Creating a common language: defining individualized, personalized and precision prevention in public health.

Background: Because of the limited success of population-based prevention methods and due to developments in genomic screening, public health professionals and health policy makers are increasingly interested in more individualized prevention strategies. However, the terminology applied in this field is still ambiguous and thus has the potential to create misunderstandings. Methods: A narrative literature review was conducted to identify how individualized, personalized and precision prevention are used in research papers and documents. Based on the findings a set of definitions were created that distinguish between these activities in a meaningful way. Results: Definitions were found only for precision prevention, not for individualized or personalized prevention. The definitions of individualized, personalized and precision medicine were therefore used to create the definitions for their prevention counterparts. By these definitions, individualized prevention consists of all types of prevention that are individual-based; personalized prevention also consists of at least one form of -omic screening; and precision prevention further includes psychological, behavioral and socioeconomic data for each patient. Conclusions: By defining these three key terms for different types of individual-based prevention both researchers and health policy makers can differentiate and use them in their proper context.

Impact of Hearing Aid Technology on Outcomes in Daily Life III: Localization.

OBJECTIVE: Compared to basic-feature hearing aids, premium-feature hearing aids have more advanced technologies and sophisticated features. The objective of this study was to explore the difference between premium-feature and basic-feature hearing aids in horizontal sound localization in both laboratory and daily life environments. We hypothesized that premium-feature hearing aids would yield better localization performance than basic-feature hearing aids. DESIGN: Exemplars of premium-feature and basic-feature hearing aids from two major manufacturers were evaluated. Forty-five older adults (mean age 70.3 years) with essentially symmetrical mild to moderate sensorineural hearing loss were bilaterally fitted with each of the four pairs of hearing aids. Each pair of hearing aids was worn during a 4-week field trial and then evaluated using laboratory localization tests and a standardized questionnaire. Laboratory localization tests were conducted in a sound-treated room with a 360°, 24-loudspeaker array. Test stimuli were high frequency and low frequency filtered short sentences. The localization test in quiet was designed to assess the accuracy of front/back localization, while the localization test in noise was designed to assess the accuracy of locating sound sources throughout a 360° azimuth in the horizontal plane. RESULTS: Laboratory data showed that unaided localization was not significantly different from aided localization when all hearing aids were combined. Questionnaire data showed that aided localization was significantly better than unaided localization in everyday situations. Regarding the difference between premium-feature and basic-feature hearing aids, laboratory data showed that, overall, the premium-feature hearing aids yielded more accurate localization than the basic-feature hearing aids when high-frequency stimuli were used, and the listening environment was quiet. Otherwise, the premium-feature and basic-feature hearing aids yielded essentially the same performance in other laboratory tests and in daily life. The findings were consistent for both manufacturers. CONCLUSIONS: Laboratory tests for two of six major manufacturers showed that premium-feature hearing aids yielded better localization performance than basic-feature hearing aids in one out of four laboratory conditions. There was no difference between the two feature levels in self-reported everyday localization. Effectiveness research with different hearing aid technologies is necessary, and more research with other manufacturers' products is needed. Furthermore, these results confirm previous observations that research findings in laboratory conditions might not translate to everyday life.

Cannula Versus Sharp Needle for Placement of Soft Tissue Fillers: An Observational Cadaver Study.

BACKGROUND: Soft-tissue fillers have become important products for facial rejuvenation. Deep fat compartments and facial bones lose volume during the natural aging process. For the most natural-looking results, deep volumetric injections at strategic sites are therefore preferred. Supraperiosteal placement is performed with a sharp needle or a non-traumatic cannula. OBJECTIVES: The primary objective was to determine whether there is a difference in precision between supraperiosteal placement with a sharp needle compared with a non-traumatic cannula in cadaver specimens. A secondary objective was to analyze the safety profiles of both injection techniques. METHODS: Cadaver heads were injected with dye material and soft-tissue fillers at multiple aesthetic facial sites on the supraperiosteum and subsequently dissected for observation of dye and filler placement. RESULTS: The non-traumatic cannula technique resulted in product being confined to the deep anatomic layers. In contrast, with the sharp needle technique, material was placed in multiple anatomic layers, from the periosteum to more superficial skin layers. For both techniques results were consistent for all facial sites. CONCLUSIONS: Although direct extrapolation from cadavers to the in vivo situation cannot be made, cannulae showed more precision in placement of product. With the sharp needle, the material was injected on the periosteum, and then migrated in a retrograde direction along the trajectory of the needle path, ending up in multiple anatomic layers. The sharp needle technique also showed a higher complication risk with intra-arterial injection occurring, even though the needle tip was positioned on the periosteum and the product was injected with the needle in constant contact with the periosteum.

Impact of Hearing Aid Technology on Outcomes in Daily Life I: The Patients' Perspective.

OBJECTIVES: One of the challenges facing hearing care providers when recommending hearing aids is the choice of device technology level. Major manufacturers market families of hearing aids that are described as spanning the range from basic technology to premium technology. Premium technology hearing aids include acoustical processing capabilities (features) that are not found in basic technology instruments. These premium features are intended to yield improved hearing in daily life compared with basic-feature devices. However, independent research that establishes the incremental effectiveness of premium-feature devices compared with basic-feature devices is lacking. This research was designed to explore reported differences in hearing abilities for adults using premium- and basic-feature hearing aids in their daily lives. DESIGN: This was a single-blinded, repeated, crossover trial in which the participants were blinded. All procedures were carefully controlled to limit researcher bias. Forty-five participants used carefully fitted bilateral hearing aids for 1 month and then provided data to describe the hearing improvements or deficiencies noted in daily life. Typical participants were 70 years old with mild to moderate adult-onset hearing loss bilaterally. Each participant used four pairs of hearing aids: premium- and basic-feature devices from brands marketed by each of two major manufacturers. Participants were blinded about the devices they used and about the research questions. RESULTS: All of the outcomes were designed to capture the participant's point of view about the benefits of the hearing aids. Three types of data were collected: change in hearing-related quality of life, extent of agreement with six positively worded statements about everyday hearing with the hearing aids, and reported preferences between the premium- and basic-feature devices from each brand as well as across all four research hearing aids combined. None of these measures yielded a statistically significant difference in outcomes between premium- and basic-feature devices. Participants did not report better outcomes with premium processing with any measure. CONCLUSIONS: It could reasonably be asserted that the patient's perspective is the gold standard for hearing aid effectiveness. While the acoustical processing provided by premium features can potentially improve scores on tests conducted in contrived conditions in a laboratory, or on specific items in a questionnaire, this does not ensure that the processing will be of noteworthy benefit when the hearing aid is used in the real world challenges faced by the patient. If evidence suggests the patient cannot detect that premium features yield improvements over basic features in daily life, what is the responsibility of the provider in recommending hearing aid technology level? In the present research, there was no evidence to suggest that premium-feature devices yielded better outcomes than basic-feature devices from the patient's point of view. All of the research hearing aids were substantially, but equally, helpful. Further research is needed on this topic with other hearing aids and other manufacturers. In the meantime, providers should insist on scientifically credible independent evidence to support effectiveness claims for any hearing help devices.

Impact of Hearing Aid Technology on Outcomes in Daily Life II: Speech Understanding and Listening Effort.

OBJECTIVES: Modern hearing aid (HA) devices include a collection of acoustic signal-processing features designed to improve listening outcomes in a variety of daily auditory environments. Manufacturers market these features at successive levels of technological sophistication. The features included in costlier premium hearing devices are designed to result in further improvements to daily listening outcomes compared with the features included in basic hearing devices. However, independent research has not substantiated such improvements. This research was designed to explore differences in speech-understanding and listening-effort outcomes for older adults using premium-feature and basic-feature HAs in their daily lives. DESIGN: For this participant-blinded, repeated, crossover trial 45 older adults (mean age 70.3 years) with mild-to-moderate sensorineural hearing loss wore each of four pairs of bilaterally fitted HAs for 1 month. HAs were premium- and basic-feature devices from two major brands. After each 1-month trial, participants' speech-understanding and listening-effort outcomes were evaluated in the laboratory and in daily life. RESULTS: Three types of speech-understanding and listening-effort data were collected: measures of laboratory performance, responses to standardized self-report questionnaires, and participant diary entries about daily communication. The only statistically significant superiority for the premium-feature HAs occurred for listening effort in the loud laboratory condition and was demonstrated for only one of the tested brands. CONCLUSIONS: The predominant complaint of older adults with mild-to-moderate hearing impairment is difficulty understanding speech in various settings. The combined results of all the outcome measures used in this research suggest that, when fitted using scientifically based practices, both premium- and basic-feature HAs are capable of providing considerable, but essentially equivalent, improvements to speech understanding and listening effort in daily life for this population. For HA providers to make evidence-based recommendations to their clientele with hearing impairment it is essential that further independent research investigates the relative benefit/deficit of different levels of hearing technology across brands and manufacturers in these and other real-world listening domains.

Impact of advanced hearing aid technology on speech understanding for older listeners with mild to moderate, adult-onset, sensorineural hearing loss.

BACKGROUND: Hearing loss is one of the most common chronic health conditions of older people. Hearing aids are the customary treatment and they improve quality of life in older adults. Even so, relatively few older adults with uncomplicated, mild to moderate, adult-onset, sensorineural hearing loss use hearing aids. One reason for this is a belief that hearing aids do not provide sufficient value to justify their expense. Although modern hearing aids are available at several price points, there is minimal evidence about the relative benefits of premium-level versus basic-level hearing aid technologies. OBJECTIVE: This research was designed to demonstrate the relative effectiveness of premium hearing aids compared with basic hearing aids in improving speech understanding and quality of life. METHODS: 25 participants, including both new and experienced hearing aid users, completed blinded month-long field trials with each of four pairs of hearing aids: two basic and two premium level. Outcomes were laboratory speech understanding tests, standardized questionnaires and open-ended diary items. RESULTS: Participants reacted very positively to all the hearing aids. Both everyday speech understanding and quality of life were substantially improved with hearing aids. RESULTS for both new and experienced users were consistent with a conclusion that there were no statistically significant or clinically important differences in improvement between the premium- and basic-level hearing aids. CONCLUSIONS: It should not be assumed that more costly hearing aids always produce better outcomes. With contemporary hearing aids from two major manufacturers, the subjects obtained as much improvement in speech understanding and quality of life from lower-cost basic-level instruments as from higher-cost premium-level instruments. Regardless of technology level, comprehensive best-practice fitting protocols should be followed to optimize results for every patient.

The economic impact of anastomotic leakage after anterior resections in English NHS hospitals: are we adequately remunerating them?

AIM: Our aim was to determine the frequency and economic impact of anastomotic leakage (AL) at local and national levels in England. METHOD: All patients who underwent AR in Oxford between 2007 and 2009 were evaluated for AL. Hospital Episode Statistics (HES) data were used to determine reoperation rates after elective AR (n = 23 388) in England between 2000 and 2008. Hospital episode remuneration costs were calculated by the local commissioning department and compared with Department of Health (DH) reference index costs. RESULTS: The frequency of AL following anterior resection was 10.9% (31 out of 285) in Oxford. Laparotomy for leakage was performed in 5.6% of cases. The 30-day hospital mortality rate for all ARs was 2.1%, compared with 3.2% after AL. The national relaparotomy rate (within 28 days) and 30-day hospital mortality in English National Health Service (NHS) trusts following AR were 5.9% and 2.9%, respectively. Institutional remunerated tariffs (£6233 (SD ± 965)) were similar to DH reference costs (£6319 (SD ± 1830)) after uncomplicated AR. However, there was a significant (P = 0.008) discrepancy between the remunerated tariff for AL (£9605 (SD ± 6908)) and the actual cost (£17 220 (SD ± 9642)). AL resulted in an additional annual cost of approximately £1.1 million to £3.5 million when extrapolated nationally. CONCLUSION: The estimated economic burden of anastomotic leakage following AR is approximately double that of the remunerated tariff.

Referral proformas improve compliance to national colorectal 2-week wait targets: does this affect cancer detection rates?

AIM: To facilitate implementation of National Institute for Health and Clinical Excellence (NICE) guidelines for urgent colorectal cancer referral, local cancer networks have promoted the use of standardized proformas in primary care. This clinical audit assessed use of the proforma within the Thames Valley Cancer Network (TVCN) to see whether increased proforma use was associated with higher compliance to NICE guidelines and higher cancer detection rates. METHOD: All 2-week wait referrals for lower bowel cancer to the six Acute NHS Trusts in the TVCN received during the month of June 2010 were identified, anonymized and analysed in relation to colorectal cancer detection rates. RESULTS: Of the 586 referrals audited, proforma usage varied significantly across the six Acute NHS Trusts from 18% to 96%. Referral letters from primary care had NICE compliance ranging from 30 to 50%. In those which received a referral protocol, 50-90% were NICE compliant. Proforma use was associated with higher cancer detection rates (P = 0.03). CONCLUSION: These results have wide-ranging implications since they suggest that the adoption of a simple proforma in primary care can improve the effectiveness of referral for suspected cancer.

Implications of high-frequency cochlear dead regions for fitting hearing aids to adults with mild to moderately severe hearing loss.

OBJECTIVES: A cochlear dead region (DR) occurs at a given frequency when there is a loss of normal functioning of inner hair cells tuned to that frequency. It has been suggested that existence of high-frequency DRs has implications for hearing aid fitting, and that the optimal amount of high-frequency gain is reduced for these patients. However, the data supporting this suggestion has been obtained using listeners with severe or profound hearing loss. It is uncertain whether these results would apply for listeners with the mild to moderately severe hearing loss that is more typical of hearing aid users. This investigation used laboratory and field measurements to examine the effects of reduced high-frequency gain in typical hearing aid users with high-frequency DRs compared with matched users without DRs. DESIGN: The study was a double-blinded, nonrandomized intervention design with 18 matched pairs of adult subjects. In each pair, one subject had high-frequency DRs (usually at one or two test frequencies) and the other subject had no DR. Each subject was fitted unilaterally with a hearing aid having two active programs. One program used a National Acoustics Laboratories (NAL) prescription target for average speech (NAL condition). The other program was identical to NAL except for reduced gain in the high frequencies (low-pass [LP] condition). Outcomes included aided speech recognition in quiet and noise measured in the laboratory, ratings of speech understanding in daily life, and final preference for the NAL or LP program. RESULTS: In laboratory testing, speech recognition in quiet was significantly better when using the NAL program. This result was seen for subjects with DRs and without DRs. When listening in noise, speech recognition was significantly better when using the NAL program for subjects without DRs. For subjects with DRs, results were equivalent for the NAL and LP programs. In daily life, the NAL program received significantly higher ratings for speech understanding, and this result was seen for subjects with and without DRs. When asked about their preference for using the NAL or LP program in daily life, subjects did not always choose the program they had rated as giving better speech understanding, but their preference was not associated with having DRs. About one-third of subjects preferred the LP program. The reason most frequently given for preferring the LP program was that the NAL was too loud. CONCLUSIONS: Overall, adult hearing aid wearers with mild to moderately severe hearing loss benefitted from high-frequency gain whether or not they had DRs. In laboratory testing, but not in daily life, subjects with DRs tended to obtain less benefit than those without DRs. However, provision of NAL high-frequency gain never resulted in poorer performance in either group. These results suggest that identification of high-frequency DRs at one or two frequencies does not call for any a priori modification of the target hearing aid prescription for listeners with mild to moderately severe hearing loss.

The Dutch Hyacorp® filler catastrophe: new EU legislation will prevent this from happening again

Background: In 2014, the hyaluronic acid-based fillers, Hyacorp-1000 and Hyacorp H-S (H-800), were withdrawn from the Dutch market after concerns about their safety Objectives: To determine the most plausible factors for the increased number of adverse events, either patient-related factors or those inherent to the filler itself. We also assessed how new European legislation will affect the approval process for new fillers and improve related safety issues Materials & Methods: A total of 42 patients­37 women (88%) and five men (11%)­were included. Patients were separated into three groups: 13 patients injected with Hyacorp-1000 and Hyacorp H-S (H-800) who had reported inflammatory adverse events; 12 injected with Hyacorp-1000 and Hyacorp H-S (H-800) who had not reported inflammatory adverse events; and 17 injected with other HA fillers who had reported inflammatory adverse events Results: Patients treated with Hyacorp-1000 and Hyacorp-S (H-800) who reported adverse events were significantly older than those in the Hyacorp-1000 and Hyacorp-S (H-800) group without adverse events, and the filler remained in situ for significantly longer than in patients who had adverse events related to another HA filler Conclusion: Hyacorp-1000 and Hyacorp-S (H-800) filler is associated with an increased chance of developing adverse events compared to other HA fillers, probably because it remains in the body for a longer period of time. The upcoming legislative EU update of the Medical Device Regulation (MDR) will prevent unsafe filler from entering the EU market and will enable issues related to safety to be identified much earlier

A split-face comparative performance evaluation of injectable hyaluronic acid-based preparations HCC and CPM-HA20G in healthy females.

INTRODUCTION: Skin revitalizers are used for skin quality improvement purposes. Hyaluronan hybrid cooperative complexes (HCC, Profhilo®, IBSA Pharmaceuticals) are an anti-aging treatment with a large amount of pure hyaluronic acid (HA) based on stable, cooperative, and hybrid complexes. Cohesive polydensified matrix Hyaluronic Acid (CPM-HA20, Belotero Revive®, Merz Pharmaceuticals GmbH) is a slightly cross-linked HA (20 mg/ml) with glycerol (17.5 mg/ml). AIMS: To evaluate the performance of HCC and CPM-HA20G for skin quality improvement in healthy female subjects. METHODS: This was a split-face, single-blinded study that enrolled 24 healthy female subjects. Injections were given on three separate occasions. HCC was injected on the right cheek, while CPM-HA20G was injected on the left cheek. A battery of skin property measurements was used to evaluate the skin. Skin properties and overall satisfaction were analyzed using mixed models with the values at baseline, at week 1, week 8, and week 14 as an outcome and a random effect of subject and fixed effects of treatment, visit, and the treatment by visit interaction. RESULTS: Both products showed evidence of effect relative to baseline on surface hydration (AU), elasticity (N/m) TEWL (g/m2 h), and melanin (AU). CPM-HA20G also showed significant evidence of effect relative to baseline on water content (%), and HCC on pore count (n) and hemoglobin (AU). Satisfaction reported by the subjects themselves showed positive trends of satisfaction over time for multiple skin properties. There were no significant differences between the tested products in the observed skin characteristics over time. CONCLUSION: These devices are effective and safe treatments for skin quality improvement, especially moisturization, with high patient satisfaction and generally mild and transient side effects.

Determination of (235)U, (239)Pu, (240)Pu, and (241)Am in a nuclear bomb particle using a position-sensitive α-γ coincidence technique.

A nuclear bomb particle containing 1.6 ng of Pu was investigated nondestructively with a position-sensitive α detector and a broad-energy HPGe γ-ray detector. An event-mode data acquisition system was used to record the data. α-γ coincidence counting was shown to be well suited to nondestructive isotope ratio determination. Because of the very small background, the 51.6 keV γ rays of (239)Pu and the 45.2 keV γ rays of (240)Pu were identified, which enabled isotopic ratio calculations. In the present work, the (239)Pu/((239)Pu+(240)Pu) atom ratio was determined to be 0.950 ± 0.010. The uncertainties were much smaller than in the previous more conventional nondestructive studies on this particle. Obtained results are also in good agreement with the data from the destructive mass spectrometric studies obtained previously by other investigators.

Evaluating the Effect of Incobotulinumtoxin A for Glabellar, Forehead, and Crow's Feet Lines Using A High Dilution.

BACKGROUND: As aesthetic preferences have evolved and patients wish their muscles to be relaxed, but not frozen, a higher dilution of incobotulinumtoxinA (INCO) has allowed for increased spread using fewer units, yet no studies to date have investigated the efficacy, longevity, and safety of hyperdiluted INCO. OBJECTIVE: We evaluated the effect of incobotulinumtoxinA (INCO) in glabellar, forehead, and lateral periorbital lines using a high dilution. METHODS: Subjects with moderate-to-severe upper facial lines at rest according to the Merz Aesthetics Scales™ (Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany) received 15U of INCO to the glabellar (n=4 injection sites), 10U to the rest of the forehead (n=10 injection sites), and 5U to the lateral periorbital lines (n=3 injection sites/eye). Primary outcomes were physician- and subject-rated improvement at one month using the Global Aesthetic Improvement Scale (GAIS) and changes in line severity using the Merz Aesthetics Scales™. RESULTS: The study included 15 women aged 35 to 65 years. At one month, physician GAIS scores indicated 91.2% of subjects were very much improved and 8.8% were much improved; 91.5%, 78.0%, and 57.6% of participants remained at least improved at four, five, and six months, respectively. Subject GAIS scores at one month were in agreement with physician scores. At one month, an improvement of at least one point in Merz Aesthetics Scales™ scores in glabellar, forehead, and lateral periorbital lines was reported in 88.9%, 98.3%, and 94.8% of participants, respectively. Subject satisfaction was high throughout the study. No treatment-related adverse events were observed. CONCLUSION: Hyperdilute INCO was effective at improving overall appearance and reducing line severity in individuals with moderate-to-severe upper facial lines. Patient satisfaction was maintained up to six months and treatment was well tolerated.

Development of APHAB norms for WDRC hearing aids and comparisons with original norms.

OBJECTIVES: This study was undertaken for two purposes: First, to provide a comparison of subjective performance and benefit measured with the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire for two groups. One group included hearing-impaired individuals using 1990s-era linear processing hearing aids. The other group included hearing-impaired individuals using more current wide-dynamic range compression (WDRC)-capable hearing aids fit using current practice protocols. The second purpose of this study was to determine whether APHAB norms derived from scores for current hearing aid users were different from the original 1995 norms. It was hypothesized that technology improvements would result in improved subjective performance for modern hearing aid wearers. DESIGN: A systematic sampling method was used to identify and recruit subjects from seven private-practice audiology clinics located across the United States. Potential subjects were limited to older hearing-impaired individuals who were wearing hearing aids capable of WDRC processing. One hundred fifty-four subjects returned completed APHAB questionnaires. Participants reported mostly moderate to moderately severe subjective hearing difficulty. RESULTS: No differences in perceived difficulty with speech communication were observed between the two groups. However, aversiveness of amplified sound was less frequently reported for users of WDRC-capable hearing aids. Norms were generated using data from all of the operationally defined successful hearing aid users in the sample and compared with the original 1995 norms. Differences between the 1995 and 2005 norms were minimal for the speech communication subscales. However, the 2005 group consistently reported less frequent difficulties with sound aversiveness (AV subscale) in the aided condition. In addition to these findings, an improvement was observed in the rate of successful adjustment to hearing aids between 1995 (43%) and 2005 (82%). CONCLUSIONS: Overall, problems understanding amplified speech did not decrease in frequency when hearing aids transitioned from linear to compression processing; however, the compression capabilities of current hearing aids (with a possible contribution from noise reduction algorithms) have resulted in less negative reactions to amplified environmental sounds. This suggests that modern technology has ameliorated (to some extent) the common complaint that hearing aids cause many everyday sounds to become objectionably loud. Although the results of this study suggest that the advantages of improved technology do not lie in the domains of improved subjective speech communication performance, substantial improvement in the rate of successful adjustment to hearing aids between the 1995 and 2005 subject groups provides evidence that modern hearing aid technology has produced progress in other outcome domains.

Delayed Inflammatory Reactions to Hyaluronic Acid Fillers: A Literature Review and Proposed Treatment Algorithm.

BACKGROUND AND OBJECTIVES: There is a wide diversity of opinions regarding the management of delayed inflammatory reactions (DIRs) secondary to hyaluronic acid (HA)-based fillers. The plethora of approaches has led the authors to conduct a review regarding management and treatment of DIRs as well as establish therapeutic guidelines for this purpose. MATERIALS AND METHODS: A review of the literature was performed through databases such as PubMed using keywords including HA-fillers and complications, delayed HA filler sequelae and therapy, soft tissue and dermal filler reactions and management. Additionally, a survey comprised of questions regarding the management and treatment of DIRs was sent to 18 physicians highly experienced with soft-tissue filler injections in 10 countries. Their answers and recommendations were analyzed and debated amongst these panelists. RESULTS: Sixteen panelists favored antibiotic therapy as first-line treatment for DIRs, specifically dual antibiotic therapy consisting of a fluoroquinolone along with a tetracycline or macrolide for a period of 3-6 weeks. The majority refrained from the use of intralesional (IL) or systemic steroids except in the case of disfiguring or recalcitrant reactions. IL hyaluronidase was recommended by 13 panelists; however, some preferred a watchful waiting approach for a period of 48 hours to 2 weeks prior to IL hyaluronidase, and in cases where antibiotics did not lead to improvement. CONCLUSION: A consensus was reached and summarized to propose a clear, easy-to-follow, stepwise algorithm for the treatment of DIRs.

Direct gene transfer into mouse muscle in vivo.

RNA and DNA expression vectors containing genes for chloramphenicol acetyltransferase, luciferase, and beta-galactosidase were separately injected into mouse skeletal muscle in vivo. Protein expression was readily detected in all cases, and no special delivery system was required for these effects. The extent of expression from both the RNA and DNA constructs was comparable to that obtained from fibroblasts transfected in vitro under optimal conditions. In situ cytochemical staining for beta-galactosidase activity was localized to muscle cells following injection of the beta-galactosidase DNA vector. After injection of the DNA luciferase expression vector, luciferase activity was present in the muscle for at least 2 months.

Biochemical control and toxicity after intensity-modulated radiation therapy for prostate cancer.

Intensity modulated radiation therapy (IMRT) has achieved widespread use for prostate cancer; however, in relation to this use, outcomes studies are still relatively sparse. We report a single-institutional experience in outcomes analysis with the use of IMRT for the primary management of prostate cancer. One hundred thirty consecutive patients with adenocarcinoma of the prostate were treated at a single institution using IMRT with curative intent. Thirty-six (28%) patients were classified as low-risk, 69 (53%) as intermediate-risk, and 25 (19%) as high-risk. The median dose prescription was 76 Gy to the planning target volume. Sixty-five (50%) patients received androgen deprivation therapy (ADT) for a median 4 months, starting 2 months prior to IMRT. Biochemical failure was defined as PSA < post-treatment nadir+2. Gastrointestinal (GI) and Genitourinary (GU) toxicity were defined by RTOG criteria. Median follow-up was 53 months. By NCCN risk category, 4-year biochemical control was 97%, 94%, and 87% for low, intermediate, and high-risk patients, respectively. Among disease factors, multivariable analysis demonstrated the strongest association between biochemical control and Gleason score < or =6 (p=0.0371). Therapy was well tolerated with no Grade 4 toxicity and limited grade 3 GI or GU toxicity. Acute Grade 3+ GI and GU toxicity rates were 0% and 2%, and maximal late Grade 3+ GI and GU toxicity rates were 5% and 6%, respectively. Late rectal toxicity was associated with higher volumes of RT to the rectum. By last follow-up late Grade 3+ toxicity was 2% for both GI and GU systems. In conclusion, patients treated with IMRT for prostate cancer have excellent rates of biochemical control and low rates of severe toxicity of treatment.

The Joint Impact of Age at Death and Dementia on Long-Term Care Use in the Last Years of Life: Changes From 1996 to 2013 in Finland.

Welfare states increasingly rely on aging in place policies and have cut back on institutional long-term care (LTC) provision. Simultaneously, the major determinants of LTC use, that is, dementia and living to very old age, are increasing. We investigated how increasing longevity and concomitant dementia were associated with changes in round-the-clock LTC use in the last 5 years of life between 1996 and 2013. Retrospective data drawn from national registers included all those who died aged 70+ in 2007 and 2013, plus a 40% random sample from 2001 (N = 86,554). A generalized estimating equations (GEE) were used to estimate the association of dementia and age with LTC use during three study periods 1996-2001, 2002-2007, and 2008-2013. Between the study periods, the total number of days spent in LTC increased by around 2 months. Higher ages at death and the increased number of persons with dementia contributed to this increase. The group of the most frequent LTC users, that is, people aged 90+ with or without dementia, grew the most in size, yet their LTC use decreased. The implications of very old age and concomitant dementia for care needs must be acknowledged to guarantee an adequate quantity and quality of care.

Use of calcium hydroxylapatite in the upper third of the face: Retrospective analysis of techniques, dilutions and adverse events.

Calcium hydroxylapatite (CaHA) is a commonly used soft tissue filler for aesthetic facial improvement, in particular for the lower and mid-face. The golden standard for upper facial filler indications is hyaluronic acid (HA) injection. In this report we investigate the safety, efficacy and complication rates after injections of CaHA to the upper third of the face using a variety of different techniques. This was a retrospective analysis performed on patients who had received CaHA in 2016 and 2017 at various dilutions in the upper third of the face (frontal area, eyebrows and temporal hollows) using a number of injection techniques and both blunt-tipped cannulas as well as sharp needles. Records of adverse events and side effects were studied. Seventy patients had been injected with CaHA in the upper third of the face. There were 36 treatments to the frontal area, most with a cannula in the subgaleal space with standard dilution of CaHA (16.7% lidocaine containing epinephrine). There were 13 treatments to the brow, mostly with a cannula and multilevel technique, and 66 treatments to the temporal hollows, mostly with a cannula in the interfascial space with standard CaHA dilution. No serious complications were recorded. CaHA was effective and well-tolerated for a range of upper-face indications. More (prospective) research is required to further determine the value of CaHA treatments in these areas.