Care for Adolescents With Polycystic Ovary Syndrome: Development and Prescribing Patterns of a Multidisciplinary Clinic.

STUDY OBJECTIVE: Based on updated guidelines and expressed patient needs, we created a multidisciplinary clinic including endocrinology, gynecology/adolescent medicine, dermatology, psychology, and nutrition to provide comprehensive care to adolescent girls with polycystic ovary syndrome (PCOS). We describe the patient population presenting to this clinic, and prescribing patterns when a multidisciplinary approach is used. DESIGN: Retrospective chart review. SETTING: Tertiary care hospital. PARTICIPANTS: Female patients, aged 11-24 years, presenting for initial assessment in a multidisciplinary PCOS clinic. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Medical history, physical examination findings, laboratory measurements and prescribed therapies. RESULTS: A total of 92 patients seen from 2014 to 2018 are described (age 15.9 years, range 11-24 years, body mass index 35.6 kg/m2, range 19.9-53.5). Metabolic syndrome features were common: 26% had a prediabetes hemoglobin A1c (>5.6%), 83% had a high-density lipoprotein (HDL) <50 mg/dL, 40% had a systolic blood pressure >120 mm Hg, and 43% had an alanine aminotransferase level of >30 U/L. Dermatologic findings included acne 93%, hirsutism 38%, acanthosis nigricans 85%, hidradenitis suppurativa 16%, and androgenic alopecia 2%. Of the patients, 33% had a diagnosis of depression or anxiety, 16% of patients had a diagnosis of obstructive sleep apnea, and an additional 59% had symptoms warranting a sleep study The most commonly prescribed medications were topical acne preparations (62%), followed by estrogen-containing hormonal therapy (56%) and metformin (40%). CONCLUSION: In adolescents with PCOS and obesity, metabolic, dermatologic, and psychologic co-morbidities are common. The use of a multidisciplinary clinic model including dermatology in addition to endocrinology, gynecology, psychology, and lifestyle experts provides care for most aspects of PCOS.

Barriers and strategies for oral medication adherence among children and adolescents with Type 2 diabetes.

AIMS: Examine barriers for taking glucose-lowering oral medications, associated baseline characteristics, strategies used, and the adherence impact in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. METHODS: We studied youth prescribed oral diabetes medications over two years (N = 611, 583, and 525 at 6, 12, and 24 months). Clinicians documented barriers (e.g. forgetting, routines, other concerns) in the subsample that reported missed doses (N = 423 [69.2%], 422 [72.4%], and 414 [78.9%] at 6, 12, and 24 months, respectively). Adherence strategies were also assessed (e.g. family, schedule, reminder device) using standard questions. Logistic regression was used to analyze associations with medication adherence. RESULTS: Those missing doses were not different from the total sample (61.5% female, 13.9 ±â€¯2.0 years, >80% racial/ethnic minorities). No baseline demographic or clinical predictors of barriers to medication adherence were identified. Among those for whom barriers were assessed, "forgetting" with no reason named (39.3%) and disruptions to mealtime, sleep, and schedule (21.9%) accounted for the largest proportion of responses. Family support was the primary adherence strategy identified by most youth (≥50%), followed by pairing the medication regimen with daily routines (>40%); the latter strategy was associated with significantly higher adherence rates (p = 0.009). CONCLUSIONS: Family supported medication adherence was common in this mid-adolescent cohort, but self-management strategies were also in evidence. Findings are similar to those reported among youth with other serious chronic diseases. Prospective studies of multi-component family support and self-management interventions for improving medication adherence are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00081328.

Weight change in the management of youth-onset type 2 diabetes: the TODAY clinical trial experience.

BACKGROUND: The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial documented that metformin plus rosiglitazone, but not metformin plus lifestyle intervention, provided superior durability of glycemic control relative to metformin monotherapy. OBJECTIVES: We examined weight changes among TODAY participants that completed at least 6 months of treatment, evaluated predictors of lifestyle outcome, and examined whether weight changes were related to cardiometabolic outcomes across treatment arms. METHODS: The 595 youth with type 2 diabetes, (85.1% of randomized participants aged 11-17 years) completed assessments of weight-related and cardiometabolic measures at months 0, 6, 12 and 24. Repeated measures models were used to investigate associations over time. RESULTS: Lifestyle intervention did not enhance outcome relative to metformin alone and no predictors of response to lifestyle treatment were identified. However, changes in percent overweight across treatment arms were associated with changes in multiple cardiometabolic risk factors, and decreases of ≥ 7% in overweight were associated with significant benefits over 24 months. CONCLUSIONS: Although adjunctive intensive lifestyle intervention did not improve weight-related outcomes, weight changes in the full TODAY sample were associated with small, but significant improvements in cardiometabolic status, highlighting the importance of optimizing weight management in youth with T2DM.

[Revision of the Taxonomic Position of the Olkhon Mountain Vole (Rodentia, Cricetidae)].

An analysis of the phylogenetic position of the Olkhon mountain vole (Alticolaolchonensis Litvinov 1960) using the sequences of four nuclear (BRCA, GHR, LCAT, and IRBP) and one mitochondrial (cyt. b) genes was undertaken. It was noted that, until recently, multiple studies of the systematic position of this vole had been based exclusively on morphological data, while the major taxonomic traits contained contradictory information regarding both the subgeneric status of this species and its genus. It was established that the molecular data and morphology data allow us to attribute the Lake Baikal vole unambiguously to the nominative subgenus Alticola instead of Aschizomys.

A cluster of invasive meningococcal disease revealed by the characterization of a novel serogroup B meningococcal clone.

The incidence of invasive infections due to Neisseria meningitidis in Israel is about 1/100 000 population annually. Three cases of meningococcal meningitis were reported in employees at a single plant; the first case appeared in March 2013 and the second and third cases appeared in December, almost 9 months later. N. meningitidis serogroup B was isolated from cerebrospinal fluid samples. Multilocus sequence typing assigned the three meningococcal isolates to ST10418, a new sequence type and a member of the ST32 clonal complex. The clonality was confirmed by performance of pulsed-field gel electrophoresis. Post-exposure antibiotic prophylaxis was administered to close contacts of the first case. Upon the diagnosis of the additional two cases, post-exposure prophylaxis was administered to all the plant employees. This report demonstrates the importance of combining public health measures and advanced laboratory studies to confirm clonality and to prevent further disease spread in a closed setting.

Characteristics of a large mumps outbreak: Clinical severity, complications and association with vaccination status of mumps outbreak cases.

In recent years, large mumps outbreaks, involving mainly adolescents and young adults, have re-emerged in several countries. We investigated a large mumps outbreak, evaluated the association between mumps clinical severity (complications, hospitalization) and vaccination status (number of previous measles, mumps and rubella - MMR vaccine doses), and assessed vaccine effectiveness. The first mumps cases emerged in an ultra-orthodox boys' school in Jerusalem and were epidemiologically linked to the mumps outbreak in New York. Overall, 3130 mumps cases were notified in the Jerusalem district during September 2009-August 2011 (median age 13y, 64% males). Most cases were reported from community clinics. Patients with systemic symptoms and/or complications (419, 13.4%) were either hospitalized (n = 79) or treated in an emergency medical center (n = 340). The main complications included orchitis (3.8% males> age 12y) and meningoencephalitis (0.5%). The mumps virus genotype was G5. The distribution of previous MMR vaccine doses (n = 0,1,2) was: 24.8%, 28.3% and 46.9%, respectively. The number of previous vaccine doses was inversely associated with clinical severity. Adjusted values for MMR vaccine effectiveness against complications were estimated as 52.1% (95% CI -4 -78%) for one vaccine dose and 62.7% (95% CI 25.7-81.3%) for 2 doses. The outbreak was characterized by predominance of male students; the majority of whom had been previously vaccinated. The reported complication rate was relatively low. Vaccination status was associated with age and disease severity. The combination of limited mumps vaccine effectiveness and the specific school setting (dense learning and living conditions) probably contributed to the disease spread.

Who are the children at risk? Lessons learned from measles outbreaks.

We investigated a measles outbreak in the Jerusalem district in 2007-2008 (992 cases). Most cases (72·6%) were aged <15 years, 42·9% aged <5 years, and 12·8% were infants aged <1 year. The peak incidence rate was in infants aged 6-12 months (916·2/100 000). This represents a significant shift from former outbreaks in 2003-2004, where the peak incidence was in the 1-4 years age group. Of children aged <5 years the proportion aged 6-12 months tripled (7·7% vs. 25·6%). In a case-control study (74 cases, 148 controls) children who developed measles were less likely to be registered in a well-baby clinic and had lower overall immunization coverage. The differences in proportions for registration, DTaP3 and MMR1 coverage were 35·1%, 48·6% and 80·8%, respectively (all P<0·001). Rising birth order of cases and their siblings was associated with non-registration and non-compliance with MMR immunization. The vulnerability of young infants and the risk markers noted above should be taken into account in planning intervention programmes.

[Supraspecies relationships in the subfamily (Rodentia, Cricetidae, Arvicolinae): unexpexted result of nuclear genes analysis].

Phylogenetic analysis of supraspecies relationships in one of the most young and species rich group of myomorph rodents - subfamily Arvicolinae was carried out on the base of two nuclear genes. Results have shown that mole-voles - Ellobiusini, steppe voles - (Lagurini) and grey voles (Arvicolini) are sister groups. This divergence is the most late, third wave of radiation within the family. The sister clade to this group is the tribe of red-back voles - Myodini (=Clethrionomini) - "second radiation". The order of divergence for earliest radiation remains still unresolved (Ondatrini, Prometheomyini, Dicrostonychini, Lemmini). New data on the close relationships of mole voles, grey voles and steppe voles are unexpected one and contradict to the conventional views. The latter ideas on the significant ancientry and separation of Ellobiusini from all other voles is based on extreme simplicity of their rooted molars and very peculiar structure of the skull and postcranial skeleton. However, many of these characters most likely indicate on significant degree of adaptation to the subterranean life and have no phylogenetic signal.

[Genetic variation and phylogeography of the bank vole (Clethrionomys glareolus, Arvicolinae, Rodentia) in Russia with special reference to the introgression of the mtDNA of a closely related species, red-backed vole (C. rutilus)].

Totally, 294 bank voles (Clethrionomys glareolus) and 18 red-backed voles (C. rutilus) from 62 sites of European Russia were studied. Incomplete sequences (967 bp) of the mitochondrial cytochrome b gene were determined for 93 C. glareolus individuals from 56 sites and 18 C. rutilus individuals from the same habitats. Analysis of the cytochrome b gene variation has demonstrated that practically the entire European part of Russia, Ural, and a considerable part of Western Europe are inhabited by bank voles of the same phylogroup, displaying an extremely low genetic differentiation. Our data suggest that C. glareolus very rapidly colonized over the presently occupied territory in the post-Pleistocene period from no more than two (central European and western European) refugia for ancestral populations with a small efficient size. PCR typing of the mitochondrial cytochrome b gene allowed us to assess the scale of mtDNA introgression from a closely related species, C. rutilus, and to outline the geographical zone of this introgression. Comparison with the red-backed vole haplotypes in the habitats shared by both species favors the hypothesis of an ancient hybridization event (mid-Holocene) and a subsequent introgression. These results suggest that the hybridization took place in the southern and middle Pre-Ural region.

The changing panorama of bacterial enteric infections.

We studied the age-specific population-based incidence of bacterial enteric infections caused by Shigella, Salmonella and Campylobacter, in Jerusalem. During 1990-2008, 32,408 cases were reported (incidence rate 232.1/100,000 per annum). The patterns of Shigella (47.4% of cases), Salmonella (34.4%) and Campylobacter (18.2%) infections evolved noticeably. Campylobacter rates increased from 15.0 to 110.8/100,000 per annum. Salmonella rates increased from 74.2 to 199.6/100,000 in 1995 then decreased to 39.4/100,000. Shigella showed an endemic/epidemic pattern ranging between 19.7 and 252.8/100,000. Most patients (75%) were aged <15 years; children aged <5 years comprised 56.4% of cases, despite accounting for only 12.9% of the population. Campylobacter was the predominant organism in infants aged <1 year and Shigella in the 1-4 years group. The hospitalization rates were: Shigella, 1.8%; Campylobacter, 2.3%; Salmonella, 6.9%. Infants were 2.2 times more likely to be hospitalized than children aged 1-14 years (P=0.001). Household transmission occurred in 21.2% of Shigella cases compared with 5% in the other bacteria.

Mumps outbreak in Jerusalem affecting mainly male adolescents.

From mid-September 2009 to 7 December 2009, 173 cases of mumps have been reported in the Jerusalem District. Most cases (82.1%) were male adolescents (median age 14.5 years) who are students in religious boarding schools. The majority of them (74%) are appropriately vaccinated for their age; 67% had received two doses of mumps-containing vaccine. An epidemiologic connection has been reported with visitors from New York, some of whom had recently had mumps.

An outbreak of measles in an ultra-orthodox Jewish community in Jerusalem, Israel, 2007--an in-depth report.

Measles elimination in Europe is hindered by recurrent outbreaks, typically in non-immunised specific sub-populations. In 2003 and 2004, two measles outbreaks occurred in Jewish ultra-orthodox communities in Jerusalem, Israel. In 2007, another measles outbreak emerged in Jerusalem. Epidemiological investigation and control activities were initiated. Three measles cases (15 years old, 22 years old and an infant; all unvaccinated) were diagnosed in Jerusalem in August 2007. All three belonged to Jewish ultra-orthodox communities in London, United Kingdom, and had had contact with patients in London. The epidemiological investigation did not reveal any connection between these cases other than their place of origin. The disease spread rapidly in extremely ultra-orthodox sub-groups in Jerusalem. Until 8 January 2008, 491 cases were reported. Most patients (70%) were young children (0-14 years old), 96% unimmunized. Frequently, all the children in a large family were infected; two thirds of the cases belonged to family clusters of more than two patients per family (in part due to non-compliance with post-exposure prophylaxis recommendations). The high age-specific incidence among infants 0-1-year- (408.5/100,000) and 1-4-year-olds (264.1/100,000) is a cause for concern. The hospitalisation rate was 15% (71/491), mainly due to fever, patients (26.7%) presented with pneumonitis or pneumonia and two patients presented with encephalitis. There have not been any deaths to date. The outbreak was apparently caused by measles importation into unprotected groups. Despite a high national immunisation coverage (94-95%), programmes to increase and maintain immunisation coverage are essential, with special focus on specific sub-populations.

[Evaluation of the gene encoding translation termination factor eRF3 as a possible phylogenetic marker].

We have tested if a part of nuclear gene GSPT2 encoding N and M domains of translation termination factor eRF3b could be applied as a new molecular marker, using order Rodentia as a model group. The proposed fragment cannot be used as a phylogenetic marker at intrageneric level because of low variability within families and impossibility to resolve relationships in family Cricetidae. However, this part of GSPT2 gene allows to divide higher taxa reliably. Phylogenetic relationships between families established using the proposed molecular marker mainly correspond with contemporary conceptions. The new marker indicates close relationship of genus Acomys with family Gerbillidae in agreement with other molecular data but opposing to morphological ones. Thus the part of gene GSPT2 encoding N and M domains of eRF3b protein can be applied as an adequate phylogenetic marker in placental mammals at family and higher taxonomic levels. Also it can be used while solving controversial questions of phylogeny and taxonomy.

Invasive meningococcal disease in children in Jerusalem.

Neisseria meningitidis is an important cause of childhood meningitis and septicaemia. Between 1999 and 2005, 133 invasive meningococcal disease (IMD) cases occurred in Jerusalem, 112 (84.2%) of them in children aged 0-14 years. The annual incidence rate in Jerusalem was higher than the national average (2.45+/-0.6 vs. 1.13+/-0.16/100 000 population, P=0.002). Most of the children (82.1%) were from low socio-economic Arab and Jewish ultra-orthodox communities; mortality was higher among Arab than Jewish children (1.3 vs. 0.22/100 000 person-years, P=0.004). A cluster of 10 children with severe meningococcal sepsis (three fatalities) emerged in the winter of 2003-2004. Compared to the other 102 cases in 1999-2005 both meningococcaemia (100% vs. 51%, P=0.003) and mortality (30% vs. 6.9%, P=0.014) rates were higher. Serogroup B comprised 77.6% of the bacterial isolates. Pulsed-field gel electrophoresis showed considerable variability among cluster isolates, but significant resemblance in Arab cases throughout 1999-2005. The increased susceptibility of specific sub-populations to IMD necessitates further evaluation.

Measles outbreaks affecting children in Jewish ultra-orthodox communities in Jerusalem.

In 2003 and 2004 two measles outbreaks occurred in Jewish ultra-orthodox communities in Jerusalem. The index case of the first outbreak (March 2003) was a 2-year-old unvaccinated child from Switzerland. Within 5 months, 107 cases (mean age 8.3+/-7.5 years) emerged in three crowded neighbourhoods. The first cases of the second outbreak (June 2004) were in three girls aged 4-5 years in one kindergarten in another community. By November 2004, 117 cases (mean age 7.3+/-6.5 years) occurred. The virus genotypes were D8 and D4 respectively. Altogether, 96 households accounted for the two outbreaks, with two or more patients per family in 79% of cases. Most cases (91.5%) were unvaccinated. Immunization coverage was lower in outbreak than in non-outbreak neighbourhoods (88.3% vs. 90.3%, P=0.001). Controlling the outbreaks necessitated a culture-sensitive approach, and targeted efforts increased MMR vaccine coverage (first dose) to 95.2%. Despite high national immunization coverage (94-95%), special attention to specific sub-populations is essential.

Improved resuscitation outcome in emergency medical systems with increased usage of sodium bicarbonate during cardiopulmonary resuscitation.

BACKGROUND: The use of sodium bicarbonate (SB) in cardiopulmonary resuscitation (CPR) is controversial. This study analyzes the effects of SB use on CPR outcome in the Brain Resuscitation Clinical Trial III (BRCT III), which was a multicenter randomized trial comparing high-dose to standard-dose epinephrine during CPR. Sodium bicarbonate use in BRCT III was optional. METHODS: The entire BRCT III database was reviewed. Analysis included only patients who arrested out of the hospital and whose time from collapse to initiation of ACLS was no longer than 30 min (total n = 2122 patients). Sodium bicarbonate use by the 16 participating study sites was analyzed. The study sites were divided according to their SB usage profile: 'low SB user' sites administered SB in less than 50% of CPRs and their first epinephrine to SB time exceeded 10 min; and 'high SB user' sites used SB in over 50% of CPRs and their first epinephrine to SB time was <10 min. RESULTS: Sites' SB usage rates ranged between 3.1% and 98.2% of CPRs. Sodium bicarbonate usage rates correlated inversely with the sites' intervals from collapse (r = - 0.579 P = 0.018) from initiation of ACLS (r = - 0.685 P = 0.003) and from first epinephrine (r = - 0.611 P = 0.012) to SB administration. Mean ROSC rate in the 'high SB user' sites was 33.5% (CI = 30.0-37.0) compared to 25.7% (CI = 23.1-28.4) in the 'low SB user' sites. In the 'high SB user' sites, hospital discharge rate was 5.3% (CI = 3.6-7.0) compared to 3% (CI = 2.0-4.0) in the 'low SB user' sites, and 5.3% (CI = 3.6-7.0) had a favorable neurological outcome compared to 2.1% (CI = 1.2-3.0) in the 'low SB user' sites. Collapse to ACLS interval was 8.5 min (CI = 8.1-9.0) in the 'high SB user' sites compared to 10.2 min (CI = 9.8-10.6) in the 'low SB user' sites, and their ACLS to first epinephrine interval was 7.0 min (CI = 6.5-7.5) compared to 9.7 min (CI = 9.3-10.2). Multivariate regression analysis found that belonging to 'high SB user' sites independently increased the chances for ROSC (OR 1.36, CI 1.08-1.7) and for achieving a good neurological outcome (OR 2.18, CI 1.23-3.86). CONCLUSIONS: Earlier and more frequent use of SB was associated with higher early resuscitability rates and with better long-term outcome. Sodium bicarbonate may be beneficial during CPR, and it should be subjected to a randomized clinical trial.