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Rationale: Targeted cancer therapies have revolutionized the field of oncology by selecting for specific molecular pathways, thus improving overall clinical prognosis. However, many of these targeted treatments have been reported to have adverse kidney effects, including acute kidney injury, interstitial nephritis, and glomerular disease. Furthermore, some of these targeted therapies have also been found to cause an asymptomatic rise in serum creatinine levels through inhibition of active tubular secretion. Presenting concerns: A 79-year-old woman was being followed for stage 4 A2 chronic kidney disease secondary to type 2 diabetes and longstanding hypertension. She was diagnosed with invasive mammary carcinoma and was initiated on letrozole, an aromatase inhibitor, and palbociclib, a selective cyclin-dependent kinase inhibitor, was subsequently added. Prior to the initiation of her treatments, her baseline estimated glomerular filtration rate (eGFR) fluctuated between 25 and 28 mL/min/1.73 m2 over the previous year. After initiating palbociclib, her serum creatinine progressively increased, despite having well-controlled blood pressure and diabetes. In addition, there was no history of pre-renal events nor any sonographic evidence of obstruction. Within 7 months, her eGFR based on serum creatinine had decreased down to 12 mL/min/1.73 m2. Interventions: Given that there were no clinical or other biochemical changes suggestive of worsening renal function, a serum cystatin C was measured using an immunoturbidimetric assay, which was 1.71 mg/L and correlated with an eGFR of 33 mL/min/1.73 m2 based on the chronic kidney disease epidemiology collaboration (CKD-EPI) cystatin C equation (2012). This value was consistent with her previous baseline. Based on these findings, the significant decrease in eGFR measured by serum creatinine was attributed to the inhibitory effects of palbociclib on tubular creatinine secretion, rather than representing true kidney damage. Thus, a kidney biopsy was not performed in this context. Outcomes: Seven months later, a repeat serum cystatin C was repeated to assess for any worsening of the patient’s kidney function and revealed an eGFR of 35 mL/min/1.73 m2 based on the CKD-EPI cystatin C equation (2012), thus revealing stable kidney function and reinforcing the inhibitory effects of palbociclib on tubular creatinine secretion through its direct effects on kidney transporters. Teaching points: This case report and literature review acknowledges the importance of using alternative methods of assessing kidney function when patients are undergoing targeted cancer therapies known to affect tubular creatinine secretion, which include cyclin-dependent kinase 4/6 inhibitors, poly(adenosine diphosphate-ribose) polymerase inhibitors, tyrosine kinase inhibitors, and mesenchymal-epithelial transition inhibitors. The use of non–creatinine-based markers of glomerular filtration rate (GFR), such as cystatin C and nuclear renal scans, will allow for more accurate estimation of kidney function in the appropriate setting, thus avoiding invasive diagnostic tests and unnecessary adjustments of treatment plans. However, certain targeted cancer therapies have also been proven to cause true kidney injury; therefore, physicians must still maintain a high degree of suspicion and consider invasive investigations and/or cessation or reduction of treatments when alternative measurements of kidney function do not suggest an underestimation of GFR via serum creatinine.

We undertook a systematic review of the diagnostic accuracy of artificial intelligence-based software for identification of radiologic abnormalities (computer-aided detection, or CAD) compatible with pulmonary tuberculosis on chest x-rays (CXRs). We searched four databases for articles published between January 2005-February 2019. We summarized data on CAD type, study design, and diagnostic accuracy. We assessed risk of bias with QUADAS-2. We included 53 of the 4712 articles reviewed: 40 focused on CAD design methods (“Development” studies) and 13 focused on evaluation of CAD (“Clinical” studies). Meta-analyses were not performed due to methodological differences. Development studies were more likely to use CXR databases with greater potential for bias as compared to Clinical studies. Areas under the receiver operating characteristic curve (median AUC [IQR]) were significantly higher: in Development studies AUC: 0.88 [0.82–0.90]) versus Clinical studies (0.75 [0.66–0.87]; p-value 0.004); and with deep-learning (0.91 [0.88–0.99]) versus machine-learning (0.82 [0.75–0.89]; p = 0.001). We conclude that CAD programs are promising, but the majority of work thus far has been on development rather than clinical evaluation. We provide concrete suggestions on what study design elements should be improved.

A rapid method, using PCR-restriction fragment length and single-strand conformation polymorphism (SSCP), was applied to screen for mutations of the fluoroquinolone resistance determinants in Streptococcus pneumoniae . One hundred nonduplicate Streptococcus pneumoniae isolates with ciprofloxacin MICs of ≥4.0 μg/ml from the Prince of Wales Hospital, Hong Kong, years 2000 to 2003, were examined. For each isolate, PCR amplicons of quinolone resistance-determining regions (QRDRs) of gyrA , gyrB , parC , and parE genes were digested with AluI, HinfI, Sau3AI, and MspI, respectively, and analyzed by SSCP. Each SSCP pattern was given a number, and each isolate obtained a four-digit code, e.g., 1111, that represented the SSCP profile. The SSCP patterns were correlated to mutations characterized from sequence analyses of PCR amplicons. The most common SSCP profile obtained was no. 5232 (40%), which included strains with two amino acid substitutions in the ParC (Lys-137-Asn) and ParE (Ile-460-Val) genes, followed by the SSCP profile 5223 (17%), which included strains with amino acid substitutions in the ParE (Ile-460-Val) gene only. Ten isolates (10%) with amino acid substitutions at GyrA and ParE (±ParC) genes were resistant to levofloxacin with a MIC of ≥16 μg/ml. Other SSCP profiles were unique in distinguishing the common amino acid substitutions in GyrA (Ser-81-Phe) and ParC (Lys-137-Asn, Ser-79-Phe plus Lys-137-Asn, Asp-83-Asn plus Lys-137-Asn, Ser-79-Phe, and Glu-96-Asp). SSCP analysis of restricted fragments generated patterns that were highly discriminative for mutations present in the QRDRs of gyrA , gyrB , parC , and parE . This method provides a database of high resolution profiles on these mutations and allows rapid screening for new mutations of the fluoroquinolone resistance genes.

Our objective was to examine health-related quality of life (HRQOL) in publicly insured children with special health care needs (CSHCN). Data were obtained from 183 caregivers of CSHCN (M = 10 years; 54% African American) in urban health clinics. CSHCN had poorer physical and psychosocial HRQOL than children in a normative sample. In regression analysis, children who had more health problems and more health visits in the previous 12 months had poorer physical HRQOL. Poorer psychosocial HRQOL was associated with more health problems and urban life stressors. Implications for practice and policy are discussed.

This study examined the relationship of community-level stressors to behavioral and emotional problems among African-American and white children with special health care needs.The authors interviewed 257 low-income caregivers of children with special health care needs in an urban Midwestern city who brought their child for a primary health care visit to a community health center between September 2001 and May 2002. Sociodemographic characteristics as well as information about the children's behavioral and emotional problems, the health status of the children, perceptions of urban community stress, access to health care, and satisfaction with health care were collected to determine racial differences in the impact of urban stress on behavioral and emotional problems.Urban community stressors, race, and child's health status were significantly associated with behavioral and emotional problems among children with special health care needs. The association between urban stress and total behavioral problems did not differ by race.When caring for children with special health care needs, especially those with emotional or behavioral problems, primary care providers may be better able to identify important aggravating factors if they also assess urban stress. Systems of care are needed that can assist in addressing urban community-level stressors.

This study examined caregiver perceptions of mental health problems and counseling needs in low-income children with special health care needs (CSHCN). Interviewers collected data from 257 caregivers of CSHCN (61% males; 60% African American; Mean age = 8.4 years) attending six Midwestern inner-city health clinics. Measures included the Child Behavior Checklist (CBCL) and an investigator-designed questionnaire. CBCL T-scores indicated that 38% of CSHCN had a behavioral or mental health problem, but only 26% of caregivers perceived the need for treatment or counseling. CSHCN should be assessed and referred appropriately for behavioral and mental health problems during routine health care visits.

Abstract 2074 Introduction: Patients hospitalized with acute medical illness have an elevated risk of venous thromboembolism (VTE). ACCP guidelines list various risk factors including active cancer, congestive heart failure (CHF), respiratory failure, chronic obstructive pulmonary disease (COPD), sepsis, advanced age, history of VTE and immobility. These guidelines also recommend prophylactic anticoagulation using fondaparinux, low molecular-weight heparin, or low-dose unfractionated heparin. This study examined pharmacologic prophylaxis against VTE among hospitalized medically ill patients and assessed demographic and clinical correlates related to VTE prophylaxis. Methods: A retrospective observational study was conducted with electronic medical records (EMR) in a large Midwestern U.S. public hospital and its network of outpatient clinics between 1999 and 2010. Patients >=40 years old were included if they were hospitalized with a primary diagnosis (ICD-9 code) of CHF, pneumonia, cancer, stroke, infectious diseases, sepsis, severe respiratory disorders (including COPD, asthma, and acute respiratory failure), inflammatory bowel disease (IBD), or neurologic disorders, or were hospitalized for VTE within the year before the index admission. Each patient's first qualifying hospitalization during the 12-year period was included in the analysis. Patients were excluded if the length of stay was 15,000 units/day) or enoxaparin (>40 mg/day) was started within one day of admission. Patients treated with warfarin (and not heparin or enoxaparin) were also excluded. Fondaparinux was not on the formulary. Prophylaxis was defined as present if the first dose (during the hospital stay) of anticoagulation with SC heparin or enoxaparin was lower than the treatment dose levels defined above. All IV heparin was considered to be at treatment-level doses. SC heparin records with missing doses were considered to be at prophylaxis-level doses. Logistic regression was used to examine factors associated with VTE prophylaxis. Results: Of 13,029 patients eligible for the study, mean age was 58.6 years; 51% were women; 47% were white, 47% African-American, 6% other; 58% had public healthcare coverage, 15% commercial insurance, 27% self-pay. Among patients with a BMI stored in the EMR, 44% were obese, 23% overweight, and 28% normal. There was a history of cigarette smoking in 44% and atrial fibrillation in 8%. The primary hospital diagnoses were infectious diseases 21.2%, cancer 19.9%, severe respiratory disorders 14.5%, pneumonia 12.7%, CHF 12.2%, stroke 9.6%, sepsis 8.9%, IBD The overall prophylaxis rate was 22.1% (14.8% for 1999–2002, 22.0% for 2003–2006, 28.5% for 2007–2010), including 11.8% with enoxaparin and 10.3% with SC heparin. Multivariable logistic regression showed that VTE prophylaxis was significantly associated with year of hospitalization (OR=2.2 for ‘07-’10, OR=1.7 for ‘03-’06 vs. ‘99-’02, P Conclusion: Pharmacologic VTE prophylaxis has increased significantly over the past 12 years but is still largely underused in patients hospitalized with acute medical illness. Multiple demographic, behavioral and clinical factors are associated with VTE prophylaxis during hospitalization. Further research is needed to examine if VTE prophylaxis is associated with reduced VTE risk and healthcare utilization. Disclosures: Rosenman: Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding. Liu:Pfizer: Employment. Phatak:Bristol-Myers Squibb: Employment. Qi:Pfizer: Research Funding; Bristol-Myers Squibb: Research Funding. Teal:Pfizer: Research Funding; Bristol-Myers Squibb: Research Funding. Nisi:Pfizer: Research Funding; Bristol-Myers Squibb: Research Funding. Liu:Pfizer: Employment, Equity Ownership. Ramacciotti:Bristol-Myers Squibb: Employment.

Worldwide, stigma and discrimination have been identified as tremendous barriers to addressing the HIV/AIDS epidemic, beginning with Jonathan Mann in the 1980s (Mann, 1987), and by others (UNAIDS, 2001, 2008; Reidpath, Brijnath and Chan, 2005; APN+, 2004). Stigma was defined by Goffman (1963) nearly half a century ago as a discrediting attribute about an individual or group that serves to devalue that person or group in the eyes of the society. More recent theoretical frameworks suggest that stigmatization and discrimination are manifest in a number of contexts, including within families, communities, schools, employment, travel/ migration opportunities, health-care settings and HIV/AIDS programmes (Parker and Aggleton, 2002), and in religion and the media (Malcolm and others, 1998). A study in four countries in Asia found pervasive discrimination, with 80 per cent of respondents having experienced AIDS-related discrimination, including nearly one in five facing discrimination within their families and in their workplaces (APN+, 2004). In a review of interventions to reduce HIV/AIDS stigma, Brown, MacIntyre and Trujillo (2003) noted that stigma affects prevention behaviours, test-seeking, care-seeking, quality of care provided to positive clients, and perceptions and treatment of people living with HIV and AIDS by communities and families. Parker and others (2002) contend that HIV/AIDS-related stigma is often layered upon other stigma, for example, the one associated with engaging in illegal behaviour, such as sex work and drug use. Furthermore, families with HIV-positive members often face stigma from the community. In order to combat stigma and the associated discrimination, it is important to understand the knowledge, beliefs and attitudes and how they vary across groups within a country. Such knowledge is critical for designing interventions to reduce stigma and discrimination.