Antibiotic use by dentists in Germany: a review of prescriptions, pathogens, antimicrobial resistance and antibiotic stewardship strategies.

BACKGROUND: In Germany, 85% of all antibiotics are prescribed in the outpatient care sector, and dentists account for 11% of the total outpatient antibiotic prescriptions. OBJECTIVE AND METHOD: Summarise published literature on antibiotic use, pathogens and antibiotic resistance in odontogenic infections and German clinical guidelines and interventions for antibiotic use in dental care. RESULTS: In contrast to other outpatient physicians, the volume of antibiotics prescribed by dentists in Germany did not decrease over the last decade. Penicillins and aminopenicillins are the most frequently prescribed antibiotics (70% of all prescriptions), followed by clindamycin (26%). Streptococcus spp. and Staphylococcus spp. are frequent pathogens isolated from odontogenic infections. However, the infections are often polybacterial with a mixed growth of anaerobic and aerobic bacteria. While the widespread use of penicillin class antibiotics is compatible with German recommendations on empiric antibiotic therapy, there is evidence that pathogens from odontogenic infections frequently exhibit resistance against them. Moreover, the high prescription volume of clindamycin (⟩25%) appears to be inadequate, since relatively high resistance rates are observed and clindamycin is not recommended as first-line choice in empiric antibiotic therapy. National and international studies show that continuous education of patients and dentists, individual prescription feedback as well as evidence-based guidelines are important measures to improve antibiotic prescription patterns among dentists. CONCLUSION: To promote rational antibiotic use in outpatient dental care, antibiotic stewardship measures are necessary that include prescription guidelines based on AMR surveillance data as well as continuous education of dentists.

Factors influencing GPs' perception of specialised palliative homecare (SPHC) importance - results of a cross-sectional study.

BACKGROUND: General Practitioners (GPs) are the main providers of primary palliative care (PPC). At the same time they are the main initiators of specialised palliative homecare (SPHC). In Germany, little is known about factors which influence GPs in their involvement of SPHC. Aim of our study is to identify factors that drive GPs to give value to and involve SPHC. METHODS: A cross-sectional survey was performed. In 2018, questionnaires were mailed to 6000 randomly selected GPs from eight German federal states, focusing on the extent of GPs' palliative care activities and their involvement of SPHC. RESULTS: With a response rate of 19.4% and exclusion of GPs working in SPHC-teams, n = 1026 questionnaires were appropriate for analysis. GPs valued SPHC support as the most "important/very important" for both "technical/invasive treatment measures" (95%) and availability outside practice opening hours (92%). The most relevant factor influencing perceived SPHC-importance was GPs' self-reported extent of engagement in palliative care (ß = - 0.283; CI 95% = - 0.384;-0.182), followed by the perceived quality of utilised SPHC (ß = 0.119; CI 95% = 0.048;0.190), involvement in treatment of palliative patients after SPHC initiation (ß = 0.088; CI 95% = 0.042;0.134), and conviction that palliative care should be a central part of GPs' work (ß = - 0.062; CI 95% = - 0.116;-0.008). Perceived SPHC-importance is also associated with SPHC-referrals (ß =0.138; p < 0.001). The lower the engagement of GPs in palliative care, the more they involve SPHC and vice versa. CONCLUSIONS: GPs with low reported activity in palliative care are more likely to initialise SPHC for palliative care activities they do not deliver themselves for various reasons, which might mean that the involvement of SPHC is substitutive instead of complementary to primary palliative care. This finding and its interpretation should be given more attention in the future policy framework for (specialised) palliative homecare. TRIAL REGISTRATION: German Clinical Trials Register DRKS00014726 , 14.05.2018.

[Pain registries and similar data collections : A systematic review]. / Schmerzregister und verwandte Datensammlungen : Eine Übersichtsarbeit.

BACKGROUND: Registries and similar data collections are a valuable addition to prospective studies as they provide data from real life treatment. In pain medicine only few such data collections exist so far. OBJECTIVE: Aim of the study was to identify German-language registries or similar data collections that record patient-reported and pain-associated outcomes together with other data. MATERIAL AND METHODS: A systematic search was carried out, which included the following sources: the data bases PubMed/MEDLINE and Embase, the German Registry for Clinical Trials (DRKS), ClinicalTrials.gov and registry portals known to us. Furthermore, an extended internet search was carried out via Google Scholar. References from personal scientific contacts and from operators of registries were also included. Questionnaires regarding registry items were sent to registry operators. RESULTS: Out of 381 search hits, 37 potentially relevant projects received a questionnaire and 35 answered. From the 35 responders 23 registries or similar data collections fulfilling inclusion criteria could be identified: 5 primarily pain-associated, 3 therapy-associated, 2 population-associated and 13 disease-associated (rheumatism/arthritis 5, joints/spine 4, hernias 1 and cancer 3). CONCLUSION: The reader obtains contact information on relevant data collections associated with pain, the contents, objectives and the pain assessment instruments applied. This review could give an important impulse for increased networking in health services research on pain. A limitation of the study was that identification of registries was made difficult due to an inconsistent definition and application of the term "registry", incomplete or insufficiently updated registry portals, missing scientific publications as well as two non-responders.

[Use and potential risks of over-the-counter analgesics]. / Gebrauch und potenzielle Risiken durch nicht verschreibungspflichtige Schmerzmittel.

BACKGROUND AND AIM: We investigated the use of prescription and non-prescription (over-the-counter, OTC) analgesics and the associated risks in elderly patients with multiple morbidities. METHODS: Pain medication use was evaluated from the baseline data (2008/2009) of the MultiCare cohort enrolling elderly patients with multiple morbidities who were treated by primary care physicians (trial registration: ISRCTN89818205). We considered opioids (N02A), other analgesics, and antipyretics (N02B) as well as nonsteroidal anti-inflammatory drugs (NSAIDs; M01A). OTC use, duplicate prescription, dosages, and interactions were examined for acetylsalicylic acid, diclofenac, (dex)ibuprofen, naproxen, and acetaminophen. RESULTS: Of 3,189 patients with multiple morbidities aged 65-85 years, 1,170 patients reported to have taken at least one prescription or non-prescription analgesic within the last 3 months (36.7 %). Of these, 289 patients (24.7 % of 1,170) took at least one OTC analgesic. Duplicate prescription was observed in 86 cases; 15 of these cases took the analgesics regularly. In two cases, the maximum daily dose of diclofenac was exceeded due to duplicate prescription. In 235 cases, patients concurrently took a drug with a potentially clinically relevant interaction. In 43 cases (18.3 % of 235) an OTC analgesic, usually ibuprofen, was involved. DISCUSSION: About one third of the elderly patients took analgesics regularly or as needed. Despite the relatively high use of OTC analgesics, the proportions of duplicate prescription, medication overdoses, and adverse interactions due to OTC products was low.

Healthcare utilization of back pain patients: results of a claims data analysis.

OBJECTIVES: The high life-time prevalence of chronic back pain (25-30% according to surveys in small samples) suggests that it may be a major source of healthcare cost and that prevention of chronic back pain may be both ethically and economically recommendable. To obtain valid economic data on the cost of back pain in Germany, a retrospective claims data analysis was performed. METHODS: Using data from 2006 of 5.2 million beneficiaries of a German statutory health insurance fund (DAK Unternehmen Leben) covering ~7% of the German population, mean value analyses report on key healthcare utilization figures from a sickness funds? perspective. In contrast to other studies, cost data are primary data and not extrapolated, but clinical characteristics include surrogate markers as no clinical case descriptions were available. RESULTS: Based on previously investigated diagnosis patterns three types of back pain could be identified: (other) specific back pain (n=211,216), pain due to spinal disk disease (n=195,712), and non-specific back pain (n=534,272). Of all back pain patients, 25.8% were identified as at risk to develop chronic pain, where only 2.6% were detected as patients with chronic back pain. Mean resource utilization and related healthcare costs were significantly higher for beneficiaries with indicators for chronic back pain than for beneficiaries with only risk factors for developing chronic back pain. This especially holds for outpatient analgesic prescriptions (p<0.05), for in-hospital multimodal pain therapy (p<0.05), for in-hospital care in general (p<0.05), as well as for direct cost of care (p<0.05). CONCLUSION: The results show the potential that could be made accessible by an early detection of back pain patients who bear a risk of pain becoming chronic, both in terms of quality-of-life as well as in financial terms.

[Opioid therapy in patients with back pain. Claims data analysis for patient group characterization, influence on opioid therapy and work disability]. / Opioidtherapie bei Versicherten mit Rückenschmerzen. Sekundärdatenanalyse zur Charakterisierung von Patientengruppen, Einfluss auf Opioidtherapie und Arbeitsunfähigkeit.

This study features an analysis of the analgesic therapy of patients with back pain focusing on opioid administration. Using claims data of a German statutory health insurance fund the analysis focuses on prescription patterns, the association between opioids and antiemetics as well as between opioid therapy and work disability. Based on typical diagnosis patterns three types of back pain could be identified: (other) specific back pain (46.0%), pain due to spinal disc diseases (23.5%) and non-specific back pain. The proportion of patients receiving continuous opioid therapy ranged between 24.3% and 48.8%. The prescription of antiemetics was associated with a higher chance of continuous opioid therapy (odds ratio [OR] 1.93; 95% confidence interval [CI] 1.79-2.08). The chance of continuous opioid therapy was higher in pain patients with spinal disc diseases and patients with (other) specific back pain (OR 1.62 and 1.76, respectively; 95% CI 1.56-1.69 and 1.69-1.83, respectively). Continuous opioid therapy appears to increase the probability of a lower number of days off work due to disability (incidence rate ratio [IRR] 0.76; 95% CI 0.70-0.84). Adequate prospective studies should test if the associations found can be confirmed.

[Pain-specific diagnosis patterns in claims data - Identification by means of classification and regression trees (CART)]. / Schmerztypische Diagnosemuster in Routinedaten - Identifikation mittels Classification and Regression Trees (CART).

The identification of beneficiaries with persistent, recurrent or chronic pain in claims data by means of individual diagnoses or analgesic prescription is not sufficient and reliable. By using CLASSIFICATION AND REGRESSION TREES (CART) it was possible to identify specific diagnosis patterns for patients suffering from pain. Diagnosis patterns are considered as specific if they occur more frequently among beneficiaries with at least two opioid prescriptions within one year compared with beneficiaries who did not receive any analgesic therapy. Diagnosis and prescription data of 2006 were provided by the German sickness fund DAK. As a result, 65 diagnosis patterns occurred more frequently among beneficiaries treated with opioids than among the control group. These 65 patterns can be classified as follows: cancer-related pain (4), specific back pain/osteoporosis (8), spine-related pain (6), arthritis-related pain/rheumatoid arthritis (22), pain after traumatic fractures (5), pain in multimorbid, dependent patients (3), neuropathic pain (7), headache (5), non-specific back pain (5). The derived diagnosis patterns showed high predictive values (sensitivity: 78%, specificity: 66%) and are suitable for the identification of beneficiaries suffering from pain - the first step towards health services research in pain-based on claims data.

[Identification and grouping of pain patients according to claims data]. / Identifikation und Gruppierung von Schmerzpatienten anhand von Routinedaten einer Krankenkasse.

The ICD classification does not provide the opportunity to adequately identify pain patients. Therefore we developed an alternative method for the identification and classification of pain patients which is based on prescription and diagnoses data from the year 2006 of one nationwide sickness fund (DAK) and which is led by two main assumptions: 1. Beneficiaries without prescription of an analgetic drug but with a diagnosis pattern that is characteristic of patients who are treated with opioids are also likely to be pain patients. 2. Each combination of diagnosis groups can be traced back to one primary diagnosis out of a diagnosis group according to the patient classification system CCS (Clinical Classifications Software). The selection of this diagnosis group (CCS) allows for the allocation of the beneficiary to only one pain type. As a result we identified 65 combinations of CCS diagnosis groups--aggregated to nine "CCS pain types"--to which 77.1% of all patients with at least two opioid prescriptions can be allocated: 26.3% to pain due to arthrosis, 18.0% to pain due to intervertebral disc illnesses, 13.1% to other specific back pain, 6.7% to neuropathic pain, 4.5% to unspecific back pain, 4.2% to headache, 2.4% to pain after traumatic fractures, 1.3% to pain of multimorbid, high-maintenance patients, and 0.6% to cancer pain. Based on our method beneficiaries who have a high probability of suffering from moderate to strong pain can be identified and included in further claims data analyses of health care delivery and utilization pattern of pain-related disorders in Germany.

[Splenic rupture after ERCP]. / Milzruptur nach ERCP.

We report on a 52 year old woman, who developed splenic rupture after endoscopic sphincterotomy for multiple biliary stones. After hemorrhagic shock had developed, the diagnosis was established by computed tomography and ultrasound guided paracentesis. The patient was treated by emergency splenectomy. The case report stresses the necessity to be aware of splenic rupture as a rare complication after ERCP. A review of the current literature regarding splenic rupture is provided and mechanisms of splenic trauma and risk factors are discussed.

[Therapy of abdominal and thoracic chylous effusions 18 years after radiation therapy]. / Therapie abdomineller und thorakaler chylöser Ergüsse 18 Jahre nach Radiatio.

Chylothorax and chylascites are rare complications of neoplasm or surgical, but also non-surgical trauma. Extremely rare causes are a subclavian i.v. line, a mesenterical hamartoma, retrosternal goiter, liver cirrhosis, portal vein thrombosis, filariasis, tuberculosis, ruptured aortic aneurysm and radiotherapy. We report on a 60-year-old male with bilateral chylothorax and chylascites resistant to therapy 18 years after irradiation of the iliacal, paraaortal and mediastinal (46 Gray) and the left-sided supraclavicular (40 Gray) lymph nodes for a seminoma (T3N1M0 i.e. IIa, Lugano classification). A fat-free parenteral nutrition was started in order to bring the lymphatic flow down to a minimum. Chyle flow ceased after 3 1/2 weeks of treatment. An oral diet with middle chain triglycerides (MCT-diet), which are transported to the liver via the portal vein instead of the lymphatic system, achieved good control of residual chylous effusions.

Safety and efficacy of repeated shockwave lithotripsy of gallstones with and without adjuvant bile acid therapy.

BACKGROUND & AIMS: The value of adjuvant bile acid dissolution therapy after extracorporeal shockwave lithotripsy (ESWL) of gallbladder stones is under debate. A double-blind, randomized, multicenter trial was conducted to determine the safety and efficacy of repeated ESWL with and without adjuvant bile acid therapy. METHODS: At five centers, 153 patients with gallstones and good gallbladder emptying were randomized to undergo up to six high-energy lithotripsy sessions combined with ursodeoxycholic acid (UDCA, 750 mg/day; n = 77) or placebo (n = 76). RESULTS: Six months after the initial treatment, 77% of patients with small single stones (< or = 20 mm in diameter), 60% with large single stones (> 20 mm in diameter), and 41% with multiple stones were free of stones. Administration of UDCA had no effect on stone disappearance in the whole study group but tended to improve stone disappearance rates in patients with large single stones and tended to decrease biliary adverse effects in patients with multiple stones. CONCLUSIONS: Repeated high-energy ESWL without adjuvant bile acid therapy represents a safe and effective treatment in patients with small single stones and good gallbladder emptying. In patients with large single stones and multiple stones, adjuvant bile acid therapy may be beneficial.

Selection of atrazine tolerant soybean calli and expression of that tolerance in regenerated plants.

Lines of soybean [Glycine max (L.)] tolerant of atrazine were developed by an in vitro and in vivo atrazine challenge. Cotyledonary node plus epicotyl explants from mature germinated seed of soybean introduction PI 438489B were cultured on RV-5 medium containing 48 mg active ingredient (a.i.)/l atrazine for one month. Most of the explants (66%) on medium containing atrazine, and 10% on medium without atrazine died. Explants surviving exposure to atrazine callused and organogenically regenerated shoots developed. Soil around R0 plants regenerated from atrazine tolerant shoots and nonatrazine challenged shoots (controls) were subsequently tested in vivo for atrazine tolerance. All controls died. Seeds were collected from atrazine tolerant R0 plants. Two weeks after planting, emerged R1 seedlings were tested in vivo for atrazine tolerance as the R0 plants were. This procedure was repeated on the R2 plants. All nonatrazine selected control plants died when exposed to this herbicide. Atrazine tolerant R2 plants were maintained in atrazine amended soil and appeared as healthy and vigorous as the control growing in atrazine free soil.

Salt tolerant sugarbeet progeny from tissue cultures challenged with multiple salts.

Lines of sugarbeet (Beta vulgaris L.) tolerant of multiple salts was accomplished by an in vitro multiple salt challenge. Petioles were placed on RV medium amended with 5 different salts along with Murashige and Skoog base salts for one month. Surviving shoots were cultured on RV medium to obtain petioles for subsequent challenges. During the first, second and third challenges, organogenically regenerated shoots developed from 5%, 46%, and 80% of the petioles, respectively. After the third multiple salt challenge, tolerant shoots were rooted and transplanted in soil. Salt was added to this soil at 1.0% by weight and plants were observed for 2 months. The ten most salt tolerant plants were vernalized to obtain seed. The R1 seed and controls were planted in soil containing 0%, 0.61% or 0.77% multiple salts per dry soil weight. Emergence of R1 seedlings was significantly greater than the controls under salt stress. Multiple salt tolerant R1 plants were maintained in salt amended soil to the 8-10 leaf stage and appeared as healthy and vigorous as the control growing in salt free soil.

Somaclonal variation in soybean plants regenerated from tissue culture.

Callus cultures of soybean (Glycine max (L.) Merr.) genotypes PI 88788, PI 438489B, and cultivar Bedford were initiated in vitro from seedling explants consisting of the cotyledonary node plus epicotyl from germinated mature seed. Plants were regenerated from these callus cultures and subsequently evaluated for qualitative variation in three to four subsequent generations. Variant phenotypes observed that have not been previously reported from tissue culture include lanceolate leaves, leaf variegation (chimeral variegated plants), pod variegation on otherwise normal plants, and change in growth habit from indeterminate to determinate. The lanceolate leaf, chimeral variegated plant, and change from indeterminate to determinate growth habit characters were inherited through at least three generations (R0-R2), and segregation occurred in each generation. Pod variegation was inherited through the two generations tested thus far and segregation occurred in each generation. No variation was observed in control plants derived from normal seed. Variants appeared more frequently in regenerants from PI 88788 and PI 438489B than from Bedford. These results confirm and extend the finding that certain tissue culture techniques may be used to induce novel plant formation from somatic tissue of soybean.

An improved medium for adventitious shoot formation and callus induction in Beta vulgaris L. in vitro.

Six sugarbeet (Beta vulgaris L.) lines (GWI-248, SPB-11, MonoHy 55, SMS-1, EL45 and FC607) were tested for regeneration. Shoot cultures were initiated in vitro from naked, sterilized embryos obtained from mature seed. Excised petioles from cultured shoots were plated on Gamborg's B5 medium and four modified Murashige and Skoog (MS) media. A medium containing MS inorganic salts supplemented with 0.4 mg/1 N(6)-benzyladenine, 0.1 mg/1 indole-3-butyric acid, ten vitamins and six amino acids, termed RV, was superior for both adventitious shoot and callus formation. Callus was observed only on RV medium and only on petioles that did not develop adventitious buds directly. Rooting of regenerated shoots and development of complete plants was accomplished by transfer to Gamborg's B5 medium with 5 mg/l indole-3-butyric acid as the sole phytohormone. The complete process of regeneration through adventitious shoot production took from 4 to 6 weeks from explants to rooted plants. The callus that formed on nonorganogenic petioles was regenerative when transferred to fresh RV medium. Regeneration from callus occurred mainly by shoot organogenesis but also by somatic embryogenesis at a low frequency.

Association of transformation of xenosomes from nonkiller to killer with extrachromosomal DNA.

Extrachromosomal DNA in the form of covalently closed circular DNA molecules was isolated from killer and nonkiller xenosomes, bacterial endosymbionts of the marine protozoan Parauronema acutum. Restriction endonuclease digests of these molecules derived from 12 isolates revealed consistent, readily identifiable, differences in the pattern of fragments of the killer as compared with those present in the nonkiller. Transformation of the nonkiller to killer by infection is also accompanied by a change from the nonkiller to killer pattern. Based on analysis of fragments resulting from restriction endonuclease digests, two circular duplex DNA molecules, each 63 kilobase pairs (kbp) in length, were identified in the 263-20 nonkiller stock and mapped. The maps revealed that each possesses a single BamHI site and multiple BglI, BstIIE, PstI, and SalI sites. A distinguishing feature of these maps is that the two molecules share a region about 17 kbp in length in which multiple restriction sites are in register with each other. Allowing for a 0.5-kbp insertion or deletion and the introduction or removal of only a few restriction sites, an additional stretch extending approximately 31 kbp beyond this sequence could also be considered to be homologous. The structure of the killer plasmid appears to be more complex, and we have been unable, as yet, to construct physical maps for this DNA. We postulate that the killer plasmid DNA is composed of three, perhaps four, circular 63-kbp duplexes, at least one which contains a single BamHI site and another which contains two BamHI sites. The remaining molecules may represent copies of either or both of the other two, modified to contain additional restriction sites. Transformation from the nonkiller to the killer is visualized as the insertion of restriction sites at various points along parent nonkiller plasmid DNA molecules. The mechanism by which these sites are introduced is unknown.

Influence of age, hexobarbital, and aniline on NADPH/NADH dependent hydrogen peroxide production in rat hepatic microsomes.

Hepatic microsomal H2O2 production (oxidase function of microsomal cytochrome P-450) is strongly dependent on NADPH or NADH concentration. NADH increases H2O2 production after the addition of a supraoptimal concentration of NADPH to the incubation mixture in all age groups. Maximum activities are found in 60-day-old male Wistar rats. Hexobarbital increased in a dose dependent manner both NADPH, NADH, and NADPH/NADH dependent H2O2 production. Aniline had no effect or slightly decreased H2O2 production. Hexobarbital enhanced NADPH/NADH dependent H2O2 production in all age groups (5-240 days of age) to the same degree. Hence it is concluded that H2O2 production is due to the decay of the peroxycytochrome P-450 complex after the second reduction step via cytochrome b5 and that in all age groups reducibility of cytochrome P-450, which is enhanced by hexobarbital, is rate limiting. As the age course of H2O2 production is similar to that of ethylmorphine N-demethylation, it is concluded that the phenobarbital-inducible cytochrome P-450 subspecies predominantly catalyse H2O2 production.

[Bioavailability and tolerance of xanthinol nicotinate depot preparations. Comparison of a conventional 500 mg xanthinol nicotinate depot tablet with new 500 mg and 1 g depot tablets]. / Bioverfügbarkeit und Verträglichkeit verschiedener Xantinolnicotinat-Retardformen. Vergleich einer herkömmlichen 500-mg-Xantinolnicotinant-Retardtablette mit neuen 500-mg-und 1-g-Retardtabletten.

Bioavailability (therapeutic blood levels) and tolerance of two 500-mg xanthinol nicotinate retard tablet forms and one 1-g xanthinol nicotinate retard tablet (Complamin special) were tested in 11 (12) healthy volunteers. Despite the fact that both 500-mg retard tablets had different in vitro release rates the blood levels in man were similar. These results suggest that in vitro release rates of tablets do not predict corresponding blood levels in man. The tablet with a lower release rate also showed a distinctly lower flush rate. In respect to bioavailability and tolerance the 1-g xanthinol nicotinate retard tablet was comparable with corresponding dosages of 500-mg retard tablets. The dosage given was 2 X 500 mg or 1 g xanthinol nicotinate t.i.d. over a period of 10 days each.