Gender Disparities in Financial Relationships Between Industry and Orthopaedic Surgeons.

BACKGROUND: Recent studies in a number of surgical subspecialties have demonstrated that financial relationships with industry differ between men and women. This study aimed to determine if gender disparities exist in industry relationships with orthopaedic surgeons. METHODS: This retrospective study utilized publicly available data from the Centers for Medicare & Medicaid Services (CMS) at OpenPayments.cms.gov. Data were extracted for payments made to orthopaedic surgeons from industry for royalties, licensing, or consulting fees from 2016 to 2017. A physician's profile was used to determine name, gender, practice location, and subspecialty. Years of experience were recorded from publicly available websites. Total number of payments and amounts were compared among men and women, subspecialties, and locations. Multivariable linear regression models were used to determine predictors of total payments and number of payments. RESULTS: Royalties and consulting fees were paid to 3,418 individual physicians (11% of 29,996 physicians in the American Academy of Orthopaedic Surgeons [AAOS] census) and accounted for 88% of total payments. The majority of the total payment amount (99.6%) was made to men, while only 0.4% went to women. Male gender was a predictor of total number of payments (ß = 5.17, p < 0.001), as were years of experience (ß = 0.15 [95% confidence interval (CI): 0.10 to 0.20], p < 0.001), Mountain region (ß = 2.77 [95% CI: 0.37 to 5.17], p = 0.02), and adult reconstructive subspecialty (ß = 4.07 [95% CI: 1.89 to 6.25], p < 0.001). Years of experience (ß = 0.046 [95% CI: 0.039 to 0.052], p < 0.001), male gender (ß = 1.09 [95% CI: 0.67 to 1.51], p < 0.001), Mountain region (ß = 0.35 [95% CI: 0.020 to 0.68], p = 0.04), and adult reconstructive subspecialty (ß = 0.33 [95% CI: 0.030 to 0.63], p = 0.03) were associated with higher payments. CONCLUSIONS: Male gender, years of experience, Mountain region, and adult reconstructive subspecialty are independent predictors of a higher number of industry payments and payment amount. These disparities in industry payments may contribute to continued inequities in scholarship, academic rank, and leadership opportunities.

Randomised trial of high frequency oscillatory ventilation or conventional ventilation in babies of gestational age 28 weeks or less: respiratory and neurological outcomes at 2 years.

BACKGROUND: The long term outcome of children entered into neonatal trials of high frequency oscillatory ventilation (HFOV) or conventional ventilation (CV) has been rarely studied. OBJECTIVE: To evaluate respiratory and neurodevelopmental outcomes for children entered into the United Kingdom Oscillation Study, which was designed to evaluate these outcomes. METHODS: Surviving infants were followed until 2 years of age corrected for prematurity. Study forms were completed by local paediatricians at routine assessments, and parents were asked to complete a validated neurodevelopmental questionnaire. RESULTS: Paediatricians' forms were returned for 73% of the 585 surviving infants. Respiratory symptoms were common in all infants, and 41% had received inhaled medication. Mode of ventilation had no effect on frequency of any symptoms. At 24 months of age, severe neurodevelopmental disability was present in 9% and other disabilities in 38% of children, but the prevalence of disability was similar in children who received HFOV or CV (relative risk 0.93; 95% confidence interval 0.74 to 1.16). The prevalence of disability did not vary by gestational age, but boys were more likely to have overall disability. Developmental scores were unaffected by mode of ventilation (relative risk 1.13; 95% confidence interval 0.78 to 1.63) and were lower in infants born before 26 weeks gestation compared with babies born at 26-28 weeks. CONCLUSIONS: Initial mode of ventilation in very preterm infants has no impact on respiratory or neurodevelopmental morbidity at 2 years. HFOV and CV appear equally effective for the early treatment of respiratory distress syndrome.

The mechanical joint score: a new clinical index of joint damage in rheumatoid arthritis.

OBJECTIVES: To evaluate the mechanical joint score (MJS) in terms of its reliability between observers and over time, its ease of use and its relationship with conventional measures of rheumatoid arthritis (RA) disease activity, severity and functional outcome. METHODS: The MJS was evaluated in 103 patients with reference to the following joints: total proximal interphalangeal (PIP) joints, total metacarpophalangeal (MCP) joints, wrists, elbows, shoulders, hips, knees, ankles and total metatarsophalangeal (MTP) joints. The score was based on the appearance of the joints on a scale of 0-3, 0 representing no abnormality and 3 severe abnormality or previous surgery. The MJS was evaluated in terms of its intra- and inter-observer variability and its content, construct and criterion validities. A subset of 29 patients were re-evaluated after 5 yr to examine change in MJS over time. RESULTS: The MJS performed well in terms of inter-observer and intra-observer reliability. The MJS showed strong correlation with the Larsen X-ray score of hands and feet (Spearman correlation coefficient 0.74) and with the modified Health Assessment Questionnaire (Spearman correlation coefficient 0.56) and only weak correlation with indices of disease activity, such as the Ritchie index and erythrocyte sedimentation rate. The MJS showed highly significant positive change over time. CONCLUSION: The MJS is a reliable clinical index of joint damage and may be a useful new outcome measure in RA.

HLA-DR and -DQ polymorphism in Cameroon.

HLA-DRB1, -DQA1 and -DQB1 allele frequencies were determined by high-resolution polymerase chain reaction using sequence-specific oligonucleotide probes (PCR-SSOP) and/or DNA sequencing in 126 healthy individuals in Cameroon. Eighteen DRB1, 11 DQA1, and 18 DQB1 alleles were observed. The most common alleles at each locus were DRB1*1503 (29%), DRB1*1301 (13%); DQA1*0102 (38%), DQA1*0302 (11%), DQA1*0401 (11%); and DQB1*0602 (31%), DQB1*0301 (13%), DQB1*0501 (12%). Forty-four different haplotypes were identified including 12 novel haplotypes demonstrating the HLA class II diversity resulting from allele combinations in this population. A single predominant DRB1*1503-DQA1*0102-DQB1*0602 haplotype was observed with a frequency of 27%. In summary, this study of HLA class II polymorphism in Cameroon demonstrates the extent of diversity in this population.

The current status of Balint groups in US family practice residencies: A 10-year follow-up study, 1990-2000.

BACKGROUND AND OBJECTIVES: In 1990, the first and, to date, only objective study of Balint groups in US family practice residencies was conducted to measure their prevalence, composition, leadership, and function. The study reported here collected similar information about Balint groups. METHODS: Surveys were sent to all 464 US family practice residency program directors, with a 1-month follow-up to nonrespondents. The survey included questions about the existence, leadership, meeting frequency, and objectives of Balint training. RESULTS: A total of 298 (64%) residencies responded. Almost half (48%) of US responding residences reported conducting Balint groups, and 40% of those residencies have more than one group. The frequency of Balint group meetings has shifted in the past 10 years. In 1990, 55% of groups met weekly; in 2000, only 15% of groups met weekly. Sixty-five percent of residencies require Balint participation. One third of Balint groups are conducted without a coleader and the number of physicians leading groups is 22%, a decrease of 10% from 10 years ago. Forty-four percent of groups are led by psychologists, an increase of 19% from 10 years ago. Respondents indicated uncertainly about whether their groups were true Balint groups or simply resident support groups. CONCLUSIONS: About half of US family practice residencies operate groups described as Balint groups. They meet less frequently then 10 years ago and are less likely to have a physician involved in group leadership. Some of the groups may actually be support groups rather than Balint groups.

HLA-B allele frequencies in Côte d'Ivoire defined by direct DNA sequencing: identification of HLA-B*1405, B*4410, and B*5302.

Direct automated DNA sequencing was used to analyze exons 2 and 3 of HLA-B alleles present in forty-four unrelated individuals residing in the village of Adiopodoume, Côte d'Ivoire (Ivory Coast). Of the 23 HLA-B alleles observed, the most frequently detected allele was HLA-B*5301 (22.7%), which is believed to confer resistance to severe Plasmodium falciparum malaria. B*4501 (9.1%), B*1503 (8.0%), B*0705 (5.7%), B*1510 (5.7%) and B*3501 (5.7%) occurred frequently in the population. A second allele of B53 was identified; B*5302 contains a single amino acid variation at residue 171 (Y-->H). Two additional novel alleles, B* 1405 (a single amino acid variant of B*1402) and B*4410 (a five amino acid variant of B*4403) were characterized.

Gastric antral vascular ectasia in systemic sclerosis: complete resolution with methylprednisolone and cyclophosphamide.

A case of severe, transfusion dependent anaemia in a 72 year old woman, which on endoscopy was found to be due to gastric antral vascular ectasia (GAVE), is reported. Repeated endoscopic sclerotherapy was ineffective. She subsequently developed Raynaud's phenomenon and on further investigation was found to have classical systemic sclerosis with lung involvement. Treatment with pulses of intravenous methylprednisolone and cyclophosphamide resulted in significant improvement in her pulmonary function tests and skin score. Coincidentally, her haemoglobin stabilised and further endoscopic examinations were normal. This is the first report of cyclophosphamide and methylprednisolone leading to complete and sustained resolution of GAVE in association with systemic sclerosis.

The Balint movement in America.

Michael Balint's (1896-1970) career evolultion from general practitioner (1918) to psychoanalyst (1926) and subsequently to general practitioner educator (1950) began at his home in Budapest and then moved from London to sites in the United States. His frequent visits to America, together with his wife Enid, were an influential force in promoting and training US-based Balint group leaders. Michael and Enid Balint's influence, together with the support of US physicians, South African physicians who became US citizens, and behavioral scientists, laid the foundation for the formation of an American Balint Society in 1990. The Society's educational and research efforts occurred primarily in family practice residencies and have grown over the past 10 years. The Society, is presently working to standardize credentialing of Balint group leaders to assure continued quality growth in the American Balint movement.

HLA type of EBV-transformed human B cell lines.

This appendix lists reference Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines (B-LCL) and the HLA types expressed by these cell lines. These B-LCL are useful for studies of cellular immunity (e.g., restriction of antigen-specific responses), biochemical characterization of histocompatibility molecules, and as controls for DNA-based typing methods.

A Dendroctonus bark engraving (Coleoptera: Scolytidae) from a middle Eocene Larix (Coniferales: Pinaceae): early or delayed colonization?

An engraving made by a scolytid bark beetle, assigned to the genus Dendroctonus of the tribe Tomicini, has been identified on a mummified, middle Eocene (45 Ma) specimen of Larix altoborealis wood from the Canadian High Arctic. Larix altoborealis is the earliest known species of Larix, a distinctive lineage of pinaceous conifers that is taxonomically identifiable by the middle Eocene and achieved a broad continental distribution in northern North America and Eurasia during the late Cenozoic. Dendroctonus currently consists of three highly host-specific lineages that have pinaceous hosts: a basal monospecific clade on Pinoideae (Pinus) and two sister clades that consist of a speciose clade associated exclusively with Pinoideae and six species that breed overwhelmingly in Piceoideae (Picea) and Laricoideae (Pseudotsuga and Larix). The middle Eocene engraving in L. altoborealis represents an early member of Dendroctonus that is ancestral to other congeneric species that colonized a short-bracted species of Larix. This fossil occurrence, buttressed by recent data on the phylogeny of Pinaceae subfamilies and Dendroctonus species, indicates that there was phylogenetically congruent colonization by these bark-beetle lineages of a Pinoideae + (Piceoideae + Laricoideae) host-plant sequence. Based on all available evidence, an hypothesis of a geochronologically early invasion during the Early Cretaceous is supported over an alternative view of late Cenozoic cladogenesis by bark beetles onto the Pinaceae. These data also suggest that host-plant chemistry may be an effective species barrier to colonization by some bark-beetle taxa over geologically long time scales.

Diversity is demonstrated in class I HLA-A and HLA-B alleles in Cameroon, Africa: description of HLA-A*03012, *2612, *3006 and HLA-B*1403, *4016, *4703.

To examine the genetic diversity in west Africa, class I HLA-A and HLA-B alleles of 92 unrelated individuals from two areas in the Cameroon, the capital Yaoundé and the village of Etoa, were identified by direct automated DNA sequencing of exons 2 and 3 of the HLA-B locus alleles and sequence-specific oligonucleotide probe (SSOP) and/or sequencing of the HLA-A locus alleles. HLA-A*2301 (18.7%), A*2902 (10.4%), B*5301 (10.9%), and B*5802 (10.9%) were the most frequently detected alleles, present in at least 10% of the population. A total of 30 HLA-A locus and 33 HLA-B locus alleles, including six novel alleles, were detected. The novel alleles were HLA-A*03012, A*2612, A*3006 and HLA-B*1403, B*4016, and B*4703. HLA-B*4703 contains a novel amino acid sequence that is a combination of the first 5 amino acids of the Bw6 epitope and the last 2 residues of the Bw4 epitope. The addition of 6 alleles to the ever-expanding number of known class I HLA alleles supports our hypothesis that extensive genetic diversity, including previously undescribed alleles, would be observed in this African population. In the Yaoundé population, the allele frequency distribution at the HLA-A locus is consistent with distributions indicative of balancing selection. Extensive HLA-A-B haplotypes were observed in this population suggesting that only a fraction of the Cameroon HLA-A-B haplotype diversity has been observed.

The chest radiograph appearances of very premature infants at 36 weeks post-conceptional age.

The chest radiograph of very premature infants at 36 weeks post-conceptional age (PCA) was evaluated with regard to the degree of hyperinflation and cardiomegaly, and the presence of fibrosis/interstitial shadowing, cystic elements, air bronchograms and opacification. The evolution of abnormalities was assessed by comparing the radiograph appearance at 36 weeks PCA with that at 28 days post-natal age (PNA). Three scoring systems were used to determine how any abnormalities present could be best quantified to reflect disease severity as determined by chronic dependency upon supplementary oxygen status. Chest radiographs at 36 weeks PCA from 60 infants (median gestational age 26 weeks (range 24-28)) were studied. 47 infants also had radiographs at 28 days PNA. Only three infants had no chest radiograph abnormalities at 36 weeks PCA, although 24 infants were not dependent upon supplementary oxygen. The most common abnormalities were interstitial shadowing and hyperinflation, while cystic elements and cardiomegaly were rare. The radiographic appearance had deteriorated from 28 days PNA to 36 weeks PCA (p < 0.05); more infants at 36 weeks PCA were hyperinflated (p < 0.01). The chest radiograph appearances of infants who were dependent upon supplementary oxygen scored higher than those who were not (p < 0.01) using all three scoring systems. The system that assessed only the presence of interstitial shadowing, cystic elements and hyperinflation had the highest specificity in identifying oxygen dependency beyond 36 weeks PCA and had the highest area under the respective receiver operator characteristic curve. In conclusion, the majority of very immature infants have an abnormal chest radiograph appearance at 36 weeks PCA. The appearance can, however, be meaningfully scored by evaluating only three abnormalities.

Characterization of conserved T- and B-cell epitopes in Plasmodium falciparum major merozoite surface protein 1.

Vaccines for P. falciparum will need to contain both T- and B-cell epitopes. Conserved epitopes are the most desirable, but they are often poorly immunogenic. The major merozoite surface protein 1 (MSP-1) is currently a leading vaccine candidate antigen. In this study, six peptides from conserved or partly conserved regions of MSP-1 were evaluated for immunogenicity in B10 congenic mice. Following immunization with the peptides, murine T cells were tested for the ability to proliferate in vitro and antibody responses to MSP-1 were evaluated in vivo. The results showed that one highly conserved sequence (MSP-1#1, VTHESYQELVKKLEALEDAV; located at amino acid positions 20 to 39) and one partly conserved sequence (MSP-1#23, GLFHKEKMILNEEEITTKGA; located at positions 44 to 63) contained both T- and B-cell epitopes. Immunization of mice with these peptides resulted in T-cell proliferation and enhanced production of antibody to MSP-1 upon exposure to merozoites. MSP-1#1 stimulated T-cell responses in three of the six strains of mice evaluated, whereas MSP-1#23 was immunogenic in only one strain. Immunization with the other four peptides resulted in T-cell responses to the peptides, but none of the resulting peptide-specific T cells recognized native MSP-1. These results demonstrate that two sequences located in the N terminus of MSP-1 can induce T- and B-cell responses following immunization in a murine model. Clearly, these sequences merit further consideration for inclusion in a vaccine for malaria.

Assessing the binding of four Plasmodium falciparum T helper cell epitopes to HLA-DQ and induction of T-cell responses in HLA-DQ transgenic mice.

A subunit vaccine for Plasmodium falciparum malaria will need to contain well-defined T helper cell epitopes that induce protective immune responses to the parasite. One major barrier to the use of subunit vaccines is the requirement for T helper cell epitopes to be presented by the HLA class II molecules that are present in the population being vaccinated. Since the majority of malaria studies have focused on HLA-DR, little information on the role of HLA-DQ in the binding and immune response to malarial epitopes is available. This study used an in vitro peptide-binding assay to predict the extent of HLA-DQ binding of four conserved T helper cell epitopes identified from asexual-stage malaria vaccine candidate antigens. Epstein-Barr virus (EBV)-transformed human B-cell lines expressing 14 different DQ molecules (DQ2.1, -2.2, -4.1, -4.2, -5.1 to -5.3, -6.1, -6.2, -6.4, -7.1, -7.3, -8, and -9) representing all broad serological specificities, including common DQ molecules present in populations in areas where malaria is endemic, were used in the binding assay. Moreover, an HLA-DQ transgenic mouse model was employed to evaluate the correlation between the in vitro DQ binding of the peptides and the generation of in vivo immune responses following peptide immunization. This study identified two broad DQ-binding peptides, ABRA#14 and SERA#9. ABRA#14 also induced T-cell proliferation and Th1-associated cytokine production in DQ8(+) transgenic mice. The combination of peptide binding to EBV-transformed cell lines and DQ transgenic mice provides a method for identifying additional T-cell epitopes for inclusion in a vaccine.

The epidemiology of Plasmodium falciparum malaria in two Cameroonian villages: Simbok and Etoa.

In support of ongoing immunologic studies on immunity to Plasmodium falciparum, demographic, entomologic, parasitologic, and clinical studies were conducted in two Cameroonian villages located 3 km apart. Simbok (population = 907) has pools of water present year round that provide breeding sites for Anopheles gambiae, whereas Etoa (population = 485) has swampy areas that dry up annually in which A. funestus breed. Results showed that individuals in Simbok receive an estimated 1.9 and 1.2 infectious bites per night in the wet and dry season, respectively, whereas individuals in Etoa receive 2.4 and 0.4 infectious bites per night, respectively. Although transmission patterns differ, the rate of acquisition of immunity to malaria appears to be similar in both villages. A prevalence of 50-75% was found in children < 10 years old, variable levels in children 11-15 years old, and 31% in adults. Thus, as reported in other parts of Africa, individuals exposed to continuous transmission of P. falciparum slowly acquired significant, but not complete, immunity.

A simple chest radiograph score to predict chronic lung disease in prematurely born infants.

A simple scoring system has been evaluated with regard to its ability to characterize the pre-term infant's chest radiograph appearance at 28 days and predict oxygen dependency beyond 36 weeks post-conceptional age (PCA). Chest radiographs taken at approximately 1 month of age in 42 infants (median gestational age 28 weeks) were assessed by the scoring system for the presence of fibrosis/interstitial shadows, cystic elements and degree of hyperinflation (maximum score 8). The system's results were then compared with those obtained using two previously published scoring systems. Using all three systems, there were significant differences in the scores of infants who were and were not oxygen dependent at 28 days (p < 0.001) and 36 weeks PCA (p < 0.001). For the three systems, the positive predictive values of a score of 3 or more to predict oxygen dependency at 36 weeks (PCA) were between 67% and 80% and similar receiver operating characteristic curves were obtained. We conclude that scoring only three abnormalities of the 28 day chest radiograph appearance of pre-term infants gives useful predictive information.

Balint group observations: the white knight and other heroic physician roles.

BACKGROUND: This article reports a typology of five roles that resident family physicians on occasion assume when relating to troubling patients presented in Balint group seminars. The five roles include the white knight (my way or no way), the Pogo look-alike (I feel your pain), the missing link (you made me do it), the surrogate (I can help), and the revolutionary (let me show you). Each role reflects a particular physician's coping behavior in the context of a specific troubling relationship and is driven, in large part, by unrealistic professional expectations. The roles intend to perform a heroic function in rescuing or protecting the patient, the family, or the physician from a distressing medical situation. Balint group work provides participants with the opportunity to derive clinically useful meaning from their presentations. Residents begin to imagine a variety of therapeutic (helpful) roles to replace the ones they were induced to fill. This process has implications for practicing physicians and physician teachers for improving patient and doctor satisfaction and well-being.