Pharmacy Residency School-wide Match Rates and Modifiable Predictors in ACPE-accredited Colleges and Schools of Pharmacy.

Objective. To analyze the modifiable predictors of institution-wide residency match rates. Methods. This was a retrospective analysis of colleges and schools of pharmacy data and school-wide PGY-1 pharmacy residency match rates for 2013 through 2015. Independent variables included NAPLEX passing rates, history of ACPE probation, NIH funding, academic health center affiliation, dual-degree availability, program length, admit-to-applicant ratio, class size, tuition, student-driven research, clinically focused academic tracks, residency affiliation, U.S. News & World Report rankings, and minority enrollment. Results. In a repeated measures model, predictors of match results were NAPLEX pass rate, class size, academic health center affiliation, admit-to-applicant ratio, U.S. News & World Report rankings, and minority enrollment. Conclusion. Indicators of student achievement, college/school reputation, affiliations, and class demographics were significant predictors of institution-wide residency match rates. Further research is needed to understand how changes in these factors may influence overall match rates.

Gonadal suppressive and cross-sex hormone therapy for gender dysphoria in adolescents and adults.

Individuals with gender dysphoria experience distress associated with incongruence between their biologic sex and their identified gender. Gender dysphoric natal males receive treatment with antiandrogens and estrogens to become feminized (transsexual females), whereas natal females with gender dysphoria receive treatment with androgens to become masculinized (transsexual males). Because of the permanence associated with cross-sex hormone therapy (CSHT), adolescents diagnosed with gender dysphoria receive gonadotropin-releasing hormone analogs to suppress puberty. High rates of depression and suicide are linked to social marginalization and barriers to care. Behavior, emotional problems, depressive symptoms, and global functioning improve in adolescents receiving puberty suppression therapy. Gender dysphoria, psychological symptoms, quality of life, and sexual function improve in adults who receive CSHT. Within the first 6 months of CSHT, changes in transsexual females include breast growth, decreased testicular volume, and decreased spontaneous erections, and changes in transsexual males include cessation of menses, breast atrophy, clitoral enlargement, and voice deepening. Both transsexual females and males experience changes in body fat redistribution, muscle mass, and hair growth. Desired effects from CSHT can take between 3 and 5 years; however, effects that occur during puberty, such as voice deepening and skeletal structure changes, cannot be reversed with CSHT. Decreased sexual desire is a greater concern in transsexual females than in transsexual males, with testosterone concentrations linked to sexual desire in both. Regarding CSHT safety, bone mineral density is preserved with adequate hormone supplementation, but long-term fracture risk has not been studied. The transition away from high-dose traditional regimens is tied to a lower risk of venous thromboembolism and cardiovascular disease, but data quality is poor. Breast cancer has been reported in both transsexual males and females, but preliminary data suggest that CSHT does not increase the risk. Cancer screenings for individuals of both natal and transitioned sexes should occur as recommended. More long-term studies are needed to ensure that CSHT regimens with the best outcomes can continue to be prescribed for the transsexual population.

Safety of alternative antiviral agents for neonatal herpes simplex virus encephalitis and disseminated infection.

OBJECTIVE: To review the evidence describing the safety of ganciclovir and foscarnet in neonates in order to guide treatment for central nervous system or disseminated herpes simplex infections in cases of acyclovir shortage or resistance. METHODS: PubMed, Ovid Medline, and International Pharmaceutical Abstracts were searched using the thesaurus and text-word terms "ganciclovir" and "foscarnet," with birth to 1 month age limits. Thirty-two eligible publications describing safety in neonates were identified. RESULTS: In 340 neonates treated for cytomegalovirus (CMV), life-threatening neutropenia (absolute neutrophil count <0.5 × 10(9)/L) was reported in 8.8% of patients following up to 12 months of ganciclovir administered intravenously. Neutropenia and thrombocytopenia occurred in 25.6% and 6.2% of neonates, respectively. Changes in serum creatinine concentration of >0.2 mg/dL occurred in <1% of neonates. Hepatic transaminase increases or unspecified changes in liver function tests were reported in 6.2% of neonates with hyperbilirubinemia being observed in 3.5% of total neonates. Three out of four neonates receiving foscarnet for acyclovir-resistant herpes infection or CMV survived with minimal sequelae. Neither nephrotoxicity nor electrolyte or mineral imbalances were reported. CONCLUSIONS: Similar to what is seen in adolescents and adults, ganciclovir use in neonates is commonly associated with neutropenia, and the frequency of occurrence is comparable. The link between hepatotoxicity and ganciclovir should be interpreted with caution because of overlapping clinical manifestations of CMV. Only case reports are available describing foscarnet use in neonates, but adverse drug reactions were not observed. More research on these two agents is needed to draw conclusions about adverse drug reaction rates in the neonatal population.

Recommendations for meeting the pediatric patient's need for a clinical pharmacist: a joint opinion of the Pediatrics Practice and Research Network of the American College of Clinical Pharmacy and the Pediatric Pharmacy Advocacy Group.

Children warrant access to care from clinical pharmacists trained in pediatrics. The American College of Clinical Pharmacy Pediatrics Practice and Research Network (ACCP Pediatrics PRN) released an opinion paper in 2005 with recommendations for improving the quality and quantity of pediatric pharmacy education in colleges of pharmacy, residency programs, and fellowships. Although progress has been made in increasing the availability of pediatric residencies, there is still much to be done to meet the direct care needs of pediatric patients. The purpose of this joint opinion paper is to outline strategies and recommendations for expanding the quality and capacity of pediatric clinical pharmacy practitioners by elevating the minimum expectations for pharmacists entering pediatric practice, standardizing pediatric pharmacy education, expanding the current number of pediatric clinical pharmacists, and creating an infrastructure for development of pediatric clinical pharmacists and clinical scientists. These recommendations may be used to provide both a conceptual framework and action items for schools of pharmacy, health care systems, and policymakers to work together to increase the quality and quantity of pediatric training, practice, and research initiatives.

Identification and molecular characterization of a novel Chlamydomonas reinhardtii mutant defective in chlorophyll biosynthesis.

The green micro-alga Chlamydomonas reinhardtii is an elegant model organism to study all aspects of oxygenic photosynthesis. Chlorophyll (Chl) and heme are major tetrapyrroles that play an essential role in energy metabolism in photosynthetic organisms and are synthesized via a common branched tetrapyrrole biosynthetic pathway. One of the enzymes in the pathway is Mg chelatase (MgChel) which inserts Mg (2+) into protoporphyrin IX (PPIX, proto) to form magnesium-protoporphyrin IX (MgPPIX, Mgproto), the first biosynthetic intermediate in the Chl branch. MgChel is a multimeric enzyme that consists of three subunits designated CHLD, CHLI and CHLH. Plants have two isozymes of CHLI (CHLI1 and CHLI2) which are 70%-81% identical in protein sequences. Although the functional role of CHLI1 is well characterized, that of CHLI2 is not. We have isolated a non-photosynthetic light sensitive mutant 5A7 by random DNA insertional mutagenesis that is devoid of any detectable Chl. PCR based analyses show that 5A7 is missing the CHLI1 gene and at least eight additional functionally uncharacterized genes. 5A7 has an intact CHLI2 gene. Complementation with a functional copy of the CHLI1 gene restored Chl biosynthesis, photo-autotrophic growth and light tolerance in 5A7. We have identified the first chli1 (chli1-1) mutant of Chlamydomonas reinhardtii and in green algae. Our results show that in the wild type Chlamydomonas CHLI2 protein amount is lower than that of CHLI1 and the chli1-1 mutant has a drastic reduction in CHLI2 protein levels although it possesses the CHLI2 gene. Our chli1-1 mutant opens up new avenues to explore the functional roles of CHLI1 and CHLI2 in Chl biosynthesis in Chlamydomonas, which has never been studied before.

Recommendations for Meeting the Pediatric Patient's Need for a Clinical Pharmacist: A Joint Opinion of the Pediatrics Practice and Research Network of the American College of Clinical Pharmacy and the Pediatric Pharmacy Advocacy Group.

Children warrant access to care from clinical pharmacists trained in pediatrics. The American College of Clinical Pharmacy Pediatrics Practice and Research Network (ACCP Pediatrics PRN) released an opinion paper in 2005 with recommendations for improving the quality and quantity of pediatric pharmacy education in colleges of pharmacy, residency programs, and fellowships. While progress has been made in increasing the availability of pediatric residencies, there is still much to be done to meet the direct care needs of pediatric patients. The purpose of this Joint Opinion paper is to outline strategies and recommendations for expanding the quality and capacity of pediatric clinical pharmacy practitioners by 1) elevating the minimum expectations for pharmacists entering practice to provide pediatric care; 2) standardizing pediatric pharmacy education; 3) expanding the current number of pediatric clinical pharmacists; and 4) creating an infrastructure for development of pediatric clinical pharmacists and clinical scientists. These recommendations may be used to provide both a conceptual framework and action items for schools of pharmacy, health care systems, and policymakers to work together to increase the quality and quantity of pediatric training, practice, or research initiatives.

Risk of venous thromboembolism with drospirenone in combined oral contraceptive products.

OBJECTIVE: To review primary literature regarding the risk of venous thromboembolism (VTE) in users of combined oral contraceptives (COCs) containing drospirenone compared to COCs containing other progestins. DATA SOURCES: A literature search of MEDLINE and EMBASE (1950-January 2010) was conducted using the following search terms: VTE, thrombosis, thromboembolism, COC, combined hormonal contraceptives, drospirenone, Yasmin, and Yaz. Additional references were retrieved from reference citations. STUDY SELECTION AND DATA EXTRACTION: All English-language primary literature studies were evaluated for relevance. Five studies were identified for evaluation: 1 prescription event monitoring study, 2 prospective postmarketing cohort studies, 1 validation study, and 1 retrospective cohort study. DATA SYNTHESIS: Use of a COC is associated with a 3- to 6-fold increase in VTE risk compared to nonuse. This risk may vary among different oral contraceptives due to the progestin component. Studies evaluated showed that women utilizing a drospirenone-containing COC did not have a higher risk of VTE when compared to women utilizing other progestins. The crude incidence rate ratio for VTE in women taking a COC containing drospirenone compared to a COC containing other progestins ranged from 0.9 to 1.7 (95% CI 0.5 to 2.4). While the studies evaluating VTE risk were mostly large and long term, most failed to consider important risk factors for VTE such as prolonged immobility, obesity, smoking history, and family history of VTE (which could suggest a genetic predisposition to thrombotic events). It was also unclear with some of the studies whether equivalent estrogen doses were used in the comparisons. CONCLUSIONS: Several studies have evaluated the risk of VTE in users of COC-containing drospirenone compared with other progestins, and none were able to show a significantly increased risk of VTE with drospirenone. The recent media attention regarding VTE risk and drospirenone-containing COCs does not seem to be well supported by the research currently available.

Acarbose for polycystic ovary syndrome.

OBJECTIVE: To review the evidence for use of acarbose in the management of polycystic ovary syndrome (PCOS). DATA SOURCES: Relevant publications were identified through a systematic search of PubMed English-language literature (1950-February 2008) using the MeSH terms and key words acarbose and polycystic ovary syndrome. STUDY SELECTION AND DATA EXTRACTION: The literature search retrieved 6 primary literature citations. Three randomized controlled clinical trials and one open-label study were evaluated. The other 2 citations were not evaluated due to only a peripheral mention of PCOS in relation to diabetes. DATA SYNTHESIS: PCOS is a complex disorder presenting most commonly with oligomenorrhea or amenorrhea, infertility, hirsutism, acne, and obesity. Acarbose is a promising therapy for PCOS because of its effects on postprandial insulin levels. In multiple clinical studies, acarbose improved hirsutism, acne, and menstrual irregularities through reduction in androgen concentrations and through increased androgen binding. When compared with metformin in women with PCOS and clomiphene-resistant infertility, acarbose induced greater weight loss and improved menstrual regularity and signs of fertility to a similar degree. Markers of cardiovascular risk were also significantly improved following 6 months of acarbose therapy in obese women with PCOS. Adverse effects, specifically gastrointestinal, were documented. Despite promising results, the studies were limited by small sample sizes and, in some cases, methods that were not clearly defined. CONCLUSIONS: Several trials have evaluated the use of acarbose in the management of PCOS with positive clinical evidence, but the results of these trials have not been corroborated by more rigorous studies.

Pediatric pharmacotherapeutic education: current status and recommendations to fill the growing need.

The Accreditation Council for Pharmacy Education and the Canadian Council for Accreditation of Pharmacy Programs state that their respective programs should provide a curriculum appropriate to produce general practitioners of pharmacy. Millions of prescriptions are written for infants and children each year, and relatively few pharmacists practice in environments devoid of pediatric patients. To fulfill the stated mandate, professional pharmacy curricula must include adequate content dedicated to pharmaceutical care of the pediatric patient. Current pediatric curricula are inadequate and must be improved. Pediatric topics should be introduced early in the curriculum to increase students' awareness of the special needs of this vulnerable population. Other recommendations include the provision at least 25 hours of didactic instruction in core pediatric areas and at least one pediatric clinical rotation to all students. Pharmaceutical care of pediatric patients can also be improved by offering pediatric rotations to all pharmacy practice residents and encouraging their participation. However, a change in attitude may be most important. The contention that pediatric pharmacy practice is an isolated subspecialty can no longer be supported.

The role of pamidronate in pediatric patients with severe osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heritable bone disorder with clinical features that include bone fragility, blue sclerae, and short stature. There are four main subtypes of OI, encompassing a wide range of clinical severity. The majority of patients have mutations in either the COL1A1 or COL1A2 gene that ultimately lead to an abnormal synthesis of or a decrease in the production of collagen. Bisphosphonates have been used effectively in adults and children to treat other bone disorders, since they have been proven to increase bone density through inhibition of bone resorption. Recent studies have demonstrated the advantages of pamidronate therapy in the treatment of children and adolescents with the more severe forms of OI. Pamidronate consistently increases bone mass, vertebral growth, and quality-of-life while decreasing the number of fractures in children with severe OI. Long-term effects are promising, and benefits of pamidronate therapy appear to outweigh the possible risks.

Acute and conditioned hyperalgesic responses to illness.

It has been argued that pain functions to facilitate recovery from injury and/or illness by stimulating recuperative behaviors. If this is the case, then hyperalgesia might be expected to be part of the constellation of adaptations that occur during sickness. The present series of studies tested two agents that induce illness (lithium chloride and bacterial cell-wall endotoxin (lipopolysaccharide)) to determine their acute effects on pain responsivity in rats. Both agents produced hyperalgesia as measured by the tail-flick and formalin tests. This enhanced responsivity appears to be specific to pain since (a) no enhanced response was observed to a non-painful stimulus (6 g von Frey hairs), and (b) the effect could not be accounted for by changes in tail skin temperature. In addition, a conditioned taste aversion paradigm was used to examine the possibility that illness-induced hyperalgesia could be conditioned to a novel taste (saccharine). This procedure was successful in producing a conditioned hyperalgesia which was comparable in magnitude and duration to acute illness induced pain facilitation. Taken together, this series of studies suggests that such pain facilitation might have adaptive functions similar to those ascribed to other illness-induced behaviors.