Size and environment: The effect of phonon localization on micro-Brillouin imaging.

Specifically designed samples have been analyzed to test the ability of Brillouin spectroscopy to provide reliable mechanical characterization of micro and nano-objects. The selected samples are polymeric films, whose transversal sizes from hundreds of nano- to some micro-meters cover the entire range of length-scales relevant in Brillouin scattering process. The experimental data highlight how, the size of the extended collective oscillation (acoustic phonons, in brief) is the lowest spatial resolution reachable in Brillouin mechanical characterization. Conversely, in the limit condition of phonon confinement, the technique provides the mechanical properties of nano-objects whose characteristic size is comparable with the phonon wavelength (⁓300 nm). Investigating acoustically heterogeneous materials, both size of heterogeneity and acoustic mismatch between adjacent regions are shown to be relevant in shaping the Brillouin response. In particular, a transition from a confined to a non-confined condition is obtained modulating the acoustic mismatch between the micro-objects and their local environment. The provided results and the derived analytic models for the data analysis will guide the interpretation of Brillouin spectra acquired in complex nano-structured samples such as cells, tissues or biomimetic materials. Our analysis can therefore generate new insights to tackle fundamental problems in mechanobiology or to characterize new bioengineered materials.

EORTC QLU-C10D value sets for Austria, Italy, and Poland.

OBJECTIVE: To develop Austrian, Italian, and Polish general population value sets for the EORTC QLU-C10D, a cancer-specific utility instrument based on the EORTC QLQ-C30, and to descriptively compare their index scores for distinct health states. METHODS: The QLU-C10D descriptive system comprises 10 health attributes and each can take on 4 levels. A standardised and pre-tested methodology has been applied for valuations including a web-based discrete choice experiment (DCE). It was administered in 1000 general population respondents per country recruited via online panels, aiming at representativeness for core socio-demographic variables. RESULTS: In all three countries, the attributes with the largest impact on utility were physical functioning, pain, and role functioning. Cancer-specific dimensions with the largest impact were nausea and fatigue or bowel problems. Utility values of the worst health state (i.e. severe problems on all 10 dimension) were -0.111 (Austria), 0.025 (Italy), and 0.048 (Poland). Country-specific utilities differed for a selection of health states across the continuum. Austrian utilities were systematically lower for moderately and severely impaired health states. CONCLUSION: QLU-C10D cancer-specific utilities can now be calculated in three more countries. Differences between countries indicate that careful consideration is required when using non-country-specific value sets in economic evaluations.

Time to deterioration in cancer randomized clinical trials for patient-reported outcomes data: a systematic review.

PURPOSE: The time to deterioration (TTD) approach has been proposed as a modality of longitudinal analysis of patient-reported outcomes (PROs) in cancer randomized clinical trials (RCTs). The objective of this study was to perform a systematic review of how the TTD approach has been used in phase III RCTs to analyze longitudinal PRO data. METHODS: A systematic literature search was conducted in PubMed/MEDLINE, the Cochrane Library and through manual search to identify studies published between January 2014 and June 2018. All phase III cancer RCTs including a PRO endpoint using the TTD approach were considered. We collected general information about the study, PRO assessment and the TTD approach, such as the event definition, the choice of reference score and whether the deterioration was definitive or not. RESULTS: A total of 1549 articles were screened, and 39 studies were finally identified as relevant according to predefined criteria. Among these 39 studies, 36 (92.3%) were in advanced and/or metastatic cancer. Several different deterioration definitions were used in RCTs, 10 studies (25.6%) defined the deterioration as "definitive", corresponding to a deterioration maintained over time until the last PRO assessment available for each patient. The baseline score was explicitly stated as the reference score to qualify the deterioration for most studies (n = 31, 79.5%). CONCLUSION: This review highlights the lack of standardization of the TTD approach for the analysis of PRO data in RCTs. Special attention should be paid to the definition of "deterioration", and this should be based on the specific cancer setting.

The impact of comorbidity on health-related quality of life in elderly patients with chronic myeloid leukemia.

The primary objective of this study was to investigate whether the presence of comorbidities was associated with a lower health-related quality of life (HRQOL) in elderly patients with chronic myeloid leukemia (CML). A sample of 174 CML patients aged 60 years or above was analyzed. HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). A number of pre-selected sociodemographic and disease-related factors were considered as potential confounding factors for the association between comorbidity and HRQOL. Mean age of the 174 patients analyzed was 70 years (range 60-87 years) and 55 % were male. Overall, 111 patients (64 %) reported at least one comorbidity. Analysis stratified by age group category showed a greater proportion of patients with comorbidities in the older sub-group population (≥70 years) compared to younger patients (60 to 69 years). Differences in HRQOL outcomes between patients with no comorbidity at all and those with two or more comorbid conditions were at least twice the magnitude of a clinically meaningful difference in all the physical and mental health scales of the SF-36. In multivariate analysis, after adjusting for key confounding factors, the following scales were significantly lower in those with comorbidity: general health (p < 0.001), bodily pain (p < 0.001), physical functioning (p = 0.002), and vitality (p = 0.002). Assessing comorbidity in elderly patients with CML is important to facilitate identification of those most in need of HRQOL improvements.

Accuracy of physician assessment of treatment preferences and health status in elderly patients with higher-risk myelodysplastic syndromes.

Higher-risk myelodysplastic syndromes (MDS) are rarely curable and have a poor prognosis. We investigated the accuracy of physicians' perception of patients' health status and the patients' preferences for involvement in treatment decisions. We examined 280 newly diagnosed higher-risk elderly MDS patients paired with their physicians. Survey tools included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and the Control Preference Scale. Overall concordance was 49% for physician perception of patient preferences for involvement in treatment decisions. In 36.4% of comparisons there were minor differences and in 14.6% there were major differences. In 44.7% of the patients preferring a passive role, physicians perceived them as preferring an active or collaborative role. Absence of the patient's request for prognostic information (P=0.001) and judging the patient as having a poor health status (P=0.036) were factors independently associated with the physicians' attitude toward a lower degree of patient involvement in clinical decisions. Agreement on health status was found in 27.5% of cases. Physicians most frequently tended to overestimate health status of patients who reported low-level health status. The value of decision aid-tools in the challenging setting of higher-risk MDS should be investigated to further promote patient-centered care.

Preference for involvement in treatment decisions and request for prognostic information in newly diagnosed patients with higher-risk myelodysplastic syndromes.

BACKGROUND: The main objective of this study was to assess preferences for involvement in treatment decisions and requests for prognostic information in newly diagnosed higher-risk myelodysplastic syndrome (MDS) patients. PATIENT AND METHODS: This was a prospective cohort observational study that consecutively enrolled MDS patients with an international prognostic scoring system (IPSS) risk category of intermediate-2 or high risk (summarized as 'higher risk'). The control preference scale was used to assess patient preferences for involvement in treatment decisions, and whether a request by patients for prognostic information during consultation was made, was also recorded. All of the patients were surveyed at the time of diagnosis before receiving treatment. Univariate and multivariate analyses were carried out to assess how sociodemographic, clinical and laboratory data related to decision-making preferences and requests for prognostic information. Relationship with the health-related quality of life (HRQOL) profile was also examined. RESULTS: A total of 280 patients were enrolled, 74% with intermediate-2 and 26% with high-risk IPSS. The mean age of patients was 70-year old (range: 32-89 years). One hundred thirty-two patients (47%) favored a passive role in treatment decision-making, whereas only 14% favored an active role. The remaining 39% of patients favored a shared decision-making approach. Patients with lower hemoglobin levels were more likely to prefer a passive role (P=0.037). HRQOL was generally better in patients preferring an active role versus those preferring a passive one. Overall, 61% (N=171) of patients requested prognostic information on survival during consultation. The likelihood of not requesting prognostic information was higher for older patients (P = 0.003) and for those with lower education (P=0.010). CONCLUSION: Decision-making preferences vary among patients with newly diagnosed higher-risk MDS. Current findings suggest that patients with worse underlying health conditions are more likely to prefer less involvement in treatment decisions.

Chronic fatigue is the most important factor limiting health-related quality of life of chronic myeloid leukemia patients treated with imatinib.

Health-related quality of life (HRQOL) is an important goal of therapy for chronic myeloid leukemia (CML) patients treated with current molecular-targeted therapies. The main objective of this study was to investigate factors associated with long-term HRQOL outcomes of CML patients receiving imatinib. Analysis was performed on 422 CML patients recruited in an observational multicenter study. HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Key socio-demographic and clinical data were investigated for their association with HRQOL outcomes. Chronic fatigue and social support were also investigated. Univariate and multivariate linear regression analyses were used to identify independent factors associated with HRQOL outcomes. Fatigue was the only variable showing an independent and consistent association across all physical and mental HRQOL outcomes (P<0.01). Differences between patients reporting low versus high fatigue levels were more than eight and seven times the magnitude of a clinically meaningful difference, respectively, for the role physical (Δ=70 points) and emotional scale (Δ=63 points) of the SF-36. Fatigue did not occur as an isolated symptom and was most highly correlated with musculoskeletal pain (r=0.511; P≤0.001) and muscular cramps (r=0.448; P≤0.001). Chronic fatigue is the major factor limiting HRQOL of CML patients receiving imatinib.

Investigating factors associated with adherence behaviour in patients with chronic myeloid leukemia: an observational patient-centered outcome study.

BACKGROUND: Optimal adherence to imatinib therapy is of paramount importance to maximise treatment effectiveness in patients with chronic myeloid leukaemia (CML). The main objective of this study was to investigate patient-reported personal factors associated with adherence behaviour. METHODS: Analysis was conducted on 413 CML patients receiving long-term therapy with imatinib. Adherence behaviour was measured with the Morisky Medication Adherence Scale and personal factors investigated included: quality of life, perceived social support, fatigue, symptom burden, psychological wellbeing and desire for additional information. Key socio-demographic and treatment-related factors were also taken into account. Univariate and multivariate logistic regression analyses were used to investigate factors associated with optimal adherence to therapy. RESULTS: In all, 53% of patients reported an optimal adherence behaviour. The final multivariate model retained the following variables as independent predictors of optimal adherence to therapy: desire for more information (ref. no), odds ratio (OR)=0.43 (95% confidence interval (CI), 0.29-0.66; P<0.001), social support (higher score representing greater support), OR=1.29 (95% CI, 1.11-1.49; P<0.001) and concomitant drug burden (ref. no), OR=1.82 (95% CI, 1.18-2.80; P=0.006). CONCLUSION: This study suggests that a higher level of social support, satisfaction with information received and concomitant drug burden are the main factors associated with greater adherence to long-term imatinib therapy.

Nonlinear energy harvesting.

Ambient energy harvesting has been in recent years the recurring object of a number of research efforts aimed at providing an autonomous solution to the powering of small-scale electronic mobile devices. Among the different solutions, vibration energy harvesting has played a major role due to the almost universal presence of mechanical vibrations. Here we propose a new method based on the exploitation of the dynamical features of stochastic nonlinear oscillators. Such a method is shown to outperform standard linear oscillators and to overcome some of the most severe limitations of present approaches. We demonstrate the superior performances of this method by applying it to piezoelectric energy harvesting from ambient vibration.

In-vacuum optical isolation changes by heating in a Faraday isolator.

We describe a model evaluating changes in the optical isolation of a Faraday isolator when passing from air to vacuum in terms of different thermal effects in the crystal. The changes are particularly significant in the crystal thermal lensing (refraction index and thermal expansion) and in its Verdet constant and can be ascribed to the less efficient convection cooling of the magneto-optic crystal of the Faraday isolator. An isolation decrease by a factor of 10 is experimentally observed in a Faraday isolator that is used in a gravitational wave experiment (Virgo) with a 10 W input laser when going from air to vacuum. A finite element model simulation reproduces with a great accuracy the experimental data measured on Virgo and on a test bench. A first set of measurements of the thermal lensing has been used to characterize the losses of the crystal, which depend on the sample. The isolation factor measured on Virgo confirms the simulation model and the absorption losses of 0.0016 +/- 0.0002/cm for the TGG magneto-optic crystal used in the Faraday isolator.

Chlorhexidine lavage in the treatment of experimental intra-abdominal infection.

HYPOTHESIS: Closed postoperative peritoneal lavage (CPPL) with chlorhexidine gluconate reduces the number of intraperitoneal bacteria and improves the outcome of intra-abdominal infection. DESIGN: Laboratory animal trial. INTERVENTIONS: Intra-abdominal infection was produced in mice by the cecal ligation and puncture technique. After 16 to 18 hours, the animals underwent relaparotomy and placement of an intra-abdominal catheter for CPPL. In the first experiment animals were randomly divided into 4 groups: no lavage (served as a control), CPPL with chlorhexidine. CPPL with cefoxitin, and CPPL with lactated Ringer solution (LR). Lavage was continued intermittently every 8 hours for 24 hours. All animals received systemic cefoxitin every 8 hours for 7 days. Mortality was recorded every 8 hours for 10 days. In the second experiment, animals were divided into 3 groups: no lavage (served as a control), CPPL with chlorhexidine, and CPPL with LR. Lavage was continued intermittently every 8 hours for 24 hours. The animals were killed 48 hours after reoperation. Bacterial counts from peritoneal fluid and biopsy specimens, as well as peritoneal white blood cell counts, were measured before and after lavage. RESULTS: Closed postoperative peritoncal lavage with chlorhexidine reduced mortality from 71% in a control group to 37% (P = .003). There was no survival benefit in either the CPPL with cefoxitin (91% mortality) (P = .14) or CPPL with LR groups (90% mortality) (P = .17). The statistically significant findings of analysis of variance evaluation demonstrated a decrease in bacterial counts after cecal excision in all 3 groups. There was a greater reduction in bacterial counts in the chlorhexidine group compared with the control group (P<.05). Bacterial counts decreased in peritoneal fluid, as well as in tissue biopsy specimens, after cecal excision. White blood cell counts significantly decreased after cecal excision in all 3 groups. There was no difference in white blood cell counts between the groups. Correlation analyses demonstrated weak interaction between bacterial and white blood cell counts before or after treatment in all the groups. Pearson r ranged from -0.37 to +0.35, none of which were statistically significant. CONCLUSIONS: In our experiments chlorhexidine lavage resulted in a 50% reduction in mortality and a significant reduction in bacterial counts compared with the control group. There was no survival benefit from lavage with either cefoxitin or LR. There was no reduction in bacterial counts in the LR group relative to the control group. Thus, the survival benefit and the reduction in bacterial numbers are attributed to the antibacterial properties of chlorhexidine rather than to the mechanical washing of the abdominal cavity. Closed postoperative peritoneal lavage with 0.05% chlorhexidine gluconate might be useful in the multimodal treatment of intra-abdominal infection.

Needle-localized breast biopsy for mammographic abnormalities: a community hospital experience.

Increased awareness of benefits of early detection of breast cancer has resulted in increased numbers of screening mammographies and breast biopsies for nonpalpable lesions. Tertiary hospital studies have demonstrated positive biopsy rates from abnormal mammographic findings at 18 to 32 per cent. We examined the effectiveness of needle biopsy for nonpalpable radiographic abnormalities in our community hospital. We reviewed 167 records of patients biopsied over a 2-year period. Mammographic assessment, biopsy, and pathological assessment were performed using accepted methods. Malignancy was detected in 34 of 167 biopsies (20%). The biopsy yield rate was highest for mammographic findings of spiculated or stellate masses (75%, P < 0.01). Most biopsies (83%) were performed because of mammographic findings of microcalcifications or circumscribed enlarging masses/nodular developing densities for a positive biopsy yield rate of 16 per cent. Rates were higher in patients with personal (44%) or family history (30%) of breast cancer and in postmenopausal women (30%). These results demonstrate that 1) factors such as age, personal or family history of breast cancer, and certain mammographic features of breast lesions are associated with high biopsy yield rates, and 2) the biopsy yield rate in our community setting is comparable to tertiary hospital experience.

Iliopsoas abscess: etiology, diagnosis, and treatment.

Iliopsoas abscess is a rarely encountered entity. Early diagnosis is hindered by a nonspecific clinical presentation. The resulting delays in therapy increase morbidity and mortality rates. Our recent experience with three cases of iliopsoas abscess is presented. Based on a review of the literature, diagnostic and treatment recommendations are made.

Surgical treatment of Meckel's diverticulum.

Meckel's diverticula are the result of incomplete degeneration of the vitelline duct. It is generally believed that less than 5% of them become symptomatic, the frequency decreasing with age. Meckel's diverticula are most commonly manifested in children by painless lower gastrointestinal bleeding and in adults, as an inflammatory process or obstruction. Definitive diagnosis is usually made at surgery, though the Meckel's scan may suggest a diagnosis preoperatively, especially in the pediatric population. All symptomatic and pathologic Meckel's diverticula should be removed with a segment of ileum. The use of stapling devices, with their ease of use and low complication rate, make it reasonable to remove any Meckel's diverticulum that easily fits in the device. If a diverticulum found incidentally is so broad-based or short that stapling cannot be done without difficulty, it is unlikely to become symptomatic and should be left undisturbed.

Abdominal and anorectal surgery and the acquired immune deficiency syndrome in heterosexual intravenous drug users.

Over a period of seven years, 474 patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex were admitted on 782 occasions to the St. Francis Medical Center, Trenton, New Jersey. Abdominal surgery was performed on 16 (3.4 percent) patients, 14 (88 percent) of whom were heterosexual intravenous drug users. Anorectal surgery was performed on 20 (4.2 percent), 14 (70 percent) of whom were intravenous drug users. Intravenous drug users undergoing abdominal surgery had the same types of surgical abdominal conditions that occur in the general population. None required surgery for complications secondary to cytomegalovirus, visceral lymphoma, or visceral Kaposi's sarcoma. The postoperative morbidity rate was 72 percent. The postoperative mortality rate (30 day) was 0 percent. No intravenous drug users who underwent anorectal surgery had associated anorectal malignancies or infectious diseases. Five of six homosexual patients had either an anorectal malignancy or an associated anorectal infectious disease. Anorectal wounds did not heal within one month in one third of the intravenous drug users. The rate of wound healing was inversely related to the white blood cell count. One third of the intravenous drug users undergoing anorectal surgery were dead within six months.