Persistence and adherence to parenteral osteoporosis therapies: a systematic review.

Osteoporosis is a chronic disease of low bone mass and fragility. Treatment is frequently compromised by suboptimal medication compliance causing increased morbidity. This review investigates adherence and persistence to parenteral osteoporosis therapies. Findings reveal parenteral medications requiring reduced dosing frequency have higher compliance than oral therapies. This systematic review examines real-world adherence to parenteral osteoporosis therapies. We searched PubMed, Medline, and EMBASE databases for English language observational studies that examined patient adherence and/or persistence to parenteral osteoporosis treatments (teriparatide sc, ibandronate iv, zoledronic acid iv, and denosumab sc) in adults with osteoporosis published up to September 2018. Studies with only self-reported adherence or persistence data and those with less than 20 patients were excluded. Quality assessment of included studies was completed using the Newcastle-Ottawa quality assessment scale (NOS). We identified 40 eligible studies. Teriparatide was examined in 29 studies, with persistence rates of 10-87% (median 55%) at 1 year and 10-69% (median 29.5%) at 2 years, and adherence rates of 21-89% (median 53%) at 1 year and 37-68% (median 40%) at 2 years. Ten studies of zoledronic acid reported persistence rates of 34-73% (median 42%) for second dose and 20-54% (median 35.8%) for third dose. Ten studies of ibandronate adherence reported and 2-year persistence rates of 31-58% (median 47.5%) in 1 year and 13-35% (median 25%) at 2 years, and adherence rates of 21-72% (median 47.3%) and 15-58% (median 36.5%) respectively. Denosumab was reported in 19 studies, with second (1 year) and fourth (2 year) dose persistence rates of 61-100% (median 81%) and 36-99% (median 45.5%). There is substantial heterogeneity in reports of persistence and adherence rates with parenteral osteoporosis therapies. Most of the published data are from short-term studies and evaluations of long-term adherence and persistence with parenteral therapies for osteoporosis are needed.

Kappaphobia is the elephant in the fret room.

FRET is both a phenomenon and a spectroscopic technique, capable of measuring one geometric quantity: kappa-squared divided by the sixth power of the donor-acceptor distance. Kappa-squared is often replaced by a constant even though such a replacement may lead to serious errors. Kappaphobia, the fear of kappa or the reluctance to deal with kappa-squared adequately, is a looming presence in the FRET community. Unfortunately, this reluctance, or fear, is often tolerated, and sometimes encouraged. A decrease in kappaphobia will lead to an increase in the impact and success of FRET.

Systematic review: pre- and post-operative prognostic value of cardiopulmonary exercise testing in liver transplant candidates.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is the gold standard for the objective assessment of functional status. In many conditions, CPET outperforms the traditional variables in predicting mortality. AIM: In patients with cirrhosis listed for liver transplantation, our primary aim was to determine the prognostic value of CPET for pre-and post-transplant mortality and, in particular, whether CPET remained predictive after adjustment for liver disease severity. METHODS: A systematic literature review was conducted in databases Medline, Scopus, Embase and PubMed. Where possible, data were pooled for meta-analyses using a DerSimonian and Laird random effects model. RESULTS: A total of seven studies were retrieved, including 1107 patients with a mean MELD of 14.2 (standard deviation 1.6) and peak baseline VO2 of 17.4 mL/kg/min. In all of the studies in which multivariable analysis was performed, CPET variables were independent predictors of pre-transplant mortality (three studies) and post-transplant mortality (four studies). In the three studies where we could aggregate post-transplant mortality data, post-transplant mortality was predicted by AT with a mean difference of 2.0 (95% confidence interval, CI: 0.42-3.59; Z = 2.48, P = 0.01) between survivors and nonsurvivors. The peak VO2 was not significant (0.77 95% CI: -1.36 to 2.90; Z = 0.71, P = 0.48). CONCLUSIONS: Patient's listed for liver transplant have significant functional limitations, with a weighted mean VO2 below the threshold level required for independent living. Although heterogeneity in study designs with respect to timing, CPET variables, and cut-off values precluded the determination of CPET mortality thresholds, the studies support CPET as an objective and independent predictor of pre- and post-transplant mortality.

Diagnostic thresholds for gestational diabetes and their impact on pregnancy outcomes: a systematic review.

AIMS: To assess different diagnostic thresholds for gestational diabetes on outcomes for mothers and their offspring in the absence of treatment for gestational diabetes. This information was used to inform a National Institutes of Health consensus conference on diagnosing gestational diabetes. METHODS: We searched 15 electronic databases from 1995 to May 2012. Study selection was conducted independently by two reviewers. Randomized controlled trials or cohort studies were eligible if they involved women without known pre-existing diabetes mellitus and who did not undergo treatment for gestational diabetes. One reviewer extracted, and a second reviewer verified, data for accuracy. Two reviewers independently assessed methodological quality. RESULTS: Thirty-eight studies were included. Three large, methodologically strong studies showed a continuous positive relationship between increasing glucose levels and the incidence of Caesarean section and macrosomia. When data were examined categorically (i.e. women meeting or not meeting specific diagnostic thresholds), women with gestational diabetes across all glucose criteria had significantly more Caesarean sections, shoulder dystocia, macrosomia (except for International Association of Diabetes in Pregnancy Study Groups' criteria) and large for gestational age. Higher glucose thresholds did not consistently demonstrate greater risk for all outcomes. CONCLUSIONS: Higher glucose thresholds did not consistently demonstrate greater risk, possibly because studies did not compare mutually exclusive groups of women. A pragmatic approach for diagnosis of gestational diabetes using Hyperglycemia and Adverse Pregnancy Outcome Study odds ratio 2.0 thresholds warrants further consideration until additional analysis of the data comparing mutually exclusive groups of women is provided and large randomized controlled trials investigating different diagnostic and treatment thresholds are completed.

Meta-analysis: oral or enteral nutritional supplementation in cirrhosis.

BACKGROUND: Malnutrition is a common and clinically significant problem in patients with cirrhosis. The impact of nutritional therapy remains unclear. AIM: To provide an up-to-date systematic review and meta-analysis of RCTs of oral or enteral nutritional supplementation (ONS or ENS) on nutritional and clinical outcomes in adult patients with cirrhosis. METHODS: The primary outcome measure was survival. Included: full-text English language RCTs investigating ONS or ENS vs. a standard nonsupplemented diet in patients with cirrhosis. Excluded: parenteral or branched chain amino acids intervention; treatment duration ≤7 days, exclusive evaluation of posttransplant, postsurgical or quality of life outcomes. RESULTS: Six trials (4 ONS/2 ENS) and 470 patients were included with 71% males and median age 53 years. When all studies were combined, there was no reduction in mortality [Relative risk (RR): 0.75 (0.42, 1.32), P = 0.31]. Subgroup analysis of 3 of the 4 ONS studies did demonstrate a mortality reduction [RR: 0.40 (0.18, 0.90), P = 0.03]. Of the 2 ENS studies, one included the sickest patients in the meta-analysis (82% Child Pugh C) and the other had the shortest mean intervention duration (8.6 days), possibly impacting the potential for benefit. Study quality was suboptimal (median Jadad = 2). CONCLUSIONS: Although there is insufficient evidence to definitively state that oro-enteral nutritional supplementation impacts clinical outcomes, on the basis of this analysis, one can be cautiously optimistic that there is the potential for benefit without an increase in adverse events. Adequately powered, Child Pugh stratified studies of at least 1 month in duration are needed to clarify the impact on relevant clinical outcomes.

Granulocyte colony-stimulating factor for hepatitis C therapy-associated neutropenia: systematic review and economic evaluation.

Hepatitis C virus (HCV) treatment requires maximal adherence to pegylated interferon (Peg-IFN) and ribavirin to achieve a sustained virologic response (SVR). Neutropenia is the most common cause for Peg-IFN dose reduction. Our objectives were to evaluate the effectiveness, safety and cost-effectiveness of granulocyte colony-stimulating factor (G-CSF) versus Peg-IFN dose reduction for HCV therapy-associated neutropenia in treatment naïve adults. We conducted a systematic review to identify controlled trials and observational studies. Study selection, quality assessment and data extraction were completed independently by two investigators. Cost-effectiveness and cost-utility analyses compared G-CSF with dose reduction. Nineteen studies were included. In one trial, the SVR for those receiving G-CSF was 54.5% (95% CI: 34.7-73.1) compared with 26.3% (95% CI: 11.8-48.8) for dose reduction. The remaining studies were case series or retrospective cohorts and provided weak evidence for the relationship between SVR and G-CSF. The risk of adverse events, including infection, associated with G-CSF was low (13.1%; 95% CI: 8.0-20.8) and clinically insignificant. G-CSF had an incremental cost-effectiveness ratio of $41,701 per SVR achieved in genotype 1, and $16,115 per SVR achieved in genotype 2 or 3. Estimates were robust under a variety of resource and intervention scenarios. While administration of G-CSF may enable patients to remain on or resume optimal HCV therapy, there was weak evidence that this improves the likelihood of SVR compared with dose reduction. Adverse effects of G-CSF are mild. The economic evaluation was inconclusive.

Intravenous immunoglobulin for presumed viral myocarditis in children and adults.

BACKGROUND: Case reports and case series have described dramatic responses to IVIG in adults and children with presumed viral myocarditis. Administration of IVIG has become commonplace in the management of this condition. OBJECTIVES: To compare the outcome of patients with presumed viral myocarditis treated with IVIG to patients who did not receive IVIG. SEARCH STRATEGY: We searched CENTRAL (Issue 2, 2003), MEDLINE/PubMed (1966-2003), EMBASE (1988-2003), CINAHL (1982-2003), Web of Science (1975-2003), trials registries and conference proceedings. We contacted authors of trials and checked reference lists of relevant papers. SELECTION CRITERIA: Studies were included if: (1) patients had a clinical diagnosis of acute myocarditis with either a left ventricular ejection fraction (LVEF) <= 0.45, LVEDD of >2 SDs above the norm, or a shortening fraction (SF) >2 SDs below the mean and the duration of cardiac symptoms was less than six months; (2) patients had no evidence of non-infectious or bacterial cardiac disease; and, (3) patients were randomised to receive at least 1 gm/kg of IVIG versus no IVIG or placebo. Studies were excluded if: (1) patients had received immunosuppression prior to outcome assessment; or, (2) onset of myocarditis was less than six months postpartum. DATA COLLECTION AND ANALYSIS: Searches were screened and inclusion criteria applied independently by two reviewers. Quality was assessed by two reviewers using the Jadad scale and allocation concealment. Data were extracted independently by two reviewers. Meta-analysis was not possible because only one relevant study was found. MAIN RESULTS: The relevant study involved 62 adults with acute myocarditis randomized to receive IVIG or an equivalent volume of 0.1% albumin in a blinded fashion. The incidence of death or requirement for cardiac transplant or placement of a left ventricular assist device was low in both groups (OR for event-free survival was 0.52 ,95% CI 0.12 to 2.30). Follow-up at six and 12 months showed equivalent improvement in LVEF (mean difference 0.00, 95% CI -0.07 to 0.07 at six months, mean difference 0.01, 95% CI -0.06 to 0.08 at 12 months). Functional capacity as assessed by peak oxygen consumption was equivalent in the two groups at 12 months (mean difference -0.80, 95% CI -4.57 to 2.97). Infusion-related side effects were more common in the treated group, but all appeared to be mild (OR 30.16, 95% CI 1.69 to 539.42). AUTHORS' CONCLUSIONS: Evidence from one trial does not support the use of IVIG for the management of adults with presumed viral myocarditis. There are no randomized paediatric trials. Further studies of the pathophysiology of this entity would lead to improved diagnostic criteria which would facilitate future research.