Pharmacological mechanism-based modeling was refined and used to develop an in silico model of antimalarial drug treatment validated against clinical and field data. We used this approach to investigate key features of antimalarial drug action and effectiveness, with emphasis on the current generation of artemisinin combination therapies. We made the following conclusions. (i) The development of artemisinin tolerance and resistance will, unless checked, have an immediate, large impact on the protection afforded to its partner drug and on the likely clinical efficacy of artemisinin combination therapies. (ii) Long follow-up periods are required in clinical trials to detect all drug failures; the follow-up periods of 28 days recommended by the World Health Organization are likely to miss at least 50% of drug failures, and we confirmed recent suggestions that 63 days would be a more appropriate follow-up period. (iii) Day 7 serum drug concentrations are a significant risk factor of failure, although, paradoxically, receiver operating characteristic curve analysis revealed that their predictive power is relatively poor. (iv) The pharmacokinetic properties of the partner drugs in artemisinincontaining combination therapies are the most important determinants of treatment outcome, particularly the maximum killing rate. We discuss the assumptions made in such modeling approaches and how similar approaches may be refined in future work.

Oral health disparities between individuals with disabilities and the general population are widely reported in the literature, and malocclusion is no exception. As the number of people living with disabilities grows, so does the need to explore their oral health status. This review examines the reported prevalence of malocclusion in individuals with Down syndrome (DS), cerebral palsy (CP), cleft disorders, mental disabilities, and physical disabilities from 1976 to 2004. Malocclusion was assessed according to Angle's classifications, the Dental Aesthetic Index (DAI), and selected occlusion characteristics. The prevalence of malocclusion was higher in individuals with disabilities than in controls without disabilities. Malocclusion was more frequent when the handicap was mental rather than physical in origin. Class II and Class III malocclusions were common in individuals with CP and DS, respectively. Crowding, anterior diastema, and >1/2 cusp antero-posterior molar relations were frequent among people with disabilities. Findings varied according to disability, but were attributed to musculoskeletal abnormalities, altered cranial-base relationships, premature tooth eruption, corrective surgery, and lip incompetence. Only a deep bite was more frequent in controls compared to the individuals with disabilities.

To further reduce medications for BPSD, obstacles to services and alternative therapies must be mitigated. Caregiver perceptions that medications are generally safe and effective contribute to their continued use. Guidelines and policies for BPSD management should incorporate the caregiver position that medications, including antipsychotics, are sometimes justified and required to alleviate patient suffering.

For long-stay seniors on antipsychotics, reporting of schizophrenia, Tourette's, and Huntington's began increasing in 2012 and at almost triple the rate CMS described for the general long-stay population. The increased reporting of these diagnoses described by CMS since 2012 appears to be new and concentrated in residents on antipsychotics Clinical Implications: Since antipsychotics prescribed for schizophrenia, Tourette's, and Huntington's are excluded from quality-measure auditing, apparent reductions in inappropriate long-stay antipsychotic use since the National Partnership may be exaggerated.

Background: Guidelines, policies, and warnings have been applied to reduce the use of medications for behavioral and psychological symptoms of dementia (BPSD). Because of rare dangerous side effects, antipsychotics have been singled out in these efforts. However, antipsychotics are still prescribed "off label" to hundreds of thousands of seniors residing in nursing homes and communities. Our objective was to evaluate how and why primary-care physicians (PCPs) employ nonpharmacologic strategies and drugs for BPSD.Methods: Semi-structured interviews analyzed via template, immersion and crystallization, and thematic development of 26 PCPs (16 family practice, 10 general internal medicine) in full time primarycare practice for at least 3 years in Northwestern Virginia.Results: PCPs described 4 major themes regarding BPSD management: (1) nonpharmacologic methods have substantial barriers; (2) medication use is not constrained by those barriers and is perceived as easy, efficacious, reasonably safe, and appropriate; (3) pharmacologic policies decrease the use of targeted medications, including antipsychotics, but also have unintended consequences such as increased use of alternative risky medications; and (4) PCPs need practical evidence-based guidelines for all aspects of BPSD management.Conclusions: PCPs continue to prescribe medications because they meet patient-oriented goals and because PCPs perceive drugs, including antipsychotics and their alternatives, to be more effective and less dangerous than evidence suggests. To optimally treat BPSD, PCPs need supportive verified prescribing guidelines and access to nonpharmacologic modalities that are as affordable, available, and efficacious as drugs; these require and deserve significant additional research and payer support. Community PCPs should be included in BPSD policy and guideline development. (J Am Board Fam Med 2018;31: 9 -21.)

There are a variety of methods used to estimate the effectiveness of antimalarial drugs in clinical trials, invariably on a per-person basis. A person, however, may have more than one malaria infection present at the time of treatment. We evaluate currently used methods for analysing malaria trials on a per-individual basis and introduce a novel method to estimate the cure rate on a per-infection (clone) basis. We used simulated and real data to highlight the differences of the various methods. We give special attention to classifying outcomes as cured, recrudescent (infections that never fully cleared) or ambiguous on the basis of genetic markers at three loci. To estimate cure rates on a per-clone basis, we used the genetic information within an individual before treatment to determine the number of clones present. We used the genetic information obtained at the time of treatment failure to classify clones as recrudescence or new infections. On the per-individual level, we find that the most accurate methods of classification label an individual as newly infected if all alleles are different at the beginning and at the time of failure and as a recrudescence if all or some alleles were the same. The most appropriate analysis method is survival analysis or alternatively for complete data/per-protocol analysis a proportion estimate that treats new infections as successes. We show that the analysis of drug effectiveness on a per-clone basis estimates the cure rate accurately and allows more detailed evaluation of the performance of the treatment.

The management of asthma changed significantly after the LABA warning. The use of LABAs combined with inhaled corticosteroids plummeted, while the use of inhaled corticosteroid monotherapy increased. More than half of patients who discontinued LABAs were not placed on alternative maintenance therapy.

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