Introduction and Aims
This paper proposes an approach for evaluating the validity of alternative low-risk drinking guidelines.
Design and Methods
Twenty-seven alternative guidelines were evaluated in terms of their ability to predict 9 measures of concurrent and prospective alcohol-related harm, using longitudinal data from a nationally representative sample of U.S. adults (n=26,438 to 12,339 depending upon outcome). Parameters compared included sensitivity, specificity, adjusted odds ratios and measures of model fit.
Performance varied by harm. The guidelines that best predicted concurrent alcohol-related harm comprised daily-only limits of 4/3 drinks for men/women, but gender-invariant limits of 4/4 drinks also performed well. Adding weekly limits did little to improve the prediction of concurrent harm. The guidelines that best predicted prospective harm comprised daily limits of 4/4 drinks combined with weekly limits of 14 drinks for men and 7 drinks for women, with weekly limits of 14/14 drinks running second. When concurrent and incident harms were aggregated, daily-only limits of 4/3 drinks performed nearly on a par with the combination of 14/14 drinks per week and 4/3 drinks per day.
This paper supported gender-specific daily limits and suggested that optimal guidelines might take daily limits from analyses of concurrent harms and weekly limits from analyses of prospective harms.
This paper illustrates a mechanism for validating the ability of low-risk drinking guidelines to accurately predict a range of alcohol-related harms, whereby countries could use their own data on consumption and its association with harm to evaluate their low-risk drinking guidelines.
drinking guidelines; alcohol-related harm; validity; prediction
Associations between overweight and obesity and medical conditions have been extensively studied, but little is known about their relationships to psychiatric disorders.
To present nationally representative findings on the prospective relationships between overweight and obesity and DSM-IV substance use, mood and anxiety disorders.
Design, Setting and Participants
Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative sample of 34,653 U.S. adults.
Main Outcome Measures
Incidence of DSM-IV substance use, mood and anxiety disorders and changes in BMI status during the 3-year follow-up.
Regression analyses that controlled for a wide array of covariates showed that overweight and obese women were at increased risk for incident major depressive disorder (MDD) during the follow-up period. Overweight men and obese men were at decreased risk of incident drug abuse and alcohol dependence, respectively. Obese women had a decreased risk of incident alcohol abuse and drug dependence. Men with drug dependence and women with specific phobia had a decreased risk of becoming overweight or obese during the follow-up.
The NESARC excluded adolescents and the homeless and weight was self-reported, but highly correlated with external validating data.
Increased risk of MDD among overweight and obese women could be attributed to stigma and greater body dissatisfaction among women in Western cultures. Overweight and obesity may serve as protective factors against developing incident substance use disorders possibly due to shared neural functions in the brain underlying addictions to numerous substances. Results are discussed in terms of their clinical implications including the need to update treatment guidelines for the management of overweight, obesity and MDD.
Objectives. To determine the incidence and type of premalignant or malignant changes in mammaplasty specimens and to determine the incidence of these changes according to age distribution. Methods. Retrospective database review of patients who underwent a reduction mammaplasty between 1999 and 2009 was performed from pathology records at a single institution. Results. 700 patients were identified. Of the 644 patients who had bilateral reductions, 25 (4%) had significant pathologic findings. The likelihood of finding premalignant changes or cancer increased with advancing patient age (0.8 percent for patients <40 years old and 10 percent for patients >60 years old). Of the 56 patients who underwent unilateral mammaplasty, 12 patients (21%) had significant pathologic findings. The incidence of finding premalignant changes or cancer in this population also increased with advancing patient age (0 for patients <40 years old to 25 percent for patients >60 years old). Conclusions. When a unilateral mammaplasty is performed to match a breast reconstructed after cancer surgery, the likelihood of identifying premalignant changes or cancer increases more than fourfold. Therefore, one should consider additional radiologic imaging in the preoperative workup of patients with a history of carcinoma prior to undergoing unilateral mammaplasty.
Prior research has demonstrated the dimensionality of Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria. The purpose of this study was to examine the dimensionality of hallucinogen and inhalant/solvent abuse and dependence criteria. In addition, we assessed the impact of elimination of the legal problems abuse criterion on the information value of the aggregate abuse and dependence criteria, another proposed change for DSM- IV currently lacking empirical justification.
Factor analyses and item response theory (IRT) analyses were used to explore the unidimisionality and psychometric properties of hallucinogen and inhalant/solvent abuse and dependence criteria using a large representative sample of the United States (U.S.) general population.
Hallucinogen and inhalant/solvent abuse and dependence criteria formed unidimensional latent traits. For both substances, IRT models without the legal problems abuse criterion demonstrated better fit than the corresponding model with the legal problem abuse criterion. Further, there were no differences in the information value of the IRT models with and without the legal problems abuse criterion, supporting the elimination of that criterion. No bias in the new diagnoses was observed by sex, age and race-ethnicity.
Consistent with findings for alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria, hallucinogen and inhalant/solvent criteria reflect underlying dimensions of severity. The legal problems criterion associated with each of these substance use disorders can be eliminated with no loss in informational value and an advantage of parsimony. Taken together, these findings support the changes to substance use disorder diagnoses recommended by the DSM-V Substance and Related Disorders Workgroup, that is, combining DSM-IV abuse and dependence criteria and eliminating the legal problems abuse criterion.
Hallucinogen use disorder; inhalant/solvent use disorder; DSM-V; item response theory; dimensionality
Research focusing on the development of a dimensional representation of DSM-IV nicotine dependence is scarce and prior research has not assessed the role of nicotine use criteria in that a dimensional representation, nor the invariance of the DSM-IV nicotine dependence criteria across important population subgroups.
Using a large, representative sample of the U.S. population, this study utilized item response theory (IRT) analyses to explore the dimensionality of DSM-IV nicotine dependence criteria and several candidate criteria for cigarette use among past-year cigarette smokers (n = 10,163).
Factor analyses demonstrated the unidimensionality of nicotine dependence criteria and IRT analyses demonstrated good fit of the observed responses and the underlying, unobserved latent trait of dependence severity. The model containing all seven DSM-IV dependence criteria, along with the consumption criterion of smoking at least a quarter of a pack of cigarettes in a day in the past year, was identified as the best-fitting model. No differential criterion functioning was shown across sex, race-ethnicity, and age subgroups.
Major implications of this study are discussed in terms of the addition of a dimensional representation of nicotine dependence to pre-existing categorical representations of the disorder in the DSM-V, and the need for a nicotine consumption criterion to improve representations of nicotine dependence severity.
Nicotine dependence; Item response theory; Nicotine use criterion; Psychiatric assessment; DSM-V revision
To examine variation in patients' access to a set of cancer drugs through publicly funded provincial drug programs.
Data Sources/Study Design:
We surveyed provincial drug program managers about their highest-expenditure intravenous and oral cancer drugs. We then investigated whether the same cancer drugs account for the highest expenditures across the provincial programs. We also compared the rates at which these drugs are accessed through these programs.
While there is moderate consistency in the selection of cancer drugs that account for the highest provincial expenditures, considerable differences were found in the rates at which some drugs are accessed across provincial programs.
The study demonstrates the existence of interprovincial variation in publicly funded access to cancer drugs even after these drugs have been approved for public coverage.
We previously reported the development of a human monoclonal antibody (CS-D7, IgG1) with specificity and affinity for the iron regulated surface determinant B (IsdB) of Staphylococcus aureus. CS-D7 mediates opsonophagocytic killing in vitro and protection in a murine sepsis model. In light of recent data indicating that IsdB specific T cells (CD4+, Th17), not Ab, mediate protection after vaccination with IsdB, it is important to investigate the mechanism of protection mediated by CS-D7. The mAb was examined to determine if it blocked heme binding to IsdB in vitro. The mAb was not found to have heme blocking activity, nor did it prevent bacterial growth under in vivo conditions, in an implanted growth chamber. To assess the role of the mAb Fc a point mutation was introduced at aa 297 (CS-D7·N297A). This point mutation removes Fc effector functions. In vitro analysis of the mutein confirmed that it lacked measurable binding to FcγR, and that it did not fix complement. The mutein had dramatically reduced in vitro opsonic OP activity compared to CS-D7. Nonetheless, the mutein conferred protection equivalent to the wild type mAb in the murine sepsis model. Both wild type and mutein mAbs were efficacious in FcγR deletion mice (including both FcγRII−/− mice and FcγRIII−/− mice), indicating that these receptors were not essential for mAb mediated protection in vivo. Protection mediated by CS-D7 was lost in Balb/c mice depleted of C3 with cobra venom factor (CFV), was lost in mice depleted of superoxide dismutase (SOD) in P47phox deletion mice, and as previously reported, was absent in SCID mice (Joshi et al., 2012). Enhanced clearance of S. aureus in the liver of CS-D7 treated mice and enhanced production of IFN-γ, but not of IL17, may play a role in the mechanism of protection mediated by the mAb. CS-D7 apparently mediates survival in challenged mice through a mechanism involving complement, phagocytes, and lymphocytes, but which does not depend on interaction with FcγR, or on blocking heme uptake.
iron regulated surface determinant B (IsdB); Staphylococcus aureus; vaccination; passive immunization; opsonophagocytosis
This study examined the prevalence of nicotine dependence (ND) and its associations with DSM-IV personality disorders (PDs) among current smokers (n=7,078), controlling for sociodemographic characteristics and comorbid Axis I and II disorders. Data were derived from a nationally representative sample of the U.S. population. Although all PDs were significantly associated with ND when sociodemographic factors were controlled, only schizotypal, borderline, narcissistic and obsessive-compulsive PDs were associated with ND after adding controls for Axis I and other Axis II disorders. These associations remained significant after controlling for degree of smoking exposure. The results suggest that both shared and PD-specific pathogenetic factors underlie these PD-ND associations. Implications are also discussed in terms of the relationship between personality features of schizotypal, borderline, narcissistic and obsessive-compulsive PDs and the self-medication hypothesis and the role of neurotransmission.
personality disorders; nicotine dependence; epidemiology; neurobiology; smoking exposure; self-medication hypothesis
The objective of this study was to present nationally representative findings on sociodemographic and psychopathologic predictors of first incidence of DSM-IV substance, mood and anxiety disorders using the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. One-year incidence rates of DSM-IV substance, mood and anxiety disorders were highest for alcohol abuse (1.02) alcohol dependence (1.70), major depressive disorder (MDD: 1.51) and generalized anxiety disorder (GAD: 1.12). Incidence rates were significantly greater (p < 0.01) among men for substance use disorders and greater among women for mood and anxiety disorders except bipolar disorder and social phobia. Age was inversely related to all disorders. Black individuals were at decreased risk of incident alcohol abuse and Hispanic individuals were at decreased risk of GAD. Anxiety disorders at baseline more often predicted incidence of other anxiety disorders than mood disorders. Reciprocal temporal relationships were found between alcohol abuse and dependence, MDD and GAD, and GAD and panic disorder. Borderline and schizotypal personality disorders predicted most incident disorders. Incidence rates of substance, mood and anxiety disorders were comparable to or greater than rates of lung cancer, stroke, and cardiovascular disease. The greater incidence of all disorders in the youngest cohort underscores the need for increased vigilance in identifying and treating these disorders among young adults. Strong common factors and unique factors appear to underlie associations between alcohol abuse and dependence, MDD and GAD, and GAD and panic disorder. The major results of this study are discussed with regard to prevention and treatment implications.
Incidence; epidemiology; prospective study; substance use disorders; mood disorders; anxiety disorders
To report the long-term outcomes and toxicity of a regimen of infusional paclitaxel delivered concurrently with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).
Between 1995 and 1999, 35 patients with non-metastatic stage III or IV SCCHN were treated with 3 cycles of paclitaxel as a 120-hour continuous infusion beginning days 1, 21, and 42 concurrent with radiation. The initial 16 patients received 105 mg/m2/cycle, and the subsequent 19 patients received 120 mg/m2/cycle. External beam radiation was delivered to 70.2–72 Gy in 5 fractions per week. Patients were followed to evaluate disease outcomes and the late toxicity of this regimen.
Median follow-up for all patients is 56.5 months. The median survival was 56.5 months and the median time to local recurrence was not reached. Fifteen patients (43%) developed hypothyroidism. Eleven of the 33 patients who underwent percutaneous endoscopic gastrostomy tube (PEG) placement were PEG-dependent until death or last follow-up. Five patients (14%) required a tracheostomy until death, while 3 patients (9%) suffered from severe esophageal stricture. All evaluated long term survivors exhibited salivary hypofunction. Fibrosis in the radiation field occurred in 24 patients (69%).
Concurrent chemo-radiation therapy with a 120-hour infusion of paclitaxel provides long-term local control and survival in patients with SCCHN.Xerostomia, hypothyroidism, esophageal and pharyngeal complications, and subcutaneous fibrosis were common long-term toxicities; however, the vast majority of toxicities were grade 1 or 2.
paclitaxel; radiation; toxicity; head and neck
Gluteus medius (GM) dysfunction is associated with many musculoskeletal disorders. Rehabilitation exercises aimed at strengthening GM appear to improve lower limb kinematics and reduce pain. However, there is a lack of evidence to identify which exercises best activate GM. In particular, as GM consists of three distinct subdivisions, it is unclear if GM activation is consistent across these subdivisions during exercise. The aim of this study was to determine the activation of the anterior, middle and posterior subdivisions of GM during weight-bearing exercises.
A single session, repeated-measures design. The activity of each GM subdivision was measured in 15 pain-free subjects using surface electromyography (sEMG) during three weight-bearing exercises; wall squat (WS), pelvic drop (PD) and wall press (WP). Muscle activity was expressed relative to maximum voluntary isometric contraction (MVIC). Differences in muscle activation were determined using one-way repeated measures ANOVA with post-hoc Bonferroni analysis.
The activation of each GM subdivision during the exercises was significantly different (interaction effect; p < 0.001). There were also significant main effects for muscle subdivision (p < 0.001) and for exercise (p < 0.001). The exercises were progressively more demanding from WS to PD to WP. The exercises caused significantly greater activation of the middle and posterior subdivisions than the anterior subdivision, with the WP significantly increasing the activation of the posterior subdivision (all p < 0.05).
Posterior GM displayed higher activation across all three exercises than both anterior and middle GM. The WP produced the highest %MVIC activation for all GM subdivisions, and this was most pronounced for posterior GM. Clinicians may use these results to effectively progress strengthening exercises for GM in the rehabilitation of lower extremity injuries.
To describe an asthma management protocol used in a nurse-staffed pediatric After-Hours Call Center (AHCC) that incorporates severity-based home treatment recommendations and follow-up call assessments. Call records for asthma advice from January 1, 2004 to June 30, 2004 were identified retrospectively and reviewed. Descriptive statistics were used to report patient demographics, frequencies of symptom severity zones (Red, Yellow, or Green) at initial calls, frequencies of call dispositions designating care advice provided (including home treatment recommendations and seeking emergency department [ED] care), and changes in severity zones between initial calls and follow-up calls when nurses reassessed patients after recommended home treatment. During the study period, 3,632 asthma calls (2,439 initial; 1,193 follow-up) were managed by AHCC nurses. Initial calls were classified mostly as Red (28%) or Yellow (42%) severity zones; 27% were Green zone and 3% could not be categorized. Fifty-two percent of initial calls with Red or Yellow severity zones involved home treatment recommendations; 50% of those Red zone and 63% of those Yellow zone calls had improved severity zones at follow-up call assessments. Twenty-eight percent of patients with home treatment recommendations were referred to the ED at the time of follow-up call nurse reassessment. This telephone-based nurse-staffed pediatric acute asthma management protocol includes provision of severity-based home treatment recommendations and follow-up assessments, and improved symptoms for many children with acute exacerbations. This protocol may also be successful in other locations and may improve outcomes, such as reduction in ED visits.
asthma; child; call center
To present nationally representative findings on prevalence, sociodemographic correlates, disability, and comorbidity of narcissistic personality disorder (NPD) among men and women.
Face-to-face interviews with 34,653 adults participating in the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions.
Prevalence of lifetime NPD was 6.2%, with rates greater for men (7.7%) than women (4.8%). NPD was significantly more prevalent among Black men and women and Hispanic women, younger adults, and separated/divorced/widowed and never married adults. NPD was associated with mental disability among men but not women. High co-occurrence rates of substance use, mood, anxiety, and other personality disorders (PDs) were observed. With additional comorbidity controlled for, associations with bipolar I disorder, PTSD, and schizotypal and borderline PDs remained significant, but weakened, among men and women. Similar associations were observed between NPD and specific phobia, generalized anxiety disorder, and bipolar II disorder among women; and alcohol abuse, alcohol dependence, drug dependence, and histrionic and obsessive-compulsive PDs among men. Dysthymia was significantly and negatively associated with NPD.
NPD is a prevalent PD in the general U.S. population and is associated with considerable disability among men, whose rates exceed those of women. NPD may not be as stable as previously recognized or described in the DSM-IV. The results highlight the need for further research from numerous perspectives to identify the unique and common genetic and environmental factors underlying the disorder-specific associations with NPD observed in this study.
To present nationally representative findings on prevalence, sociodemographic correlates, disability, and comorbidity of BPD among men and women.
Face-to-face interviews with 34,653 adults participating in the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions.
Prevalence of lifetime BPD was 5.9% (99% CI: 5.4–6.4). There were no differences in the rates of BPD among men (5.6%, 99% CI: 5.0–6.2) and women (6.2%, 99% CI: 5.6–6.9). BPD was more prevalent among Native American men, younger and separated/divorced/widowed adults, and those with lower incomes and education, and less prevalent among Hispanic men and women and Asian women. BPD was associated with substantial mental and physical disability, especially among women. High co-occurrence rates of mood and anxiety disorders with BPD were similar. With additional comorbidity controlled, associations with bipolar disorder and schizotypal and narcissistic PDs remained strong and significant. Associations of BPD with other specific disorders were no longer significant or were considerably weakened.
Prevalence of BPD in the general population is much greater than previously recognized, equal prevalent among men and women, and associated with considerable mental and physical disability, especially among women. Unique and common factors may differentially contribute to disorder-specific comorbidity with BPD and some of these associations appear to be sex-specific. There is a need for future epidemiologic, clinical and genetically-informed studies to identify unique and common factors that underlie disorder-specific comorbidity with BPD. Important sex differences observed in rates of and associations with BPD can inform more focused, hypothesis-driven investigations of these factors.
Magnetic resonance imaging (MRI) provides superior visualization of the prostate and surrounding anatomy, making it the modality of choice for imaging the prostate gland. This pilot study was performed to determine the feasibility and dosimetric quality achieved when placing high-dose-rate prostate brachytherapy catheters under MRI guidance in a standard “closed-bore” 1.5T scanner.
Methods and Materials:
Patients with intermediate-risk and high-risk localized prostate cancer received MRI-guided high-dose-rate brachytherapy boosts before and after a course of external beam radiotherapy. Using a custom visualization and targeting program, the brachytherapy catheters were placed and adjusted under MRI guidance until satisfactory implant geometry was achieved. Inverse treatment planning was performed using high-resolution T2-weighted MRI.
Ten brachytherapy procedures were performed on 5 patients. The median percentage of volume receiving 100% of prescribed minimal peripheral dose (V100) achieved was 94% (mean, 92%; 95% confidence interval, 89–95%). The urethral V125 ranged from 0% to 18% (median, 5%), and the rectal V75 ranged from 0% to 3.1% (median, 0.3%). In all cases, lesions highly suspicious for malignancy could be visualized on the procedural MRI, and extracapsular disease was identified in 2 patients.
High-dose-rate prostate brachytherapy in a standard 1.5T MRI scanner is feasible and achieves favorable dosimetry within a reasonable period with high-quality image guidance. Although the procedure was well tolerated in the acute setting, additional follow-up is required to determine the long-term safety and efficacy of this approach.
Prostate cancer; Brachytherapy; MRI; Image guidance
Angiogenesis, the development and recruitment of new blood vessels, plays an important role in tumour growth and metastasis. Vascular endothelial growth factor (VEGF) is an important stimulator of angiogenesis. Circulating and urinary VEGF levels have been suggested as clinically useful predictors of tumour behaviour, and investigations into these associations are ongoing. Despite recent interest in measuring VEGF levels in patients, little is known about the factors that influence VEGF levels in biospecimens. To begin to address this question, urine samples were collected from patients with solid tumours undergoing radiotherapy and healthy volunteers. Four factors were examined for their effects on VEGF concentrations as measured by chemiluminescent immunoassay: time from sample collection to freezing, number of specimen freeze-thaw cycles, specimen storage tube type and the inclusion or exclusion of urinary sediment. The results of this study indicate that time to freeze up to 4 hrs, number of freeze-thaw cycles between one and five, and different types of polypropylene tubes did not have statistically significant effects on measured urinary VEGF levels. Urinary sediment had higher VEGF levels than supernatant in five of six samples from healthy patients. It is not clear whether there is an active agent in the sediment causing this increase or if the sediment particles themselves are affecting the accuracy of the assay. Therefore, we recommend centrifuging urine, isolating the supernatant, and freezing the sample in polypropylene microcentrifuge tubes or cryogenic vials within 4 hrs of collection. In addition, we recommend the use of samples within five freeze-thaw cycles.
angiogenesis; VEGF; tumour markers; urine; biospecimens
To test whether intrarectal Amifostine limits symptoms of radiation proctitis as measured by the RTOG GI toxicity score and the expanded prostate cancer index composite (EPIC) score.
Methods and Materials
Patients with localized prostate cancer recieved Amifostine as a rectal suspension 30–45 min before daily 3D-conformal radiation treatments (3D-CRT). The first 18 patients received 1gm of Amifostine and the next 12 patients received 2gm. Toxicity was assessed at baseline, during treatment, and at follow-up visits using RTOG grading and the EPIC Quality of Life (QoL) 50 item questionnaire. The “Bowel Function” subset of the bowel domain (EPIC-BF), which targets symptom severity, and “Bowel Bother” subset of the bowel domain (EPIC-BB), which assesses quality of life, were evaluated and compared to the RTOG GI toxicity score.
Median follow-up was 30 months (range 18–36). Overall, the EPIC-BF and EPIC-BB scores both track closely with the RTOG GI toxicity score. Seven weeks after the start of radiation therapy, the incidence of RTOG Grade 2 toxicity was 33% in the 1gm group (6/18) compared with 0% (0/12) in the 2gm group and trended towards statistical significance (p=0.06). A significant difference between Amifostine groups was observed using the EPIC-BF score at 7 weeks (p=0.04). A difference in EPIC-BB score between dose groups was evident at 7 weeks (p=0.07) and was significant at 12 months (p=0.04).
Higher doses of Amifostine produce significant improvements in acute and late bowel QoL (up to one year following therapy) as measured by the EPIC score.
Amifostine; Prostate; Radiation-induced Proctitis; EPIC; Quality of Life
This study presents test-retest reliability statistics and information on internal consistency for new diagnostic modules and risk factor of alcohol, drug, and psychiatric disorders the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV (AUDADIS-IV). Test-retest statistics were derived from a random sample of 1,899 adults selected from 34,653 respondents who participated in the 2004–2005 Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Internal consistency of continuous scales was assessed using the entire Wave 2 NESARC. Both test and retest interviews were conducted face-to-face. Test-retest and internal consistency results for diagnoses and symptom scales associated with posttraumatic stress disorder, attention-deficit/hyperactivity disorder, and borderline, narcissistic, and schizotypal personality disorders were predominantly good (kappa > 0.63; ICC > 0.69; alpha > 0.75) and reliability for risk factor measures fell within the good to excellent range (intraclass correlations = 0.50–0.94; alpha = 0.64–0.90). The high degree of reliability found in this study suggests that new AUDADIS-IV diagnostic measures can be useful tools in research settings. The availability of highly reliable measures of risk factors of alcohol, drug, and psychiatric disorders will contribute to the validity of conclusions drawn from future research in the domains of substance use disorder and psychiatric epidemiology.
Reliability; alcohol and drug use disorders; risk factors; test-retest reliability; general population; internal consistency
To assess the feasibility and early toxicity of selective, IMRT-based dose escalation (simultaneous integrated boost) to biopsy proven dominant intra-prostatic lesions visible on MRI.
Patients with localized prostate cancer and an abnormality within the prostate on endorectal coil MRI were eligible. All patients underwent a MRI-guided transrectal biopsy at the location of the MRI abnormality. Gold fiducial markers were also placed. Several days later patients underwent another MRI scan for fusion with the treatment planning CT scan. This fused MRI scan was used to delineate the region of the biopsy proven intra-prostatic lesion. A 3 mm expansion was performed on the intra-prostatic lesions, defined as a separate volume within the prostate. The lesion + 3 mm and the remainder of the prostate + 7 mm received 94.5/75.6 Gray (Gy) respectively in 42 fractions. Daily seed position was verified to be within 3 mm.
Three patients were treated. Follow-up was 18, 6, and 3 months respectively. Two patients had a single intra-prostatic lesion. One patient had 2 intra-prostatic lesions. All four intra-prostatic lesions, with margin, were successfully targeted and treated to 94.5 Gy. Two patients experienced acute RTOG grade 2 genitourinary (GU) toxicity. One had grade 1 gastrointestinal (GI) toxicity. All symptoms completely resolved by 3 months. One patient had no acute toxicity.
These early results demonstrate the feasibility of using IMRT for simultaneous integrated boost to biopsy proven dominant intra-prostatic lesions visible on MRI. The treatment was well tolerated.
Fibrosis is a common side effect after treatment with ionizing radiation. Several methods to ameliorate debilitating fibrosis have been employed but without consistent results. The goal of this pilot study is to determine if Pirfenidone, a novel regulator of cytokine gene expression, has the potential to ameliorate established radiation-induced fibrosis.
Open label, prospective pilot study of 800 mg three times/day, orally administered Pirfenidone was administered to enrolled patients who were had completed radiation therapy and who had established radiation-induced fibrosis. Range of motion (ROM) was assessed using standard measures, and subjective measures of pain, fatigue, disability and global health were measured every three months.
Seven patients were enrolled of whom 3 had ROM assessments of 1 site and 2 had ROM assessments of 2 sites. Of these assessments, 6 revealed increased ROM during drug intervention while 1 revealed a decreased ROM. There was an overall improvement in the mental composite score of the SF36 while physical composite score was decreased and the vitality score was unchanged. Two patients were removed from the study because of syncopal episodes.
Several patients experienced improved function of at least 25% and reported subjective improvement. Pirfenidone may benefit patients with radiation-induced fibrosis and is worthy of a larger well controlled trial.
The majority of existing human papillomavirus (HPV) genotyping assays are based on multiplex PCR using consensus or degenerate primers. We developed a Templex HPV assay that simultaneously detects and identifies 25 common HPV genotypes in a single-tube reaction using type-specific primers for the HPV-specific E6 and E7 genes. The analytical sensitivities of the Templex assay for HPV type 16 (HPV-16), -18, and -56 were 20, 100, and 20 copies per reaction mixture, respectively. The Templex assay provides semiquantitative information on each type when multiple HPV types coexist in one reaction. We tested 109 clinical cervical specimens previously evaluated with the Digene HC2 high-risk HPV DNA test and found 95.4% concordance between the assay results. The Templex assay provided type-specific results and found multiple types in 29.2% (14 of 48) of high-risk HPV-positive samples. The entire Templex procedure, including DNA extraction, can be completed within 5 hours, providing a rapid and reliable diagnostic tool for HPV detection and typing that is amenable to automation.
To report early observation of transient PSA elevations on this pilot study of external beam radiation therapy and magnetic resonance imaging (MRI) guided high dose rate (HDR) brachytherapy boost.
Materials and methods
Eleven patients with intermediate-risk and high-risk localized prostate cancer received MRI guided HDR brachytherapy (10.5 Gy each fraction) before and after a course of external beam radiotherapy (46 Gy). Two patients continued on hormones during follow-up and were censored for this analysis. Four patients discontinued hormone therapy after RT. Five patients did not receive hormones. PSA bounce is defined as a rise in PSA values with a subsequent fall below the nadir value or to below 20% of the maximum PSA level. Six previously published definitions of biochemical failure to distinguish true failure from were tested: definition 1, rise >0.2 ng/mL; definition 2, rise >0.4 ng/mL; definition 3, rise >35% of previous value; definition 4, ASTRO defined guidelines, definition 5 nadir + 2 ng/ml, and definition 6, nadir + 3 ng/ml.
Median follow-up was 24 months (range 18–36 mo). During follow-up, the incidence of transient PSA elevation was: 55% for definition 1, 44% for definition 2, 55% for definition 3, 33% for definition 4, 11% for definition 5, and 11% for definition 6.
We observed a substantial incidence of transient elevations in PSA following combined external beam radiation and HDR brachytherapy for prostate cancer. Such elevations seem to be self-limited and should not trigger initiation of salvage therapies. No definition of failure was completely predictive.
In the laboratory situation the preferences of dogs and cats for food seem to be relatively uniform. Cats prefer fish and commercial cat food to rats. Dogs prefer beef, pork and lamb to chicken, liver and horsemeat and strongly prefer meat to cereal diets. They prefer canned meat to fresh meat, ground meat to cubed meat and cooked meat to raw meat. Canned or semimoist preparations are preferred to dry ones. Pet dogs have much more variable preferences according to their owner's subjective evaluation. A variety of factors seem to be related in an as yet unknown way to some flavor preferences of pet dogs, i.e. the dog's sex/reproductive status, weight and relationship to owners and the content of the dog's meals. The complicated interaction between (a) a pet's taste, texture and olfactory sensation, (b) its owner's perception of the pet and its preferences and (c) its physical and social environment deserves further investigation.
Obesity can result from endocrinological causes such as those following ovariohysterectomy, but most cases appear to be related to owner-induced variables. In a kennel situation most, but not all, dogs can be allowed free access to palatable food without becoming obese.