2016 updated EULAR evidence-based recommendations for the management of gout.

BACKGROUND: New drugs and new evidence concerning the use of established treatments have become available since the publication of the first European League Against Rheumatism (EULAR) recommendations for the management of gout, in 2006. This situation has prompted a systematic review and update of the 2006 recommendations. METHODS: The EULAR task force consisted of 15 rheumatologists, 1 radiologist, 2 general practitioners, 1 research fellow, 2 patients and 3 experts in epidemiology/methodology from 12 European countries. A systematic review of the literature concerning all aspects of gout treatments was performed. Subsequently, recommendations were formulated by use of a Delphi consensus approach. RESULTS: Three overarching principles and 11 key recommendations were generated. For the treatment of flare, colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), oral or intra-articular steroids or a combination are recommended. In patients with frequent flare and contraindications to colchicine, NSAIDs and corticosteroids, an interleukin-1 blocker should be considered. In addition to education and a non-pharmacological management approach, urate-lowering therapy (ULT) should be considered from the first presentation of the disease, and serum uric acid (SUA) levels should be maintained at<6 mg/dL (360 µmol/L) and <5 mg/dL (300 µmol/L) in those with severe gout. Allopurinol is recommended as first-line ULT and its dosage should be adjusted according to renal function. If the SUA target cannot be achieved with allopurinol, then febuxostat, a uricosuric or combining a xanthine oxidase inhibitor with a uricosuric should be considered. For patients with refractory gout, pegloticase is recommended. CONCLUSIONS: These recommendations aim to inform physicians and patients about the non-pharmacological and pharmacological treatments for gout and to provide the best strategies to achieve the predefined urate target to cure the disease.

Hair cortisol in relation to job stress and depressive symptoms.

BACKGROUND: Measurement of hair cortisol concentration (HCC) may be used as a biomarker for chronic stress. However, the association between stress and HCC has rarely been investigated in a working population. AIMS: To explore associations between (i) HCC and various stress measures and (ii) HCC and symptoms of depression in Belgian workers. METHODS: Hair samples were collected from workers in two production companies and cortisol content was determined by liquid chromatography tandem mass spectrometry. Participants completed a questionnaire including socio-demographics, health behaviours and standardized measures for assessing stress. RESULTS: After excluding those workers suffering from a psychiatric or neuroendocrine disease and those treated with glucocorticoids, there were a total of 102 workers with both questionnaire, cortisol results and anthropometric measures. Median HCC was 5.73 pg/mg hair (interquartile range = 4.52-9.06). No significant associations were found between cortisol and the standardized measures related to several work psychosocial risk factors. A significantly lower mean HCC was found in shift workers compared with dayworkers, adjusted for age. Additionally, a significant higher mean HCC was found in workers with symptoms of depression compared with those without symptoms of depression, after adjustment for age. CONCLUSIONS: HCC showed a limited applicability as a biomarker for job stress in this sample, although the results suggest this method may be a suitable marker for detecting early symptoms of depression. Further research is needed to investigate the applicability of HCC in the working environment and within job stress research.

Subtherapeutic triazole concentrations as result of a drug-drug interaction with lumacaftor/ivacaftor.

Lumacaftor/ivacaftor (Orkambi®, LUM/IVA) is indicated for the treatment of cystic fibrosis (CF) patients aged ≥ 2 years with homozygous F580del mutation in the CFTR gene. Triazole fungal agents are used to treat fungal disease in CF. The use of triazoles is limited by pharmacokinetic challenges, such as drug-drug interactions. The most notable drug-drug interaction between triazoles and LUM/IVA is due to strong induction of CYP3A4 and UGT by LUM. In this real-world retrospective observational study, we described the effect of LUM/IVA on the trough concentration of triazoles. Concomitant use of LUM/IVA with itraconazole, posaconazole or voriconazole resulted in subtherapeutic triazole levels in 76% of the plasma samples. In comparison, in patients with triazole agents without LUM/IVA only 30.6% of the plasma samples resulted in subtherapeutic concentrations. Subtherapeutic plasma concentrations of triazoles should be considered in CF patients on LUM/IVA and further research is warranted for other dosing strategies and alternative antifungal therapy.

What the pulmonary specialist should know about the new inhalation therapies.

A collaboration of multidisciplinary experts on the delivery of pharmaceutical aerosols was facilitated by the European Respiratory Society (ERS) and the International Society for Aerosols in Medicine (ISAM), in order to draw up a consensus statement with clear, up-to-date recommendations that enable the pulmonary physician to choose the type of aerosol delivery device that is most suitable for their patient. The focus of the consensus statement is the patient-use aspect of the aerosol delivery devices that are currently available. The subject was divided into different topics, which were in turn assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. To achieve consensus, draft reports and recommendations were reviewed and voted on by the entire panel. Specific recommendations for use of the devices can be found throughout the statement. Healthcare providers should ensure that their patients can and will use these devices correctly. This requires that the clinician: is aware of the devices that are currently available to deliver the prescribed drugs; knows the various techniques that are appropriate for each device; is able to evaluate the patient's inhalation technique to be sure they are using the devices properly; and ensures that the inhalation method is appropriate for each patient.

Alanine/EPR dosimetry applied to the verification of a total body irradiation protocol and treatment planning dose calculation using a humanoid phantom.

PURPOSE: To avoid complications in total body irradiation (TBI), it is important to achieve a homogeneous dose distribution throughout the body and to deliver a correct dose to the lung which is an organ at risk. The purpose of this work was to validate the TBI dose protocol and to check the accuracy of the 3D dose calculations of the treatment planning system. METHODS: Dosimetry based on alanine/electron paramagnetic resonance (EPR) was used to measure dose at numerous locations within an anthropomorphic phantom (Alderson) that was irradiated in a clinical TBI beam setup. The alanine EPR dosimetry system was calibrated against water calorimetry in a Co-60 beam and the absorbed dose was determined by the use of "dose-normalized amplitudes" A(D). The dose rate of the TBI beam was checked against a Farmer ionization chamber. The phantom measurements were compared to 3D dose calculations from a treatment planning system (Pinnacle) modeled for standard dose calculations. RESULTS: Alanine dosimetry allowed accurate measurements which were in accordance with ionization chamber measurements. The combined relative standard measurement uncertainty in the Alderson phantom was U(r)(A(D))=0.6%. The humanoid phantom was irradiated to a reference dose of 10 Gy, limiting the lung dose to 7.5 Gy. The ratio of the average measured dose midplane in the craniocaudal direction to the reference dose was 1.001 with a spread of +/- 4.7% (1 sd). Dose to the lung was measured in 26 locations and found, in average, 1.8% lower than expected. Lung dose was homogeneous in the ventral-dorsal direction but a dose gradient of 0.10 Gy cm(-1) was observed in the craniocaudal direction midline within the lung lobe. 3D dose calculations (Pinnacle) were found, in average, 2% lower compared to dose measurements on the body axis and 3% lower for the lungs. CONCLUSIONS: The alanine/EPR dosimetry system allowed accurate dose measurements which enabled the authors to validate their TBI dose protocol. Dose calculations based on a collapsed cone convolution dose algorithm modeled for regular treatments are accurate within 3% and can further be improved when the algorithm is modeled for TBI.

Real-time selected ion flow tube mass spectrometry to assess short- and long-term variability in oral and nasal breath.

Breath-based non-invasive diagnostics have the potential to provide valuable information about a person's health status. However, they are not yet widely used in clinical practice due to multiple factors causing variability and the lack of standardized procedures. This study focuses on the comparison of oral and nasal breathing, and on the variability of volatile metabolites over the short and long term. Selected ion flow tube mass spectrometry (SIFT-MS) was used for online analysis of selected volatile metabolites in oral and nasal breath of 10 healthy individuals five times in one day (short-term) and six times spread over three weeks (long-term), resulting in nearly 100 breath samplings. Intra-class correlation coefficients (ICCs) were used to assess short- and long-term biological variability. Additionally, the composition of ambient air was analyzed at different samplings. The selected volatiles common in exhaled breath were propanol, 2,3-butanedione, acetaldehyde, acetone, ammonia, dimethyl sulfide, isoprene, pentane, and propanal. Additionally, environmental compounds benzene and styrene were analyzed as well. Volatile metabolite concentrations in ambient air were not correlated with those in exhaled breath and were significantly lower than in breath samples. All volatiles showed significant correlation between oral and nasal breath. Five were significantly higher in oral breath compared to nasal breath, while for acetone, propanal, dimethyl sulfide, and ammonia, concentrations were similar in both matrices. Variability depended on the volatile metabolite. Most physiologically relevant volatiles (acetone, isoprene, propanol, acetaldehyde) showed good to very good biological reproducibility (ICC > 0.61) mainly in oral breath and over a short-term period of one day. Both breathing routes showed relatively similar patterns; however, bigger differences were expected. Therefore, since sampling from the mouth is practically more easy, the latter might be preferred.

Use of a mobile application for self-management of pancreatic enzyme replacement therapy is associated with improved gastro-intestinal related quality of life in children with Cystic Fibrosis.

BACKGROUND: Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency (PI), leading to fat malabsorption, malnutrition, abdominal discomfort and impaired growth. Pancreatic enzyme replacement therapy (PERT) is effective, but evidence based guidelines for dose adjustment are lacking. A mobile app for self-management of PERT was developed in the context of the HORIZON 2020 project MyCyFAPP. It contains an algorithm to calculate individual PERT-doses for optimal fat digestion, based on in vitro and in vivo studies carried out in the same project. In addition, the app includes a symptoms diary, educational material, and it is linked to a web tool allowing health care professionals to evaluate patient's data and provide feedback. METHODS: A 6-month open label prospective multicenter interventional clinical trial was performed to assess effects of using the app on gastro-intestinal related quality of life (GI QOL), measured by the CF-PedsQL-GI (shortened, CF specific version of the Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Module). RESULTS: One hundred and seventy-one patients with CF and PI between 2 and 18 years were recruited at 6 European CF centers. Self-reported CF-PedsQL-GI improved significantly from month 0 (M0) (84.3, 76.4-90.3) to month 6 (M6) (89.4, 80.35-93.5) (p< 0.0001). Similar improvements were reported by parents. Lower baseline CF-PedsQL-GI was associated with a greater improvement at M6 (p < 0.001). CONCLUSIONS: The results suggest that the MyCyFAPP may improve GI QOL for children with CF. This tool may help patients to improve self-management of PERT, especially those with considerable GI symptoms.

Systemic corticosteroids for acute gout.

BACKGROUND: Gout is one of the most frequently occurring rheumatic diseases, worldwide. Given the well-known drawbacks of the regular treatments for acute gout (non-steroidal anti-inflammatory drugs (NSAIDs), colchicine), systemic corticosteroids might be safe alternatives. OBJECTIVES: To assess the efficacy and safety of systemic corticosteroids in the treatment of acute gout in comparison with placebo, NSAIDs, colchicine, other active drugs, other therapies, or no therapy. SEARCH STRATEGY: Searches were done in the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007); MEDLINE (1966 to 2007) through PubMed; EMBASE (1974 to 2007); Web of Science (1975 to 2007); LILACS (1986 to 2007); and databases of ongoing trials (up to April 2007). SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials investigating the use of systemic corticosteroids in the treatment of acute gout were included. DATA COLLECTION AND ANALYSIS: Two review authors decided independently which trials to include. The same review authors also collected the data in a standardised form and assessed the methodological quality of the trial using validated criteria. When possible, continuous and dichotomous data were summarised statistically. MAIN RESULTS: Three head to head trials involving 148 patients (74 systemic corticosteroids; 74 comparator drugs) were included. Placebo-controlled trials were not found. In the studies, different kinds of systemic corticosteroids and different kinds of control drugs were used, both administered in different routes. Intramuscular triamcinolone acetonide was compared respectively to oral indomethacine, and intramuscular adrenocorticotropic hormone (ACTH); oral prednisolone (together with a single intramuscular diclophenac injection) was compared to oral indomethacine (together with a single placebo injection). Outcome measurements varied: average number of days until total relief of signs, mean decrease of pain per unit of time in mm on a visual analogue scale (VAS) - during rest and activity. In the triamcinolone-indomethacine trial the clinical joint status was used as an additional outcome. Clinically relevant differences between the studied systemic corticosteroids and the comparator drugs were not found; important safety problems attributable to the used corticosteroids were not reported. The quality of the three studies was graded as very low to moderate. Statistical pooling of results was not possible. AUTHORS' CONCLUSIONS: There is inconclusive evidence for the efficacy and effectiveness of systemic corticosteroids in the treatment of acute gout. Patients with gout did not report serious adverse effects from systemic corticosteroids, when used short term.

Facemasks and aerosol delivery by metered dose inhaler-valved holding chamber in young children: a tight seal makes the difference.

A facemask on a valved holding chamber (VHC) facilitates the inhalation of aerosols from metered dose inhalers (MDI) for young children. Only recently the facemask has been recognized as a vital part for efficient aerosol delivery. Several in vitro and in vivo studies show that a tight seal of the facemask is crucial for optimal aerosol deposition to the lungs. Even a small leak can reduce the dose delivered to the lungs considerably. However, a tight seal is difficult to obtain when a child is not cooperative. Depending on the design of the facemask, it is easier to obtain a good seal. Factors such as dead space, shape, and material should be considered when designing a facemask. However, when a child is upset and not cooperative during the administration, aerosol deposition will be minimal, even with the best-designed facemask.

[Gout not induced by diuretics in a case-control study in general practice]. / Jicht niet uitgelokt door diuretica in een patiënt-controleonderzoek in de huisartspraktijk.

OBJECTIVE: To determine the relation between diuretics and the development of gout, taking into account the possible confounding by hypertension and cardiovascular diseases. DESIGN: Case-control study. METHOD: With the aid of the data on morbidity and medication from the electronic medical files ofa dispensing general practitioner, all patients with a first gout registration during the period from October 1994 to September 2002 were identified as cases; in the same practice, for each patient, 3 controls of the same age and sex who were known not to have gout were selected at random. Conditional logistic regression analyses were carried out to estimate the odds ratio (OR) for gout in patients who had used diuretics for at least 3 months and in patients suffering from hypertension, heart failure, or myocardial infarction. The statistical interaction between variables was investigated after stratification for diuretic use. RESULTS: Via the medical files, 70 gout patients (59 men), with a mean age of 55.1 years (SD: 13.5) were identified, plus 210 matched controls. When assessed without correction, the use ofdiuretics seemed to be associated with a definite risk of gout: OR: 2.8 (95% CI: 1.2-6.6). But after adjustment for the cardiovascular variables hypertension, heart failure and myocardial infarction, the risk of gout associated with diuretic use disappeared: OR: 0.6 (95% CI: 0.2-2.0). An independent risk of gout was demonstrated for hypertension (OR: 3.9; 95% CI: 1.6-10.0), and to a lesser degree for myocardial infarction (OR: 1.5; 95% CI: 0-5-4.1). The risk of gout associated with heart failure was also calculated (OR: 40.1; 95% CI: 3.8-437.2), but diuretic independency could not be proven as all patients with heart failure were on diuretics and there was no heart failure among those not using diuretics. CONCLUSION: In this case-control study, the use of diuretics did not increase the risk of gout. The cardiovascular indications for prescribing diuretics were significant confounders.

Pharmacokinetics and Tolerability of Once Daily Double Dose Tobramycin Inhalation in Cystic Fibrosis Using Controlled and Conventional Nebulization.

BACKGROUND: Better treatment outcomes in cystic fibrosis (CF) may be expected by changing standard twice daily (BID) tobramycin inhalation with the conventional nebulizer to once daily (OD) inhalation at double the standard BID dose with a controlled-inhalation nebulizer. We aimed to determine the pharmacokinetics and tolerability of inhaled double-dose tobramycin with the controlled-inhalation AKITA(®) and conventional PARI-LC(®) Plus nebulizer in patients with CF. METHODS: Randomized, open label, crossover study. Pharmacokinetics were assessed in 10 adult CF patients following inhalation of tobramycin (Bramitob(®)) at double the recommended BID dose with the AKITA (300 mg fill dose) and PARI-LC Plus (600 mg fill dose). RESULTS: No significant differences were found in pharmacokinetic parameters between the two nebulizers. Median maximum serum levels were 3.44 (2.25-5.49) and 2.84 (0.82-6.63) mg/L for AKITA and PARI-LC Plus, respectively. Trough serum levels were very low for both nebulizers: 0.03 (0.00-0.09) and 0.02 (0.00-0.06) mg/L for AKITA and PARI-LC Plus, respectively. Time to maximum level was comparable: 0.44 (0.08-0.96) and 0.40 (0.08-0.96) hours for AKITA and PARI-LC Plus, respectively. Serum levels were well below the toxic limit. Inhalations were well tolerated and no serious adverse events occurred. Nebulization time was 33% shorter with the AKITA. CONCLUSIONS: OD tobramycin inhalation of the double standard BID dose with a controlled-inhalation and conventional nebulizer resulted in similar pharmacokinetics in the doses given, with serum levels below the toxic limit. Further research demonstrating clinical efficacy and safety of this treatment approach is required. Dutch trial register number NTR4525.

Real life data on incidence and risk factors of severe asthma exacerbations in children in primary care.

Real-life data on the incidence rates (IR) and risk factors of severe asthma exacerbations in children are sparse. We aimed to assess IR and risk factors of severe asthma exacerbations in children in real life. We conducted a population-based cohort study using a Dutch GP database containing complete medical records of >1 million patients. All records of children with physician-diagnosed asthma aged 5-18 years between 2000 and 2012 were examined for exacerbations, defined as either hospitalization, emergency department visit or need of systemic steroids for asthma. IR was expressed as number of exacerbations per person year (PY). We identified 14,303 asthmatic children with 35,118 PY of follow-up and 732 exacerbations. The overall IR was 2.1/100PY (95% CI 1.9-2.2), 4.1/100PY (3.8-4.4) for children on asthma treatment. Re-exacerbation occurred in 2% (1.3-4.3) of patients within 1 month, in 25% (20.6-28.8) within 1 year. Predictors for (frequent) exacerbations were age, medication use and prior exacerbations (all p < 0.001). The overall IR of severe asthma exacerbations was 4/100PY in children on asthma treatment, highest in spring and fall. 25% of the patients with an exacerbation will experience a next exacerbation within 1 year. More severe asthma is a predictor of subsequent and future exacerbations.

Limited premature termination codon suppression by read-through agents in cystic fibrosis intestinal organoids.

Premature termination codon read-through drugs offer opportunities for treatment of multiple rare genetic diseases including cystic fibrosis. We here analyzed the read-through efficacy of PTC124 and G418 using human cystic fibrosis intestinal organoids (E60X/4015delATTT, E60X/F508del, G542X/F508del, R1162X/F508del, W1282X/F508del and F508del/F508del). G418-mediated read-through induced only limited CFTR function, but functional restoration of CFTR by PTC124 could not be confirmed. These studies suggest that better read-through agents are needed for robust treatment of nonsense mutations in cystic fibrosis.

A bioassay using intestinal organoids to measure CFTR modulators in human plasma.

Treatment efficacies of drugs depend on patient-specific pharmacokinetic and pharmacodynamic properties. Here, we developed an assay to measure functional levels of the CFTR potentiator VX-770 in human plasma and observed that VX-770 in plasma from different donors induced variable CFTR function in intestinal organoids. This assay can help to understand variability in treatment response to CFTR potentiators by functionally modeling individual pharmacokinetics.

The raising and characterization of cortisol-binding antiserum.

Synthesis of a cortisol-albumin compound and the raising of antibodies against cortisol in rabbits are described in detail. The steroid-protein complex is characterized by a number of reactions regarding the amount of cortisol coupled and the ability of the coupled steroid to react as such. The specificity of the harvested antiserum and transcortin towards the coupling of several related steroids are compared; the rabbit antiserum appears to be the more selective binding agent.

High-percentage lung delivery in children from detergent-treated spacers.

Pressurized metered-dose inhalers attached to spacers are now the most common form of delivery of anti-asthma medication in children. However, no reliable data are available of how much drug reaches the lungs in children of different ages. This information is crucial, as it determines the efficacy of therapy. In this study, we present information on the amount of drug reaching the lungs in children from a pressurized metered-dose inhaler attached to a detergent-coated spacer. We studied 18 asthmatic children inhaling radiolabeled salbutamol through detergent treated spacers to minimize electrostatic charge on the spacer wall. Lung deposition was much higher than expected when using detergent-coated spacers. Mean (SD) lung deposition, expressed as a percentage of the total actuated dose (five actuations), was 16.4% (5.5) in younger children inhaling through a small volume spacer, and 28.2% (6.7) and 41.8% (3. 8) in older children inhaling with different breathing patterns through a large volume spacer. These findings have major implications for dosage regimens for inhaled anti-asthma medication in children. Lower doses may be sufficient for adequate drugs delivered through spacers treated for static to achieve a desired clinical response.

Endocrinological aspects of aging in men: is hormone replacement of benefit?

Age-related decreases of serum testosterone (total, free and bioavailable), DHEA, DHEA-S, growth hormone (GH) and IGF-I are well established in elderly healthy men. Although substantial, the decrease of these hormones is small compared to the estrogen changes observed in postmenopausal women. Elderly men also loose bone and muscle, gain fat and have less sexual appetite. Therefore, the assumption that hormonal therapy is a potential 'fountain of youth' appears logical. At present, however, the effects of replacement of testosterone, DHEA and GH in healthy elderly men have been studied in only a few randomised placebo-controlled trials. These studies were small and of short duration. Although some significant overall effects of either androgen or GH replacement on body composition (less fat and more muscle) were found, the effects of such therapy on muscle strength, on metabolic and sexual function and on skeletal homeostasis have been less consistent. Also, the safety of such therapy should be better documented. Moreover, data obtained in healthy elderly men cannot be transposed to non-healthy elderly men. In conclusion, more scientific work is needed before general replacement of the 'falling hormones' should be regarded as beneficial for elderly men.

The Sophia Anatomical Infant Nose-Throat (Saint) model: a valuable tool to study aerosol deposition in infants.

Relatively little is known about the variables that influence lung deposition of inhaled aerosols in children. A model of the upper airways of an infant could be a useful tool to study these variables in vitro. The objective of this study was to construct an anatomically correct model of the upper airways of a young child. A routine three-dimensional (3D) CT scan of the skull and neck of a child was selected that included the airway from the nasal cavity down to the subglottic region. The CT scan was edited to obtain an anatomically correct distinction between air and mucosa. Next, a model was constructed with a stereolithographic technique using a UV-sensitive resin. To validate the model, a 3D CT scan of the model was made and compared to the anatomy of the original image. To study aerosol deposition, the model was connected to a breathing simulator. Medical aerosols were delivered to the model by MDI/spacer during stimulated breathing. An upper airway model was made of a 9-month-old child that needed reconstructive surgery for a skull deformity and with normal anatomy of the upper airways. The nasal airway of the model was open for air passage and the oral airway was closed. The CT scan of the model matched the original in vivo CT scan closely. Aerosol deposition measurements showed that dose passing the model, or lung dose, was comparable with in vivo lung deposition data. We have constructed an anatomically correct model of the upper airways of a child, using a stereolithographic method for in vitro studies of aerosol deposition in young children. This model will be used to obtain insight in aerosol treatment that cannot be obtained in vivo.

Neutron field measurements for alara purposes around a Van de Graaff accelerator building.

The Institute for Reference Materials and Measurements operates a 7.0 MV Van de Graaff accelerator to generate monoenergetic neutron radiation for experimental applications. Owing to increased intensities of generated neutron fields and the more stringent regulation related to the maximum dose for the public, a concrete shielding wall surrounding the experimental building was constructed. This paper presents a study aiming at evaluating the effect of the shielding on the neutron field outside the wall. For this purpose, the following measurements were carried out around the building: (1) cartography of the neutron field for different experimental conditions; (2) measurement of neutron spectra using multiple Bonner spheres; (3) activation measurements using gold discs followed by low-level gamma spectrometry. From the measurements, it can be concluded that the wall fulfils its purpose to reduce the neutron dose rate to the surrounding area to an acceptable level.

A protocol for extraocular muscle surgery after orbital floor fracture ("blow-out")

PURPOSE: If, after primary repair of an orbital fracture by maxillo-facial surgeons, diplopia persists, extraocular muscle surgery may be necessary. It was the purpose of this study to examine proposed surgical treatment in these cases to determine their efficacy. SUBJECTS AND METHODS: We analyzed, retrospectively, the files of 14 patients who were treated in our strabismological department for persistent diplopia caused by injury to the extraocular muscles and/or to the surrounding structures. The aim of our treatment protocol was to restore comfortable binocular single vision in primary position and downgaze. The selection of the surgical procedure depended on the deviation in primary position and on the degree of ocular muscle imbalance. Surgery consisted of recession of the inferior rectus muscle of the affected eye in 4 cases, resection of the inferior rectus muscle of the affected eye in 4 other cases, and large recessions of the vertical muscles of the contralateral normal eye in 6 cases. RESULTS: In all 14 patients, we obtained the desired comfortable field of binocular single vision, considered "good" (20 degrees up to 30 degrees downgaze) or "satisfactory" (a useful field). In 11 cases this was achieved in one procedure. Two patients needed a reintervention because of initial overcorrection, and one patient for an initial undercorrection. All 14 patients had a "good" or "satisfactory" final result (useful binocular single vision). CONCLUSIONS: When extraocular muscle surgery is necessary, we recommend in patients with limited forced elevation, recession of the taut rectus inferior muscle; in patients with the clinical characteristics of an inferior rectus palsy, a resection of this muscle; and in cases with a normal or only slightly limited forced duction test, weakening the contralateral synergists.