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What is known and Objective There has been astounding progress made in the treatment of disease over recent years. This progress is particularly marked in cell therapy and in the personalization of therapy based on genetic insight, an approach known as genomic medicine. Our objective is to comment on the progress made in cell and genomic medicine against an historical backcloth of the search for rejuvenation. Comment In 1741, close to seven decades after Antoine van Leeuwenhoek first saw his microscopic animalcules, Abraham Trembley, a tutor in Leiden, reported on an organism that could regenerate itself. The strange organism was thought to hold the secret of life. If it does, we have yet to prise the secret out. However, the ensuing study of cell programming and induced stem cells has shed considerable light on cellular development and provided new insights on the rejuvenative capacity of organisms. Inventive scientists have provided a deeper understanding of cell replication and, from this, developed new medicines for an increasing range of diseases. Targeted therapies, oligonucleotide therapy, therapeutic monoclonal antibodies and pharmacogenetics are all new therapeutic areas originating from the improved insights. More will surely follow. What is new and conclusion Immortality is for the gods, but man's search for its elusive secrets, perhaps as old as man himself, will continue. Huge leaps have been made, and effective medicines have been developed from our improved insights into the mechanism of life. However, only the foolish will predict how far this new knowledge will lead us, and more particularly, at what speed new therapies will follow., Genomic medicine is delivering on its promise. Its reach extends from vaccine development to pharmacogenetics, stem‐cell therapy, oligonucleotide therapy and gene editing.

Omicron is a variant of the COVID-19 virus that is causing considerable concern worldwide, with an increasing number of countries re-imposing national lockdowns. Our objective is to comment on its impact and to suggest that, threatening as it is, Omicron may well contribute to a resolution of the current pandemic.On 31 December 2019, the World Health Organization (WHO) reported on a cluster of cases of pneumonia in Wuhan, China. Soon after, Chinese investigators who made the discovery identified the causative virus as a new coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An effective vaccine was licenced for emergency use within a year of its first sequencing. SARS-CoV-2, in common with many respiratory viruses, mutates rapidly, and the challenge for vaccine developers is to obtain vaccines that are effective against the new variants. The licenced first-generation vaccines were fortunately all highly effective against the variant known as Delta. The variant of greatest current concern is the Omicron variant, a highly infectious agent, which seems to show a significant vaccine escape with existing vaccines. Infection protects against further infection. If Omicron turns out to cause less severe disease, it may well be a contributor to ending the pandemic.It is unlikely that the available vaccines will bring rapid control of the current pandemic, given their patchy availability worldwide and the residual pool of unvaccinated people. New vaccines take time to develop and to deploy even in the age of mRNA vaccines. If Omicron turns out to be relatively mild, it may well be that when we look back at the history of the current pandemic, the variant would be seen as a contributor to its solution. The hand of nature may well show more largesse than the developed nations in immunizing the world.

What is known and objective: Every prescriber knows that patients often do not take their medicines as prescribed. Hippocrates, the wise man of Kos, knew over two millennia ago. Our objective is to comment on the types of studies aimed at understanding and optimizing drug usage and to draw attention to the need to seek approval before using or citing the Morisky adherence scale. Comment: The study of prescribing and how patients use their medicines is important. As part of this effort, the results of investigations of how patients adhere to drug prescriptions can be informative. However, the results are meaningful only if the methods used for doing the measurements are valid and made explicit. We were surprised when a team of our authors were threatened with legal action for citing the Morisky Adherence Scale and explaining how some authors had obtained their adherence scores. Adherence studies are but one facet of the study of prescribing aimed at improving clinical outcomes. Other aspects include investigating the quality of prescribing, and how unnecessary medicines can be deprescribed to improve the quality of care and reduce the risk of adverse effects. What is new and conclusion: The study of optimal prescribing is an important endeavour and adherence studies are but one aspect. We report that using and citing the Morisky Adherence scale in any detail is a risky business. Prior approval is required unless one is prepared to pay up, retrospectively. We require all authors to certify they have no conflicts of interest with respect to the scale.

Summary What is known and Objective: In analgesic trials, pain relief is often assessed using a pain-relief score. We aimed to assess, through a meta-analysis, whether absence of need for rescue medication (NNR) is a reliable outcome measure in the evaluation of acute pain relief. Methods: Individual-patient meta-analysis of placebo-controlled trials of single-dose naproxen sodium 220 or 440 mg in dental pain. Efficacy estimates were based on NNR and compared with the more commonly used 50% maximum total pain relief score (50% TOTPAR). The trials included were the full set of trials sponsored by one manufacturer. Results and Discussion: Need for rescue medication and 50% TOTPAR gave comparable estimates of efficacy of naproxen sodium (220 and 440 mg) relative to placebo in dental pain at both 8 and 12 h after dosing. What is new and Conclusion: No need for rescue medication is a reliable outcome measure for use in acute pain trials. As it is more readily understandable than 50% TOTPAR, it should be the preferred primary outcome measure in acute pain trials.

Background Minocycline is a tetracycline antibiotic that is commonly used in the treatment of moderate to severe acne vulgaris. Although it is more convenient for patients to take than first-generation tetracyclines, as it only needs to be taken once or twice a day and can be taken with food, it is more expensive. Concerns have also been expressed over its safety following the deaths of two patients taking the drug. There is a lack of consensus among dermatologists over the relative risks and benefits of minocycline. As most acne prescribing is undertaken by general practitioners, it is important that guidelines issued to them are based on the best available evidence rather than personal judgements. Objectives To collate and evaluate the evidence on the clinical efficacy of minocycline in the treatment of inflammatory acne vulgaris. Specific objectives were to compare the efficacy of minocycline with other drug treatments for acne and to collate information on the incidence of adverse drug reactions. Search strategy Randomised controlled trials (RCTs) of minocycline for acne vulgaris were identified by searching the following electronic databases; MEDLINE, EMBASE, Biosis, Biological Abstracts, International Pharmaceutical Abstracts, Cochrane Skin Group's Trial Register, Theses Online, BIDS ISI Science Citation Index, National Research Register, Current Controlled Trials and Bids Index to Scientific and Technical Proceedings. Other strategies used were scanning the references of articles retrieved, hand-searching of major dermatology journals and personal communication with trialists and drug companies. Selection criteria To be eligible for the review, studies had to be RCTs comparing the efficacy of minocycline at any dose to active or placebo control, in subjects with inflammatory acne vulgaris. Diagnoses of papulo-pustular, polymorphic and nodular acne were also accepted. Trials were not excluded on the basis of language. Data collection and analysis Twenty-seven randomised controlled trials met the inclusion criteria and were included in this review. The comparators used were placebo (two studies), oxytetracycline (one), tetracycline (six), doxycycline (seven), lymecycline (two), topical clindamycin (three), topical erythromycin/zinc (one), cyproterone acetate/ ethinyloestradiol (one), oral isotretinoin (two), topical fusidic acid (one) and there was one dose response study. Two studies are ongoing and it remains to be clarified whether one further study is a RCT. Major outcome measures used in the trials included lesion counts, acne grades/severity scores, doctors' and patients' global assessments, adverse drug reactions and drop-out rates. The quality of each study was assessed independently by two assessors and an effect size calculated where possible. An additional three RCTs and three safety studies were identified by searches conducted in November 2002; these will be reviewed for a major update in early 2003 when it is anticipated that the results of the two ongoing studies will be available. Main results The trials were generally small and of poor quality and in many cases the published reports were inadequate for our purpose. Pooling of the studies was not attempted due to the lack of common outcome measures and endpoints and the unavailability of some primary data. Although minocycline was shown to be an effective treatment for acne vulgaris, in only two studies was it found to be superior to other tetracyclines. Both of these were conducted under open conditions and had serious methodological problems. A third study showed it to be more effective than 2% fusidic acid, applied topically, against inflammatory lesions in mild to moderate acne. Differences in the way adverse drug reactions were identified could have accounted for the wide variation between studies in numbers of events reported. This meant that no overall evaluation could be made of incidence rates of adverse events associated with minocycline therapy. No RCT evidence was found to support the benefits of minocycline in acne resistant to other therapies and the dose response has only been evaluated up to eight weeks of therapy. Authors' conclusions Minocycline is likely to be an effective treatment for moderate acne vulgaris, but this review found no reliable RCT evidence to justify its continued use first-line, especially given the price differential and the concerns that still remain about its safety. Its efficacy relative to other acne therapies could not be reliably determined due to the poor methodological quality of the trials and lack of consistent choice of outcome measures. Similarly the relative risk of adverse drug reactions could not be ascertained reliably and no recommendations can be made concerning the appropriate dose that should be used. It is hoped that this review will highlight the inadequacy of acne trials in general and encourage improvements in methodological quality and standards of reporting. Plain Language Summary Minocycline for acne vulgaris: efficacy and safety The cause of acne is not fully understood but pores in the skin become blocked and infected due to a build up of excess skin oil, bacteria and other tissue. Antibiotics reduce bacteria and inflammation and minocycline is commonly prescribed to treat acne. It is however more expensive than other similar antibiotics and there are concerns about its safety. The review found that there was no reliable evidence that minocycline was better than any other acne treatment and that more research is needed.