Outcomes after treatment of nonsevere gram-negative clinical mastitis with ceftiofur hydrochloride for 2 or 5 days compared with negative control.

A study was conducted at 3 commercial dairies in California to compare outcomes of treating nonsevere (mild and moderate) gram-negative (GN) clinical mastitis (CM) with intramammary (IMM) ceftiofur HCl (125 mg of ceftiofur HCl per tube) in either 2-d (SP2) or 5-d (SP5) treatment programs compared with nontreatment (CON). In addition, we contrasted results from cases classified as mild and moderate. Four hundred fifteen cases were included in the final dataset, including 135 CON, 133 SP2, and 147 SP5. Milk from quarters with CM was sampled for on-farm culture (OFC) to differentiate gram-positive (GP) and GN bacteria, with results known within 24 h. Those with GN infections were randomly assigned to experimental groups, while those with GP, mixed infections, and contaminated samples did not continue in the study and received standard farm therapy. For cows with GN infections, a sample was submitted for MALDI-TOF assay. Only nonsevere cases were enrolled, and all quarters yielded monocultures of GN species. Clinical scores were obtained 0, 1, 2, 3, 4, 5, 14, 21, and 28 ± 3 d relative to enrollment. Milk samples were collected from quarters 14, 21, and 28 ± 3 d after enrollment, and submitted for routine culture and, when appropriate, submitted to MALDI-TOF evaluation. For many response criteria, there were significant interactions between treatments and CM severity scores at the time of enrollment, with effectiveness of ceftiofur HCl treatment being more beneficial compared with CON as mastitis clinical severity increased. While most treatment responses were significant for animals with mild or moderate GN mastitis, the largest responses were noted among cows with moderate CM cases.

A vanguard randomised feasibility trial comparing three regimens of peri-operative oxygen therapy on recovery after major surgery.

International recommendations encourage liberal administration of oxygen to patients having surgery under general anaesthesia, ostensibly to reduce surgical site infection. However, the optimal oxygen regimen to minimise postoperative complications and enhance recovery from surgery remains uncertain. The hospital operating theatre randomised oxygen (HOT-ROX) trial is a multicentre, patient- and assessor-blinded, parallel-group, randomised clinical trial designed to assess the effect of a restricted, standard care, or liberal peri-operative oxygen therapy regimen on days alive and at home after surgery in adults undergoing prolonged non-cardiac surgery under general anaesthesia. Here, we report the findings of the internal vanguard feasibility phase of the trial undertaken in four large metropolitan hospitals in Australia and New Zealand that included the first 210 patients of a planned overall 2640 trial sample, with eight pre-specified endpoints evaluating protocol implementation and safety. We screened a total of 956 participants between 1 September 2019 and 26 January 2021, with data from 210 participants included in the analysis. Median (IQR [range]) time-weighted average intra-operative Fi O2 was 0.30 (0.26-0.35 [0.20-0.59]) and 0.47 (0.44-0.51 [0.37-0.68]) for restricted and standard care, respectively (mean difference (95%CI) 0.17 (0.14-0.20), p < 0.001). Median time-weighted average intra-operative Fi O2 was 0.83 (0.80-0.85 [0.70-0.91]) for liberal oxygen therapy (mean difference (95%CI) compared with standard care 0.36 (0.33-0.39), p < 0.001). All feasibility endpoints were met. There were no significant patient adverse events. These data support the feasibility of proceeding with the HOT-ROX trial without major protocol modifications.

A pilot randomised controlled trial of the management of systolic blood pressure during endovascular thrombectomy for acute ischaemic stroke.

It is unknown whether systolic blood pressure augmentation during endovascular thrombectomy improves clinical outcomes. This pilot randomised controlled trial aimed to assess the feasibility of differential systolic blood pressure targeting during endovascular thrombectomy procedures for anterior circulation ischaemic stroke. Fifty-one eligible patients fulfilling the national criteria for endovascular thrombectomy were randomly assigned to receive either standard or augmented systolic blood pressure management from the start of anaesthesia to recanalisation of the target vessel. Systolic blood pressure targets for the standard and augmented groups were 130-150 mmHg and 160-180 mmHg, respectively. The study achieved all feasibility targets, including a recruitment rate of 3.5 participants per week and median (IQR [range]) of mean systolic blood pressure separation between groups of 139 (135-143 [115-154]) vs. 167 (150-175 [113-188]) mmHg, p < 0.001. Data completeness was 99%. Independent functional recovery at 90 days (modified Rankin Scale 0, 1 or 2) was achieved in 30 (59%) patients, which is consistent with previously published data. There were no safety concerns with trial procedures. In conclusion, a large randomised controlled efficacy trial of standard vs. augmented systolic blood pressure management during endovascular thrombectomy is feasible.

National risk prediction model for perioperative mortality in non-cardiac surgery.

BACKGROUND: Many multivariable models to calculate mortality risk after surgery are limited by insufficient sample size at development or by application to cohorts distinct from derivation populations. The aims of this study were to validate the Surgical Outcome Risk Tool (SORT) for a New Zealand population and to develop an extended NZRISK model to calculate 1-month, 1-year and 2-year mortality after non-cardiac surgery. METHODS: Data from the New Zealand National Minimum Data Set for patients having surgery between January 2013 and December 2014 were used to validate SORT. A random 75 per cent split of the data was used to develop the NZRISK model, which was validated in the other 25 per cent of the data set. RESULTS: External validation of SORT in the 360 140 patients who underwent surgery in the study period showed good discrimination (area under the receiver operating characteristic curve (AUROC) value of 0·906) but poor calibration (McFadden's pseudo-R2 0·137, calibration slope 5·32), indicating it was invalid in this national surgical population. Internal validation of the NZRISK model, which incorporates sex and ethnicity in addition to the variables used in SORT for 1-month, 1-year and 2-year outcomes, demonstrated excellent discrimination with AUROC values of 0·921, 0·904 and 0·895 respectively, and excellent calibration (McFadden's pseudo-R2 0·275, 0·308 and 0·312 respectively). Calibration slopes were 1·12, 1·02 and 1·02 respectively. CONCLUSION: The SORT performed poorly in this national population. However, inclusion of sex and ethnicity in the NZRISK model improved performance. Calculation of mortality risk beyond 30 days after surgery adds to the utility of this tool for shared decision-making.

ANTECEDENTES: Muchos modelos multivariados de estimación del riesgo de mortalidad después de la cirugía están limitados por haberse desarrollado a partir de tamaños muestrales insuficientes o por haberse aplicados a cohortes distintas de las poblaciones de derivación. Los objetivos de este estudio fueron validar el Surgical Outcome Risk Tool (SORT) para una población de Nueva Zelanda y desarrollar un modelo NZRISK extendido para calcular la mortalidad al mes y a los 1 y 2 años de una cirugía no cardíaca. MÉTODOS: Para validar el SORT se utilizó el Conjunto Mínimo Básico de Datos de Nueva Zelanda para los pacientes sometidos a cirugía entre enero de 2013 y diciembre de 2014. Se realizó una división aleatoria del 75% de los datos para desarrollar el modelo NZRISK que, posteriormente, se validó en el otro 25% del conjunto de datos. RESULTADOS: La validación externa de SORT en 360.140 pacientes intervenidos en el periodo analizado mostró una buena discriminación (área bajo las curvas de característica operativa del receptor (area under the receiver-operator characteristic curves (AUROC) 0,906)) pero con una mala calibración (pseudo-R2 de McFaddens 0,137 y pendiente de calibración 5,32), lo que indicaba que SORT no era válido para esta población quirúrgica nacional. La validación interna del modelo NZRISK, que incorpora el género y la etnia además de las variables utilizadas en el SORT, para los resultados al mes y a los 1 y 2 años demostró una excelente capacidad de discriminación con una AUROC de 0,921, 0,904, 0,895 respectivamente y una calibración excelente, con una pseudo-R2 de McFaddens de 0,275, 0,308 y 0,312 respectivamente. Las pendientes de calibración fueron de 1,12, 1,02 y 1,02, respectivamente. CONCLUSIÓN: El SORT no fue útil en esta población nacional. Sin embargo, la inclusión del género y la etnia en el modelo NZRISK mejoró sus resultados. El cálculo del riesgo de mortalidad más allá de 30 días después de la cirugía añade utilidad a esta herramienta para la toma de decisiones compartida.

Systematic review and consensus definitions for standardised endpoints in perioperative medicine: postoperative cancer outcomes.

BACKGROUND: The Standardising Endpoints for Perioperative Medicine group was established to derive an appropriate set of endpoints for use in clinical trials related to anaesthesia and perioperative medicine. Anaesthetic or analgesic technique during cancer surgery with curative intent may influence the risk of recurrence or metastasis. However, given the current equipoise in the existing literature, prospective, randomised, controlled trials are necessary to test this hypothesis. As such, a cancer subgroup was formed to derive endpoints related to research in onco-anaesthesia based on a current evidence base, international consensus and expert guidance. METHODS: We undertook a systematic review to identify measures of oncological outcome used in the oncological, surgical, and wider literature. A multiround Delphi consensus process that included up to 89 clinician-researchers was then used to refine a recommended list of endpoints. RESULTS: We identified 90 studies in a literature search, which were the basis for a preliminary list of nine outcome measures and their definitions. A further two were added during the Delphi process. Response rates for Delphi rounds one, two, and three were 88% (n=9), 82% (n=73), and 100% (n=10), respectively. A final list of 10 defined endpoints was refined and developed, of which six secured approval by ≥70% of the group: cancer health related quality of life, days alive and out of hospital at 90 days, time to tumour progression, disease-free survival, cancer-specific survival, and overall survival (and 5-yr overall survival). CONCLUSION: Standardised endpoints in clinical outcomes studies will support benchmarking and pooling (meta-analysis) of trials. It is therefore recommended that one or more of these consensus-derived endpoints should be considered for inclusion in clinical trials evaluating a causal effect of anaesthesia-analgesia technique on oncological outcomes.

Intraoperative dexamethasone does not increase the risk of postoperative wound infection: a propensity score-matched post hoc analysis of the ENIGMA-II trial (EnDEX).

BACKGROUND: In a post hoc analysis of the ENIGMA-II trial, we sought to determine whether intraoperative dexamethasone was associated with adverse safety outcomes. METHODS: Inverse probability weighting with estimated propensity scores was used to determine the association of dexamethasone administration with postoperative infection, quality of recovery, and adverse safety outcomes for 5499 of the 7112 non-cardiac surgery subjects enrolled in ENIGMA-II. RESULTS: Dexamethasone was administered to 2178 (40%) of the 5499 subjects included in this analysis and was not associated with wound infection [189 (8.7%) vs 275 (8.3%); propensity score-adjusted relative risk (RR) 1.10; 95% confidence interval (CI) 0.89-1.34; P=0.38], severe postoperative nausea and vomiting on day 1 [242 (7.3%) vs 189 (8.7%); propensity score-adjusted RR 1.06; 95% CI 0.86-1.30; P=0.59], quality of recovery score [median 14, interquartile range (IQR) 12-15, vs median 14, IQR 12-16, P=0.10), length of stay in the postanaesthesia care unit [propensity score-adjusted median (IQR) 2.0 (1.3, 2.9) vs 1.9 (1.3, 3.1), P=0.60], or the primary outcome of the main trial. Dexamethasone administration was associated with a decrease in fever on days 1-3 [182 (8.4%) vs 488 (14.7%); RR 0.61; 95% CI 0.5-0.74; P<0.001] and shorter lengths of stay in hospital [propensity score-adjusted median (IQR) 5.0 (2.9, 8.2) vs 5.3 (3.1, 9.1), P<0.001]. Neither diabetes mellitus nor surgical wound contamination status altered these outcomes. CONCLUSION: Dexamethasone administration to high-risk non-cardiac surgical patients did not increase the risk of postoperative wound infection or other adverse events up to day 30, and appears to be safe in patients either with or without diabetes mellitus. CLINICAL TRIAL REGISTRATION: NCT00430989.

Comparing violence in schizophrenia patients with and without comorbid substance-use disorders to community controls.

OBJECTIVE: This study examined crime and violence in patients with schizophrenia with and without comorbid substance-use disorders. METHOD: A case-linkage design was used to compare patterns of violence and offending between 4168 schizophrenia patients drawn from a state-wide public mental health register, both with and without comorbid substance-use disorders, and a randomly selected community control group who had never been diagnosed with schizophrenia. RESULTS: Schizophrenia patients were significantly more likely than controls to be guilty of violent and non-violent offences, and to have been involved in family violence. Even schizophrenia patients without comorbid substance-use disorders had a significantly elevated risk of violence; this group were more than twice as likely as controls to have a violent conviction. The elevation of violence risk in schizophrenia patients was higher in females (OR = 8.59) than males (OR = 2.25). CONCLUSION: The increased risk of violent offending in schizophrenia cannot be solely attributed to the effects of comorbid substance misuse, although comorbidity certainly heightens the likelihood of criminality. In addition to offending, people with schizophrenia are more likely than community controls to come to the attention of police via their involvement in family violence incidents. Schizophrenia is a particularly strong risk factor for violence in females.

Schizophrenia disorders, substance abuse and prior offending in a sequential series of 435 homicides.

OBJECTIVE: To examine the relationship between committing homicide, the presence of schizophrenia, substance misuse and past criminality. METHOD: The study employed a data linkage design, using contacts recorded on two statewide databases, one of which recorded public mental health services contacts and the second of which recorded contacts with the police. The estimated rates of schizophrenia disorders, substance abuse and criminal convictions found among a population of 435 homicide offenders were contrasted with estimated rates in two composite comparison samples. RESULTS: Of the 435 offenders, 38 (8.7%) had been diagnosed with a schizophrenia disorder, which was RR 13.11 (95% CI 9.14-18.80) times more likely than a comparison sample. Rates of known substance abuse between homicide offenders with and without schizophrenia and community-dwelling residents with schizophrenia did not differ significantly. However, these rates were higher than those found in the general community. A similar pattern emerged for comparisons regarding offending histories between these same groups. CONCLUSION: The association between homicidal violence and having a schizophrenia disorder cannot be explained away simply on the basis of either comorbid substance abuse or prior criminal offending.

Phytochromes: photosensory perception and signal transduction.

The phytochrome family of photoreceptors monitors the light environment and dictates patterns of gene expression that enable the plant to optimize growth and development in accordance with prevailing conditions. The enduring challenge is to define the biochemical mechanism of phytochrome action and to dissect the signaling circuitry by which the photoreceptor molecules relay sensory information to the genes they regulate. Evidence indicates that individual phytochromes have specialized photosensory functions. The amino-terminal domain of the molecule determines this photosensory specificity, whereas a short segment in the carboxyl-terminal domain is critical for signal transfer to downstream components. Heterotrimeric GTP-binding proteins, calcium-calmodulin, cyclic guanosine 5'-phosphate, and the COP-DET-FUS class of master regulators are implicated as signaling intermediates in phototransduction.

Design and development of a novel automatic valve system for long-term catheterized urinary incontinence patients.

It has been estimated that over 3 million patients in the UK suffer from urinary incontinence, the result of which is often long-term catheterization. However, many catheters block prematurely through encrustation and their continuous drainage limits bladder rehabilitation. Although evidence shows that a catheter valve may overcome such weaknesses, only manual valves are currently available and many patients are not able to benefit from these owing to a lack of manual dexterity. A novel electronically controlled automatic valve system, the Shan-Lai (SL) valve system, has been designed and prototyped. The prototype is compact, reliable, and cost effective, and it has low power consumption. The mass of the overall packaged valve system is 34.2 g and it measures 4.5 cm x 4.5 cm x 1.2 cm. With an orifice of 3 mm diameter, the SL valve has achieved high flowrates with relatively low energy consumption. A flowrate-energy relationship (FER) has been introduced to assess the performance of a catheter valve, and the SL valve system prototype has achieved an FER of 0.66 m/s(-1) mJ(-1) while a commercially available electronic valve has an FER of 0.28 m/s(-1) mJ(-1). The valve demonstrated outstanding mechanical reliability after a series of performance tests and also indicated remarkable encrustation resistance in the vicinity of the valve during an in-vitro test.

A pilot study using preoperative cerebral tissue oxygen saturation to stratify cardiovascular risk in major non-cardiac surgery.

This prospective pilot study evaluated whether low preoperative cerebral tissue oxygen saturation is associated with unfavourable outcomes after major elective non-cardiac surgery. Eighty-one patients over 60 years of age, American Society of Anesthesiologists physical status 3 or 4, were recruited. Resting cerebral tissue oxygen saturation was recorded on room air, and after oxygen supplementation, using cerebral oximetry. The primary outcome was 30-day major adverse event of combined mortality or severe morbidity, and the secondary outcome was 30-day new disability. Eleven patients (13.6%) suffered a major adverse event, and 28 patients (34.6%) experienced new disability. Room air cerebral tissue oxygen saturation was significantly different between patients who had a major adverse event, 67% (95% confidence interval [CI] 65-70) versus unaffected, 71% (95% CI 70-72; P=0.04). No statistical difference was found between patients for new disability (range 70%-74%; P=0.73). Room air cerebral tissue oxygen saturation was significantly associated with major adverse events (odds ratio 1.36 (95% CI 1.03-1.79), P=0.03). Saturation levels ≤68% carried a positive likelihood ratio of 2.2 for death or severe morbidity, P=0.04. A definitive trial is required to confirm if cerebral oximetry can be used to stratify the cardiovascular risk of patients presenting for non-cardiac surgery.

A Pea Plasma Membrane Protein Exhibiting Blue Light-Induced Phosphorylation Retains Photosensitivity following Triton Solubilization.

Phosphorylation of a polypeptide of approximately 120 kD in pea (Pisum sativum L.) plasma membranes in response to blue light has been shown to be involved in phototropic curvature, but the relationship of this protein to the kinase and photoreceptor acting upon it is uncertain. Using two-phase aqueous partitioning to isolate right-side-out plasma membrane vesicles, we have obtained evidence suggesting that the photoreceptor, kinase, and substrate are localized to the plasma membrane fraction. Latent phosphorylation accessible through Triton X-100 or freeze/thaw treatments of purified plasma membrane vesicles indicates that at least the kinase moiety is present on the internal face of the plasma membrane. Effects of solubilization of vesicles on fluence-response characteristics and on phosphorylation levels provide evidence that the receptor, kinase, and protein substrate are present together in individual mixed detergent micelles, either as a stable complex or as domains of a single polypeptide. In vivo blue-light irradiation results in a small but significant decrease in mobility of the 120-kD phosphorylated protein on sodium dodecylsulfate gel electrophoresis. This mobility shift is evident on Coomassie-stained gels and on western blots probed with polyclonal antibodies raised against the 120-kD protein. Among the plasma membrane proteins bound to the reactive nucleotide analog fluorosulfonylbenzoyladenine (FSBA), a distinct protein band at 120 kD can be detected on blots probed with anti-FSBA antibodies. This band exhibits an in vivo light-dependent mobility shift identical to that observed for the protein band and antibodies specific for the 120-kD protein, implying that the 120-kD protein has an integral nucleotide binding site and consistent with the possibility that the substrate protein is also a kinase.

Blue Light-Induced Phosphorylation of a Plasma Membrane-Associated Protein in Zea mays L.

Blue light induces a variety of photomorphogenic responses in higher plants, among them phototropic curvature, the bending of seedlings toward a unidirectional light source. In dark-grown coleoptiles of maize (Zea mays L.) seedlings, blue light induces rapid phosphorylation of a 114-kD protein at fluence levels that are sufficient to stimulate phototropic curvature. Phosphorylation in response to blue light can be detected in vivo in coleoptile tips preincubated in 32Pi or in vitro in isolated membranes supplemented with [[gamma]-32P]ATP. Phosphorylation reaches a maximum level in vitro within 2 min following an inductive light pulse, but substantial labeling occurs within the first 15 s. Isolated membranes remain activated for several minutes following an in vitro blue light stimulus, even in the absence of exogenous ATP. Phosphoamino acid analysis of the 114-kD protein detected phosphoserine and a trace of phosphothreonine. The kinase involved in phosphorylating the protein in vitro is not dependent on calcium. The 114-kD protein itself has an apparent binding site for ATP, detected by incubating with the nonhydrolyzable analog, 5[prime]-p-fluorosulfonyl-benzoyladenosine. This result suggests that the 114-kD protein, which becomes phosphorylated in response to blue light, may also be capable of kinase activity.

Correlation of Blue Light-Induced Phosphorylation to Phototropism in Zea mays L.

The physiology of light-induced phototropic curvature has been studied extensively in coleoptiles of grasses, particularly in Avena and Zea mays L. In Z. mays L., we have found that, in addition to curvature, blue light also induces rapid phosphorylation of a 114-kD protein in the tips of coleoptiles, and, in a previous report, we reported several characteristics of the phosphorylated substrate protein and kinase (J.M. Palmer, T.W. Short, S. Gallagher, W.R. Briggs [1993] Plant Physiol 102: 1211-1218). Here, we compare the phosphorylation response to several known aspects of phototropism physiology. Blue light-induced phosphorylation occurs only in the upper portion of the coleoptile and is absent from the node and mesocotyl. The specific activity of phosphorylation is highest in the extreme apical portion of the tip, which is also the site of maximal sensitivity to phototropic stimuli (A. W. Galston [1959] In Physiology of Movements, Encyclopedia of Plant Physiology, Springer, Berlin). Fluence-response determinations indicate that light dosage levels that stimulate curvature also stimulate phosphorylation. However, the threshold for inducing detectable phosphorylation in maize cannot be matched to the threshold for curvature induction. The recovery of sensitivity to phototropic stimuli after exposure to high fluences of light occurs with kinetics that are very similar to those for recovery of the phosphorylation response after a previous high-fluence light exposure. In addition, wavelengths of light in the blue and near-ultraviolet regions of the spectrum that maximally stimulate phototropic curvature also maximally stimulate in vitro phosphorylation in maize. The pattern of stimulation matches the absorption spectra of flavoproteins, which have been proposed as candidates for blue light photoreceptors.

Blue Light Induces Phosphorylation at Seryl Residues on a Pea (Pisum sativum L.) Plasma Membrane Protein.

We have partially characterized the blue-light-stimulated in vitro phosphorylation of a membrane protein from etiolated Pisum sativum L. stems. Properties of the response have implicated its involvement in signal transduction of phototropic stimuli (T.W. Short, W.R. Briggs [1990] Plant Physiol 92: 179-185; P. Reymond, T.W. Short, W.R. Briggs [1992] Proc Natl Acad Sci USA 89: 4718- 4721). Analysis of proteolysis products and phosphoamino acidanalysis indicate that the substrate protein is phosphorylated on multiple seryl residues. Kinetics of the in vitro reaction show phosphorylation to be complete within 2 to 5 min at 30[deg]C in either light-exposed or dark-control plasma membrane preparations, regardless of whether the membranes were first solubilized in Triton X-100. Nucleotide competition assays show the kinase to be ATP specific. The pH optimum covers a broad range with a maximum near 7.5. A wide array of salts inhibits the phosphorylation at high concentrations, but millimolar concentrations of Mg2+ are required to form Mg.ATP complexes for maximal activity, whereas excess free Mg2+ or Ca2+ are not required for the reaction.

Do patients want physicians to inquire about their spiritual or religious beliefs if they become gravely ill?

BACKGROUND: Recognizing that many Americans draw on religious or spiritual beliefs when confronted by serious illness, some medical educators have recommended that physicians routinely ask about spirituality or religion when conducting a medical history. The most appropriate wording for such an inquiry remains unknown. OBJECTIVE: To examine patient acceptance of including the following question in the medical history of ambulatory outpatients: "Do you have spiritual or religious beliefs that would influence your medical decisions if you become gravely ill?" METHODS: Self-administered questionnaires were completed by 177 ambulatory adult patients visiting a pulmonary faculty office practice at a university teaching hospital in 1997 (83% response rate). RESULTS: Fifty-one percent of the study patients described themselves as religious and 90% believe that prayer may sometimes influence recovery from an illness. Forty-five percent reported that religious beliefs would influence their medical decisions if they become gravely ill. Ninety-four percent of individuals with such beliefs agreed or strongly agreed that physicians should ask them whether they have such beliefs if they become gravely ill. Forty-five percent of the respondents who denied having such beliefs also agreed that physicians should ask about them. Altogether, two thirds of the respondents indicated that they would welcome the study question in a medical history, whereas 16% reported that they would not. Only 15% of the study group recalled having been asked whether spiritual or religious beliefs would influence their medical decisions. CONCLUSION: Many but not all patients surveyed in a pulmonary outpatient practice welcome a carefully worded inquiry about their spiritual or religious beliefs in the event that they become gravely ill.

An overview of the role of calcium antagonists in the treatment of achalasia and diffuse oesophageal spasm.

Early studies confirmed the beneficial effects of calcium channel blockers on the normal oesophagus, which included a decrease in lower oesophageal sphincter tone in achalasia and a decrease in oesophageal contractions and amplitude in diffuse oesophageal spasm. This resulted in the enthusiastic use of the drugs in both disorders. With further experience, and with increased recognition of side effects, the role of these drugs in the 2 disorders has been better clarified. Clinical trials in general have not reflected the improvement observed in the manometric parameters. Only a minority of patients appear to derive sustained symptomatic benefit. Calcium channel blockers may be the initial choice for high or moderate risk patients with achalasia prior to proceeding with pneumatic dilatation or surgical myotomy. In diffuse oesophageal spasm, they are a reasonable first choice for all risk categories.