General practitioners' stay-at-work practices in patients with musculoskeletal disorders: using Intervention Mapping to develop a training program.

OBJECTIVES: To describe current stay-at-work practices among Danish general practitioners (GPs) in relation to patients with musculoskeletal disorders, to identify potential avenues for improvement, and to suggest a training program for the GPs. DESIGN AND SETTING: We followed the principles of Intervention Mapping. Data were collected by means of literature searches, focus group interviews with GPs, and interaction with stakeholder representatives from the Danish labour market. RESULTS: GPs' current stay-at-work practices were influenced by systemic, organisational, and legislative factors, and by personal determinants, including knowledge and skills relating to stay-at-work principles and musculoskeletal disorders, recognition of the patient's risk of long-term work disability, their role as a GP, and expectations of interactions with other stay-at-work stakeholders. GPs described themselves as important partners and responsible for the diagnostic and holistic assessments of the patient but placed themselves on the side line relying on the patient or workplace stakeholders to act. Their practices are influenced both by patients, employers, and by other stakeholders. We propose a training course for GPs that incorporate both concrete tools and behaviour change techniques. CONCLUSIONS: We have identified varied perspectives on the roles and responsibilities of GPs, as well as legislative and organisational barriers, and proposed a training program. Not all barriers identified can be addressed by a training course, and some questions are left unanswered, among others - who are best suited to help patients staying at work?

Musculoskeletal disorders are highly prevalent and one of the most common causes for visiting a GP.In many countries, GPs are important in facilitating that patients stay at work, when they are experiencing musculoskeletal pain and disability.In our research, GPs place themselves on the side line as coaches relying on the patient or workplace to act.Barriers such as role identity, systemic and organisational issues prevent GPs from being more involved in stay-at-work practices.GPs' with knowledge about stay-at-work practices may empower patients to better self-management.

Biocompatibility of Antifogging SiO-doped Diamond-Like Carbon Laparoscope Coatings.

Laparoscopes can suffer from fogging and contamination difficulties, resulting in a reduced field of view during surgery. A series of diamond-like carbon films, doped with SiO, were produced by pulsed laser deposition for evaluation as biocompatible, antifogging coatings. DLC films doped with SiO demonstrated hydrophilic properties with water contact angles under 40°. Samples subjected to plasma cleaning had improved contact angle results, with values under 5°. Doping the DLC films with SiO led to an average 40% decrease in modulus and 60% decrease in hardness. Hardness of the doped films, 12.0 - 13.2 GPa, was greater than that of the uncoated fused silica substrate, 9.2 GPa. The biocompatibility was assessed through CellTiter-Glo assays, with the films demonstrating statistically similar levels of cell viability when compared to the control media. The absence of ATP released by blood platelets in contact with the DLC coatings suggests in vivo hemocompatibility. The SiO doped films displayed improved transparency levels in comparison to undoped films, achieving up to an average of 80% transmission over the visible spectrum and an attenuation coefficient of 1.1 × 104 cm-1 at the 450 nm wavelength. The SiO doped DLC films show promise as a method of fog prevention for laparoscopes.

Bi-national outbreak of Salmonella Newport infections linked to onions: the United States experience.

From 2016-2019, dry bulb onions were the suspected cause of three multistate outbreaks in the United States. We investigated a large multistate outbreak of Salmonella Newport infections that caused illnesses in both the United States and Canada in 2020. Epidemiologic, laboratory and traceback investigations were conducted to determine the source of the infections, and data were shared among U.S. and Canadian public health officials. We identified 1127 U.S. illnesses from 48 states with illness onset dates ranging from 19 June to 11 September 2020. Sixty-six per cent of ill people reported consuming red onions in the week before illness onset. Thirty-five illness sub-clusters were identified during the investigation and seventy-four per cent of sub-clusters served red onions to customers during the exposure period. Traceback for the source of onions in illness sub-clusters identified a common onion grower in Bakersfield, CA as the source of red onions, and onions were recalled at this time. Although other strains of Salmonella Newport were identified in environmental samples collected at the Bakersfield, CA grower, extensive environmental and product testing did not yield the outbreak strain. This was the third largest U.S. foodborne Salmonella outbreak in the last 30 years. It is the first U.S. multistate outbreak with a confirmed link to dry bulb onions, and it was nearly 10-fold larger than prior outbreaks with a suspected link to onions. This outbreak is notable for its size and scope, as well as the international data sharing that led to implication of red onions as the primary cause of the outbreak. Although an environmental assessment at the grower identified several factors that likely contributed to the outbreak, no main reason was identified. The expedient identification of the outbreak vehicle and response of multiple public health agencies allowed for recall and removal of product from the marketplace, and rapid messaging to both the public and industry on actions to protect consumers; these features contributed to a decrease in cases and expeditious conclusion of the outbreak.

Evaluation of a training programme for Pharmacist Independent Prescribers in a care home medicine management intervention.

BACKGROUND: The provision of independent prescribing rights for United Kingdom (UK) pharmacists has enabled them to prescribe within their area of competence. The aim of this study was to evaluate an evidence-based training programme designed to prepare Pharmacist Independent Prescribers (PIPs) to safely and effectively assume responsibility for pharmaceutical care of older people in care homes in the UK, within a randomised controlled trial. METHODS: The training and competency assessment process included two training days, professional development planning against a bespoke competency framework, mentor support, and a viva with an independent General Practitioner (GP). Data on the PIPs' perceptions of the training were collected through evaluation forms immediately after the training days and through online questionnaires and interviews after delivery of the 6-month intervention. Using a mixed method approach each data set was analysed separately then triangulated providing a detailed evaluation of the process. Kaufman's Model of Learning Evaluation guided interpretations. RESULTS: All 25 PIPs who received the training completed an evaluation form (N = 25). Post-intervention questionnaires were completed by 16 PIPs and 14 PIPs took part in interviews. PIPs reported the training days and mentorship enabled them to develop a personalised portfolio of competence in preparation for discussion during a viva with an independent GP. Contact with the mentor reduced as PIPs gained confidence in their role. PIPs applied their new learning throughout the delivery of the intervention leading to perceived improvements in residents' quality of life and medicines management. A few PIPs reported that developing a portfolio of competence was time intensive, and that further training on leadership skills would have been beneficial. CONCLUSIONS: The bespoke training programme was fit for purpose. Mentorship and competency assessment were resource intensive but appropriate. An additional benefit was that many PIPs reported professional growth beyond the requirement of the study. TRIAL REGISTRATION: The definitive RCT was registered with the ISRCTN registry (registration number ISRCTN 17,847,169 ).

The association of peri-operative scores, including frailty, with outcomes after unscheduled surgery.

Postoperative hospital stay is longer for frail, older patients, who are more likely to experience prolonged postoperative morbidity and reduced long-term survival. We recorded in-hospital mortality, morbidity and length of stay for 164 patients aged at least 65 years after unscheduled surgery. We evaluated pre-operative frailty with the 7-point Clinical Frailty Scale: 81 patients were 'not vulnerable' (frailty score 1-3) and 83 were 'vulnerable or frail' (frailty score ≧ 4), with mean (SD) ages of 74.7 (7.5) years vs. 79.4 (8.3) years, respectively, p < 0.001. Within 30 postoperative days 8/164 (5%) patients died, all with frailty scores ≧ 4, p = 0.007. Postoperative morbidity was less frequent in patients categorised as 'not vulnerable' on four out of the six days it was measured (days 3, 5, 8, 14, 23, 28). Median (IQR [range]) postoperative stay was 9 (6-18 [2-221]) days for patients with frailty scores 1-3, and 22 (12-33 [2-270]) days for patients with score ≧ 4, p < 0.001. Four variables independently associated with hospital discharge, hazard ratio (95%CI): E-POSSUM, 0.74 (0.60-0.92), p = 0.007; ASA 2, 0.35 (0.13-0.98), p = 0.046, ASA 3, 0.17 (0.06-0.47), p = 0.001 and ASA 4/5, 0.08 (0.02-0.28), p < 0.001; operative severity 'major +', 0.69 (0.41-1.08), p = 0.10 and the Surgical Outcome Risk Tool, 7.75 (0.81-74.40), p = 0.08.

A systematic review of the use, quality and effects of pelvic examination in primary care for the detection of gynaecological cancer.

AIM: This three part systematic review gathered all the current evidence on the use, quality and effects of pelvic examination (abdominal palpation, bimanual vaginal examination ± visualisation of the cervix) in primary care in diagnosing gynaecological cancer. Research questions • Do primary care practitioners perform pelvic examination during the assessment of symptoms, which are potentially indicative of gynaecological cancer? (RQ1) • What is the quality of pelvic examination performed in primary care, in terms of technical competence and interpretation of findings? (RQ2) • Is pelvic examination associated with the referral of patients with gynaecological cancer, and if so, in what way? (RQ3) Methods: PRISMA guidelines were followed. MEDLINE, EMBASE and Cochrane databases were searched using a combination of four terms, their MeSH terms and synonyms: pelvic examination; primary care; competency and gynaecological cancer. Inclusion and exclusion criteria were defined. Citation lists of all identified papers were searched. Two authors (PW and PM or CMB or CB) independently screened titles, abstracts and the full texts of publications. Data extraction was performed by PW and duplicated in all papers by a second reviewer (PM, CMB or CB). Paper quality was assessed using CASP methodology. RESULTS: Nine hundred fifty four references were identified: 21 met the inclusion criteria: 5 RQ1; 6 RQ2; 10 RQ3. Examination rates prior to referral were generally low: one paper identified pre-referral PE in 52% of the patients; remaining papers demonstrated examination in less than half of the patients with suspicious symptoms. No papers explored GPs' competence at performing PE directly; but one paper identified 39% of 'clinically suspicious' cervices referred for colposcopy as having no abnormality. Pre-referral PE was associated with reduced diagnostic delay and early stage diagnosis. CONCLUSIONS: Pre-referral pelvic examination in symptomatic women appears to be under-performed, despite urgent suspected cancer referral guideline recommendation to do so (Healthcare Improvement Scotland 2014 ; National Institute for Health and Care Excellence 2015 ). While no evidence was found to confirm GPs' competence for performing PE, there was an association with shorter diagnostic delay and better outcomes in those women where it was performed.

Invariom refinement of a new monoclinic solvate of thiostrepton at 0.64†Šresolution.

A new monoclinic solvate containing two molecules of the thiopeptide antibiotic thiostrepton in the asymmetric unit has been crystallized in space group P2(1). Single-crystal diffraction data to a resolution of 0.64 Šwere collected at the SLS synchrotron, allowing structure solution by direct methods and resolution of the disorder present. Valence electron density can be observed in the Fourier residual density from refinement with the independent-atom model, which is a prerequisite for successful application of more sophisticated aspherical-atom scattering factors such as the invariom model when aiming to improve the structural model. Invariom refinement improves quality indicators such as R1(F) for thiostrepton, as previously demonstrated for small molecules. The nonspherical electron-density model also allows the direct derivation of a dipole moment and an electrostatic potential for the whole molecule, which is discussed in the context of antibiotic activity and molecular recognition.

Incidence and drug treatment of emotional distress after cancer diagnosis: a matched primary care case-control study.

BACKGROUND: Emotional distress is common in cancer patients. This study aimed to describe, in the year after a cancer diagnosis: the incidence of anxiety, depression and excessive alcohol use; the pattern of these diagnoses and treatment over time; and the nature and duration of the prescribed treatment. METHODS: A matched case-control study was conducted using routinely collected primary care data from 173 Scottish general practices. A presumptive diagnosis of emotional distress (anxiety, depression and/or excessive alcohol use) was based on prescription data or diagnostic code. Prescriptions for psychotropic drugs were described in terms of drug class, volume and treatment duration. RESULTS: In total, 7298 cancer cases and 14 596 matched-controls were identified. Overall, 1135 (15.6%) cases and 201 (1.4%) controls met criteria for emotional distress (odds ratio 13.7, 95% confidence interval 11.6-16.1). Psychotropic drugs were prescribed in the 6 months following initial cancer diagnosis for 1066 (14.6%) cases and 161 (1.1%) controls. The volume and duration of anxiolytic and antipsychotic prescribing was significantly different between cases and controls. CONCLUSION: This study quantified the higher incidence of new emotional distress in cancer patients in the first year post diagnosis. Clinicians should be aware of the possibility of emotional distress at any time in the year after cancer diagnosis.

Perinatal fluoxetine exposure results in social deficits and reduced monoamine oxidase gene expression in mice.

Perinatal antidepressant drug exposure increases risk for autism spectrum disorder, yet the molecular and neurobehavioral effects of maternal antidepressant drug use on offspring remain poorly understood. In this study, we administered the selective serotonin reuptake inhibitor (SSRI) fluoxetine non-invasively to female mice throughout gestation and early lactation, and then examined social interaction behaviors in offspring. In addition, we measured whole brain gene expression levels of monoamine oxidase A (MAOA), the primary metabolizing enzyme for serotonin. We found deficits in sociability and social novelty-seeking behavior in the juvenile offspring of SSRI-treated mice, and these behaviors persisted into young adulthood. Furthermore, we found decreased MAOA expression in the brains of offspring of SSRI-treated mice. Our findings suggest that exposure to antidepressants during the prenatal and early postnatal period may negatively affect social development. Moreover, reduced MAOA expression may play a role in the mechanistic pathway linking SSRI exposure and behavioral deficits symptomatic of autism.

Two mammalian genes transcribed from opposite strands of the same DNA locus.

This report describes the characterization of a genomic locus in the rat that encodes overlapping genes occupying both strands of the same piece of DNA. One gene (strand) encodes gonadotropin-releasing hormone (GnRH). A second gene, SH, is transcribed from the other DNA strand to produce RNA of undefined function. The RNAs transcribed from each DNA strand are spliced and polyadenylated, and share significant exon domains. GnRH is expressed in the central nervous system while SH transcripts are present in the heart. Thus, the genome of a mammalian organism encodes two distinct genes by using both strands of the same DNA.

Small-conductance, calcium-activated potassium channels from mammalian brain.

Members of a previously unidentified family of potassium channel subunits were cloned from rat and human brain. The messenger RNAs encoding these subunits were widely expressed in brain with distinct yet overlapping patterns, as well as in several peripheral tissues. Expression of the messenger RNAs in Xenopus oocytes resulted in calcium-activated, voltage-independent potassium channels. The channels that formed from the various subunits displayed differential sensitivity to apamin and tubocurare. The distribution, function, and pharmacology of these channels are consistent with the SK class of small-conductance, calcium-activated potassium channels, which contribute to the afterhyperpolarization in central neurons and other cell types.

Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3.

In excitable cells, small-conductance Ca2+-activated potassium channels (SK channels) are responsible for the slow after-hyperpolarization that often follows an action potential. Three SK channel subunits have been molecularly characterized. The SK3 gene was targeted by homologous recombination for the insertion of a gene switch that permitted experimental regulation of SK3 expression while retaining normal SK3 promoter function. An absence of SK3 did not present overt phenotypic consequences. However, SK3 overexpression induced abnormal respiratory responses to hypoxia and compromised parturition. Both conditions were corrected by silencing the gene. The results implicate SK3 channels as potential therapeutic targets for disorders such as sleep apnea or sudden infant death syndrome and for regulating uterine contractions during labor.

Noble gases confirm plume-related mantle degassing beneath Southern Africa.

Southern Africa is characterised by unusually elevated topography and abnormal heat flow. This can be explained by thermal perturbation of the mantle, but the origin of this is unclear. Geophysics has not detected a thermal anomaly in the upper mantle and there is no geochemical evidence of an asthenosphere mantle contribution to the Cenozoic volcanic record of the region. Here we show that natural CO2 seeps along the Ntlakwe-Bongwan fault within KwaZulu-Natal, South Africa, have C-He isotope systematics that support an origin from degassing mantle melts. Neon isotopes indicate that the melts originate from a deep mantle source that is similar to the mantle plume beneath Réunion, rather than the convecting upper mantle or sub-continental lithosphere. This confirms the existence of the Quathlamba mantle plume and importantly provides the first evidence in support of upwelling deep mantle beneath Southern Africa, helping to explain the regions elevation and abnormal heat flow.

Episodic ataxia results from voltage-dependent potassium channels with altered functions.

Episodic ataxia (EA) is an autosomal dominant human disorder that produces persistent myokymia and attacks of generalized ataxia. Recently, familial EA has been linked to the voltage-dependent delayed rectifier, Kv1.1, on chromosome 12. Six EA families have been identified that carry distinct Kv1.1 missense mutations; all individuals are heterozygous. Expression in Xenopus oocytes demonstrates that two of the EA subunits form homomeric channels with altered gating properties. V408A channels have voltage dependence similar to that of wild-type channels, but with faster kinetics and increased C-type inactivation, while the voltage dependence of F184C channels is shifted 20 mV positive. The other four EA subunits do not produce functional homomeric channels but reduce the potassium current when coassembled with wild-type subunits. The results suggest a cellular mechanism underlying EA in which the affected nerve cells cannot efficiently repolarize following an action potential because of altered delayed rectifier function.

Contributions of the C-terminal domain to gating properties of inward rectifier potassium channels.

Two inward rectifier potassium channels, the G protein-dependent GIRK1 and the G protein-independent BIR10, display large differences in rectification and macroscopic kinetics. A chimeric channel was constructed in which the putative intracellular carboxy-terminal domain of the G protein-dependent channel replaced the corresponding domain of the G protein-independent channel. The chimeric channel conducted potassium ions without the requirement of activated G proteins, yet displayed activation and deactivation kinetics and rectification properties similar to those of the G protein-dependent channel. The results demonstrate that structural elements in the C-terminus can independently control gating but not G protein signal transduction. The voltage dependence, time course, and kinetics of gating suggest a mechanism in which the pore may be occluded by reversible interactions with charged residues in the C-terminus.

Calcium-activated potassium channels expressed from cloned complementary DNAs.

Calcium-activated potassium channels were expressed in Xenopus oocytes by injection of RNA transcribed in vitro from complementary DNAs derived from the slo locus of Drosophila melanogaster. Many cDNAs were found that encode closely related proteins of about 1200 aa. The predicted sequences of these proteins differ by the substitution of blocks of amino acids at five identified positions within the putative intracellular region between residues 327 and 797. Excised inside-out membrane patches showed potassium channel openings only with micromolar calcium present at the cytoplasmic side; activity increased steeply both with depolarization and with increasing calcium concentration. The single-channel conductance was 126 pS with symmetrical potassium concentrations. The mean open time of the channels was clearly different for channels having different substituent blocks of amino acids. The results suggest that alternative splicing gives rise to a large family of functionally diverse, calcium-activated potassium channels.

Clinical and economic outcomes of involving pharmacists in the direct care of critically ill patients with infections.

OBJECTIVE: To determine whether the absence or presence of clinical pharmacists in intensive care units (ICUs) results in differences in mortality rates, length of ICU stay, and ICU charges for Medicare patients with nosocomial-acquired infections, community-acquired infections, and sepsis. DESIGN, SETTING, AND PATIENTS: The type and level of pharmacy services provided to ICUs were obtained from a 2004 national survey. Clinical pharmacy services were defined as having at least a partial pharmacist full-time equivalent specifically devoted to the ICU for the purpose of direct involvement in patient care. Infections were defined using International Classification of Diseases, Ninth Revision, Clinical Modification codes. ICU outcome data were drawn from the 2004 modified Medicare provider analysis and review. Depending on the infection studied, the involvement of clinical pharmacists was evaluated in 8,927-54,042 patients from 265 to 276 hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN OUTCOMES: Mortality rates, length of ICU stay, Medicare charges, drug charges, and laboratory charges for each of the infections categorized according to the absence or presence of clinical pharmacists. Compared to ICUs with clinical pharmacists, mortality rates in ICUs that did not have clinical pharmacists were higher by 23.6% (p < 0.001, 386 extra deaths), 16.2% (p = 0.008, 74 extra deaths), and 4.8% (p = 0.008, 211 extra deaths) for nosocomial-acquired infections, community-acquired infections, and sepsis, respectively. Similarly, ICU length of stay was longer by 7.9% (p < 0.001, 14,248 extra days), 5.9% (p = 0.03, 2855 extra days), and 8.1% (p < 0.001, 19,215 extra days) for nosocomial-acquired infections, community-acquired infections, and sepsis, respectively. ICUs that did not have clinical pharmacists had greater total Medicare billings of 12% (p < 0.001, $132,978,807 extra billing charges), 11.9% (p < 0.001, $32,240,378 extra billing charges), and 12.9% (p < 0.001, $224,694,784 extra billing charges) for nosocomial-acquired infections, community-acquired infections, and sepsis, respectively. Similar findings were observed for Medicare drug charges and laboratory charges. CONCLUSION: The involvement of clinical pharmacists in the care of critically ill Medicare patients with infections is associated with improved clinical and economic outcomes. Hospitals should consider employing clinical ICU pharmacists.

2006 national clinical pharmacy services survey: clinical pharmacy services, collaborative drug management, medication errors, and pharmacy technology.

STUDY OBJECTIVE: To determine the extent of 15 hospital-based clinical pharmacy services, 51 different drugs managed under protocol by pharmacists, medication errors, and pharmacy technology in United States hospitals. DESIGN: A survey was mailed, as well as sent electronically, to pharmacists in 2893 hospitals. RESULTS: A total of 1125 surveys were returned (38.9% response rate). The 1125 hospitals had 14,315,506 patients admitted, which represented 45.7% of the 31,324,496 admissions to all U.S. hospitals in 2006. The proportion of clinical pharmacy services provided by Veterans Affairs (VA) hospitals was higher compared with non-VA hospitals. In all hospitals, the clinical pharmacy services with the greatest growth from 1989-2006 were pharmacist-provided admission drug histories (300% increase), pharmacist participation on medical rounds (292.3% increase), drug protocol management (208% increase), pharmacist-conducted clinical research (166.7% increase), pharmacist-provided drug information (150% increase), and pharmacist-provided pharmacokinetic consultation (117.5% increase). A total of 864 hospitals (76.8%) had pharmacists providing drug protocol management (collaborative drug management). Pharmacists managed a mean +/- SD of 9.18 +/- 10.23 different drugs/hospital (7932 protocols). Drugs commonly managed included aminoglycosides (64.4% of hospitals), vancomycin (63.8%), warfarin (37.8%), low-molecular-weight heparins (32.7%), unfractionated heparin (30.0%), fluoroquinolones (30.0%), antiparkinsonian drugs (22.8%), proton pump inhibitors (22.7%), human immunodeficiency virus drugs (21.9%), and cephalosporins (19.7%). The mean number of medication errors reported/hospital increased by 151.4% between 1995 and 2006. The percentage of patients who experienced a medication error increased from 4.7% to 6.5% between 1995 and 2006 (a 38.3% increase). A total of 220 hospitals (19.6%) had computerized prescriber order entry systems, 263 (23.4%) had bar coding for drug administration, and 439 (39.0%) used robotics for dispensing. CONCLUSION: This study provides continuing evidence of the growth and value of clinical pharmacy services and clinical pharmacists in our nation's hospitals. These data will guide hospital pharmacy directors and clinical coordinators in allocating resources to optimally meet their patients' needs.

The debate continues: a prospective, randomised, single-blind study comparing Coblation and bipolar tonsillectomy techniques.

OBJECTIVES: Tonsillectomy is a common procedure with significant post-operative pain. This study was designed to compare post-operative pain, returns to a normal diet and normal activity, and duration of regular analgesic use in Coblation and bipolar tonsillectomy patients. METHODS: A total of 137 patients, aged 2-50 years, presenting to a single institution for tonsillectomy or adenotonsillectomy were recruited. Pain level, diet, analgesic use, return to normal activity and haemorrhage data were collected. RESULTS: Coblation tonsillectomy was associated with significantly less pain than bipolar tonsillectomy on post-operative days 1 (p = 0.005), 2 (p = 0.006) and 3 (p = 0.010). Mean pain scores were also significantly lower in the Coblation group (p = 0.039). Coblation patients had a significantly faster return to normal activity than bipolar tonsillectomy patients (p < 0.001). CONCLUSION: Coblation tonsillectomy is a less painful technique compared to bipolar tonsillectomy in the immediate post-operative period and in the overall post-operative period. This allows a faster return to normal activity and decreased analgesic requirements.