Kenneth Bender

 on hemodialysis (HD) was found to be higher in a cross-sectional study in Mexico City than in other large population studies, but with the same contributing factors.

Juan Carlos Hernández Rivera, MD, Department of Nephrology, Mexican Institute of Social Security (IMSS), Mexico City, and colleagues ascertained prevalence and related factors in a population treated in Mexico City, and compared their findings to those from other large studies.

"On account of its high frequency, its impact on the patients' quality of life, and mainly because it is susceptible to intervention, the control of anemia is considered a quality-of-care indicator and has been included in international studies such as Dialysis Outcomes and Prescription Patterns Study (DOPPS) as an evaluation criteria," Rivera and colleagues wrote.

Although these large international studies have contributed to establishing the reference values associated with favorable clinical outcomes, Rivera and colleagues note that only developed countries participate in these studies. "Nevertheless, its extension to developing countries is also highly important," they asserted.

The investigators analyzed the medical records of 747 patients with CKD on HD in the northern metropolitan area of Mexico City who were receiving treatment as of December 31, 2019. Patients were excluded from the study if they were receiving less than 3 HD sessions per week, or presented with chronic or acute infectious disease at the beginning of the HD program.

Also excluded were pregnant patients and patients with bleeding history within 3 months prior to the study.The most frequent etiology for CKD was diabetes mellitus (24.9% of patients) and arterial hypertension (16.3%); with primary glomerulopathies implicated in 5.5%.

With reference to the WHO definition and the KDIGO Clinical practice Guideline for Anemia in Chronic Kidney Disease specifying anemia with hemoglobin (Hb) levels of <13 g/dL in men and <12 g/dL in women, 94.2% (n = 676) of the study population was anemic.The investigators contrast that prevalence to the approximate 70% of Stage 5 CKD patients in other studies.In the Mexico City population, the mean Hb was 9.7 g/dL; and the mean corpuscular volume (MCV) mean was 92.29 fl.

In this study, Rivera and colleagues stratified patient datainto 2 groups, below and above 10g/dl Hb.With this cut-off, they determined that patients with lower levels were older, had higher phosphorous and lower iron levels. With further analysis, they determined that risk factors for Hb <10 g/dL included male gender, diabetes, hyperphosphatemia, higher calcium-phosphate product and iron deficiency. Protective factors included female gender, glomerulopathies, hypophosphatemia, and serum ferritin >500ng/dl.

Rivera and colleagues point out several quantitative differences in anemia-related factors from large population studies, including those from the GGC-DOPPS (Gulf Cooperation Council—Dialysis Outcomes and Practices Patterns Study).The Mexico Citycohort had lower Hb levels and lower iron-status indicators such as ferritin and transferrin saturation, and required higher doses of erythropoetin (EPO).They also noted that the GCC-DOPPSreported broader prescribing of erythropoiesis stimulating agents, higher IV iron doses and lower oral iron use.

"Periodic studies such as the one...are necessary to detect improvement opportunities in the quality of care to decrease morbidity and mortality in HD patients," Rivera and colleagues concluded.

Factors Related to the Presence of Anemia in Patients with Chronic Kidney Disease in Hemodialysi

Articles

Prevalence of anemia in patients with chronic kidney disease on hemodialysis found higher in Mexico than studied populations, with similar contributing factors.

Anemia Prevalence Greater in Mexican Patients on Hemodialyis

An original version of this article was published by sister publication Contagion.

A new orally administered adsorbent could prevent antibiotic disruption of intestinal flora against 

 (C diff) in patients with hematologic malignancies, according to new research.

An investigational formulation of an adsorbent to protect against antibiotic disruption of intestinal microbiota and colonization of 

 will be evaluated in a phase 3 clinical trial in patients with hematologic malignancies who require antibiotics for severe infections while receiving intensive chemotherapy.

Authorizations from 2 European regulatory agencies, the French National Agency for Medicines and Health Products Safety (ANSM) and the Hungarian National Institute of Pharmacy and Nutrition (OGYÉI), were received by the French biopharmaceutical company, Da Volterra, to begin recruitment for a phase 3 trial of the efficacy of DAV132 in reducing occurrence of 

 in a population described in the company's 

 as "cancer patients for whom antibiotic use is both life-saving and life-threatening."

DAV132, characterized by the manufacturer as a "first-in-class microbiota protector," is an orally administered formulation that releases 5gm of activated charcoal from a 7.5 gm dosage into, or after passage through the ileum.

 described by the manufacturer, 7.5gm of DAV132 administered 3 times daily to elderly patients receiving oral or intravenous fluoroquinolone antibiotics demonstrated protection against antibiotic-induced disruption of intestinal microbiota.

According to the manufacturer's summary of the trial results, the adsorbent product significantly reduced free fecal concentrations of fluoroquinolones without affecting their plasma levels, and therefore without affecting their efficacy in treating the patients' infections.

Testing conducted at Leeds Teaching Hospitals and University of Leeds, Leeds, United Kingdom, reportedly determined that the feces obtained from the patients receiving DAV132 and fluoroquinolones were not be permissive for the 

, in contrast to the relative proliferation of 

after inoculation in feces of patients receiving the antibiotics without DAV132.

There was no significant difference in adverse events between groups.

The delayed release of the activated charcoal ingredient was also found in a phase 1 study to avoid the potential interaction with concurrently administered drugs. That study was conducted with healthy volunteers receiving a 7.5gm dose of DAV132 concurrently with either 5mg of the anticoagulant warfarin, or 1mg of the antiepileptic clonazepam.

 that that DAV132 had not impacted the pharmacokinetics of either drug.

"We have demonstrated once again that the adsorbent within DAV132 was not delivered before the late ileum," stated Annie Ducher, MD, then Chief Medical Officer, , Da Volterra, in their press release. "This is of tremendous importance as it means that DAV132 can be safely administered with narrow therapeutic index drugs without any risk of interference with their absorption in the small intestine."

The phase 3 trial of DAV132 in patients with hematologic malignancies who require antibiotics will be conducted in collaboration with the European-based COMBACTE-NET consortium of clinics and hospitals ready to conduct clinical trials and clinical drug development testing.

Fabien Vitry, MD, current Chief Medical Officer, Da Volterra, indicated that commencement of the phase 3 trial marked a potentially important change in the treatment of hemato-oncology patients who develop serious infections and are at heightened risk for 

 opportunistic infection from antibiotic treatments.

"Now, for the first time, we will be able to protect the microbiome of these patients in spite of their massive antibiotic use," Vitry predicted.

In results from a phase 2 trial  show 7.5gm of DAV132 administered three times daily demonstrated protection against antibiotic-induced disruption of intestinal microbiota.

New Adsorbent Protects Against C Diff for Patients with Hematologic Malignancies

 was originally published on HCPLive.com.

Long-term outcomes in systemic lupus erythematosus (SLE) have improved over time, but unmet needs include glucorticoid dependency and comorbidity burden, according to a review which implicates a number of factors including demographic and socio-economic for the heterogeneity of the clinical presentation.

The review was conducted by Laurent Arnaud, MD, PhD, Department of Rheumatology, Hôpitaux Universitaires de Strasbourg, INSERM, and Centre National de Référence des Maladies Auto-immunes Systémiques Rares (RESO), and Maria Tektonidou, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens.

"Earlier diagnosis and treatment advances have resulted in improved outcomes over the past decades," Arnaud and Tektonidou observed. "However, increased morbidity and mortality risks persist in SLE, indicating that several unmet needs are still present among SLE patients."

The reviewers find persistent disease activity and flares despite progress to date. In addition, they point to the persistence of glucocorticoid treatment dependency, comorbidity burden, reduced health-related quality of life, and inconsistent access to high-quality care.

"Better understanding of SLE pathogenesis, optimization of prevention, a treat-to-target approach and introduction of safe and effective treatments based on better-designed trials and clinical research tools, taking the heterogeneity of the disease into account as well, is crucial for improving outcomes," Arnaud and Tektonidou declared.

The reviewers consider how long-term outcomes with SLE have changed with developments in treatments and health care access. The principal outcomes they consider are long-term remission or recurrent flares, end-stage renal disease, nervous system involvement, and cardiovascular and infections burden.

Arnaud and Tektonidou note that non-white patients with SLE have tended to develop more severe clinical phenotypes and more damage accrual than whites. The reviewers find that socio-economic factors can confound those associations, but that an increased genetic risk burden remains in analysis of population incidence that corrects for these conditions.

"Increased awareness of the above high-risk populations can help to improve long-term outcomes in SLE," the reviewers suggested.

Although lupus nephritis (LN) remains a major cause of morbidity and mortality among patients with SLE, Arnaud and Tektonidou credit use of the histological classification for LN management and prognosis, better understanding of the pathogenetic basis of LN, and advances in immunosuppressive treatments for the substantial improvement of renal survival in SLE over the past 5 decades.

The reviewers note that several recent clinical trials of interventions for LN have failed to meet their primary endpoints. This indicates, they suggested, that not only is there continued need for evaluation of innovative treatments, but that the trial designs must reevaluate patient selection according to clinical phenotypes and biologic markers.

Neuropsychiatric symptoms and involvement of the peripheral as well as central nervous system remain among the most challenging manifestations of SLE, according to the reviewers. Diagnosis has remained elusive, they indicate, essentially obtained through "presumption and exclusion," and often confirmed retrospectively based on response to treatment. This status has not been helped, they point out, by recent clinical trials in SLE excluding patients with severe neuropsychiatric manifestations.

Arnaud and Tektonidou find that there has been a bifurcation in efforts to reduce long-term organ damage in SLE, with some targeting remission while others are directed at maintaining low-disease activity (lupus low disease activity state (LLDAS). Considering clinical trial outcomes, they find that remission is a more beneficial outcome than the LLDAS, although the latter is more likely to be achieved.

In addition to basic and clinical sciences, the reviewers point to the need for increased attention to social factors. They noted for example that poor adherence to therapeutic regimens continues to be common.

"The accurate identification of non-adherence is crucial, as it may help avoid unnecessary treatment escalation," Arnaud and Tektonidou indicated.

They also identify cigarette smoking as a continuing risk factor for SLE, which negatively influences the disease course and response to treatment. Despite this well known association, however, SLE patients rarely report receiving cessation counseling.

Arnaud and Tektonidou conclude that several unmet needs in SLE remain, including a variety of disease-related, treatment, comorbidity and access-to-care factors.

"Despite a substantial improvement in SLE diagnosis and treatment over the years, some long-term outcomes are still not adequately improved," they indicated.

Arnaud L, Tektonidou MG. Long-term outcomes in systemic lupus erythematosus: trends over time and major contributors. 

. 2020;59(Supplement_5):v29-v38. doi:10.1093/rheumatology/keaa382

Trends in Long-Term Lupus Outcomes

An examination of Medicaid prior authorization policies for medication treatment of attention-deficit/hyperactivity disorder (ADHD) finds policies are inconsistent across states, which could influence whether treatments are consistent with, or differ from recommended practices.

Rachel Hulkower, JD, MSPH, Public Health Analyst, Cherokee Nation Assurance, Public Health Law Program, Office for State, Tribal, Local and Territorial Support, Arlington, Virginia, and colleagues point out that ADHD treatment recommendations are not always followed.

"When best-practice recommendations are compared with indicators of clinical practice, it appears that current practices and best practices for pediatric ADHD treatment are misaligned," Hulkower and colleagues indicate.

They note that the American Academy of Pediatrics (AAP) recommends evidence-based parent and/or teacher-administered behavior therapy as first-line treatment for preschool-aged children, with medication reserved if behavior therapy fails to substantially improve the child's functioning and there is moderate to severe continued disturbance in the child's function. A combination of such therapy with medication is recommended for older children.

Some of the highest rates of ADHD diagnosis are among children with public health insurance, however, investigators suggest that states' Medicaid policies and prior authorization requirements could have a substantial impact of how this condition is treated.

"Some state Medicaid programs have implemented policies to try to manage the use of ADHD medications," explain the investigators. "These policies include prescription medication prior authorization policies and prescription drug lists that restrict coverage approvals to patients of a certain age or require additional provider involvement before payment is granted. These policies may guide physicians toward preferred pediatric ADHD treatments."

"The NCBDDD (National Center on Birth Defects and Developmental Disabilities) has identified Medicaid prior authorization policy interventions as a set of strategies that may control the use of ADHD medication among patients diagnosed with ADHD and may guide clinicians towards referral for behavior therapy," Hulkower said, elaborating in an interview reported in 

To characterize the states' Medicaid pediatric ADHD medication prior authorizations, the investigators conducted a cross-sectional mapping study of states' policies as of November 1, 2015. The data on policy characteristics and authorization criteria included data on age restrictions and fail-first behavior therapy requirements.

The investigators report, among their findings, that 27 state Medicaid programs have prior authorization policies for ADHD medications prescribed to children and adolescents, 16 of which were applicable only to children <6 years of age. In 2 states, Medicaid coverage is expressly denied for ADHD medication prescriptions for patients younger than specified age: Minnesota denies all ADHD medications for children <3 years; Texas denies immediate-release medications <3 years, and denies extended-release and non-stimulant formulations for children <6 years.

Twenty-five states have policies that list criteria for approval; with the most common approval criterion, found in 23 states, a documented ADHD diagnosis. Less common criteria include: ruling out other causes for symptoms; ADHD symptoms persisting for a specified duration; patient impairment demonstrated in social environments, and the administration of a psychological evaluation.

Several of the states' policy ask the prescriber to confirm that an alternative treatment has been considered, and 7 state policies ask whether non-medication treatments such as behavior therapy had been attempted before the requested medication coverage. One state, Florida, requires the prescriber demonstrate not only that non-medication treatments are considered, but that an adequate trial failed to improve a patient's symptoms.

Hulkower indicated that the database developed from this study, available to the public, will next be analyzed in conjunction with Medicaid claims data for diagnosis and treatment of ADHD with prescription medications and psychological services to ascertain effects on ADHD treatment patterns.

"Research has not yet examined how prior authorization policies impact receipt of the recommended first-line treatment for these families, which is behavior therapy," Hulkower told 

.  "Evaluation of the impact of prior authorization policies on behavior therapy rates would document whether prior authorization policies are effectively supporting best practices for young children with ADHD."

 policies for medication treatment of ADHD was published in the November/December issue of 

Fibromyalgia Patients Show High Co-Occurrence of Adult ADHD

Few US Children with ADHD Receive Recommended Psychosocial Treatment

Methylphenidate Formulation Modeled to Maximize Benefit in ADHD

Medicaid prior authorization policies could influence whether ADHD treatments follow or diverge from best practices. 