A review of the genus Neogreenia MacGillivray (Hemiptera: Coccomorpha: Qinococcidae) with descriptions of two new species.

The species of Neogreenia MacGillivray (Hemiptera: Coccomorpha: Qinococcidae) are reviewed. The genus is distributed in the Oriental and Palaearctic Regions and now contains seven species. The present study provides updated generic descriptions of all the developmental stages and a brief account of the biology and life cycle of Neogreenia. The genotype, Neogreenia zeylanica (Green, 1896), is redescribed. The following are described and illustrated for the first time: the second-instar nymph, third-instar female, and male third-instar nymph and pupa of N. zizyphi Tang; the second-instar nymph of N. lonicera Wu & Nan; and the second-instar nymph of N. sophorica Wu. Two new species are described and illustrated: Neogreenia ficus Zheng & Wu, sp. n. based on the adult female and Neogreenia tangi Zheng & Wu, sp. n. based on all female instars. These new species bring the total number of described species of Neogreenia to seven. An identification key to all the developmental stages of Neogreenia, and identification keys to species based on adult females and available nymphal instars are provided.

A new species of the mealybug genus Ceroputo Sulc 1898 (Hemiptera: Coccomorpha: Pseudococcidae) from China, and notes on Ceroputo pilosellae Sulc 1898 in China.

A new mealybug species, Ceroputo liquidambaris Zhang & Watson sp. n. (Hemiptera: Coccomorpha: Pseudococcidae), collected on leaves and branches of Liquidambar formosana (Altingiaceae), is described and illustrated from Jiangxi, China. The new species differs from all other known species of Ceroputo in having dorsal multilocular disc pores. Notes on some aspects of Ceroputo pilosellae Sulc collected in China and a key to the adult females of Ceroputo species are provided.

A new mealybug species in the genus Dysmicoccus Ferris (Hemiptera: Coccomorpha: Pseudococcidae), with a key to Chinese species.

A new mealybug species, Dysmicoccus lushanensis Zhang, Wang & Watson sp. n. (Hemiptera: Coccomorpha: Pseudococcidae), collected on the branches of Rhododendron simsii Planch. (Ericaceae) in Jiangxi Province, China, is described and illustrated. It is similar to another species recorded feeding on Rhododendron, D. wistariae (Green 1923), in having small conical dorsal setae and most cerarii containing more than 2 conical setae, but differs from it in having each anal lobe cerarius(C18) with more than two conical setae, and translucent pores present on the hind femur and tibia. The new species also resembles D. finitimus (Williams 1994), which is only known to feed on palms (Arecaceae), in possessing anal lobe cerarius(C18) each with more than 2 conical cerarian setae, but differs in having minute, conical dorsal setae and in lacking translucent pores on the hind coxa. In addition, D. debregeasiae (Green 1922) is recorded from China for the first time. A key to the Chinese species of Dysmicoccus is provided.

THE SCALE INSECTS OF IRAN (HEMIPTERA: COCCOMORPHA)PART 2 THE MEALYBUGS (PSEUDOCOCCIDAE AND RHIZOECIDAE) AND PUTOIDAE.

Iran is situated at the junctions of the Palaearctic and Oriental zoogeographical Regions, and the Caspian, Baluchi and Irano-Turanian floral zones, so it has a very diverse scale insect fauna. Scale insects (Hemiptera: Coccomorpha) are economically important in forestry, agriculture and horticulture. This taxonomic work on the mealybugs (Pseudococcidae and Rhizoecidae) and Putoidae of Iran is the second of three parts planned to cover all the scale insects (Hemiptera: Coccomorpha) in the country. It provides a resource for accurate laboratory identification of all the species known to occur in Iran or that are likely to be found there. Keys to the genera and species of mealybug found in Iran29 genera and 62 species of Pseudococcidae, and one genus and one species in each of the families Rhizoecidae and Putoidaeare provided. Detailed line drawings of all the species are given to facilitate identification. These are accompanied by detailed descriptions, distribution data, information on natural enemies, economic importance and host-plants recorded in Iran. The main purpose of the work is to provide agricultural staff concerned with pest control and quarantine inspection in Iran with a reliable means of species identification. The species Dysmicoccus walkeri (Newstead), Peliococcus marrubii (Kiritshenko) and Phenacoccus transcaucasicus Hadzibejli are recorded for the first time from Iran, and Artemicoccus poacearum Moghaddam Watson sp. n. and Spilococcus williamsi Moghaddam Watson sp. n. are described.

Acipimox in Mitochondrial Myopathy (AIMM): study protocol for a randomised, double-blinded, placebo-controlled, adaptive design trial of the efficacy of acipimox in adult patients with mitochondrial myopathy.

BACKGROUND: Mitochondrial disease is a heterogenous group of rare, complex neurometabolic disorders. Despite their individual rarity, collectively mitochondrial diseases represent the most common cause of inherited metabolic disorders in the UK; they affect 1 in every 4300 individuals, up to 15,000 adults (and a similar number of children) in the UK. Mitochondrial disease manifests multisystem and isolated organ involvement, commonly affecting those tissues with high energy demands, such as skeletal muscle. Myopathy manifesting as fatigue, muscle weakness and exercise intolerance is common and debilitating in patients with mitochondrial disease. Currently, there are no effective licensed treatments and consequently, there is an urgent clinical need to find an effective drug therapy. AIM: To investigate the efficacy of 12-week treatment with acipimox on the adenosine triphosphate (ATP) content of skeletal muscle in patients with mitochondrial disease and myopathy. METHODS: AIMM is a single-centre, double blind, placebo-controlled, adaptive designed trial, evaluating the efficacy of 12 weeks' administration of acipimox on skeletal muscle ATP content in patients with mitochondrial myopathy. Eligible patients will receive the trial investigational medicinal product (IMP), either acipimox or matched placebo. Participants will also be prescribed low dose aspirin as a non-investigational medical product (nIMP) in order to protect the blinding of the treatment assignment. Eighty to 120 participants will be recruited as required, with an interim analysis for sample size re-estimation and futility assessment being undertaken once the primary outcome for 50 participants has been obtained. Randomisation will be on a 1:1 basis, stratified by Fatigue Impact Scale (FIS) (dichotomised as < 40, ≥ 40). Participants will take part in the trial for up to 20 weeks, from screening visits through to follow-up at 16 weeks post randomisation. The primary outcome of change in ATP content in skeletal muscle and secondary outcomes relating to quality of life, perceived fatigue, disease burden, limb function, balance and walking, skeletal muscle analysis and symptom-limited cardiopulmonary fitness (optional) will be assessed between baseline and 12 weeks. DISCUSSION: The AIMM trial will investigate the effect of acipimox on modulating muscle ATP content and whether it can be repurposed as a new treatment for mitochondrial disease with myopathy. TRIAL REGISTRATION: EudraCT2018-002721-29 . Registered on 24 December 2018, ISRCTN 12895613. Registered on 03 January 2019, https://www.isrctn.com/search?q=aimm.

Methenamine hippurate compared with antibiotic prophylaxis to prevent recurrent urinary tract infections in women: the ALTAR non-inferiority RCT.

BACKGROUND: Daily, low-dose antibiotic prophylaxis is the current standard care for women with recurrent urinary tract infection. Emerging antimicrobial resistance is a global health concern, prompting research interest in non-antibiotic agents such as methenamine hippurate, but comparative data on their efficacy and safety are lacking. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of methenamine hippurate (Hiprex®; Mylan NV, Canonsburg, PA, USA) compared with current standard care (antibiotic prophylaxis) for recurrent urinary tract infection prevention in adult women. DESIGN: Multicentre, pragmatic, open-label, randomised, non-inferiority trial of 12 months' treatment with the allocated intervention, including an early, embedded qualitative study and a 6-month post-treatment observation phase. The predefined non-inferiority margin was one urinary tract infection per person-year. SETTING: Eight UK NHS secondary care sites. PARTICIPANTS: A total of 240 adult women with recurrent urinary tract infection requiring preventative treatment participated in the trial. INTERVENTIONS: A central randomisation system allocated participants 1 : 1 to the experimental (methenamine hippurate: 1 g twice daily) or control (once-daily low-dose antibiotics: 50/100 mg of nitrofurantoin, 100 mg of trimethoprim or 250 mg of cefalexin) arm. Crossover between treatment arms was permitted. MAIN OUTCOME MEASURES: The primary clinical outcome was incidence of symptomatic antibiotic-treated urinary tract infection during the 12-month treatment period. Cost-effectiveness was assessed by incremental cost per quality-adjusted life-year gained, extrapolated over the patient's expected lifetime using a Markov cohort model. Secondary outcomes included post-treatment urinary tract infections, total antibiotic use, microbiologically proven urinary tract infections, antimicrobial resistance, bacteriuria, hospitalisations and treatment satisfaction. RESULTS: Primary modified intention-to-treat analysis comprised 205 (85%) randomised participants [102/120 (85%) participants in the antibiotics arm and 103/120 (86%) participants in the methenamine hippurate arm] with at least 6 months' data available. During treatment, the incidence rate of symptomatic, antibiotic-treated urinary tract infections decreased substantially in both arms to 1.38 episodes per person-year (95% confidence interval 1.05 to 1.72 episodes per person-year) for methenamine hippurate and 0.89 episodes per person year (95% confidence interval 0.65 to 1.12 episodes per person-year) for antibiotics (absolute difference 0.49; 90% confidence interval 0.15 to 0.84). This absolute difference did not exceed the predefined, strict, non-inferiority limit of one urinary tract infection per person-year. On average, methenamine hippurate was less costly and more effective than antibiotics in terms of quality-adjusted life-years gained; however, this finding was not consistent over the longer term. The urinary tract infection incidence rate 6 months after treatment completion was 1.72 episodes per year in the methenamine hippurate arm and 1.19 in the antibiotics arm. During treatment, 52% of urine samples taken during symptomatic urinary tract infections were microbiologically confirmed and higher proportions of participants taking daily antibiotics (46/64; 72%) demonstrated antibiotic resistance in Escherichia coli cultured from perineal swabs than participants in the methenamine hippurate arm (39/70; 56%) (p-value = 0.05). Urine cultures revealed that during treatment higher proportions of participants and samples from the antibiotic arm grew E. coli resistant to trimethoprim/co-trimoxazole and cephalosporins, respectively. Conversely, post treatment, higher proportions of participants in the methenamine hippurate arm (9/45; 20%) demonstrated multidrug resistance in E. coli isolated from perineal swabs than participants in the antibiotic arm (2/39; 5%) (p = 0.06). All other secondary outcomes and adverse events were similar in both arms. LIMITATIONS: This trial could not define whether or not one particular antibiotic was more beneficial, and progressive data loss hampered economic evaluation. CONCLUSIONS: This large, randomised, pragmatic trial in a routine NHS setting has clearly shown that methenamine hippurate is not inferior to current standard care (daily low-dose antibiotics) in preventing recurrent urinary tract infections in women. The results suggest that antimicrobial resistance is proportionally higher in women taking prophylactic antibiotics. RECOMMENDATIONS FOR RESEARCH: Future research should include evaluation of other non-antibiotic preventative treatments in well-defined homogeneous patient groups, preferably with the comparator of daily antibiotics. TRIAL REGISTRATION: This trial is registered as ISRCTN70219762 and EudraCT 2015-003487-36. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 23. See the NIHR Journals Library website for further project information.

Women with recurrent urine infections often require preventative treatment to reduce the frequency of infection episodes. Daily low-dose antibiotic medication is a guideline-recommended treatment option for these women. There is increasing concern globally regarding antibiotic-resistant infections, which has led researchers to look at alternative treatments. This trial was conducted to find out whether or not taking an alternative treatment that is not an antibiotic [i.e. methenamine hippurate (Hiprex^®; Mylan NV, Canonsburg, PA, USA)] was as effective as the standard daily low-dose antibiotics. A total of 240 women from across the UK took part in the trial. They were divided equally into two groups; half of the women were given methenamine hippurate and the other half were given standard low-dose antibiotics. Both treatments were prescribed to be taken every day for 1 year. To make a fair comparison, people were put into the two groups at random using a computer program. Aspects of the trial that could be improved were identified through telephone interviews with patients and recruiting staff. Feedback from these telephone interviews helped to ensure the successful conduct of the trial. Patients were followed up for 18 months, comprising the 12 months when they were taking treatment and a 6-month follow-up phase after they had finished treatment. We found that the non-antibiotic option of methenamine hippurate was no worse than the current standard treatment of daily antibiotics in preventing urinary tract infection episodes in adult women. For both treatments, patients expressed high levels of satisfaction. One advantage of the methenamine hippurate treatment was that infecting bacteria were slightly less likely to develop resistance to antibiotics. We also evaluated health-care costs of both treatments and found that methenamine hippurate seemed worthwhile to the NHS in the short term, but there was uncertainty over longer-term costs and benefits. These results will help patients with repeated urinary tract infections to decide on treatment options, particularly if they want to avoid prolonged courses of preventative antibiotics.

Towards identification of the scale insects (Hemiptera: Coccomorpha) of continental Africa: 2. Checklists and keys to six archaeococcoid families.

Scale insects (Hemiptera: Sternorrhyncha: Coccomorpha) feed on plant sap; some are damaging pests in agriculture and forestry. However, the scale insects found in continental Africa have not been extensively studied and the available means of identification are incomplete. This synoptic work, the second in this series, covers the six archaeococcoid scale insect families found in continental Africa: Kuwaniidae, Margarodidae, Matsucoccidae, Monophlebidae, Ortheziidae and Putoidae. The work provides identification keys to a total of 29 genera and 137 species, and a checklist for each family. Pseudaspidoproctus zimmermanni (Newstead) (Monophlebidae) is transferred to Aspidoproctus, as Aspidoproctus zimmermanni (Newstead), comb. n. Praelongorthezia praelonga (Douglas) (Ortheziidae) is recorded from Gambia for the first time.

The genera Coccus and Prococcus (Hemiptera: Coccomorpha: Coccidae) in China, with two new combinations and descriptions of two new species.

The Chinese soft scale species in the genus Coccus Linnaeus, 1758 (Hemiptera: Coccomorpha: Coccidae) were studied. Coccus cambodiensis Takahashi and the Malaysian species C. cameronensis Takahashi are considered to be non-congeneric with Coccus hesperidum Linnaeus, 1758, the type species of Coccus, and are transferred to Prococcus Avasthi, 1993, as Prococcus cambodiensis (Takahashi, 1942), comb. n. and Prococcus cameronensis (Takahashi, 1952), comb. n. The generic diagnosis of Prococcus is revised. In the genus Coccus, two new species are described and illustrated based on adult females: Coccus nanningensis Cao Feng, sp. n. from Guangxi, China, on Ficus carica (Moraceae), and Coccus cephalotaxus Cao Feng, sp. n. from Shannxi, China, on Cephalotaxus sinensis (Taxaceae). Identification keys to separate adult females of Prococcus from Coccus, the 14 species of Coccus found in China, and all three species of Prococcus are provided.

Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority trial.

OBJECTIVE: To test and compare the efficacy of methenamine hippurate for prevention of recurrent urinary tract infections with the current standard prophylaxis of daily low dose antibiotics. DESIGN: Multicentre, open label, randomised, non-inferiority trial. SETTING: Eight centres in the UK, recruiting from June 2016 to June 2018. PARTICIPANTS: Women aged ≥18 years with recurrent urinary tract infections, requiring prophylactic treatment. INTERVENTIONS: Random assignment (1:1, using permuted blocks of variable length via a web based system) to receive antibiotic prophylaxis or methenamine hippurate for 12 months. Treatment allocation was not masked and crossover between arms was allowed. MAIN OUTCOME MEASURE: Absolute difference in incidence of symptomatic, antibiotic treated, urinary tract infections during treatment. A patient and public involvement group predefined the non-inferiority margin as one episode of urinary tract infection per person year. Analyses performed in a modified intention-to-treat population comprised all participants observed for at least six months. RESULTS: Participants were randomly assigned to antibiotic prophylaxis (n=120) or methenamine hippurate (n=120). The modified intention-to-treat analysis comprised 205 (85%) participants (antibiotics, n=102 (85%); methenamine hippurate, n=103 (86%)). Incidence of antibiotic treated urinary tract infections during the 12 month treatment period was 0.89 episodes per person year (95% confidence interval 0.65 to 1.12) in the antibiotics group and 1.38 (1.05 to 1.72) in the methenamine hippurate group, with an absolute difference of 0.49 (90% confidence interval 0.15 to 0.84) confirming non-inferiority. Adverse reactions were reported by 34/142 (24%) in the antibiotic group and 35/127 (28%) in the methenamine group and most reactions were mild. CONCLUSION: Non-antibiotic prophylactic treatment with methenamine hippurate might be appropriate for women with a history of recurrent episodes of urinary tract infections, informed by patient preferences and antibiotic stewardship initiatives, given the demonstration of non-inferiority to daily antibiotic prophylaxis seen in this trial. TRIAL REGISTRATION: ISRCTN70219762.

Adjuvant Rituximab-Exploratory Trial in Young People With Graves Disease.

CONTEXT: Remission rates in young people with Graves hyperthyroidism are less than 25% after 2 years of thionamide antithyroid drug (ATD). OBJECTIVE: We explored whether rituximab (RTX), a B-lymphocyte-depleting agent, would increase remission rates when administered with a short course of ATD. METHODS: This was an open-label, multicenter, single-arm, phase 2 trial in young people (ages, 12-20 years) with Graves hyperthyroidism. An A'Hern design was used to distinguish an encouraging remission rate (40%) from an unacceptable rate (20%). Participants presenting with Graves hyperthyroidism received 500 mg RTX and 12 months of ATD titrated according to thyroid function. ATDs were stopped after 12 months and primary outcome assessed at 24 months. Participants had relapsed at 24 months if thyrotropin was suppressed and free 3,5,3'-triiodothyronine was raised; they had received ATD between months 12 and 24; or they had thyroid surgery/radioiodine. RESULTS: A total of 27 participants were recruited and completed the trial with no serious side effects linked to treatment. Daily carbimazole dose at 12 months was less than 5 mg in 21 of 27 participants. Thirteen of 27 participants were in remission at 24 months (48%, 90% one-sided CI, 35%-100%); this exceeded the critical value (9) for the A'Hern design and provided evidence of a promising remission rate. B-lymphocyte count at 28 weeks, expressed as a percentage of baseline, was related to likelihood of remission. CONCLUSION: Adjuvant RTX, administered with a 12-month course of ATD, may increase the likelihood of remission in young people with Graves hyperthyroidism. A randomized trial of adjuvant RTX in young people with Graves hyperthyroidism is warranted.

Preventing Cardiomyopathy in DMD: A Randomized Placebo-Controlled Drug Trial.

OBJECTIVE: To determine whether a combination of 2 heart medications would be tolerated and could prevent/delay the onset of cardiomyopathy in boys with Duchenne muscular dystrophy (DMD) compared with placebo. METHODS: This multicenter, parallel group, 1:1 patient randomized, placebo-controlled study of prophylactic perindopril and bisoprolol recruited boys with DMD aged 5-13 years, with normal ventricular function. Repeat assessments of left ventricular (LV) function, electrocardiogram, and adverse event reporting were performed 6 monthly. The primary outcome was change in ejection fraction between arms after 36 months. The study was approved by the National Research Ethics Service Committee East Midlands-Derby. RESULTS: Eighty-five boys were recruited (76% on steroid therapy) and randomized to combination heart drugs or matched placebo. Group change in left ventricular ejection fraction (LVEF%) at 36 months from baseline was -2.2% ± 6.0% and -2.9% ± 6.1% in active and placebo arms (adjusted mean difference: -2.1, 95% CI -5.2 to 1.1). There was no difference between treatment arms over repeated assessments (analysis of variance) up to 36 months (trial arms p = 0.53); arm-over-time (p = 0.44). Four participants on placebo but none on active therapy were withdrawn due to deteriorations in LV function. Secondary outcomes did not differ between arms either. Thirty-six serious adverse events occurred none due to cardiac events or trial medication. CONCLUSIONS: Combination therapy was well tolerated. Consistent with the previous prophylactic perindopril heart study, there was no evidence of group benefit after 36-month treatment. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that combination perindopril-bisoprolol therapy was well tolerated but did not change decline in LVEF significantly in boys with DMD.

A checklist of the scale insects (Hemiptera: Coccomorpha) of Kenya, with some new combinations.

The checklist of scale insect species recorded from Kenya comprises 14 families, 128 genera and 304 species, of which 207 (68.0%) are probably of African origin, 91 (29.9%) have been introduced from outside Africa and six (2.0%) are of unknown origin. Out of the 207 African species, only 11 (5.3%) have been recorded damaging plants, whereas out of the 91 introduced species, 45 (49.5%) have caused or are highly likely to cause plant damage in Kenya. The most economically important scale insect families in Kenya are (in order of importance) the Pseudococcidae, Coccidae and Diaspididae. Four new combinations are made: Eurycoccus glomerulus De Lotto is transferred to Trionymus, as Trionymus glomerulus (De Lotto) comb. n.; Trionymus sativus James is transferred to Paracoccus, as Paracoccus sativus (James) comb. n.; Pseudococcus masakensis James is transferred to Nipaecoccus as Nipaecoccus masakensis (James) comb. n., and Spilococcus commiphorae De Lotto is transferred to Paracoccus, as Paracoccus commiphorae (De Lotto) comb. n.

Towards the identification of the scale insects (Hemiptera: Coccomorpha) of continental Africa: 1. Identification of the families.

Scale insects (Hemiptera: Sternorrhyncha: Coccomorpha) are obligate plant parasites feeding on plant sap; some are damaging pests in agriculture, horticulture and forestry. Despite their economic importance, the scale insects found in continental Africa have not been extensively studied and the keys for identifying them are incomplete and scattered through the literature in several languages. The aim of this study is to improve our understanding of the African scale insect fauna. As a first step towards their identification, we provide a key to the 23 families currently known from continental Africa, based on slide-mounted adult females, covering Aclerdidae, Asterolecaniidae, Cerococcidae, Coccidae, Conchaspididae, Dactylopiidae, Diaspididae, Eriococcidae, Halimococcidae, Kermesidae, Kerriidae, Kuwaniidae, Lecanodiaspididae, Margarodidae, Matsucoccidae, Micrococcidae, Monophlebidae, Ortheziidae, Phoenicococcidae, Pseudococcidae, Putoidae, Rhizoecidae and Stictococcidae.

The Infraorder Coccomorpha (Insecta: Hemiptera).

The scale insects (infraorder Coccomorpha) are the most morphologically specialised members of the Hemiptera. They form a monophyletic group within the suborder Sternorrhyncha, having one-segmented tarsi and a single claw (all other hemipterans have a double claw). They show extreme sexual dimorphism: the more-or-less sessile adult females are wingless and larviform, whereas the motile adult males mostly are winged and lack mouthparts. Within the Coccomorpha, 54 families are currently recognised, of which 20 are known only from fossils and 34 are extant (García Morales et al. 2016).

THE SCALE INSECTS OF IRAN Part 1 THE ARMOURED SCALES (HEMIPTERA: COCCOMORPHA: DIASPIDIDAE).

Iran is situated at the junctions of the Palaearctic and Oriental zoogeographical regions, and the Caspian, Baluchi and Irano-Tiranian floral zones, so it has a very diverse scale insect fauna. Scale insects (Hemiptera: Coccomorpha) are economically important in forestry, agriculture and horticulture. This taxonomic account of the armoured scales (Diaspididae) of Iran is the first of three works planned to cover all the scale insects in the country. It provides a resource for accurate laboratory identification of all the species known to occur in Iran or that are likely to be found there. Keys to the families of scale insects found in Iran, and to the 49 genera and 144 species of Diaspididae found there, are provided. Detailed line drawings of all the species known to occur in Iran are provided to facilitate identification. These are accompanied by detailed descriptions, distribution data, information on natural enemies, economic importance and host-plants recorded in Iran. The main purpose of the work is to provide agricultural entomologists concerned with pest control and quarantine inspection worldwide with a reliable means of species identification.

Use of proton pump inhibitors to treat persistent throat symptoms: multicentre, double blind, randomised, placebo controlled trial.

OBJECTIVE: To assess the use of proton pump inhibitors (PPIs) to treat persistent throat symptoms. DESIGN: Pragmatic, double blind, placebo controlled, randomised trial. SETTING: Eight ear, nose, and throat outpatient clinics, United Kingdom. PARTICIPANTS: 346 patients aged 18 years or older with persistent throat symptoms who were randomised according to recruiting centre and baseline severity of symptoms (mild or severe): 172 to lansoprazole and 174 to placebo. INTERVENTION: Random blinded allocation (1:1) to either 30 mg lansoprazole twice daily or matched placebo twice daily for 16 weeks. MAIN OUTCOME MEASURES: Primary outcome was symptomatic response at 16 weeks measured using the total reflux symptom index (RSI) score. Secondary outcomes included symptom response at 12 months, quality of life, and throat appearances. RESULTS: Of 1427 patients initially screened for eligibility, 346 were recruited. The mean age of the study sample was 52.2 (SD 13.7) years, 196 (57%) were women, and 162 (47%) had severe symptoms at presentation; these characteristics were balanced across treatment arms. The primary analysis was performed on 220 patients who completed the primary outcome measure within a window of 14-20 weeks. Mean RSI scores were similar between treatment arms at baseline: lansoprazole 22.0 (95% confidence interval 20.4 to 23.6) and placebo 21.7 (20.5 to 23.0). Improvements (reduction in RSI score) were observed in both groups-score at 16 weeks: lansoprazole 17.4 (15.5 to19.4) and placebo 15.6 (13.8 to 17.3). No statistically significant difference was found between the treatment arms: estimated difference 1.9 points (95% confidence interval -0.3 to 4.2 points; P=0.096) adjusted for site and baseline symptom severity. Lansoprazole showed no benefits over placebo for any secondary outcome measure, including RSI scores at 12 months: lansoprazole 16.0 (13.6 to 18.4) and placebo 13.6 (11.7 to 15.5): estimated difference 2.4 points (-0.6 to 5.4 points). CONCLUSIONS: No evidence was found of benefit from PPI treatment in patients with persistent throat symptoms. RSI scores were similar between the lansoprazole and placebo groups after 16 weeks of treatment and at the 12 month follow-up. TRIAL REGISTRATION: ISRCTN Registry ISRCTN38578686 and EudraCT 2013-004249-17.