Informed consent and trial prioritization for clinical studies during the COVID-19 pandemic. Stakeholder experiences and viewpoints.

BACKGROUND: Very little is known about the practice-oriented challenges and potential response strategies for effective and efficient translation of informed consent and study prioritization in times of a pandemic. This stakeholder interview study aimed to identify the full spectrum of challenges and potential response strategies for informed consent and study prioritization in a pandemic setting. METHODS: We performed semi-structured interviews with German stakeholders involved in clinical research during the COVID-19 pandemic. We continued sampling and thematic text analysis of interview transcripts until thematic saturation of challenges and potential response strategies was reached. RESULTS: We conducted 21 interviews with investigators, oversight bodies, funders and research support units. For the first topic informed consent we identified three main themes: consent challenges, impact of consent challenges on clinical research, and potential strategies for consent challenges. For the second topic prioritization of clinical studies, we identified two main themes: perceived benefit of prioritization and potential strategies for prioritization. All main themes are further specified with subthemes. A supplementary table provides original quotes from the interviews for all subthemes. DISCUSSION: Potential response strategies for challenges with informed consent and study prioritization partly share common ground. High quality procedures for study prioritization, for example, seem to be a core response strategy in dealing with informed consent challenges. Especially in a research environment with particularly high uncertainty regarding potential treatment effects and further limitations for valid informed consent should the selection of clinical trials be very well justified from a scientific, medical, and ethics viewpoint.

Research encouraging off-label use of quetiapine: A systematic meta-epidemiological analysis.

BACKGROUND: Researchers often conduct small studies on testing a drug's efficacy in off-label indications. If positive results from these exploratory studies are not followed up by larger, randomized, double-blinded trials, physicians cannot be sure of a drug's clinical value. This may lead to off-label prescriptions of ineffective treatments. We aim to describe the way clinical studies fostered off-label prescription of the antipsychotic drug quetiapine (Seroquel). METHODS: In this systematic meta-epidemiological analysis, we searched EMBASE, MEDLINE, Cochrane CENTRAL and PsycINFO databases and included clinical studies testing quetiapine for unapproved indications between May 1995 and May 2022. We then assessed the frequency with which publications providing low-level evidence suggesting efficacy of quetiapine for off-label indications was not followed up by large, randomized and double-blinded trials within 5 years. RESULTS: In total, 176 published studies were identified that reported potential efficacy of quetiapine in at least 26 indications. Between 2000 and 2007, publication of exploratory studies suggesting promise for off-label indications rapidly outpaced publication of confirmatory trials. In the 24 indications with a minimum of 5 years of follow-up from the first positive exploratory study, 19 (79%) were not followed up with large confirmatory trials within 5 years. At least nine clinical practice guidelines recommend the use of quetiapine for seven off-label indications in which published confirmatory evidence is lacking. CONCLUSION: Many small, post-approval studies suggested the promise of quetiapine for numerous off-label indications. These findings generally went unconfirmed in large, blinded, randomized trials years after first being published. The imbalance of exploratory and confirmatory studies likely encourages ineffective off-label treatment.

Reporting of patient involvement: a mixed-methods analysis of current practice in health research publications using a targeted search strategy.

OBJECTIVES: To evaluate the extent and quality of patient involvement reporting in examples of current practice in health research. DESIGN: Mixed-methods study. We used a targeted search strategy across three cohorts to identify health research publications that reported patient involvement: original research articles published in 2019 in the British Medical Journal (BMJ), articles listed in the Patient-Centered Outcomes Research Institute (PCORI) database (2019), and articles citing the GRIPP2 (Guidance for Reporting Involvement of Patients and Public) reporting checklist for patient involvement or a critical appraisal guideline for user involvement. Publications were coded according to three coding schemes: 'phase of involvement', the GRIPP2-Short Form (GRIPP2-SF) reporting checklist and the critical appraisal guideline. OUTCOME MEASURES: The phase of the study in which patients were actively involved. For the BMJ sample, the proportion of publications that reported patient involvement. The quality of reporting based on the GRIPP2-SF reporting guideline. The quality of patient involvement based on the critical appraisal guideline. Quantitative and qualitative results are reported. RESULTS: We included 86 publications that reported patient involvement. Patients were most frequently involved in study design (90% of publications, n=77), followed by study conduct (71%, n=61) and dissemination (42%, n=36). Reporting of patient involvement was often incomplete, for example, only 40% of publications (n=34) reported the aim of patient involvement. While the methods (57%, n=49) and results (59%, n=51) of involvement were reported more frequently, reporting was often unspecific and the influence of patients' input remained vague. Therefore, a systematic assessment of the quality and impact of patient involvement according to the critical appraisal guideline was not feasible across samples. CONCLUSIONS: As patient involvement is increasingly seen as an integral part of the research process and requested by funding bodies, it is essential that researchers receive specific guidance on how to report patient involvement activities. Complete reporting builds the foundation for assessing the quality of patient involvement and its impact on research.

Preclinical efficacy in investigator's brochures: Stakeholders' views on measures to improve completeness and robustness.

AIMS: Research ethics committees and regulatory agencies assess whether the benefits of a proposed early-stage clinical trial outweigh the risks based on preclinical studies reported in investigator's brochures (IBs). Recent studies have indicated that the reporting of preclinical evidence presented in IBs does not enable proper risk-benefit assessment. We interviewed different stakeholders (regulators, research ethics committee members, preclinical and clinical researchers, ethicists, and metaresearchers) about their views on measures to increase the completeness and robustness of preclinical evidence reporting in IBs. METHODS: This study was preregistered (https://osf.io/nvzwy/). We used purposive sampling and invited stakeholders to participate in an online semistructured interview between March and June 2021. Themes were derived using inductive content analysis. We used a strengths, weaknesses, opportunities and threats matrix to categorize our findings. RESULTS: Twenty-seven international stakeholders participated. The interviewees pointed to several strengths and opportunities to improve completeness and robustness, mainly more transparent and systematic justifications for the included studies. However, weaknesses and threats were mentioned that could undermine efforts to enable a more thorough assessment: The interviewees stressed that current review practices are sufficient to ensure the safe conduct of first-in-human trials. They feared that changes to the IB structure or review process could overburden stakeholders and slow drug development. CONCLUSION: In principle, more robust decision-making processes align with the interests of all stakeholders and with many current initiatives to increase the translatability of preclinical research and limit uninformative or ill-justified trials early in the development process. Further research should investigate measures that could be implemented to benefit all stakeholders.

The influence of artificial saliva on the cleaning force of interdental rubber picks: an in-vitro comparison.

BACKGROUND: The familiar aids for interdental cleaning such as dental floss or interdental brushes (IDB) are often associated with difficult handling or an increased potential for trauma. Interdental picks (IRP), which have no metal core and silicone flaps instead of nylon brushes, offer the alternative. However, in-vitro studies found a lower cleaning effectiveness combined with higher forces for cleaning compared with conventional IDBs. The aim of this in-vitro study was to measure the experimental cleaning forces (ECF) using IRP with versus without an artificial saliva (AS; GUM Hydral, Sunstar Suisse SA, Etoy, Switzerland). METHODS: The test set-up was developed to investigate the cleaning of 3D-printed interdental area (IDR) mimicking human teeth (Form 2, Formlabs Sommerville, MA, USA) under standardized conditions. Three different morphologies (isosceles triangle, convex, concave) and three different sizes (1.0 mm,1.1 mm,1.3 mm) were used. Two different IRPs (GUM Soft-picks Advanced: SPA versus GUM Soft-picks Advanced Plus: SPA+, Sunstar Suisse SA, Etoy, Switzerland) in three sizes (small, regular, large), were used with versus without AS. ECF during ten cleaning cycles were recorded by a load cell [N]. RESULTS: Using AS leaded to significant lower values for ECF than without (1.04 ± 0.66 N versus 1.97 ± 1.01 N, p < 0.001). In general, a lower ECF was recorded for convex IDR compared to isosceles triangle and concave morphologies (p < 0.001) as well as for gap sizes of 1.3 mm compared to the smaller sizes (p < 0.001). For SPA+ we found significantly higher force values than for SPA (1.67 ± 0.93 N versus 1.31 ± 0.97 N, p < 0.001) independent of the use of AS. CONCLUSION: Within the study´s in-vitro limitations, we found AS reduced ECF of IRPs by half and allowed using larger diameters interdentally, which could be associated with (1) a higher cleaning effectiveness and (2) a higher acceptance e.g. of patients with dry mouth. This has to be confirmed by further clinical investigations.

Influence of flow rate and different size of suction cannulas on splatter contamination in dentistry: results of an exploratory study with a high-volume evacuation system.

OBJECTIVES: SOPs recommend high-volume evacuation (HVE) for aerosol-generating procedures (AGPs) in dentistry. Therefore, in the exploratory study, the area of splatter contamination (SCON in %) generated by high-speed tooth preparation (HSP) and air-polishing (APD) was measured when different suction cannulas of 6 mm diameter (saliva ejector (SAE)), 11 mm (HC11), or 16 mm (HC16) were utilized versus no-suction (NS). MATERIALS AND METHODS: Eighty tests were performed in a closed darkened room to measure SCON (1m circular around the manikin head (3.14 m2) via plan metrically assessment through fluorescence technique. HSP (handpiece, turbine (Kavo, Germany)) or APD (LM-ProPowerTM (Finland), Airflow®-Prophylaxis-Master (Switzerland)) for 6 min plus 5 s post-treatment were performed either without suction or with low-flow (150 l/min for SAE) or high-flow rate (250 l/min/350 l/min for HC11/HC16) suction. All tests were two-tailed (p≤0.05, Bonferroni corrected for multi-testing). RESULTS: Irrespective the AGP, SCON was higher for NS (median [25th; 75th percentiles]: 3.4% [2.6; 5.4]) versus high-flow suction (1.9% [1.5; 2.5]) (p=0.002). Low-flow suction (3.5% [2.6; 4.3]) versus NS resulted in slightly lower but not statistically significantly lower SCON (p=1.000) and was less effective than high-flow suction (p=0.003). Lowest contamination values were found with HC16 (1.9% [1.5; 2.5]; p≤0.002), whereat no significant differences were found for HC11 (2.4% [1.7; 3.1]) compared to SAE (p=0.385) or NS (p=0.316). CONCLUSIONS: Within study's limitations, the lowest splatter contamination values resulted when HC16 were utilized by a high-flow rate of ≥250 l/min. CLINICAL RELEVANCE: It is strongly recommended to utilize an HVE with suction cannulas of 16mm diameter for a high-flow rate during all AGPs and afterwards also to disinfect all surface of patients or operators contacted.

Effects of Periodontal Endoscopy-Assisted Nonsurgical Treatment of Periodontitis: Four-Month Results of a Randomized Controlled Split-Mouth Pilot Study.

OBJECTIVE: Although the therapeutic effects of nonsurgical periodontal therapy (NSPT) are well established, the clinical benefits of the additional use of periodontal endoscopy (PE) remain controversial. Therefore, this randomized controlled split-mouth pilot study evaluated the effect of NSPT using PE versus NSPT without nPE on bleeding on probing (BOP) in sites with probing depth (PD)≥4 mm (primary outcome), PD, clinical attachment level (CAL), number of hard deposits (HDs), and treatment time per tooth (TrT). METHODS: Two calibrated operators performed NSPT in twenty periodontitis patients, randomized into two quadrants for PE or nPE treatment. BOP, PD, and CAL were recorded at the first visit for NSPT (T0) and during reevaluation (T1: mean (SD) 119.7 (24.6) days after T0). The average TrT and the number of sites with HDs were documented at T0. RESULTS: For BOP, no significant differences were found at the patient's level (10/10 (male/female); aged 54.3 (10.9) years) neither within or between the groups. At tooth surface level, a lower number of surfaces with BOP (p=0.026) was observed in nPE. CAL and PD improved significantly during NSPT in both groups (p ≤ 0.001), with higher PD reduction (p < 0.001) and CAL gain (p < 0.001) in nPE. There are significantly longer TrT (p < 0.001) and more surfaces with subgingival HDs evident in PE at T0 (p=0.001). CONCLUSION: Whereas subgingival HDs can be visually detected with PE during NSPT, no additional clinical benefits regarding BOP, PD, or CAL were notable compared to conventional systematic periodontal instrumentation. Additionally, PE-assisted NSPT required a longer treatment time.

Results of an experimental study of subgingival cleaning effectiveness in the furcation area.

BACKGROUND: Sufficient biofilm removal in the furcation area (FA) is a major challenge in the clinical practice of supportive periodontal therapy. The aim of the present experimental study was to simulate subgingival cleaning of the FA using a powered scaler (sonic scaler (AIR), ultrasonic scaler (US)) for conventional mechanical debridement versus two air polishing with nonabrasive powder (LAPA-1: glycine powder, LAPA-2: erythritol powder) and different nozzles for supra-/subgingival cleaning for each device. METHODS: Seven trained and calibrated operators with ≥ 2 years each of professional experience in treating periodontitis used the instruments to clean 3D-printed replicas of six molars with through-and-through FA (four 3-rooted and two 2-rooted teeth) in a manikin head. AIR and US were used in the control group; air polishing instruments were used in the test group. For reproducible evaluation, the test teeth were separated vertically into two or three parts, illuminated with ultraviolet light, photographed and evaluated planimetrically. Treatment time (TrT, in s) and relative cleaning efficacy (RCE, in %) were measured. RESULTS: Overall, 3-rooted molars (RCE in the entire FA, 23.19 ± 20.98%) could be cleaned significantly less effectively than 2-rooted molars (53.04 ± 28.45%, p < 0.001), regardless of the instrument used. In the cleaning of the entire FA, significantly higher RCE values were achieved with conventional mechanical debridement (AIR/US: 46.04 ± 25.96%/39.63 ± 22.02%; AIR vs. US: p > 0.05) than with air polishing (LAPA-1/LAPA-2: 34.06 ± 29.48%/17.09 ± 18.85%; LAPA-1 vs. LAPA-2: p < 0.001) regardless of whether a supra- or subgingival cleaning nozzle used (p < 0.001). Only LAPA-1 with a subgingival nozzle showed RCE values comparable to those of US (41.07 ± 28.95% vs. 39.63 ± 22.02%, p > 0.05). TrT was longest for US (299.40 ± 120.69 s) and shortest for LAPA-1 with a supragingival nozzle (129.67 ± 60.92 s, p < 0.001). CONCLUSIONS: All of the examined instruments were effective to some degree in removing the simulated biofilm from the FA, but they differed substantially in cleaning efficacy. Only one air polishing device (LAPA-1) with a rigid subgingival nozzle was able to achieve RCE values similar to those of US. The current investigation confirmed that conventional mechanical debridement with powered scalers were most effective, but treatment took longer with these devices than air polishing.

In vitro comparison of cleaning efficacy and force of cylindric interdental brush versus an interdental rubber pick.

BACKGROUND: Interdental brushes (IDB) are according to the actual evidence the first choice for cleaning interdental areas (IDR). Their size should be chosen individually according to the IDR morphology. However, interdental rubber picks (IRP) are appreciated better by the patients and are hence becoming more and more popular but the evidence regarding their efficacy is still limited. The aim of this in vitro study was to measure the experimental cleaning efficacy (ECE) and force (ECF) during the use of interdental brushes versus newer wireless types with rubber filaments (IRP), both fitted and non-fitted for different IDR. METHODS: The medium size of a conical IRP (regular, ISO 2) with elastomeric fingers versus four sizes (ISO 1, 2, 3, 4) of cylindric IDB with nylon filaments (all Sunstar Suisse SA, Etoy, Switzerland) were tested. Interdental tooth surfaces were reproduced by a 3D-printer (Form 2, Formlabs Sommerville, MA, USA) according to human teeth and matched to morphologically equivalent pairs (isosceles triangle, concave, convex) fitting to three different gap sizes (1.0 mm, 1.1 mm, 1.3 mm). The pre-/post brushing situations at IDR (standardized, computer aided ten cycles) were photographically recorded and quantified by digital image subtraction to calculate ECE [%]. ECF were registered with a load cell [N]. RESULTS: Overall, a higher ECE was recorded for IDB compared to IRP (58.3 ± 14.9% versus 18.4 ± 10.1%; p < 0.001). ECE significantly depended on the fitting of the IDB. ECE was significant higher in isosceles triangle compared to concave and convex IDR for both IDB and IRP (p ≤ 0.001). ECF was lower for IDB (0.6 ± 0.4N) compared to IRP (0.8 ± 0.5N; p ≤ 0.001). ECE in relation to ECF increases with smaller IDB. For IRP highest values of ECF were found in the smallest IDR. CONCLUSIONS: Within the limitations of an in vitro study, size fitted IDB cleaned more effectively at lower forces compared to conical IRP.

[Methodological Standard for the Development of Quality Indicators within Clinical Practice Guidelines - Results of a structured consensus process]. / Methodischer Standard für die Entwicklung von Qualitätsindikatoren im Rahmen von S3-Leitlinien ­ Ergebnisse einer strukturierten Konsensfindung.

BACKGROUND: Recommendations of evidence- and formally consensus-based clinical practice guidelines (CPGs) represent a valuable source of quality indicators (QIs). Nevertheless, a standardized methodological procedure for developing QIs in the context of CPGs does not yet exist in Germany for all CPGs. For this reason, a methodological standard for the guideline-based development of QIs (QI Standard) was developed based on a structured consensus process involving multiple key stakeholders. METHODS: The proposed content of the QI Standard was derived from evidence, drawing upon results of reviews and qualitative studies, and considered German manuals for guideline-based QI development of two guideline programs. A multi-perspective consensus panel, broadly representing key stakeholders from the German healthcare system with expertise in CPGs and/or quality management, was nominated to vote on recommendations for guideline-based development of QIs. The iterative, structured consensus process included a two-stage online survey based on the Delphi method ("preliminary voting") and a moderated final stakeholder conference where all those recommendations were definitely included in the QI Standard that received approval of more than 75 % (consensus criterion) of the consensus panel. RESULTS: Based on the agreed QI Standard, the QI development process starts with a criteria-based selection of "potential" QIs which - in case of adoption - are published in CPGs as "preliminary" QIs and can achieve the status "final" after successful testing. The QI Standard is composed of a total of 30 recommendations, which are allocated to six areas: A) preparatory work steps for the guideline-based recommendation of QIs, B) QI development group and cooperation with the CPG group, C) development of potential QIs, D) critical appraisal of potential QIs, E) formal adoption and publication as well as F) piloting/testing of preliminary QIs and conversion into final QIs. DISCUSSION: Before the QI Standard can be recommended for implementation in future CPGs, it should have been successfully tested in selected German CPG projects. In addition to methodological requirements for the QI development, it must be ensured that guideline groups have adequate resources for the implementation of the QI Standard. CONCLUSION: By using the QI Standard, scientifically sound and healthcare-relevant QIs can be expected.

Evaluation of a systematic digitized training program on the effectivity of subgingival instrumentation with curettes and sonic scalers in vitro.

OBJECTIVES: Whereas the key role of subgingival instrumentation in periodontal therapy is well known, the influence of operators' experience/training with different devices on treatment results is yet uncertain. Therefore, we assessed untrained undergraduate students, working on manikins, as to how effectively they learn to use curettes (GRA) and sonic scalers (AIR); hypothesizing that AIR will result in higher relative cleaning efficacy (RCE) than GRA. MATERIAL AND METHODS: Before baseline evaluation (T0), 30 operators (9 males, 21 females) received a 2-h theoretical lesson for both instruments, followed by a 12-week period with a weekly digitized training program for 45 min. During three sessions (T1-T3), the operators had to instrument six equivalent test teeth with GRA and AIR. At T0-T3, treatment time, proportion of removed simulated biofilm (RCE-b), and hard deposits (RCE-d) were measured. RESULTS: At T0, RCE-b was in mean(SD) 64.18(25.74) % for GRA, 62.25(26.69) % for AIR; (p = 0.172) and RCE-d 85.48(12.32) %/ 65.71(15.27) % (p < 0.001). At T3, operators reached highest RCE-b in both groups (GRA/AIR 71.54(23.90) %/71.75(23.05)%; p = 0.864); RCE-d GRA/AIR: 84.68(16.84) %/77.85(13.98) %; p < 0.001). Both groups achieved shorter treatment times after training. At T3, using curettes was faster (GRA/AIR 16.67(3.31) min/19.80(4.52) min; p < 0.001). CONCLUSIONS: After systematic digitized training, untrained operators were able to clean 70% of the root surfaces with curettes and sonic scalers. CLINICAL RELEVANCE: It can be concluded that a systematic digitized and interactive training program in manikin heads is helpful in the training of root surface debridement.

New experimental setup for the measurement of cleaning efficacy and force of interdental aids in 3D-reproduced interdental areas.

BACKGROUND: Interdental rubber picks (IRP) have become a frequent and convenient alternative for interdental cleaning. However, only little evidence exists supporting the effectiveness of newer designs available on the market. Therefore, a new in vitro model was evaluated to measure the experimental cleaning efficacy (ECE), as well as the force needed for insertion and during the use of IRP, with high reproducibility. METHODS: Five different sizes of commercially marketed IRP with elastomeric fingers (IRP-F) (GUM SOFT-PICKS® Advanced, Sunstar Deutschland GmbH, Schönau, Germany) or slats (IRP-S) (TePe EasyPick™, TePe D-A-CH GmbH, Hamburg, Germany) were tested. Interdental tooth surfaces were reproduced by a 3D-printer (Form 2, Formlabs Sommerville, MA, USA) according to human teeth and matched to morphologically equivalent pairs (isosceles triangle, concave, convex) fitting to different gap sizes (1.0 mm, 1.1 mm, 1.3 mm). The pre-/post brushing situations at interdental areas (standardized cleaning, computer aided ten cycles) were photographically recorded and quantified by digital image subtraction to calculate ECE [%]. Forces were registered with a load cell [N]. RESULTS: IRP-F have to be inserted with significant higher forces of 3.2 ± 1.8 N compared to IRP-S (2.0 ± 1.6 N; p < 0.001) independent of the size and type of artificial interdental area. During cleaning process IRP-S showed significantly lower values for pushing/pulling (1.0 ± 0.8 N/0.5 ± 0.4 N) compared to IRP-F (1.6 ± 0.8 N/0.7 ± 0.3 N; p < 0.001) concomitant to significantly lower ECE (19.1 ± 9.8 vs. 21.7 ± 10.0%, p = 0.002). Highest ECE was measured with largest size of IRP-F/IRP-S independent the morphology of interdental area. CONCLUSIONS: New interdental cleaning aids can be tested by the new experimental setup supported by 3D printing technology. Within the limitations of an in vitro study, IRP-F cleaned more effectively at higher forces compared to IRP-S.

How to train periodontal endoscopy? Results of a pilot study removing simulated hard deposits in vitro.

OBJECTIVES: There is uncertainty regarding the benefits of periodontal endoscopy (PE) for subgingival instrumentation. Moreover, the influence of operators' experience and training with such a device on treatment results is unclear. Therefore, we compared in an in vitro study the use of PE for scaling and root planing (SRP) with the conventional non-surgical therapy, hypothesizing that using a PE allows to remove more simulated hard deposits than without (nPE), influenced by the operators' experience and training. MATERIAL AND METHODS: A sonic device and Gracey curettes were utilized by 11 operators (six dentists, five dental hygienists) in periodontitis manikins heads. The time required for treatment and the proportion of removed simulated hard deposits by SRP were measured. RESULTS: Using the PE led to a significant difference in removal of simulated hard deposits (%) (mean ± SD) irrespective of operators' experience (PE 90.78 ± 12.10% (range 58.80-100%); nPE 79.98 ± 22.15% (range 38.10-100%, p < 0.001)), sub-analyses for different tooth types demonstrated a significant difference in favor of PE for front teeth (p < 0.001) and in the upper jaw independent of the tooth type (p < 0.001). Comparison of treatment times for two quadrants with and without PE showed a significantly longer treatment time with PE (∆22.27 ± 17.98 mins, p <0.001). CONCLUSIONS: Within the present pilot study, the use of PE led to more removal of simulated hard deposits but was concomitantly related to more time and financial effort. Using PE was most beneficial in the front area. CLINICAL RELEVANCE: PE may provide additional benefits for the removal of hard deposits compared to traditional SRP. The beneficial effect of PE seems not to be influenced by operators experience nor by pocket probing depth.

Non-Specific Low Back Pain.

BACKGROUND: For many years, low back pain has been both the leading cause of days lost from work and the leading indication for medical rehabilitation. The goal of the German Disease Management Guideline (NDMG) on nonspecific low back pain is to improve the treatment of patients with this condition. METHODS: The current update of the NDMG on non-specific low back pain is based on articles retrieved by a systematic search of the literature for systematic reviews. Its recommendations for diagnosis and treatment were developed by a collaborative effort of 29 scientific medical societies and organizations and approved in a formal consensus process. RESULTS: If the history and physical examination do not arouse any suspicion of a dangerous underlying cause, no further diagnostic evaluation is indicated for the time being. Passive, reactive measures should be taken only in combination with activating measures, or not at all. When drugs are used for symptomatic treatment, patients should be treated with the most suitable drug in the lowest possible dose and for as short a time as possible. CONCLUSION: A physician should be in charge of the overall care process. The patient should be kept well informed over the entire course of his or her illness and should be encouraged to adopt a healthful lifestyle, including regular physical exercise.

The Prevention and Treatment of Retinal Complications in Diabetes.

BACKGROUND: Microvascular complications of diabetes mellitus can cause retino pathy and maculopathy, which can irreversibly damage vision and lead to blindness. The prevalence of retinopathy is 9-16% in patients with type 2 diabetes and 24-27% in patients with type 1 diabetes. 0.2-0.5% of diabetics are blind. METHODS: The National Disease Management Guideline on the prevention and treatment of retinal complications in diabetes was updated according to recommendations developed by seven scientific medical societies and organizations and by patient representatives and then approved in a formal consensus process. These recommendations are based on international guidelines and systematic reviews of the literature. RESULTS: Regular ophthalmological examinations enable the detection of retinopathy in early, better treatable stages. The control intervals should be based on the individual risk profile: 2 years for low-risk patients and 1 year for others, or even shorter depending on the severity of retinopathy. General risk factors for retinopathy include the duration of diabetes, the degree of hyperglycemia, hypertension, and diabetic nephropathy. The general, individually adapted treatment strategies are aimed at improving the risk profile. The most important specifically ophthalmological treatment recommendations are for panretinal laser coagulation in proliferative diabetic retinopathy and, in case of clinically significant diabetic macular edema with foveal involvement, for the intravitreal application of medications (mainly, vascular endothelial growth factor [VEGF] inhibitors), if an improvement of vision with this treatment is thought to be possible. CONCLUSION: Regular, risk-adapted ophthalmological examinations, with standardized documentation of the findings for communication between ophthalmologists and the patients' treating primary care physicians/diabetologists, is essential for the prevention of diabetic retinal complications, and for their optimal treatment if they are already present.

Age-related medication adherence in patients with chronic heart failure: A systematic literature review.

BACKGROUND: Chronic heart failure (CHF) is prevalent among the elderly and is characterized by high mortality and hospitalization rates. Non-adherence to medications is frequent and related to poor clinical outcomes. It is often assumed that older age is related to poorer medication adherence compared with younger age. We analyzed the existing evidence of age as a determinant of medication adherence in patients with CHF. METHODS: A systematic search of the bibliographic database MEDLINE and all Cochrane databases was performed. Studies were included if they examined medication adherence in adult patients with CHF, evaluated factors contributing to medication adherence, and analyzed the relationship between age and medication adherence. Articles classified as studies with poor quality were excluded. RESULTS: A total of 1565 titles were found, and ultimately, 17 studies, which provide data for a total of 162,727 patients, were analyzed. Seven studies showed a statistically significant relationship between age and medication adherence: six articles demonstrated that increased age is correlated with higher medication adherence, and one study showed that patients in the age range of 57 to 64 years are affected by non-adherence to angiotensin-converting enzyme inhibitors. Ten studies found no significant relationship. CONCLUSIONS: The results suggest that older age alone is not related to poorer medication adherence compared with younger patients with CHF. More attention should be paid to younger newly-diagnosed patients with CHF. Future studies are required to explore medication adherence in CHF in different, standardized, and specific age groups and should be sufficiently powered to assess clinical endpoints.

Gaps in health care for the somatic health of outpatients with severe mental illness.

The physical health of outpatients with severe mental illness (SMI) can be improved by changes in the health-care system. Analysis of current practice is necessary to develop these strategies. We compared the number of somatic health problems of outpatients with SMI with the frequency of consulting a general practitioner (GP). This was a cross-sectional study based on interviews, and records from the GP and the pharmacy. We checked whether Dutch community pharmacies had complete and correct information about the patients' medication. We observed that all patients (n = 118) had somatic problems in need of clinical attention. Patients who visited their GP less than once a year (35%, n = 42), had a mean of 2.8 somatic health problems. This was less than patients who consulted their GP more than once a year (P ≤ 0.01). In 37% of cases, the pharmacy did not have adequate information on the drug use. Many patients with SMI seemed to have insufficient contact with their GP for their somatic health problems. Insufficient information about the patients' medication suggested that the pharmacist and GP should increase exchange of information. Mental health nurses can take a lead in coordinating the care to improve somatic health for their patients.