How can clinicians choose between conflicting and discordant systematic reviews? A replication study of the Jadad algorithm.

INTRODUCTION: The exponential growth of published systematic reviews (SRs) presents challenges for decision makers seeking to answer clinical, public health or policy questions. In 1997, an algorithm was created by Jadad et al. to choose the best SR across multiple. Our study aims to replicate author assessments using the Jadad algorithm to determine: (i) if we chose the same SR as the authors; and (ii) if we reach the same results. METHODS: We searched MEDLINE, Epistemonikos, and Cochrane Database of SRs. We included any study using the Jadad algorithm. We used consensus building strategies to operationalise the algorithm and to ensure a consistent approach to interpretation. RESULTS: We identified 21 studies that used the Jadad algorithm to choose one or more SRs. In 62% (13/21) of cases, we were unable to replicate the Jadad assessment and ultimately chose a different SR than the authors. Overall, 18 out of the 21 (86%) independent Jadad assessments agreed in direction of the findings despite 13 having chosen a different SR. CONCLUSIONS: Our results suggest that the Jadad algorithm is not reproducible between users as there are no prescriptive instructions about how to operationalise the algorithm. In the absence of a validated algorithm, we recommend that healthcare providers, policy makers, patients and researchers address conflicts between review findings by choosing the SR(s) with meta-analysis of RCTs that most closely resemble their clinical, public health, or policy question, are the most recent, comprehensive (i.e. number of included RCTs), and at the lowest risk of bias.

Phosphodiesterase 11 (PDE11) regulation of spermatozoa physiology.

Fertilization is well correlated with sperm concentration, rate of forward motility, and percentage of live, uncapacitated ejaculated spermatozoa, which is regulated in part by cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Phosphodiesterases (PDEs) hydrolyze cyclic nucleotides to their corresponding monophosphates, thereby counterbalancing the activities of cAMP and cGMP, and PDE11 is highly expressed in the testis, prostate, and developing spermatozoa. However, a physiological role of PDE11 is not known. We generated PDE11 knockout (PDE11-/-) mice to investigate the role of PDE11 in spermatozoa physiology. Ejaculated sperm from PDE11-/- mice displayed reduced sperm concentration, rate of forward progression, and percentage of live spermatozoa. Pre-ejaculated sperm from PDE11-/- mice displayed increased premature/spontaneous capacitance. These data are consistent with human data and suggest a role for PDE11 in spermatogenesis and fertilization potential. This is the first phenotype described for the PDE11-/- mouse and the first report of a physiological role for PDE11.

Risk of active tuberculosis in chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Although the global prevalence of chronic kidney disease (CKD) is increasing, the relationship between CKD and active TB is not well described. OBJECTIVE: To conduct a systematic review to evaluate active TB risk in CKD populations. METHODS: We searched Ovid Medline, EMBASE and Cochrane databases and relevant journals to identify multicentre or regional studies reporting quantitative effect estimates of an association between CKD and active TB. Risk ratios and rate ratios were used as common measures of association. Pooled estimates were generated using a random-effects model. RESULTS: Of 3406 papers screened, 12 eligible studies were identified with 71,374 end-stage renal disease (ESRD) patients and 560 TB cases. Meta-analysis of adjusted rate ratio data in dialysis populations showed an increased rate of 3.62 (95%CI 1.79-7.33, P < 0.001) compared to the general population, while unadjusted risk ratio data in transplant populations showed an increased risk of 11.35 (95%CI 2.97-43.41) compared to the general population. CONCLUSION: We found consistent evidence of an increased risk of active TB in ESRD compared to the general population. This relationship persisted despite variability in study population, design and renal replacement therapy (RRT) modality. Further research into the role of comorbidities, RRT modality and CKD stage is required to better understand the association between CKD and active TB.