Validation of a Midfacial Scale and Its Use in a Randomized, Evaluator-Blinded Study of CPM-HA-V.

BACKGROUND: Age-related loss of midfacial contour is frequently corrected using dermal fillers. A validated photonumeric scale is beneficial when evaluating post-treatment aesthetic improvement. OBJECTIVE: To present scale-development activities for the Merz Cheek Fullness Assessment Scale (MCFAS) and report pilot-study results of a hyaluronic-acid filler (Belotero Volume with Lidocaine; CPM-HA-V) to treat midfacial volume loss. METHODS: A 5-point photonumeric scale was developed to objectively assess midface volume loss. Rater reliability was evaluated using live assessments. The clinical relevance of a 1-point difference in severity grade was evaluated using photographic comparisons. Pilot-study participants, with moderate-to-severe volume loss on the MCFAS, were randomized 2:1 to treatment or untreated control. Effectiveness was evaluated using the MCFAS, and adverse events were recorded. RESULTS: The MCFAS demonstrated substantial intra- and interrater agreement among physicians (weighted kappa > 0.6). The mean absolute difference (95% confidence interval) in scale ratings was 1.12 (1.00, 1.24) for photographic pairs differing by one grade and was 0.55 (0.48, 0.63) for pairs of the same grade, suggesting a 1-point difference is clinically relevant. In the pilot study, significant  (P < 0.0001) differences were observed in MCFAS response rates between treatment and control. No safety concerns were identified. CONCLUSION: The MCFAS is a validated, reliable, and clinically relevant photonumeric scale for rating midfacial volume loss in males and females of various ages and skin types. In a pilot study, CPM-HA-V was found to be safe and tolerable, and the MCFAS was able to detect clinically meaningful post-treatment changes. J Drugs Dermatol. 2024;23(1):     doi:10.36849/JDD.7981.

Adding multiple risk factors improves Framingham coronary heart disease risk scores.

PURPOSE: Since the introduction of the Framingham Risk Score (FRS), numerous versions of coronary heart disease (CHD) prediction models have claimed improvement over the FRS. Tzoulaki et al challenged the validity of these claims by illustrating methodology deficiencies among the studies. However, the question remains: Is it possible to create a new CHD model that is better than FRS while overcoming the noted deficiencies? To address this, a new CHD prediction model was developed by integrating additional risk factors, using a novel modeling process. METHODS: Using the National Health Nutritional Examination Survey III data set with CHD-specific mortality outcomes and the Atherosclerosis Risk in Communities data set with CHD incidence outcomes, two FRSs (FRSv1 from 1998 and FRSv2 from National Cholesterol Education Program Adult Treatment Panel III), along with an additional risk score in which the high density lipoprotein (HDL) component of FRSv1 was ignored (FRSHDL), were compared with a new CHD model (NEW-CHD). This new model contains seven elements: the original Framingham equation, FRSv1, and six additional risk factors. Discrimination, calibration, and reclassification improvements all were assessed among models. RESULTS: Discrimination was improved for NEW-CHD in both cohorts when compared with FRSv1 and FRSv2 (P<0.05) and was similar in magnitude to the improvement of FRSv1 over FRSHDL. NEW-CHD had a similar calibration to FRSv2 and was improved over FRSv1. Net reclassification for NEW-CHD was substantially improved over both FRSv1 and FRSv2, for both cohorts, and was similar in magnitude to the improvement of FRSv1 over FRSHDL. CONCLUSION: While overcoming several methodology deficiencies reported by earlier authors, the NEW-CHD model improved CHD risk assessment when compared with the FRSs, comparable to the improvement of adding HDL to the FRS.

Associations between selected laboratory tests and all-cause mortality.

OBJECTIVE: Evaluate the association of selected laboratory tests including liver function, kidney function, bilirubin, and albumin, with all-cause mortality METHOD: Associations between several laboratory tests and mortality were assessed in two longitudinal datasets: (1) the Third National Health and Nutritional Examination Survey (NHANES III) with 4610 deaths during the 240,428 person-year follow up: and (2) a life insurance dataset containing historical life insurance policies issued as standard and better risk class, with 837 death claims generated during the approximate 1.4 million person-years of follow up. A Cox proportional hazards model was used to compute the hazard ratio of each selected laboratory test while adjusting for age, gender, and other health conditions. Separate analyses were conducted for laboratory results within and beyond the respective normal clinical range. RESULTS: When outside the normal clinical range, the results of several selected laboratory tests were associated with higher mortality, as indicated by a hazard ratio greater than 1. Comparisons of hazard ratios when laboratory results were within the normal range demonstrated that blood albumin and blood urea nitrogen (BUN) were both negatively associated with mortality and alkaline phosphatase (AP) was positively associated with mortality. The associations were shown to be independent and were consistent in two datasets. CONCLUSIONS: Although abnormal laboratory results are significant predictors of higher mortality, when results fall within the normal clinical range, only three tests--albumin, AP, and BUN--provided mortality differentiation. These findings support the utilization of the actual, continuous value from albumin, AP, and BUN tests to evaluate mortality during underwriting, even when these results are categorized as clinically normal. Furthermore, the results provide an insightful perspective for evaluating the utility of recently developed, laboratory test-based underwriting toools.

Relationship between selected social factors and all-cause mortality.

OBJECTIVE: Evaluate the associations between several simple-to-measure social factors and all-cause mortality to determine whether selected social factors contribute useful mortality information. METHOD: Using the Third National Health and Nutritional Examination Survey (NHANES III) and the current NHANES III Linked Mortality File datasets, associations were evaluated among 18,460 survey participants at least 20 years of age, with 5408 deaths occurring during the 280,183 person-year follow-up. Selected social factors, including education level, current employment status, and frequency of interpersonal contact with friends/relatives, were analyzed using a Cox proportional hazard model, and the impact of the selected social factors on mortality was expressed as a hazard ratio. Associations were modeled adjusting for age and gender only and also in a multivariate regression analysis; furthermore, associations were evaluated when stratified by duration of follow up. RESULTS: In a multivariate Cox model, independent hazard ratios for higher education, being employed, being married, frequent phone conversations with friends, frequent visits with friends or relatives, frequent church attendance, and participation in a social group ranged between 0.56 and 0.99. All corresponding 95% confidence intervals exclude 1. Many of the associations between social factors and mortality were stronger at shorter follow-up durations. CONCLUSION: Several easy-to-measure social factors were shown to be significantly and independently associated with all-cause mortality.

Prevalence of opioid dispensings and concurrent gastrointestinal medications in an elderly population from Ontario, Canada.

BACKGROUND: Although opioid analgesics are effective therapeutic agents, gastrointestinal (GI) side effects represent a challenging consequence of treatment. In an elderly population, age-related physiological changes, such as decreased GI functioning and dehydration, may compound the adverse effects of opioids; therefore, appropriate prophylactic treatment, utilizing laxatives and/or acid suppressants, is particularly important in an elderly population. AIM: This study describes the prevalence of outpatient opioid dispensings and the concomitant dispensing of opioids and GI medications in a population 65 years or older enrolled in the Ontario Drug Benefit Program in 2005. METHODS: Using a retrospective cohort design, dispensings of opioids, laxatives, and acid suppressants were identified using claims reimbursement data. Concurrent dispensings were defined as having at least one "GI medication-dispensed day" overlapping an "opioid-dispensed day". RESULTS: More than 18 percent of the elderly, drug plan population was dispensed an opioid in 2005. Women had more opioid dispensings and were dispensed opioids for extended periods of time as compared with men. Approximately half of patients with an opioid dispensing were concomitantly dispensed a GI medication; these medications were dispensed nearly twice as frequently among people with chronic opioid dispensings when compared with people with nonchronic opioid dispensings. CONCLUSIONS: Although laxatives are commonly recommended in patients taking opioids, only half of the older adults in Ontario who were dispensed an opioid also received a concomitant GI medication dispensing. As the elderly are more likely to develop opioid-induced constipation, the prophylactic use of laxatives and/or acid suppressant medications is often necessary to mitigate the side effects associated with their pain management.

Bartonella species in blood of immunocompetent persons with animal and arthropod contact.

Using PCR in conjunction with pre-enrichment culture, we detected Bartonella henselae and B. vinsonii subspecies berkhoffii in the blood of 14 immunocompetent persons who had frequent animal contact and arthropod exposure.

A combined approach for the enhanced detection and isolation of Bartonella species in dog blood samples: pre-enrichment liquid culture followed by PCR and subculture onto agar plates.

Historically, direct plating, lysis centrifugation, or freeze-thaw approaches have proven to be highly insensitive methods for confirming Bartonella species infection in dogs. A prospective study was designed to compare diagnostic methods for the detection of Bartonella using samples submitted to the Vector-Borne Disease Diagnostic Laboratory at North Carolina State University. Methods included indirect immunofluorescence assay, PCR, direct inoculation of a blood agar plate (trypticase soy agar with 5% rabbit blood), and inoculation into a novel pre-enrichment liquid medium, Bartonella/alpha-Proteobacteria growth medium (BAPGM). Sequential research efforts resulted in the development of a combinational approach consisting of pre-enrichment culture of Bartonella species in BAPGM, sub-inoculation of the liquid culture onto agar plates, followed by DNA amplification using PCR. The multi-faceted approach resulted in substantial improvement in the microbiological detection and isolation of Bartonella when compared to direct inoculation of a blood agar plate. Importantly, this approach facilitated the detection and subsequent isolation of both single and co-infections with two Bartonella species in the blood of naturally infected dogs. The use of a combinational approach of pre-enrichment culture and PCR may assist in the diagnostic confirmation of bartonellosis in dogs and other animals.

Detection of Bartonella henselae DNA in two dogs with pyogranulomatous lymphadenitis.

CASE DESCRIPTION: 1 dog evaluated because of inappetence and lameness of the left hind limb of 1 day's duration and 1 dog evaluated because of inappetence, fever, and lymphadenopathy of 2 weeks' duration. CLINICAL FINDINGS: Histologic examination of excisional biopsy specimens from lymph nodes revealed pyogranulomatous lymphadenitis in both dogs. Quantitative real-time PCR assays detected Bartonella henselae DNA in blood samples and affected lymph node specimens from both dogs. Antibodies against B. henselae were not detected via immunofluorescent antibody testing during active disease in either dog. TREATMENT AND OUTCOME: 1 dog recovered after 6 weeks of treatment with doxycycline (5 mg/kg [2.3 mg/lb], p.o., q 12 h), whereas the other dog recovered after receiving a combination of azithromycin (14.5 mg/kg [6.6 mg/lb], p.o., q 24 h for 21 days), doxycycline (17.3 mg/kg [7.9 mg/lb], p.o., q 24 h for 4 weeks), and immunosuppressive corticosteroid (prednisone [3 mg/kg {1.4 mg/lb}, p.o., q 24 h], tapered by decreasing the daily dose by 25% every 2 weeks) treatment. CLINICAL RELEVANCE: B. henselae is implicated as a possible cause or a cofactor in the development of pyogranulomatous lymphadenitis in dogs. In dogs with pyogranulomatous lymphadenitis, immunofluorescent assays may not detect antibodies against B. henselae. Molecular testing, including PCR assay of affected tissues, may provide an alternative diagnostic method for detection of B. henselae DNA in pyogranulomatous lymph nodes.

Bartonella DNA in dog saliva.

Bartonella species, transmitted by arthropods or animal bites and scratches, are emerging pathogens in human and veterinary medicine. PCR and DNA sequencing were used to test oral swabs collected from dogs. Results indicated the presence of 4 Bartonella species: B. bovis, B. henselae, B. quintana, and B. vinsonii subspecies berkhoffii.

The dog as a sentinel for human infection: prevalence of Borrelia burgdorferi C6 antibodies in dogs from southeastern and mid-Atlantic States.

Lyme disease is the most frequently reported human vector-associated disease in the United States. Infection occurs after the bite of an Ixodid tick that is infected with Borrelia burgdorferi. Dogs have often been reported to serve as effective sentinel animals to assess the risk of human B. burgdorferi infection. Based on published data of human Lyme disease case numbers and our clinical impressions, we hypothesized that canine exposure to B. burgdorferi would be lower in North Carolina when compared to the exposure in Virginia, Maryland, and Pennsylvania. To address this hypothesis, we evaluated B. burgdorferi exposure status utilizing a specific and sensitive C6 peptide-based enzyme-linked immunosorbent assay. Our convenience sample included 1,666 canine serum samples submitted to the Vector-Borne Disease Diagnostic Laboratory from North Carolina (n = 987), Virginia (n = 472), Maryland (n = 167), and Pennsylvania (n = 40). Comparisons among states were made using the Chisquare test or the Fisher's exact test; p-values were adjusted for multiple comparisons using the Bonferroni correction. A Chi-square test for trend was used to determine if there was an increase in the frequency of seroreactors associated with the geographical origin of the samples. The proportion of seroreactive dogs in North Carolina was markedly lower (p < 0.008) than that observed in dogs from Virginia, Maryland, and Pennsylvania. These results support the hypothesis that B. burgdorferi transmission seems to occur infrequently in North Carolina dogs as compared to dogs residing in other southeastern and mid-Atlantic states. Furthermore, they support the utility of dogs as a sentinel to characterize the risk of B. burgdorferi transmission to humans in a defined geographical location.

Novel chemically modified liquid medium that will support the growth of seven bartonella species.

Bacteria of the genus Bartonella, a member of the Alphaproteobacteria, are fastidious, gram-negative, aerobic bacilli that comprise numerous species, subspecies, and subtypes. In human and veterinary medicine, species isolation remains a vital component of the diagnostic and therapeutic management of Bartonella infection. We describe a novel, chemically modified, insect-based liquid culture medium that supports the growth of at least seven Bartonella species. This medium will also support cocultures consisting of different Bartonella species, and it facilitated the primary isolation of Bartonella henselae from blood and aqueous fluid of naturally infected cats. This liquid growth medium may provide an advantage over conventional direct blood agar plating for the diagnostic confirmation of bartonellosis.

The dog as a sentinel for human infection: prevalence of Borrelia burgdorferi C6 antibodies in dogs from southeastern and mid-Atlantic states.

Lyme disease is the most frequently reported human vector-associated disease in the United States. Infection occurs after the bite of an Ixodid tick that is infected with Borrelia burgdorferi. Dogs have often been reported to serve as effective sentinel animals to assess the risk of human B. burgdorferi infection. Based on published data of human Lyme disease case numbers and our clinical impressions, we hypothesized that canine exposure to B. burgdorferi would be lower in North Carolina when compared to the exposure in Virginia, Maryland, and Pennsylvania. To address this hypothesis, we evaluated B. burgdorferi exposure status utilizing a specific and sensitive C6 peptide-based enzyme-linked immunosorbent assay. Our convenience sample included 1,666 canine serum samples submitted to the Vector Borne Disease Diagnostic Laboratory from North Carolina (n = 987), Virginia (n = 472), Maryland (n = 167), and Pennsylvania (n = 40). Comparisons among states were made using the Chi-square test or the Fisher's exact test; p-values were adjusted for multiple comparisons using the Bonferroni correction. A Chi-square test for trend was used to determine if there was an increase in the frequency of seroreactors associated with the geographical origin of the samples. The proportion of seroreactive dogs in North Carolina was markedly lower (p < 0.008) than that observed in dogs from Virginia, Maryland, and Pennsylvania. These results support the hypothesis that B. burgdorferi transmission seems to occur infrequently in North Carolina dogs as compared to dogs residing in other southeastern and mid-Atlantic states. Furthermore, they support the utility of dogs as a sentinel to characterize the risk of B. burgdorferi transmission to humans in a defined geographical location.