Microbiological Laboratory Testing in the Diagnosis of Fungal Infections in Pulmonary and Critical Care Practice. An Official American Thoracic Society Clinical Practice Guideline.

Background: Fungal infections are of increasing incidence and importance in immunocompromised and immunocompetent patients. Timely diagnosis relies on appropriate use of laboratory testing in susceptible patients.Methods: The relevant literature related to diagnosis of invasive pulmonary aspergillosis, invasive candidiasis, and the common endemic mycoses was systematically reviewed. Meta-analysis was performed when appropriate. Recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation approach.Results: This guideline includes specific recommendations on the use of galactomannan testing in serum and BAL and for the diagnosis of invasive pulmonary aspergillosis, the role of PCR in the diagnosis of invasive pulmonary aspergillosis, the role of ß-d-glucan assays in the diagnosis of invasive candidiasis, and the application of serology and antigen testing in the diagnosis of the endemic mycoses.Conclusions: Rapid, accurate diagnosis of fungal infections relies on appropriate application of laboratory testing, including antigen testing, serological testing, and PCR-based assays.

Systematic review and meta-analysis of duplex ultrasound surveillance for infrainguinal vein bypass grafts.

OBJECTIVE: Duplex ultrasound (DUS) surveillance of infrainguinal vein bypass grafts is widely practiced, but the evidence of its effectiveness compared with other methods of surveillance remains unclear. METHODS: Following an a priori protocol developed by the guidelines committee from the Society for Vascular Surgery, this systematic review and meta-analysis included randomized and nonrandomized comparative studies that enrolled patients who underwent infrainguinal arterial reconstruction and received DUS surveillance for follow-up compared with any other method of surveillance. The search included MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, and Scopus through November 2016. Outcomes of interest included all-cause mortality, limb viability, and graft patency reports. Meta-analysis was performed using the random-effects model. RESULTS: We included 15 studies. Compared with ankle-brachial index and clinical examination, DUS surveillance was not associated with a significant change in primary, secondary, or assisted primary patency or mortality. DUS surveillance was associated with a nonstatistically significant reduction in amputation rate (odds ratio, 0.70 [95% confidence interval, 0.23-2.13]). The quality of evidence was low because of imprecision (small number of events and wide confidence intervals) and high risk of bias in the primary literature. CONCLUSIONS: A recommendation for routine DUS surveillance of infrainguinal vein grafts remains dependent on low-quality evidence. Considering that DUS offers the opportunity of early intervention and because of its noninvasive nature and low cost, vascular surgeons may incorporate DUS as they individualize the follow-up of lower extremity vein grafts.

Accuracy of thyroid nodule sonography for the detection of thyroid cancer in children: systematic review and meta-analysis.

INTRODUCTION: Thyroid ultrasound (US) is a widely used tool for evaluating thyroid nodules. Various US features have been suggested as predictors of thyroid cancer in children. OBJECTIVE: To conduct a systematic review and meta-analysis to assess the diagnostic accuracy of different thyroid US features in detecting thyroid cancer in children. METHODS: We searched multiple online databases for cohort studies that enrolled paediatric patients with thyroid nodules (age <21 years) and evaluated the accuracy of 12 relevant ultrasound features. Diagnostic measures were pooled across studies using a random effects model. RESULTS: The search strategy yielded 1199 citations, of which 12 studies met the predefined inclusion criteria (750 nodules). The prevalence of thyroid cancer was 27·2% (40·8% in patients with a history of radiation exposure and 23·2% in patients without a history of exposure to radiation). The most common cancer was papillary thyroid cancer (86·7%). The presence of internal calcifications and enlarged cervical lymph nodes were the US features with the highest likelihood ratio [4·46 (95% CI: 1·87-10·64) and 4·96 (95% CI: 2·01-12·24), respectively] for thyroid cancer. A cystic nodule was the feature with highest likelihood ratio for benign nodules [1·96 (95% CI: 0·87-4·43)]. CONCLUSION: Thyroid US features are not highly accurate predictors of benign or malignant aetiology of thyroid nodules in children. Internal calcification may predict malignancy, and cystic appearance may suggest benign aetiology.

PREDICTORS OF BIOCHEMICAL REMISSION AND RECURRENCE AFTER SURGICAL AND RADIATION TREATMENTS OF CUSHING DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVE: We conducted a systematic review and meta-analysis to synthesize the evidence about predictors that may affect biochemical remission and recurrence after transsphenoidal surgery (TSS), radiosurgery (RS), and radiotherapy (RT) in Cushing disease. METHODS: We searched multiple databases through December 2014 including original controlled and uncontrolled studies that enrolled patients with Cushing disease who received TSS (first-line), RS, or RT. We extracted data independently, in duplicates. Outcomes of interest were biochemical remission and recurrence. A meta-analysis was conducted using the random-effects model to estimate event rates with 95% confidence intervals (CIs). RESULTS: First-line TSS was associated with high remission (76% [95% CI, 72 to 79%]) and low recurrence rates (10% [95% CI, 6 to 16%]). Remission after TSS was higher in patients with microadenomas or positive-adrenocorticotropic hormone tumor histology. RT was associated with a high remission rate (RS, 68% [95% CI, 61 to 77%]; RT, 66% [95% CI, 58 to 75%]) but also with a high recurrence rate (RS, 32% [95% CI, 16 to 60%]; RT, 26% [95% CI, 14 to 48%]). Remission after RS was higher at short-term follow-up (≤2 years) and with high-dose radiation, while recurrence was higher in women and with lower-dose radiation. Remission was after RT in adults who received TSS prior to RT, and with lower radiation doses. There was heterogeneity (nonstandardization) in the criteria and cutoff points used to define biochemical remission and recurrence. CONCLUSION: First-line TSS is associated with high remission and low recurrence, while RS and RT are associated with reasonable remission rates but important recurrence rates. The current evidence warrants low confidence due to the noncomparative nature of the studies, high heterogeneity, and imprecision.

Off-hour admission and outcomes for patients with acute myocardial infarction undergoing percutaneous coronary interventions.

BACKGROUND: Prior studies have suggested that patients with acute myocardial infarction (AMI) who are admitted during off-hours (weekends, nights and holidays) have higher mortality when compared with patients admitted during regular hours. METHODS: We analyzed consecutive patients with AMI (ST-elevation myocardial infarction [STEMI] and non-STEMI) who were treated with percutaneous coronary interventions from January 1998 to June 2010 at an academic medical center. Multivariable logistic regression models were used to estimate the association between off-hour admission and clinical outcomes adjusted for demographic and clinical variables. RESULTS: There were 3,422 and 2,664 patients with AMI admitted during off-hours and regular hours, respectively. Patients admitted during off-hours were more likely to have STEMI (56% vs 48%, P < .001), have cardiogenic shock at presentation (6% vs 4%, P = .002), and develop shock after presentation (6% vs 5%, P = .004). After multivariable analyses, off-hour admission was not significantly associated with in-hospital mortality (odds ratio [OR] 1.12, 95% CI 0.84-1.49), 30-day mortality (OR 1.12, 0.87-1.45), or 30-day readmissions (OR 1.01, 0.84-1.20) but was significantly associated with composite major complications and any of emergent coronary artery bypass graft surgery, ventricular arrhythmia, stroke/transient ischemic attack, and gastrointestinal/retroperitoneal/intracranial bleeding (OR 1.27, 1.05-1.55, P = .015). There was no significant time trend in the adjusted mortality difference between off-hours and regular hours. The results were not different between STEMI and non-STEMI. CONCLUSIONS: Patients who were admitted during off-hours did not have higher mortality or readmission rates as compared with ones admitted during regular hours at an academic medical center.

Aspirin dosage for the prevention of graft occlusion in people undergoing coronary surgery: A systematic review and meta-analysis.

BACKGROUND: Aspirin is almost always used after coronary artery bypass graft (CABG) surgery; however, it is unclear what optimal dose should be prescribed. In this systematic review, we evaluated the effects of high versus low-dose aspirin in patients after CABG. METHODS: A comprehensive database search was conducted in several databases from date of inception until February 2018. There were no language restrictions. We included studies that compared different doses of aspirin in patients that had undergone CABG surgery. We included studies that evaluated patient-important outcomes (mortality, cardiovascular events, and gastrointestinal bleeding); and if not reported, we collected data on the surrogate outcome thromboxane B2 (TXB2). We collected relevant data and performed a meta-analysis. RESULTS: We identified 5903 references, and after two levels of screening by two independent reviewers, we included three randomized controlled trials in the meta-analysis with a total number of 122 participants. Mean age of trial participants was 65.63 years, and 88.68% were male. We planned to analyze all possible clinical outcomes, including mortality, recurrence, and hospitalization. However, no clinical outcomes are reported by the literature. The surrogate biochemical outcome of serum TXB2 was the only outcome reported by the eligible studies. High-dose aspirin (162-325mg once daily) achieved better suppression of TXB2 than low-dose aspirin (75-100mg once daily) (mean difference [MD], 2.00ng/mL, 95% confidence interval [CI]: 0.72-3.32; participants = 122; studies = 3; I2 = 0%). CONCLUSIONS: We found no clinical trials addressing any of the clinical outcomes of interest. High-dose aspirin was superior to low-dose aspirin in suppressing platelet function, a surrogate outcome. Trials evaluating clinical and patient-important outcomes are needed to better inform medical practice and fill this gap in clinical knowledge.

Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis.

BACKGROUND: Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method. RESULTS: We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials. CONCLUSIONS: This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.

Diagnosis of Fungal Infections. A Systematic Review and Meta-Analysis Supporting American Thoracic Society Practice Guideline.

Rationale: Prompt diagnosis of invasive fungal infections is important because of the associated morbidity and mortality; however, diagnosis is challenging because of the nonspecific symptoms and radiographic findings.Objectives: To conduct a systematic review and meta-analysis of studies that evaluated the diagnostic accuracy of serum and bronchoalveolar lavage (BAL) galactomannan (GM) and serum or BAL polymerase chain reaction (PCR) in patients with suspected invasive aspergillosis (IA), ß-d-glucan in critically ill patients at risk for candidiasis or candidemia, and serology testing and antigen detection in patients with endemic mycoses (histoplasmosis, blastomycosis, and coccidioidomycosis).Methods: Studies were selected and appraised by pairs of reviewers. Bivariate random effects meta-analysis was used to generate pooled sensitivity, specificity, and diagnostic likelihood ratios.Results: Serum GM in patients with impaired immunity suspected of having IA had sensitivity of 0.71 (95% confidence interval [CI], 0.64-0.78) and specificity of 0.89 (95% CI, 0.84-0.92). A cutoff of 1 optical density index yielded optimal sensitivity and specificity. BAL GM in patients with impaired immunity suspected of having IA had sensitivity of 0.84 (95% CI, 0.73-0.91) and specificity of 0.88 (95% CI, 0.81-0.91). Serum or whole-blood PCR in immunocompromised patients with suspected IA had sensitivity of 0.81 (95% CI, 0.73-0.86) and specificity of 0.79 (95% CI, 0.68-0.86). BAL PCR in patients at high risk for IA had high sensitivity of 0.90 (95% CI, 0.77-0.96) and specificity of 0.96 (95% CI, 0.93-0.98) for diagnosing IA. ß-d-glucan assay in patients in the intensive care unit at risk for invasive candidiasis or candidemia had sensitivity of 0.81 (95% CI, 0.74-0.86) and specificity of 0.60 (95% CI, 0.49-0.71). Data on diagnostic accuracy of antigen detection and serology testing for endemic mycoses were limited and heterogeneous (varied according to test, patient immunity, and suspected endemic disease).Conclusions: The diagnosis of invasive fungal infections remains a challenge. Various serum and BAL markers can aid in diagnosis. This evidence supports the development of clinical practice recommendations by the American Thoracic Society.

Co-located specialty care within primary care practice settings: A systematic review and meta-analysis.

BACKGROUND: Co-location of specialists in primary care has been suggested as an approach to reduce care fragmentation, inefficiency, and cost. We conducted a systematic review and meta-analysis evaluating the impact of co-located specialty care models in primary care settings. METHODS: Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus was conducted through February 2015. A manual search of the included studies' bibliographies was conducted. Randomized controlled trials (RCTs) and observational studies reporting physically co-located specialties in primary care on the following outcomes were included: patient satisfaction; provider satisfaction; health care access and utilization; clinical outcomes, and costs. RESULTS: Of 1620 articles, 22 studies met inclusion criteria, including 9 RCTs and 13 observational studies. Co-located care was observed to be associated with increased patient satisfaction (OR 2.04; 95% CI 1.04-3.98), primary care provider satisfaction (OR 6.49, 95% CI 4.28-9.85), and outpatient visits (OR 1.94; 95% CI 1.13-3.33). Co-located care was associated with reduced appointment wait time (OR 0.20, 95%CI 0.10 - 0.41). Reduced costs and improvement in quality of life and selected diabetes related outcomes were also observed. Evidence quality was limited by few studies, high risk of bias, and heterogeneity. CONCLUSIONS: Co-located specialty care in primary care settings may support the aims of high value care delivery. However, additional studies are needed to further evaluate the value of co-location of specific specialties and stronger data on impact to health outcomes and cost.

Prevention of exacerbations in patients with stable non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis of pharmacological and non-pharmacological therapies.

BACKGROUND: Several pharmacological and non-pharmacological therapies are used to treat stable bronchiectasis of non-cystic fibrosis (CF) aetiology. OBJECTIVE: We conducted a systematic review and meta-analysis to assess the evidence of the effectiveness of pharmacological and non-pharmacological treatment options in patients with stable non-CF bronchiectasis with a focus on reducing exacerbations. STUDY SELECTION: Multiple databases were searched through September 2017. Outcomes included the number of patients with exacerbation events, mean number of exacerbations, hospitalisations, mortality, quality of life measures, and safety and adverse effects. Meta-analysis was conducted using the random effects model. FINDINGS: 30 randomised controlled trials enrolled subjects with non-CF bronchiectasis using different interventions. Moderate-quality evidence supported the effect of long-term antibiotics (≥3 months) on lowering the number of patients experiencing exacerbation events (relative risk 0.77 (95% CI 0.68 to 0.89)), reducing number of exacerbations (incidence rate ratio 0.62 (95% CI 0.49 to 0.78)), improving forced expiratory volume (litre) in the first second (FEV1) (weighted mean difference (WMD); 0.02 (95% CI 0.00 to 0.04)), decreasing sputum purulence scores (numerical scale of 1-8) (WMD -0.90 (95% CI -1.58 to -0.22)) and improving quality of life scores assessed by the St George's Respiratory Questionnaire (WMD -6.07 (95% CI -10.7 to -1.43)). Bronchospasm increased with inhaled antibiotics while diarrhoea increased particularly with oral macrolide therapy. CONCLUSIONS: Moderate-quality evidence supports long-term antibiotic therapy for preventing exacerbations in stable non-CF bronchiectasis. However, data about the optimum agent, mode of therapy and length of treatment are limited. There is paucity of high-quality evidence to support the management of stable non-CF bronchiectasis including prevention of exacerbations.

Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis.

BACKGROUND: Use of menopausal hormonal therapy (MHT)-containing estrogen and a synthetic progestin is associated with an increased risk of breast cancer. It is unclear if progesterone in combination with estrogen carries a lower risk of breast cancer. Limited data suggest differences between progesterone and progestins on cardiovascular risk factors, including cholesterol and glucose metabolism. Whether this translates to differences in cardiovascular outcomes is uncertain. We conducted a systematic review and meta-analysis to synthesize the existing evidence about the effect of progesterone in comparison to synthetic progestins, each in combination with estrogens, on the risk of breast cancer and cardiovascular events. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus through 17 May 2016 for studies that enrolled postmenopausal women using progesterone vs. synthetic progestins and reported the outcomes of interest. Study selection and data extraction were performed by two independent reviewers. Meta-analysis was conducted using the random effects model. RESULTS: We included two cohort studies and one population-based case-control study out of 3410 citations identified by the search. The included studies enrolled 86,881 postmenopausal women with mean age of 59 years and follow-up range from 3 to 20 years. The overall risk of bias of the included cohort studies in the meta-analysis was moderate. There was no data on cardiovascular events. Progesterone was associated with lower breast cancer risk compared to synthetic progestins when each is given in combination with estrogen, relative risk 0.67; 95 % confidence interval 0.55-0.81. CONCLUSIONS: Observational studies suggest that in menopausal women, estrogen and progesterone use may be associated with lower breast cancer risk compared to synthetic progestin.

Early studies reported extreme findings with large variability: a meta-epidemiologic study in the field of endocrinology.

OBJECTIVES: To evaluate the presence of extreme findings and fluctuation in effect size in endocrinology. STUDY DESIGN AND SETTINGS: We systematically identified all meta-analyses published in 2014 in the field of endocrinology. Within each meta-analysis, the effect size of the primary binary outcome was compared across studies according to their order of publication. We pooled studies using the DerSimonian and Laird random-effects method. Heterogeneity was evaluated using the I(2) and tau(2). RESULTS: Twelve percent of the included 100 meta-analyses reported the largest effect size in the very first published study. The largest effect size occurred in the first 2 earliest studies in 31% of meta-analyses. When the effect size was the largest in the first published study, it was three times larger than the final pooled effect (ratio of rates, 3.26; 95% confidence interval: 1.80, 5.90). The largest heterogeneity measured by I(2) was observed in 18% of the included meta-analyses when combining the first 2 studies or 17% when combing the first 3 studies. CONCLUSIONS: In endocrinology, early studies reported extreme findings with large variability. This behavior of the evidence needs to be taken into account when used to formulate clinical policies.

Management and diagnosis of psychogenic cough, habit cough, and tic cough: a systematic review.

BACKGROUND: Several pharmacologic and nonpharmacologic therapeutic options have been used to treat cough that is not associated with a pulmonary or extrapulmonary etiology. METHODS: We conducted a systematic review to summarize the evidence supporting different cough management options in adults and children with psychogenic, tic, and habit cough. Medline, EMBASE, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched from the earliest inception of each database to September 2013. Content experts were contacted, and we searched bibliographies of included studies to identify additional references. RESULTS: A total of 18 uncontrolled studies were identified, enrolling 223 patients (46% male subjects, 96% children and adolescents). Psychogenic cough was the most common descriptive term used (90% of the studies). Most of the patients (95%) had no cough during sleep; barking or honking quality of cough was described in only eight studies. Hypnosis (three studies), suggestion therapy (four studies), and counseling and reassurance (seven studies) were the most commonly used interventions. Hypnosis was effective in resolving cough in 78% of the patients and improving it in another 5%. Suggestion therapy resolved cough successfully in 96% of the patients. The greatest majority of improvements noted with these forms of therapy occurred in the pediatric age group. The quality of evidence is low due to the lack of control groups, the retrospective nature of all the studies, heterogeneity of definitions and diagnostic criteria, and the high likelihood of reporting bias. CONCLUSIONS: Only low-quality evidence exists to support a particular strategy to define and treat psychogenic, habit, and tic cough. Patient values, preferences, and availability of potential therapies should guide treatment choice.

Anti-synthetase syndrome presenting as cryptogenic organizing pneumonia.

Interstitial lung disease (ILD) is a unique group of lung diseases that can be associated with inflammatory conditions, such as polymyositis-dermatomyositis (PM-DM). Presentation of PM-DM with ILD is not uncommon but clinical and radiological features can be similar to other conditions (e.g. atypical pneumonia) and can be challenging to diagnose. Delayed diagnosis of PM-DM can be associated with progression of pulmonary involvement and potentially increase morbidity. We report a patient presenting with pulmonary symptoms who had positive anti-Jo-1 antibodies and cryptogenic organizing pneumonia features on biopsy, which is a rare reported finding.