ABSTRACT
Alternative mode-of-inhibition of clinically validated targets is an effective strategy for circumventing existing clinical drug resistance. Herein, we report 1,3-diarylpyrazolyl-acylsulfonamides as potent inhibitors of HadAB/BC, a 3-hydroxyl-ACP dehydratase complex required to iteratively elongate the meromycolate chain of mycolic acids in Mycobacterium tuberculosis (Mtb). Mutations in compound 1-resistant Mtb mutants mapped to HadC (Rv0637; K157R), while chemoproteomics confirmed the compound's binding to HadA (Rv0635), HadB (Rv0636), and HadC. The compounds effectively inhibited the HadAB and HadBC enzyme activities and affected mycolic acid biosynthesis in Mtb, in a concentration-dependent manner. Unlike known 3-hydroxyl-ACP dehydratase complex inhibitors of clinical significance, isoxyl and thioacetazone, 1,3-diarylpyrazolyl-acylsulfonamides did not require activation by EthA and thus are not liable to EthA-mediated resistance. Further, the crystal structure of a key compound in a complex with Mtb HadAB revealed unique binding interactions within the active site of HadAB, providing a useful tool for further structure-based optimization of the series.
Subject(s)
Mycobacterium tuberculosis , Thioacetazone , Bacterial Proteins/metabolism , Mycolic Acids/chemistry , Thioacetazone/metabolism , Thioacetazone/pharmacology , Hydro-Lyases/chemistry , Hydro-Lyases/metabolism , Hydro-Lyases/pharmacologyABSTRACT
New antibiotics with either a novel mode of action or novel mode of inhibition are urgently needed to overcome the threat of drug-resistant tuberculosis (TB). The present study profiles new spiropyrimidinetriones (SPTs), DNA gyrase inhibitors having activity against drug-resistant Mycobacterium tuberculosis (Mtb), the causative agent of TB. While the clinical candidate zoliflodacin has progressed to phase 3 trials for the treatment of gonorrhea, compounds herein demonstrated higher inhibitory potency against Mtb DNA gyrase (e.g., compound 42 with IC50 = 2.0) and lower Mtb minimum inhibitor concentrations (0.49 µM for 42). Notably, 42 and analogues showed selective Mtb activity relative to representative Gram-positive and Gram-negative bacteria. DNA gyrase inhibition was shown to involve stabilization of double-cleaved DNA, while on-target activity was supported by hypersensitivity against a gyrA hypomorph. Finally, a docking model for SPTs with Mtb DNA gyrase was developed, and a structural hypothesis was built for structure-activity relationship expansion.
Subject(s)
Mycobacterium tuberculosis , Topoisomerase II Inhibitors , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Antitubercular Agents/chemistry , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , DNA Gyrase/genetics , Gram-Negative Bacteria , Gram-Positive Bacteria , Microbial Sensitivity Tests , Topoisomerase II Inhibitors/chemistry , Topoisomerase II Inhibitors/pharmacology , Topoisomerase II Inhibitors/therapeutic useABSTRACT
The Tsukamurella tyrosinosolvens PS2 strain was isolated from hydrocarbons-contaminated petrochemical sludge as a long chain alkane-utilizing bacteria. Complete genome analysis showed the presence of two alkane oxidation systems: alkane 1-monooxygenase (alkB) and cytochrome P450 monooxygenase (P450) genes with established high homology to the well-known alkane-degrading actinobacteria. According to the comparative genome analysis, both systems have a wide distribution among environmental and clinical isolates of the genus Tsukamurella and other members of Actinobacteria. We compared the expression of different proteins during the growth of Tsukamurella on sucrose and on hexadecane. Both alkane monooxygenases were upregulated on hexadecane: AlkB-up to 2.5 times, P450-up to 276 times. All proteins of the hexadecane oxidation pathway to acetyl-CoA were also upregulated. Accompanying proteins for alkane degradation involved in biosurfactant synthesis and transport of organic and inorganic molecules were increased. The change in the carbon source affected the pathways for the regulation of translation and transcription. The proteomic profile showed that hexadecane is an adverse factor causing activation of general and universal stress proteins as well as shock and resistance proteins. Differently expressed proteins of Tsukamurella tyrosinosolvens PS2 shed light on the alkane degradation in other members of Actinobacteria class. KEY POINTS: ⢠alkB and P450 systems have a wide distribution among the genus Tsukamurella. ⢠alkB and P450 systems have coexpression with the predominant role of P450 protein. ⢠Hexadecane causes significant changes in bacterial proteome.
Subject(s)
Actinomycetales , Proteomics , Actinobacteria , Actinomycetales/genetics , Actinomycetales/metabolism , Alkanes/metabolism , Bacteria/metabolism , Biodegradation, Environmental , Cytochrome P-450 CYP4A/genetics , Cytochrome P-450 CYP4A/metabolismABSTRACT
The dephenolization of palm oil mill effluent (POME) with oil palm fiber-immobilized Trametes hirsuta AK 04 was conducted in a temporary immersion bioreactor to reduce the inhibitory effects of phenolics in anaerobic digestion. Longer immersion times provided greater removal of phenolics due to a higher release of manganese peroxidase. The most effective dephenolization was observed at 6 h immersed and 2 h non-immersed time (immersion ratio 6/8) with maximum removal of 85% from 1277 mg L-1 of phenolics in 4 days. The immobilized fungus maintained its high activity during multiple repeated batch treatments. The pretreated POME of 2 h showed higher methane yields compared with the untreated POME substrate. The methane yields increased with increasing pretreatment time and dephenolization levels. The results suggested that an increased abundance of methanogens was associated with the detoxification of phenolics. The fungal biomass contained crude protein, amino acids, and essential phenolics, which can be used as animal feed supplements.
Subject(s)
Biofuels , Trametes , Animals , Bioreactors , Immersion , Industrial Waste/analysis , Palm Oil , Plant Oils , Polyporaceae , Waste Disposal, FluidABSTRACT
Phenotypic whole cell high-throughput screening of a â¼150,000 diverse set of compounds against Mycobacterium tuberculosis (Mtb) in cholesterol-containing media identified 1,3-diarylpyrazolyl-acylsulfonamide 1 as a moderately active hit. Structure-activity relationship (SAR) studies demonstrated a clear scope to improve whole cell potency to MIC values of <0.5 µM, and a plausible pharmacophore model was developed to describe the chemical space of active compounds. Compounds are bactericidal in vitro against replicating Mtb and retained activity against multidrug-resistant clinical isolates. Initial biology triage assays indicated cell wall biosynthesis as a plausible mode-of-action for the series. However, no cross-resistance with known cell wall targets such as MmpL3, DprE1, InhA, and EthA was detected, suggesting a potentially novel mode-of-action or inhibition. The in vitro and in vivo drug metabolism and pharmacokinetics profiles of several active compounds from the series were established leading to the identification of a compound for in vivo efficacy proof-of-concept studies.
Subject(s)
Antitubercular Agents/pharmacology , Cell Wall/metabolism , Mycobacterium tuberculosis/drug effects , Sulfonamides/pharmacology , Antitubercular Agents/chemical synthesis , Antitubercular Agents/chemistry , Drug Discovery , Hep G2 Cells , Humans , Microbial Sensitivity Tests , Models, Molecular , Molecular Structure , Mycobacterium tuberculosis/metabolism , Structure-Activity Relationship , Sulfonamides/chemistryABSTRACT
Screening of a library of small polar molecules against Mycobacterium tuberculosis (Mtb) led to the identification of a potent benzoheterocyclic oxime carbamate hit series. This series was subjected to medicinal chemistry progression underpinned by structure-activity relationship studies toward identifying a compound for proof-of-concept studies and defining a lead optimization strategy. Carbamate and free oxime frontrunner compounds with good stability in liver microsomes and no hERG channel inhibition liability were identified and evaluated in vivo for pharmacokinetic properties. Mtb-mediated permeation and metabolism studies revealed that the carbamates were acting as prodrugs. Toward mechanism of action elucidation, selected compounds were tested in biology triage assays to assess their activity against known promiscuous targets. Taken together, these data suggest a novel yet unknown mode of action for these antitubercular hits.
Subject(s)
Antitubercular Agents/pharmacology , Carbamates/pharmacology , Heterocyclic Compounds/pharmacology , Mycobacterium tuberculosis/drug effects , Oximes/pharmacology , Antitubercular Agents/chemistry , Antitubercular Agents/metabolism , Carbamates/chemistry , Carbamates/metabolism , Dose-Response Relationship, Drug , Heterocyclic Compounds/chemistry , Heterocyclic Compounds/metabolism , Microbial Sensitivity Tests , Molecular Structure , Mycobacterium tuberculosis/metabolism , Oximes/chemistry , Oximes/metabolism , Structure-Activity RelationshipABSTRACT
The ability of white-rot fungus, Trametes hirsuta AK04, to utilize phenolics as single and mixed substrates was determined in mineral medium and palm oil mill effluent (POME). The strain AK04 was able to rapidly metabolize all ten phenolics as single and mixed substrates at all test concentrations. With single substrates, between 78 and 98% removal was achieved within seven days. The biomass yield increased with increasing concentration from 100 to 500 mg L-1 but slightly decreased when the concentration was increased up to 1,000 mg L-1. When fitted to a Haldane model, the groups of benzoic and cinnamic acid derivatives gave significantly higher maximum specific growth rates than other phenolics. Phenol exhibited the lowest affinity and highest inhibitory effects on fungal metabolism. In mixed substrates, the total concentration ranges of phenolics mixtures between 1,000 and 6,000 mg L-1 did not affect the fungal growth rate and the strain AK04 showed a high degree of resistance to their toxic effects. The addition of glucose and yeast extract enhanced the degradation rates of individual phenolics in the substrate mixtures, demonstrating the advantage of this strain for treating complex media, such as industrial wastewater.
Subject(s)
Industrial Waste/analysis , Palm Oil , Phenols/metabolism , Trametes/growth & development , Wastewater/chemistry , Water Pollutants, Chemical/analysis , Biodegradation, Environmental , Biomass , Kinetics , Models, Theoretical , Phenols/analysis , Thailand , Trametes/metabolism , Water Purification/methodsABSTRACT
The Deepwater Horizon incident in the Gulf of Mexico in 2010 released an unprecedented amount of petroleum hydrocarbons 1500 meters below the sea surface. Few studies have considered the influence of hydrostatic pressure on bacterial community development and activity during such spills. The goal of this study was to investigate the response of indigenous sediment microbial communities to the combination of increased pressure, hydrocarbons and dispersant. Deep-sea sediment samples collected from the northern Gulf of Mexico were incubated at atmospheric pressure (0.1 MPa) and at elevated pressure (10 MPa), with and without the addition of crude oil and dispersant. After incubations at 4 °C for 7 days, Colwellia and Psychrobium were highly abundant in all samples. Pressure differentially impacted members of the Alteromonadales. The influences of pressure on the composition of bacterial communities were most pronounced when dispersant was added to the incubations. Moritella and Thalassotalea were greatly stimulated by the addition of dispersant, suggesting their roles in dispersant biodegradation. However, Moritella was negatively impacted by increasing pressure. The presence of dispersant was shown to decrease the relative abundance of a known hydrocarbon degrader, Cycloclasticus, while increasing pressure increased its relative abundance. This study highlights the significant influence of pressure on the development of microbial communities in the presence of oil and dispersant during oil spills and related response strategies in the deep sea.
Subject(s)
Bacteria , Microbial Consortia , Petroleum Pollution , Water Microbiology , Water Pollution, Chemical , Bacteria/classification , Bacteria/growth & development , Biodegradation, Environmental , Gulf of MexicoABSTRACT
A new Rhodococcus strain, capable of degrading crude oil, was isolated from the Gulf of Mexico deep-sea sediment and was investigated for its biodegradation characteristics under atmospheric as well as under deep-sea pressure (1500â¯mâ¯=â¯15â¯MPa). Additionally, the effect of dispersant (Corexit EC9500A) addition was studied. Rhodococcus sp. PC20 was shown to degrade 60.5⯱â¯10.7% of the saturated and aromatic fraction of crude oil at atmospheric pressure and 74.2⯱â¯9.1% at deep-sea level pressure within 96â¯h. Degradation rates, especially for monoaromatic hydrocarbons, were significantly higher at elevated pressure compared to atmospheric pressure. This study found a growth inhibiting effect at a dispersant to oil ratio of 1:100 and higher. This effect of the dispersant was enhanced when elevated pressure was applied.
Subject(s)
Biodegradation, Environmental , Petroleum Pollution , Petroleum/metabolism , Rhodococcus/physiology , Geologic Sediments/microbiology , Gulf of Mexico , Rhodococcus/isolation & purification , Seawater/microbiology , Water MicrobiologyABSTRACT
A significant portion of oil released during the Deepwater Horizon disaster reached the Gulf of Mexico (GOM) seafloor. Predicting the long-term fate of this oil is hindered by a lack of data about the combined influences of pressure, temperature, and sediment composition on microbial hydrocarbon remineralization in deep-sea sediments. To investigate crude oil biodegradation by native GOM microbial communities, we incubated core-top sediments from 13 GOM sites at water depths from 60-1500 m with crude oil under simulated aerobic seafloor conditions. Biodegradation occurred in all samples and followed a predictable compound class sequence dictated by molecular weight and structure. 45 to ~100% of total n-alkane and 3 to 60% of total polycyclic aromatic hydrocarbons (PAH) were depleted. In reactors incubated at 4°C and at pressures of 6-15 MPa, the depletion in total n-alkane was inversely correlated to pressure (R2 ~ 0.85), equivalent to a 4% decrease in total n-alkane depletion for every 1 MPa increase. Our results indicated a modest inhibitory effect of pressure on biodegradation over our experimental range. However, the expansion of oil exploration to deeper waters (e.g., 5000 m) opens the risk of spills at conditions at which pressure might have a more pronounced effect.
Subject(s)
Biodegradation, Environmental , Environmental Monitoring , Geologic Sediments/analysis , Petroleum/analysis , Petroleum/metabolism , Pressure , Gulf of Mexico , Oil and Gas FieldsABSTRACT
We report here the draft genome sequence of Rhodococcus qingshengii strain TUHH-12. The ability of this piezotolerant bacterium to grow on crude oil and tetracosane as sole carbon sources at 150 × 10(5) Pa makes it useful in studies of hydrocarbon degradation under simulated deep-sea conditions.
ABSTRACT
Adherence to medical advice, driven by high patient motivation, could lead to a significant reduction in risk factors during cardiac rehabilitation.During a 1-year period, 9082 patients were admitted to six cardiac rehabilitation centres. A total of 1195 highly motivated subjects were selected based on their reliable completion of a survey regarding cardiac risk factors.Study subjects had lower risk factors at baseline compared with a contemporary Austrian database. At discharge from the rehabilitation programme subjects showed further reductions in median weight, low-density lipoprotein cholesterol, blood pressure and resting pulse rate (due to increased levels of daily exercise). Smoking also decreased. Most of these changes were still significant after 1 year.The risk factors in these highly motivated patients were low to begin with and were further reduced by an inpatient rehabilitation programme. The content and method of delivery of this programme seem to be effective. Efforts should focus on increasing motivation.
Subject(s)
Coronary Disease/psychology , Coronary Disease/rehabilitation , Motivation , Patient Admission , Patient Compliance/psychology , Aged , Austria , Cohort Studies , Combined Modality Therapy , Female , Follow-Up Studies , Health Surveys , Humans , Male , Middle Aged , Patient Care Planning , Recurrence , Rehabilitation Centers , Risk Factors , Treatment OutcomeABSTRACT
BACKGROUND: Despite the increasing use of left ventricular assist devices (LVADs) in terminal heart failure, cardiac rehabilitation protocols have not yet been documented in larger LVAD patient cohorts. The aim of this study was to investigate safety and efficacy of exercise training during a rehabilitation programme after post-operative discharge of LVAD patients. METHODS: Rehabilitation data obtained between 2010-2012 from 41 LVAD patients (mean age 54.8 ± 11.6 years; 20% female) were retrospectively analysed. The exercise protocol consisted of strength exercises for lower limbs, bicycle ergometry, walking and gymnastics. The numbers of training sessions, their duration and intensity as well as adverse events were documented. Spiroergometry was performed at least once and twice in a subgroup of 15 patients (at the beginning and end of rehabilitation). RESULTS: Rehabilitation started 48 ± 38 days post LVAD implantation with an average duration of 32 ± 6 days. An increase in exercise capacity was observed. Duration (19 ± 4 vs 14 ± 2 min, p < 0.001) and intensity of bicycle ergometry increased (module number 6.2 ± 2.8 vs 2.0 ± 1.9, p < 0.001) as well as muscular strength all muscle groups trained (e.g. 33.6 ± 15.2 vs 26.6 ± 11.9 kg at the leg press, p = 0.002). Spiroergometry revealed an increase of maximal oxygen consumption (14.5 ± 5.2 vs 11.3 ± 4.1 ml/min/kg, p = 0.007) in the subgroup that underwent two examinations. In the whole population the average increase was lower (12.81 ± 4.35 ml/min/kg). One training-related adverse event (non-sustained ventricular tachycardia) was observed. CONCLUSION: Exercise training for LVAD patient as part of a multidisciplinary rehabilitation programme is effective and safe. This warrants the broad application of exercise training after LVAD implantation.
Subject(s)
Exercise Therapy/methods , Heart Failure/rehabilitation , Heart-Assist Devices , Ventricular Function, Left , Adult , Aged , Bicycling , Combined Modality Therapy , Exercise Test , Exercise Therapy/adverse effects , Exercise Tolerance , Female , Gymnastics , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Male , Middle Aged , Patient Discharge , Prosthesis Design , Recovery of Function , Resistance Training , Retrospective Studies , Time Factors , Treatment Outcome , Walking , Young AdultABSTRACT
The blowout of the Deepwater Horizon in the Gulf of Mexico in 2010 occurred at a depth of 1500 m, corresponding to a hydrostatic pressure of 15 MPa. Up to now, knowledge about the impact of high pressure on oil-degrading bacteria has been scarce. To investigate how the biodegradation of crude oil and its components is influenced by high pressures, like those in deep-sea environments, hydrocarbon degradation and growth of two model strains were studied in high-pressure reactors. The alkane-degrading strain Rhodococcus qingshengii TUHH-12 grew well on n-hexadecane at 15 MPa at a rate of 0.16 h(-1), although slightly slower than at ambient pressure (0.36 h(-1)). In contrast, the growth of the aromatic hydrocarbon degrading strain Sphingobium yanoikuyae B1 was highly affected by elevated pressures. Pressures of up to 8.8 MPa had little effect on growth of this strain. However, above this pressure growth decreased and at 12 MPa or more no more growth was observed. Nevertheless, S. yanoikuyae continued to convert naphthalene at pressure >12 MPa, although at a lower rate than at 0.1 MPa. This suggests that certain metabolic functions of this bacterium were inhibited by pressure to a greater extent than the enzymes responsible for naphthalene degradation. These results show that high pressure has a strong influence on the biodegradation of crude oil components and that, contrary to previous assumptions, the role of pressure cannot be discounted when estimating the biodegradation and ultimate fate of deep-sea oil releases such as the Deepwater Horizon event.
ABSTRACT
PURPOSE: This longitudinal study investigated long-term effects of a multidisciplinary rehabilitation program consisting of resistance and sensorimotor training, patient education, and stress management over 6 months in patients with chronic low back pain. METHODS: Ninety-six patients with chronic recurrent low back pain performed a multidisciplinary rehabilitation program. We assessed pain-free lumbar spine range of motion (ROM), strength of the lumbar extensor muscles, and pain by visual analog scale (VAS). Furthermore, the Roland-Morris (RM) questionnaire and SF-36 were used. The examinations were performed before and after rehabilitation, and a long-term follow-up was performed after 18 months. RESULTS: All outcome measurements (ROM, VAS, RM, muscle strength, and SF-36 scores) improved significantly from baseline to the post-rehabilitation evaluation. These improvements were found to persist until a follow-up evaluation 18 months after cessation of the intervention. CONCLUSIONS: Our findings confirm the results of former studies evaluating the short-term effects of multidisciplinary rehabilitation programs. In addition, our data demonstrate that well-balanced outpatient rehabilitation programs may induce persistent improvements in muscle strength, pain, function and quality of life in patients with chronic low back pain.
Subject(s)
Ambulatory Care/methods , Chronic Pain/rehabilitation , Low Back Pain/rehabilitation , Mental Health Services , Patient Education as Topic , Resistance Training , Adult , Combined Modality Therapy , Female , Humans , Interdisciplinary Communication , Longitudinal Studies , Lumbar Vertebrae/physiopathology , Male , Middle Aged , Mobility Limitation , Muscle Strength , Pain Measurement , Quality of Life , Range of Motion, Articular , Recurrence , Surveys and Questionnaires , Treatment OutcomeABSTRACT
Amorphous hybrids based on sodium salt of carboxymethyl cellulose (CMC) and tetraethoxysilane (TEOS) containing silver nanoparticles were prepared by sol-gel method. The amorphous structure, morphology and antibacterial behavior were clarified. The thermal stability of obtained hybrids decreased with the increase in silver content from 0.5 to 1.5 wt%. Infrared spectra of the material suggest that the main interaction between the cellulose ether and silica network is via hydrogen bonds (bands at approximately 3,540 and 3,625 cm(-1)). According to UV-vis spectra the silver is present in two different states Ag(+) (absorption band at approximately 210 nm) and Ag(0) (band at approximately 300 nm). The different sizes of silver particles are present as clusters. It was demonstrated that these hybrids have a well pronounced antibacterial activity against B. subtilis and E. coli K12. Even the hybrid with 0.5 wt% Ag has efficient antibacterial activity for both Gram-positive and Gram-negative bacteria.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Carboxymethylcellulose Sodium/chemistry , Carboxymethylcellulose Sodium/pharmacology , Silicon Dioxide/chemistry , Silver/chemistry , Bacillus subtilis/drug effects , Escherichia coli K12/drug effects , Metal Nanoparticles/chemistry , Silanes/chemistryABSTRACT
Antibacterial SiO2 hybrid materials based on tetraethyl orthosilicate (TEOS), hydroxypropylmethylcellulose (HPMC) and silver were prepared by the sol-gel method. The content of cellulose derivate was 5 wt% and the silver concentration varied from 0.5 wt% to 2.5 wt%. The amorphous nature, morphology and antibacterial behaviour were studied. Fourier transform infrared (FTIR) spectra of the hybrids showed characteristic peaks for SiO2 network. Scanning electron microscope (SEM) analysis confirmed the formation of spherically shaped silver nanoparticles with a size of 30 nm on the matrix surfaces. Bacillus subtilis and Escherichia coli K12 were used as model microorganisms. The hybrid materials demonstrated bacteriostatic and bactericidal effect on the tested bacteria. Highest sensitivity to the obtained hybrids was observed in B. subtilis with significant lag-phase delay and biggest inhibition zone sizes.
ABSTRACT
Here we present a draft genome of Pseudomonas stutzeri strain KOS6. This strain was isolated from industrial hydrocarbon sludge as a diazotrophic microorganism. It represents one of the major parts of the culturable community of the waste and has potential importance for phytoremediation technology.
ABSTRACT
BACKGROUND: Aim of the study was to evaluate the effects of supervised exercise training for peripheral arterial disease (PAD) on walking speed, claudication distance and quality of life. METHODS AND RESULTS: Ninety-four patients in stage IIa/IIb according to Fontaine underwent a six-month exercise training at the Center for Outpatient Rehabilitation Vienna (ZAW). Walking speed and Absolute Claudication Distance (ACD) improved significantly (p < 0,001 and p = 0,007 respectively). Increase of the Initial Claudication Distance (ICD) did not reach statistical significance (p = 0,14). Quality of life, as assessed by the questionnaire "PLC" manifested no significant change. CONCLUSIONS: The exercise training achieved considerable effects on walking speed and claudication distance. Despite these improvements, patient's quality of life revealed no relevant change. This outcome could be explained by the fact that aspects of physical functioning relevant to patients with claudicatio intermittens may be underrepresented in the PLC-questionnaire core module.
Subject(s)
Arterial Occlusive Diseases/rehabilitation , Exercise , Intermittent Claudication/rehabilitation , Peripheral Arterial Disease/rehabilitation , Physical Education and Training , Quality of Life/psychology , Walking , Aged , Ambulatory Care , Arterial Occlusive Diseases/psychology , Austria , Coronary Disease/psychology , Coronary Disease/rehabilitation , Disease Progression , Female , Humans , Intermittent Claudication/psychology , Life Style , Male , Middle Aged , Outcome and Process Assessment, Health Care , Patient Dropouts , Patient Education as Topic , Peripheral Arterial Disease/psychology , Physical Endurance , Physical Therapy Modalities , Resistance TrainingABSTRACT
BACKGROUND: This retrospective cohort study analyses effectiveness and sustainability of the current cardiac Phase III (Ph-III) rehabilitation program, provided by the Centre for Outpatient Rehabilitation (ZAR). METHODS: We analysed routine data of 451 intervention group patients (IG, with Ph-III) and 781 control group patients (KG, without Ph-III). RESULTS: In a median observation period of 2.73 years we found 30% less cases of death in the IG based on the mortality risk observed in the KG (rr = 0.70; p = 0.108). However, we registered more re-events, mainly stent implantations in the IG (rr = 1.34; p = 0.095). Groups differed in some baseline characteristics. CONCLUSIONS: The lower mortality risk by trend might be explained by the close-meshed care, the IG patients' more health conscious behaviour or a selection bias of the KG (e.g. more severe underlying disease). The causality of potential positive effects cannot be confirmed by this study because of the study design.