos and colleagues performed a systematic review of randomized clinical trials (RCTs) of palliative care (PC) interventions. The majority of RCTs included focused on oncology, with fewer in heart failure (HF). Cancer patients' often predictable decline differs from the variable illness trajectories of HF; however, both groups experience similar palliative needs, and accordingly, PC in HF continues to grow. Objective: To investigate if PC interventions differ between cancer and HF patients. Design: In this secondary analysis, we compare PC interventions for cancer and HF patients evaluated in the 2016 systematic review. Settings/Subjects: We included a total of 25 trials, 19 of which included 3730 cancer patients, and 6 of which included 1049 HF patients (mean age, 67 years). Measurements: We compared the following five characteristics among included trials: PC domains addressed, duration, location, provider specialization, and measured outcomes. Results: The content of the cancer and HF interventions was similar. HF interventions tended to include more home-based (50% vs. 37%) and specialty PC interventions (67% vs. 47%), although these results did not reach statistical significance. Both cancer and HF interventions favored longer durations (i.e., more than one month; 79% and 67%). No HF intervention RCTs included caregiver outcomes, whereas 32% of cancer interventions did. Conclusions: There were no substantial differences in content of cancer and HF interventions, although the latter tended to be delivered by PC specialists at home. There is a need for scalable interventions that incorporate the needs and preferences of individual patients, regardless of diagnosis.

Exposure to non-persistent chemicals in consumer products and fecundability: a systematic review.

BACKGROUND: Exposure to non-persistent chemicals in consumer products is ubiquitous and associated with endocrine-disrupting effects. These effects have been linked to infertility and adverse pregnancy outcomes in some studies and could affect couple fecundability, i.e. the capacity to conceive a pregnancy, quantified as time to pregnancy (TTP). OBJECTIVE AND RATIONALE: Few epidemiologic studies have examined the impact of non-persistent chemicals specifically on TTP, and the results of these studies have not been synthesized. We undertook a systematic review to summarize the strength of evidence for associations of common non-persistent chemicals with couple fecundability and to identify gaps and limitations in the literature, with the aim of informing policy decisions and future research. SEARCH METHODS: We performed an electronic search of English language literature published between 1 January 2007 and 25 August 2017 in MEDLINE, EMBASE.com, Global Health, DART/TOXLINE, POPLINE and DESTAF. We included human retrospective and prospective cohort, cross-sectional and case-control studies that examined phthalates, bisphenol A, triclosan, triclocarban, benzophenones, parabens and glycol ethers in consumer products, and considered TTP or fecundability as an outcome among women, men and couples conceiving without medical assistance. We excluded editorials, opinion pieces, introductions to special sections, articles that described only lifestyle (e.g. caffeine, stress) or clinical factors (e.g. semen parameters, IVF success). Standardized forms for screening, data extraction and study quality were developed using DistillerSR software and completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of fecundability studies. OUTCOMES: The search returned 3456 articles. There were 15 papers from 12 studies which met inclusion criteria, of which eight included biomarkers of chemical exposure. Studies varied widely in terms of exposure characterization, precluding a meta-analytic approach. Among the studies that measured exposure using biospecimens, results were equivocal for associations between either male or female phthalate exposure and TTP. There was preliminary support for associations of female exposure to some parabens and glycol ethers and of male exposure to benzophenone with longer TTP, but further research and replication of these results are needed. The results provided little to no indication that bisphenol A, triclocarban or triclosan exposure was associated with TTP. WIDER IMPLICATIONS: Despite a growing literature on couple exposure to non-persistent endocrine-disrupting chemicals and fecundability, evidence for associations between biologically measured exposures and TTP is limited. Equivocal results with different non-persistent chemical compounds and metabolites complicate the interpretation of our findings with respect to TTP, but do not preclude action, given the documented endocrine disrupting effects on other reproductive outcomes as well as fetal development. We therefore advocate for common-sense lifestyle changes in which both females and males seeking to conceive minimize their exposure to non-persistent chemicals. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42018084304.

Nimodipine improves vocal fold and facial motion recovery after injury: A systematic review and meta-analysis.

INTRODUCTION: Nimodipine is a calcium channel blocker that has been used to treat hypertension and vasospasm. Emerging evidence in the literature suggests that it is neuroprotective by reducing cellular apoptosis after neuronal injury and promoting axonal sprouting at the nodes of Ranvier. OBJECTIVES: To conduct a systematic review of the usage of nimodipine in cranial nerve injury and to perform a meta-analysis to estimate the efficacy of nimodipine on functional recovery of the injured cranial nerves. METHODS: Literature search was performed in eight databases using preferred reporting items for systematic reviews and meta analyses (PRISMA) guidelines. Human studies that used nimodipine as a monotherapy for treating cranial nerve injury were included for review. Cranial nerve function recovery was the primary outcome measure. RESULTS: 672 records were screened and 58 full texts in English were assessed. Nine studies were included in the final review. 5 of these, including 110 participants who received nimodipine for either recurrent laryngeal nerve or facial nerve injury and 556 controls, were used for meta-analysis. Nimodipine significantly increased the odds of vocal fold motion recovery (odds ratio [OR] 13.73, 95% confidence interval [CI] 6.21, 30.38, P < .01), and the odds of facial motion recovery (OR 2.78, 95% CI 1.20, 6.44, P = .02). Overall, nimodipine-treated patients had significantly higher odds of recovering vocal fold or facial motion compared with controls (OR 6.09, 95% CI 3.41, 10.87, P < .01). CONCLUSION: Existing evidence supports the positive effect of nimodipine on vocal fold and facial motion recovery after injury. Future research should focus on randomized clinical trials comparing recovery rates between nimodipine- and placebo-treated groups. Laryngoscope, 129:943-951, 2019.

The IOU Consensus Recommendations for Empirical Therapy of Cystitis in Nursing Home Residents.

OBJECTIVE: To establish consensus recommendations for empirical treatment of uncomplicated cystitis with anti-infectives in noncatheterized older nursing home residents to be implemented in the Improving Outcomes of UTI Management in Long-Term Care Project (IOU) funded by the Agency for Healthcare Research and Quality. DESIGN: Two-round modified Delphi survey. PARTICIPANTS: Expert panel of 19 clinical pharmacists. MEASUREMENTS: Comprehensive literature search and development/review/edit of draft survey by the investigative group (one geriatric clinical pharmacist, two geriatric medicine physicians, and one infectious disease physician). The expert panel members rated their agreement with each of 31 recommendations for drugs of choice, dosing medications at various levels of renal function, drug-drug interactions to avoid, and duration of therapy by sex on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree). Consensus agreement was defined as a lower 95% confidence limit of 4.0 or higher for the recommendation-specific mean score. RESULTS: The response rate was 95% for the first round, and three recommendations achieved consensus (dosing for nitrofurantoin and trimethoprim/sulfamethoxazole in those without chronic kidney disease, and drug-drug interaction between trimethoprim/sulfamethoxazole and warfarin). In the second round, 90% responded and reached consensus on an additional eight recommendations (two for nitrofurantoin or trimethoprim/sulfamethoxazole as initial drugs of choice, three for dosing ciprofloxacin, nitrofurantoin, and trimethoprim/sulfamethoxazole at various levels of chronic kidney disease, and three drug-drug interactions to avoid: trimethoprim/sulfamethoxazole with phenytoin and ciprofloxacin with theophylline or with tizanidine). CONCLUSION: An expert panel of clinical pharmacists was able to reach consensus on a set of recommendations for the empirical treatment of cystitis with oral anti-infective medications in older nursing home residents. The recommendations were incorporated into a treatment algorithm for uncomplicated cystitis in noncatheterized nursing home residents and used in educational materials for health professionals in an ongoing controlled intervention study. J Am Geriatr Soc 67:539-545, 2019.

Impact of community pharmacist-provided preventive services on clinical, utilization, and economic outcomes: An umbrella review.

Preventable diseases and late diagnosis of disease impose great clinical and economic burden for health care systems, especially in the current juncture of rising medical expenditures. Under these circumstances, community pharmacies have been identified as accessible venues to receive preventive services. This umbrella review aims to examine existing evidence on the impact of community pharmacist-provided preventive services on clinical, utilization, and economic outcomes in the United States (US). We included systematic reviews, narrative reviews and meta-analyses published in English between January 2007 and October 2017. Of 2742 references identified by our search strategy, a total of 13 research syntheses met our inclusion criteria. Included reviews showed that community pharmacists are effective at increasing immunization rates, supporting smoking cessation, managing hormonal contraception therapies, and identifying patients at high risk for certain diseases. Moreover, evidence suggests that community pharmacies are especially well-positioned for the provision of preventive services due to their convenient location and extended hours of operation. There is general agreement on the positive impact of community pharmacists in increasing access to preventive health, particularly among patients who otherwise would not be reached by other healthcare providers. The provision of preventive services at US community pharmacies is feasible and effective, and has potential for improving patient outcomes and health system efficiency. However, high-quality evidence is still lacking. As the healthcare landscape shifts towards a value-based framework, it will be important to conduct robust studies that further evaluate the impact of community pharmacist-provided preventive services on utilization and economic outcomes.

The Improving Outcomes of UTI Management in Long-Term Care Project (IOU) Consensus Guidelines for the Diagnosis of Uncomplicated Cystitis in Nursing Home Residents.

OBJECTIVES: To identify a set of signs and symptoms most likely to indicate uncomplicated cystitis in noncatheterized nursing home residents ≥65 years of age using consensus-based methods informed by a literature review. DESIGN: Literature review and modified Delphi survey with strict inclusion criteria. SETTING AND PARTICIPANTS: Expert panel of 20 physicians certified in geriatric medicine and/or medical direction, actively practicing in post-acute and long-term care settings. METHODS: The authors performed a literature review to produce a comprehensive list of potential signs and symptoms of presumptive uncomplicated cystitis, including nonspecific "quality control" items deemed unlikely to indicate uncomplicated cystitis. The expert panel rated their agreement for each sign/symptom using a 5-point Likert-type scale (1 = strongly disagree to 5 = strongly agree). Agreed upon signs and symptoms were summarized using a diagnostic algorithm for easy clinical use. RESULTS: The literature review identified 16 signs and symptoms that were evaluated in 3 Delphi survey rounds. The response rate was 100% for round 1 and 95% for the second 2 rounds. Consensus agreement for inclusion was achieved for dysuria on round 1 with exclusion of the 3 quality controls, and "offensive smelling urine." Consensus in the second round was reached for including 4 additional items (gross hematuria, suprapubic pain, urinary frequency, and urinary urgency). Round 3 evaluated dysuria alone and combinations of symptoms. Consensus that dysuria alone is sufficient for diagnosis of cystitis was not reached. CONCLUSIONS/IMPLICATIONS: The panel identified 5 signs and symptoms likely indicative of uncomplicated cystitis in nursing home residents and developed a diagnostic algorithm that can be used to promote antibiotic stewardship in nursing homes. Given similarities in populations, the algorithm may also be applicable to the older adult and the broader post-acute/long-term care populations.

Affective science and avoidant end-of-life communication: Can the science of emotion help physicians talk with their patients about the end of life?

Despite believing end-of-life (EOL) discussions with patients are important, doctors often do not have them. Multiple factors contribute to this shortfall, which interventions including reimbursement changes and communication skills training have not significantly improved to date. One commonly cited but under-researched reason for physician avoidance of EOL discussion is emotional difficulty. High occupational demand for frequent difficult discussions may overload physicians' normal emotional functioning, leading to avoidance or failure. We propose that cognitive, behavioral, and neuroscience evidence from affective science may offer helpful insights into this problem. Data from other populations show that strong emotion impairs cognitive performance and multiple demands can overload cognitive resources. We discuss several affective processes that may apply to physicians attempting EOL discussions. We then discuss selected interventions that have been shown to modify some of these processes and associated behavioral outcomes. Evidence for change in behavioral outcomes of interest includes performance and mood enhancement in healthy populations. We suggest that such mechanistically-targeted interventions may be hypothesized to help decrease physician avoidance of EOL discussion. Physicians may be motivated to adopt such interventions in order to enhance normal emotional functioning to meet supra-normal occupational demand. We propose this as a promising area of future study.

Serotonin Transporter Gene Polymorphisms and Selective Serotonin Reuptake Inhibitor Tolerability: Review of Pharmacogenetic Evidence.

Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacotherapy for mood and anxiety disorders. The common mechanism of drugs in this class is antagonism of the serotonin transporter. Within the serotonin transporter gene SLC6A4, two polymorphic sites termed 5-HTTLPR and STin2 are proposed to have functional consequences and thus have been attractive candidates for pharmacogenetic studies of SSRI efficacy and tolerability. This review summarizes approximately 15 years of study of these polymorphisms as they relate to SSRI tolerability phenotypes. Four online databases (PubMed, Cochrane CENTRAL, PsycINFO, and PharmGKB) were searched for articles on polymorphisms of SLC6A4 including 5-HTTLPR and STin2 by using a systematic approach. Specific and general psychopharmacology terms, along with adverse effect and tolerability concepts, added to the search strategy. The Human Gene Mutation Database was checked for additional references. Forty studies met the inclusion criteria. While null and occasionally opposite associations are reported, the low expression 5-HTTLPR S allele is generally associated with greater adverse drug reaction burden during SSRI therapy. The most convincing evidence is in studies of antidepressant-induced mania and gastrointestinal adverse events. Studies of STin2 are sparse and have conflicting findings. In conclusion, the S allele of 5-HTTLPR may be predictive of increased adverse event burden, and this effect appears specific to certain classes of adverse events. Limitations and challenges in interpreting this body of evidence include assay errors, dissimilar grouping of genotypes, the role of ethnicity in associations, and study methodological differences. The clinical utility of serotonin transporter genotypes is not yet delineated but will ultimately depend on genotypic effects on both tolerability and efficacy of SSRIs.