***TASK***
the task is to simplify the input abstract of a biomedical literature

***INPUT***
the input is the abstract of a biomedical literature

***OUTPUT***
the output is the simplified abstract for the input abstract of a biomedical literature

***DOCUMENTATION***

***EXAMPLES***

Input: The authors reviewed 1335 abstracts, and from these identified 21 potentially eligible abstracts. Upon detailed review, 12 studies fulfilled the entry criteria. Of these, eight were new studies that had been published since the previous version of this review. Two studies which were included in the previous version of this review were excluded because of potential for bias. The comparability of the included studies is extremely low because of differences in the specific diseases studied, differences in the therapeutic agents used, dosage, study design, and outcomes. The methodological quality of included studies was generally high, although risk of bias was unclear in random sequence generation and allocation concealment for most studies. Otherwise, the risk of bias was low for most studies in the other categories. Serious adverse events were uncommon, except for peripheral nerve toxicity in a long-term trial of dichloroacetate (DCA) in adults. One trial studied high-dose coenzyme Q10 without clinically meaningful improvement (although there were multiple biochemical, physiologic, and neuroimaging outcomes, in 30 participants). Three trials used creatine monohydrate alone, with one reporting evidence of improved measures of muscle strength and post-exercise lactate, but the other two reported no benefit (total of 38 participants). One trial studied the effects of a combination of coenzyme Q10, creatine monohydrate, and lipoic acid and reported a statistically significant improvement in biochemical markers and peak ankle dorsiflexion strength, but overall no clinical improvement in 16 participants. Five trials studied the effects of DCA: three trials in children showed a statistically significant improvement in secondary outcome measures of mitochondrial metabolism (venous lactate in three trials, and magnetic resonance spectroscopy (MRS) in one trial; total of 63 participants). One trial of short-term DCA in adults demonstrated no clinically relevant improvement (improved venous lactate but no change in physiologic, imaging, or questionnaire findings, in eight participants). One longer-term DCA trial in adults was terminated prematurely due to peripheral nerve toxicity without clinical benefit (assessments included the GATE score, venous lactate and MRS, in 30 participants). One trial using dimethylglycine showed no significant effect (measurements of venous lactate and oxygen consumption (VO2) in five participants). One trial using a whey-based supplement showed statistically significant improvement in markers of free radical reducing capacity but no clinical benefit (assessments included the Short Form 36 Health Survey (SF-36) questionnaire and UK Medical Research Council (MRC) muscle strength, in 13 participants). Despite identifying eight new trials there is currently no clear evidence supporting the use of any intervention in mitochondrial disorders. Further research is needed to establish the role of a wide range of therapeutic approaches. We suggest further research should identify novel agents to be tested in homogeneous study populations with clinically relevant primary endpoints.
Output:

The included studies are not easily comparable because of differences in the treatment being studied, the dosage of these treatments, the length of study (and other differences in the study methods), and differences in the types of participants included for the research. The studies were generally well designed in order to reduce the possibility of bias, although for most studies the methods describing how participants were randomised were not described in detail. Otherwise, the risk of bias was low for most studies in the other categories. Serious side effects of treatment were uncommon, except for nerve damage in a long-term trial of dichloroacetate in adults. One trial studied high-dose coenzyme Q10 treatment. This treatment had no clinical benefit. Three trials used creatine monohydrate: one trial reported improved muscle strength and biochemical measurements, but the other two trials reported no benefit (total of 38 participants). One trial studied the effects of a combination of coenzyme Q10, creatine monohydrate and lipoic acid, and reported a statistically significant improvement in biochemical measurements and ankle strength, but no clinical improvement (16 participants). Five trials studied the effects of dichloroacetate: three trials in children showed a statistically significant improvement in biochemical measurements but no clinical benefit on physiological measurements and exercise tests (total 63 participants); one trial of short-term therapy in adults demonstrated no clinical improvement in physiological measurements (total eight participants), and one longer-term trial in adults was terminated prematurely due to adverse effects without clinical benefit (using a combined scale of treatment effect, in 30 participants). One trial using dimethylglycine showed no significant effect on biochemical markers in five participants. One trial using a whey-based supplement demonstrated statistically significant improvement in biochemical markers but no clinical benefit in muscle strength or on health questionnaires (13 participants). Further randomised controlled trials of high quality are needed. They should strictly address outcomes which are relevant to patient care and quality of life, and study these in particular subtypes of mitochondrial disease at a time. The current repertoire of nutritional supplements have been not shown to be effective and future trials should study new treatments.