Evaluation of multidisciplinary weight loss shared medical appointments.

OBJECTIVES: A multidisciplinary weight loss shared medical appointment (SMA) was created to help patients with weight management. The study objective was to evaluate the change in weight in patients participating in weight loss SMAs. The secondary objective was to evaluate the change in patients' cardiometabolic risk factors. SETTING: The study took place in Beachwood, OH, at a family medicine clinic associated with an academic medical center. PRACTICE DESCRIPTION AND INNOVATION: Groups of 10 to 15 overweight and obese patients participated in weight loss SMAs in a family medicine clinic. The provider team included a family practice physician, a pharmacist, and a registered dietician. The pharmacist assisted with medication optimization to assist with weight management. EVALUATION: This retrospective observational study evaluated weight loss in patients who attended at least 1 weight loss SMA over a 9-month period. Weight loss and other cardiometabolic risk factors were compared from the time of the first SMA, 3 months after the first SMA, and at the end of the study period. RESULTS: A total of 222 patients attended at least 1 weight loss SMA. The mean weight loss was 4.0 ± 5.1 kg (3.8%) at 3 months and 4.4 ± 5.9 kg (4.1%) at the end of the study period. At 3 months, 38.7% of patients achieved 5% weight loss, and 41% of patients achieved 5% weight loss at the end of the study period. Patients also had a significant reduction in body mass index, blood pressure, and glycated hemoglobin. There was a significant correlation between the number of SMA visits attended and the amount of weight lost. CONCLUSION: Patients who attended a weight loss SMA lost weight and had modest improvements in cardiometabolic risk factors. Weight loss SMAs are a promising weight loss option to assist patients seen in the primary care setting.

Adjunct Antihyperglycemic Agents in Overweight and Obese Adults With Type 1 Diabetes.

OBJECTIVE: People with type 1 diabetes often have suboptimal glycemic control. The gold standard of treatment is basal-bolus insulin or subcutaneous insulin infusion via insulin pump. Although insulin therapy improves glycemic control, weight gain and hypoglycemia often limit achievement of hemoglobin A1C (A1C) goals. The number of people with type 1 diabetes who are overweight or obese is increasing, and there are many similarities between what was historically called type 1 and type 2 diabetes. Therefore, there is rationale for using antihyperglycemic agents that target other pathophysiological abnormalities to facilitate weight loss and improve glycemic control. DATA SOURCES: We performed a MEDLINE search from 1975 through October 2018 to identify articles that studied noninsulin agents in adults with type 1 diabetes and body mass index (BMI) ≥25 kg/m2. STUDY SELECTION AND DATA EXTRACTION: Identified articles were included if the study duration was ≥4 weeks, included ≥20 patients, and set mean baseline BMI ⩾25kg/m2. DATA SYNTHESIS: This review summarizes 32 clinical trials. Amylin mimetics, sodium-glucose-like transporter-2 inhibitors, and glucagon-like-peptide-1 receptor agonists demonstrate the greatest improvements in body weight and A1C. The most common adverse effects are hypoglycemia and ketosis. Relevance to Patient Care and Clinical Practice: Patients with type 1 diabetes may have interest in starting noninsulin agents. Clinicians need to be knowledgeable in the efficacy and adverse effect profile of these agents, specifically in people with type 1 diabetes. CONCLUSIONS: Adding noninsulin antihyperglycemic agents may benefit select overweight or obese adults with type 1 diabetes. These agents are off-label, and if used, close monitoring is essential.

Plasmodium falciparum merozoite surface protein 1 blocks the proinflammatory protein S100P.

The malaria parasite, Plasmodium falciparum, and the human immune system have coevolved to ensure that the parasite is not eliminated and reinfection is not resisted. This relationship is likely mediated through a myriad of host-parasite interactions, although surprisingly few such interactions have been identified. Here we show that the 33-kDa fragment of P. falciparum merozoite surface protein 1 (MSP1(33)), an abundant protein that is shed during red blood cell invasion, binds to the proinflammatory protein, S100P. MSP1(33) blocks S100P-induced NFκB activation in monocytes and chemotaxis in neutrophils. Remarkably, S100P binds to both dimorphic alleles of MSP1, estimated to have diverged >27 Mya, suggesting an ancient, conserved relationship between these parasite and host proteins that may serve to attenuate potentially damaging inflammatory responses.

Testing in mice the hypothesis that melanin is protective in malaria infections.

Malaria has had the largest impact of any infectious disease on shaping the human genome, exerting enormous selective pressure on genes that improve survival in severe malaria infections. Modern humans originated in Africa and lost skin melanization as they migrated to temperate regions of the globe. Although it is well documented that loss of melanization improved cutaneous Vitamin D synthesis, melanin plays an evolutionary ancient role in insect immunity to malaria and in some instances melanin has been implicated to play an immunoregulatory role in vertebrates. Thus, we tested the hypothesis that melanization may be protective in malaria infections using mouse models. Congenic C57BL/6 mice that differed only in the gene encoding tyrosinase, a key enzyme in the synthesis of melanin, showed no difference in the clinical course of infection by Plasmodium yoelii 17XL, that causes severe anemia, Plasmodium berghei ANKA, that causes severe cerebral malaria or Plasmodium chabaudi AS that causes uncomplicated chronic disease. Moreover, neither genetic deficiencies in vitamin D synthesis nor vitamin D supplementation had an effect on survival in cerebral malaria. Taken together, these results indicate that neither melanin nor vitamin D production improve survival in severe malaria.

Defibrotide interferes with several steps of the coagulation-inflammation cycle and exhibits therapeutic potential to treat severe malaria.

OBJECTIVE: The coagulation-inflammation cycle has been implicated as a critical component in malaria pathogenesis. Defibrotide (DF), a mixture of DNA aptamers, displays anticoagulant, anti-inflammatory, and endothelial cell (EC)-protective activities and has been successfully used to treat comatose children with veno-occlusive disease. DF was investigated here as a drug to treat cerebral malaria. METHODS AND RESULTS: DF blocks tissue factor expression by ECs incubated with parasitized red blood cells and attenuates prothrombinase activity, platelet aggregation, and complement activation. In contrast, it does not affect nitric oxide bioavailability. We also demonstrated that Plasmodium falciparum glycosylphosphatidylinositol (Pf-GPI) induces tissue factor expression in ECs and cytokine production by dendritic cells. Notably, dendritic cells, known to modulate coagulation and inflammation systemically, were identified as a novel target for DF. Accordingly, DF inhibits Toll-like receptor ligand-dependent dendritic cells activation by a mechanism that is blocked by adenosine receptor antagonist (8-p-sulfophenyltheophylline) but not reproduced by synthetic poly-A, -C, -T, and -G. These results imply that aptameric sequences and adenosine receptor mediate dendritic cells responses to the drug. DF also prevents rosetting formation, red blood cells invasion by P. falciparum and abolishes oocysts development in Anopheles gambiae. In a murine model of cerebral malaria, DF affected parasitemia, decreased IFN-γ levels, and ameliorated clinical score (day 5) with a trend for increased survival. CONCLUSION: Therapeutic use of DF in malaria is proposed.