The feasibility of home monitoring of young people with cystic fibrosis: Results from CLIMB-CF.

BACKGROUND: CF is traditionally assessed in clinic. It is unclear if home monitoring of young people with CF is feasible or acceptable. The COVID-19 pandemic has made home monitoring more of a necessity. We report the results of CLIMB-CF, exploring home monitoring's feasibility and potential obstacles. METHODS: We designed a mobile app and enrolled participants with CF aged 2-17 years and their parents for six months. They were asked to complete a variety of measures either daily or twice a week. During the study, participants and their parents completed questionnaires exploring depression, anxiety and quality of life. At the end of the study parents and participants completed acceptability questionnaires. RESULTS: 148 participants were recruited, 4 withdrew prior to starting the study. 82 participants were female with median (IQR) age 7.9 (5.2-12 years). Median data completeness was 40.1% (13.6-69.9%) for the whole cohort; when assessed by age participants aged ≥ 12 years contributed significantly less (15.6% [9.8-30%]). Data completeness decreased over time. There was no significant difference between parental depression and anxiety scores at the start and the end of the study nor in CFQ-R respiratory domain scores for participants ≥ 14 years. The majority of participants did not feel the introduction of home monitoring impacted their daily lives. CONCLUSIONS: Most participants felt home monitoring did not negatively impact their lives and it did not increase depression, anxiety or decrease quality of life. However, uptake was variable, and not well sustained. The teenage years pose a particular challenge and further work is required.

The fallacy of the two-minute acid phosphatase cut off.

Research was carried out to determine whether the likelihood of obtaining a positive Acid Phosphatase (AP) test result is affected by the make and type of paper used. Also, we aimed to investigate the frequency of AP positive reactions occurring after 2min using a series of known semen dilutions and to determine whether spermatozoa transfer onto the paper during the act of AP screening. In this research, most brands of paper tested were able to detect a 1 in 40 semen dilution within 2min. Leaving AP test papers for longer will allow the detection of greater dilutions of semen and as the amount of ejaculation is not reliably known in most casework situations and levels of AP activity can vary in different men, this will increase the seminal detection rate in sexual offence allegations.

Electrically active bioceramics: a review of interfacial responses.

Electrical potentials in mechanically loaded bone have been implicated as signals in the bone remodeling cycle. Recently, interest has grown in exploiting this phenomenon to develop electrically active ceramics for implantation in hard tissue which may induce improved biological responses. Both polarized hydroxyapatite (HA), whose surface charge is not dependent on loading, and piezoelectric ceramics, which produce electrical potentials under stress, have been studied in order to determine the possible benefits of using electrically active bioceramics as implant materials. The polarization of HA has a positive influence on interfacial responses to the ceramic. In vivo studies of polarized HA have shown polarized samples to induce improvements in bone ingrowth. The majority of piezoelectric ceramics proposed for implant use contain barium titanate (BaTiO(3)). In vivo and in vitro investigations have indicated that such ceramics are biocompatible and, under appropriate mechanical loading, induce improved bone formation around implants. The mechanism by which electrical activity influences biological responses is yet to be clearly defined, but is likely to result from preferential adsorption of proteins and ions onto the polarized surface. Further investigation is warranted into the use of electrically active ceramics as the indications are that they have benefits over existing implant materials.

Augmentation of bone tunnel healing in anterior cruciate ligament grafts: application of calcium phosphates and other materials.

Bone tunnel healing is an important consideration after anterior cruciate ligament (ACL) replacement surgery. Recently, a variety of materials have been proposed for improving this healing process, including autologous bone tissue, cells, artificial proteins, and calcium salts. Amongst these materials are calcium phosphates (CaPs), which are known for their biocompatibility and are widely commercially available. As with the majority of the materials investigated, CaPs have been shown to advance the healing of bone tunnel tissue in animal studies. Mechanical testing shows fixation strengths to be improved, particularly by the application of CaP-based cement in the bone tunnel. Significantly, CaP-based cements have been shown to produce improvements comparable to those induced by potentially more complex treatments such as biologics (including fibronectin and chitin) and cultured cells. Further investigation of CaP-based treatment in the bone tunnels during ACL replacement is therefore warranted in order to establish what improvements in healing and resulting clinical benefits may be achieved through its application.

Characterization of babies discharged from Cabell Huntington Hospital during the calendar year 2005 with the diagnoses of neonatal abstinence syndrome.

Recent concern regarding the impact of maternal drug abuse on neonatal well being was the impetus for this retrospective cohort study of newborns diagnosed with neonatal abstinence syndrome that were discharged from Cabell Huntington Hospital during the calendar year 2005. Medical records of the neonates and their mothers were analyzed for a variety of health related outcomes and healthcare cost. Forty-eight neonates were diagnosed with Neonatal Abstinence Syndrome in 2005, forty of which required NICU assistance. The average maternal age at delivery was 26; gravity was 3.1 and most were single, separated or divorced. The majority had poor or inconsistent prenatal care. Twenty-one delivered by cesarean section most often for fetal distress. Most delivered prematurely with an average gestation of 35.9 weeks. Half of the mothers went into preterm labor with half of those having premature ruptured membranes. Opiates were the most common maternal substance found, while neonates most often tested positive for methadone. Nearly 90% of the mothers smoked. Thirty-four of the mothers were found to continue illicit drug abuse while pregnant, while another eight were seen in a methadone clinic for a history of abuse. Most of the neonates required weaning with methadone. The majority of our study cases were funded by Medicaid, mostly by West Virginia with total hospital costs exceeding 1.7 million dollars. Direct cost attributed to detoxification was in excess of $180,000. The number of neonates diagnosed with Neonatal Abstinence Syndrome has nearly tripled from 2003 to 2007. The problem of maternal drug abuse and addiction during pregnancy has dramatic effects on both their unborn children and our local healthcare system. Increased awareness of this growing problem is needed so that earlier interventions can be implemented. It is our opinion that all obstetrical patients at risk should be screened early and often so that those affected individuals can be managed more aggressively to improve neonatal outcomes.

Electrical characterization of hydroxyapatite-based bioceramics.

This paper studies the AC conductivity and permittivity of hydroxyapatite (HA)-based ceramics from 0.1 Hz-1 MHz at temperatures from room temperature to 1000 degrees C. HA-based ceramics were prepared either as dense ceramics or in porous form with interconnected porosity and were sintered in either air or water vapour. Samples were thermally cycled to examine the influence of water desorption on AC conductivity and permittivity. Surface-bound water was thought to contribute to conductivity for both dense and porous materials at temperatures below 200 degrees C. At temperatures below 700 degrees C the permittivity and AC conductivity of HA was also influenced by the degree of dehydration and thermal history. At higher temperatures (700-1000 degrees C), bulk ionic conduction was dominant and activation energies were of the order of approximately 2 eV, indicating that hydroxyl ions are responsible for conductivity.

Structure-function studies of human 5-alpha reductase type 2 using site directed mutagenesis.

Site directed mutagenesis of human steroid 5alpha-reductase types 1 (5AR1) and 2 (5AR2) has been used to identify residues involved in inhibitor/substrate binding by 5AR2. Replacing residues 21-24 (GALA) in 5AR2 with the analogous residues 26-29 (AVFA) from 5AR1 did not significantly alter either the Km for testosterone or the Ki for the competitive inhibitor Finasteride. Replacement of AVFA in 5AR1 with GALA from 5AR2 however, significantly decreased the Km and increased the resistance to Finasteride. These findings confirm that 5AR1 residues 26-29 are involved in inhibitor/substrate binding but suggest residues 21-24 of 5AR2 are not. Replacing residues 20-29 (QCAVGCAVFA) of 5AR1 with the analogous residues 15-24 (ATLVALGALA) from 5AR2, changed the Km and Ki to values approaching those for wild type 5AR2. Replacing residues VAL in wild type 5AR2 with VGC from 5AR1 did not change Km or Ki but replacing ATL in 5AR2 with QCA from 5AR1 significantly decreased the Km and increased the resistance to Finasteride. Conversely, replacing QCA with ATL in 5AR1 containing GALA in place of AVFA, increased the Km and decreased resistance to Finasteride. These findings indicate residues 15-17 of human 5AR2 participate in inhibitor/substrate binding whereas residues 18-20 do not.

Severe group A streptococcal infection and streptococcal toxic shock syndrome.

PURPOSE: To review the literature on group A streptococcal toxic shock syndrome, (STSS). DATA SOURCE: Medline and EMBASE searches were conducted using the key words group A streptococcal toxic shock syndrome, alone and in combination with anesthesia; and septic shock, combined with anesthesia. Medline was also searched using key words intravenous immunoglobulin, (IVIG) and group A streptococcus, (GAS); and group A streptococcus and antibiotic therapy. Other references were included in this review if they addressed the history, microbiology, pathophysiology, incidence, mortality, presentation and management of invasive GAS infections. Relevant references from the papers reviewed were also considered. Articles on the foregoing topics were included regardless of study design. Non-English language studies were excluded. Literature on the efficacy of IVIG and optimal antibiotic therapy was specifically searched. PRINCIPAL FINDINGS: Reports of invasive GAS infections have recently increased. Invasive GAS infection is associated with a toxic shock syndrome, (STSS), in 8-14% of cases. The STSS characteristically results in shock and multi-organ failure soon after the onset of symptoms, and is associated with a mortality of 33-81%. Many of these patients will require extensive soft tissue debridement or amputation in the operating room, on an emergency basis. The extent of tissue debridement required is often underestimated before skin incision. CONCLUSIONS: Management of STSS requires volume resuscitation, vasopressor/inotrope infusion, antibiotic therapy and supportive care in an intensive care unit, usually including mechanical ventilation. Intravenous immunoglobulin infusion has been recommended. Further studies are needed to define the role of IVIG in STSS management and to determine optimal anesthetic management of patients with septic shock.

HLA-DRB1*08, DRB1*03/DRB3*0101, and DRB3*0202 are susceptibility genes for Graves' disease in North American Caucasians, whereas DRB1*07 is protective.

Graves' disease is known to be HLA-D associated; however, the primary loci involved remain unclear. We examined HLA genotypes of DRB1 and DQB1 plus DRB3 subtypes using PCR-based sequence-specific priming in two groups of North American (Gainesville, FL; and Toronto, Canada) Caucasian patients with Graves' disease. We stratified patients into those with either early age at onset (<20 yr; 13.1 +/- 4.8 yr; n = 30) and later age at onset of disease (38.8 +/- 9.7 yr; n = 62) and compared the results to 192 normal controls. As expected, we found that DRB1*03 was associated with Graves' disease, but at a higher odds ratios for early-onset than later-onset patients (3.7 vs. 2.2). The frequency of DRB1*08 was also increased in both groups of patients, but significantly so only in patients with early-onset Graves' (P = 0.001; chi2 = 10.8). DRB3 was highly associated with Graves' in both groups of patients (P = 0.009; chi2 = 6.83 and P = 0.0015; chi2 = 10.1, respectively); however, the subtypes of DRB3 revealed differential susceptibilities. Whereas the frequencies of both DRB3*0101 and DRB3*0202 were increased over the entire cohort, that of DRB3*0301 was not. Significant P values were found for DRB3*0101 in patients with early-onset and for DRB3*0202 in patients with later onset of Graves' disease. When the haplotypes of DRB1*03-DRB3 of all subtypes were removed for analysis (all DRB1*03 positive also had DRB3*0101), the frequency of DRB3*0202 remained significantly higher in the patients with later onset of Graves' disease than in controls (P = 0.0043; chi2 = 8.13), but DRB3 was no longer positively associated with the early-onset group. In addition, we found that DRB1*07 was negatively associated with both groups of patients (P = 0.024; chi2 = 5.10 and P = 0.0085; chi2 = 6.93). These data suggest that DRB3*0202 is more likely to be the primary susceptible locus than DRB1*03 for patients with later onset of Graves' disease.

A comparison of thoracic and lumbar epidural techniques for post-thoracoabdominal esophagectomy analgesia.

PURPOSE: To compare thoracic epidural analgesia (TEA) using a bupivacaine/fentanyl mixture and lumbar epidural analgesia (LEA) with morphine, in respect to the time to extubation and the quality of post-operative analgesia, in patients having thoracoabdominal esophagectomy. METHODS: Twenty two patients scheduled for elective thoracoabdominal esophagectomy were randomized to TEA or LEA. Postoperatively, the TEA group received Patient Controlled Epidural Analgesia (PCEA) with bupivacaine 0.125% and 5 microg x ml(BI) fentanyl, and the LEA group received PCEA with 0.2 microg x ml(BI) morphine. A blinded observer assessed criteria for tracheal extubation and the time of tracheal extubation was recorded. Early extubation was defined as tracheal extubation within four hours postoperatively. Visual analogue pain scores at rest (Static Visual Analogue Pain Scores, SVAPS) and with movement (Dynamic Visual Analogue Pain Scores, DVAPS) were recorded at 1, 6, 12, 18 and 24 hr post-extubation. Failure of the epidural protocol (FEP) was defined as a request for additional analgesia. RESULTS: Tracheal extubation was achieved in 70% of the LEA and 100% of the TEA at four hours postoperatively (P=NS). However, the TEA group achieved earlier extubation times when assessed with log rank testing (P = 0.01). By six hours post-extubation FEP had occurred in 50% of the LEA group but in none of the TEA group (P = 0.01). Mean SVAPS and DVAPS were lower in the TEA than in the LEA group at all measured times (P < 0.01). CONCLUSION: This study has demonstrated superior pain control in patients undergoing thoraco-abdominal esophagectomy treated with TEA than with LEA, particularly for pain with movement. Tracheal extubation occurred earlier in the TEA group, but this difference was not significant at four hours postoperatively.

The use of glycopyrrolate in a case of intermediate syndrome following acute organophosphate poisoning.

PURPOSE: This report describes a case of organophosphate intoxication refractory to atropine in which glycopyrrolate was used to reduce cholinergic symptoms, and describes the development of intermediate syndrome, an uncommon subacute complication of organophosphate poisoning. CLINICAL FEATURES: A 44-yr-old woman presented in cholinergic crisis following malathion ingestion. Treatment was initiated with atropine and pralidoxime. Despite clinical signs of adequate atropinisation, the patient continued to have profuse bronchorrhoea, which resolved with glycopyrrolate. During her course in the intensive care unit, she displayed a subacute deterioration in neuromuscular and mental status with decrement-increment phenomenon on electromyography consistent with intermediate syndrome. The patient eventually made a complete recovery. CONCLUSION: This case report describes the successful use of glycopyrrolate in organophosphate intoxication and the development of the intermediate syndrome, characterised by onset of weakness of neck flexors, proximal limb muscles, and respiratory muscles within one to four days after poisoning. Recognition of the syndrome is important in light of the potential for respiratory depression requiring ventilatory support.

Septic shock.

PURPOSE: Many patients with sepsis require surgery for their management, often on an urgent or emergency basis. Anaesthetists are commonly required to manage patients with sepsis and septic shock in the operating room, past anaesthesia recovery area, and the intensive care unit. Since little has been written in the Anaesthesia literature on sepsis and septic shock, a review of this topic was considered appropriate. SOURCE: References were obtained from computerized searches on the National Library of Medicine (English language), recent review articles and personal files. PRINCIPLES FINDINGS: Septic shock is a common cause of morbidity and mortality. Its presentation may be subtle or catastrophic. Successful management depends on an understanding of the pathophysiology of the syndrome, allowing rapid, appropriate resuscitation. This often requires aggressive correction of volume deficit, maintenance of adequate perfusion pressure with inotropic and vasopressor therapy, mechanical ventilation and correction of coagulopathy. Appropriate cultures must be taken and antibiotic therapy started, often empirically. Anaesthetic management should include careful haemodynamic monitoring. Anaesthesia induction and maintenance must be tailored to the haemodynamically unstable patient. CONCLUSIONS: The management of the septic patient in the perioperative period presents a challenge for the anaesthetist. Haemodynamic and respiratory instability should be anticipated. Management requires multisystem intervention and careful anesthetic management.

Manipulation of transcutaneous electrical nerve stimulation variables has no effect on two models of experimental pain in humans.

Two separate studies investigated the hypoalgesic effect of manipulation of Transcutaneous Electrical Nerve Stimulation (TENS) parameters on two models of experimental pain: the Submaximal Effort Tourniquet Technique and cold-pressor pain. For the first study, 32 healthy subjects (16 male and 16 female) attended once for the purpose of cold-pressor pain induction that involved immersion of the nondominant hand in a water bath at 0 degree C. Subjects were allocated to Control, Placebo, or 1 of 2 treatment groups (110 or 4-Hz TENS). Pain threshold measurements (time to withdrawal of hand in seconds) were obtained over six standardised cold pain cycles (i.e., two before stimulation onset, three during stimulation, and one cycle after stimulation). In the second study, 48 healthy volunteers (24 male and 24 female) attended on two occasions, 48 h apart, for the purposes of ischaemic pain induction. On the first attendance, baseline data were obtained and on the second, subjects were randomly allocated to Control, Placebo, or one of four treatment groups with different combinations of stimulation frequencies and pulse durations (4 or 110 Hz and 50 or 200 microseconds). Measurements of "current pain intensity" and "worst pain experienced" were obtained via the Visual Analogue Scale (VAS) and the McGill Pain Questionnaire (MPQ), respectively. Analysis of variance performed on both sets of collected data revealed no significant differences between any of the groups, thus indicating no apparent relevance of manipulation of TENS parameters using these models of pain. Several hypotheses are suggested to explain these findings.

Characterization by Multilocus Enzyme Electrophoresis of Listeria monocytogenes Isolates Involved in Ovine Listeriosis Outbreaks in Scotland from 1989 to 1991.

Initial results from a study of five small ovine listeriosis outbreaks in Scotland in 1989 to 1991 are presented. Forty-eight isolates including three from silage were typed at 10 polymorphic enzyme loci by using multilocus enzyme electrophoresis resulting in the identification of 12 electrophoretic types. Phylogenetic analysis partitioned the 12 electrophoretic types into two statistically distinct divisions distinguishing 1/2a serotypes from non-1/2a serotypes.

Incorrect positioning of nasogastric feeding tubes and the development of pneumothorax.

The authors describe 12 patients in whom feeding tubes were inadvertently placed in the bronchial tree a total of 14 times. All but four of the misplacements were complicated by pneumothorax. No deaths were directly attributable to the misplacements, although one cardiac arrest occurred as a late complication of intrapleural feeding. Careful, controlled insertion of feeding tubes and radiographic confirmation of their placement are essential to reduce morbidity and mortality.

The Quantab strip in the measurement of urinary chloride and sodium concentrations.

The "Quantab" strip (Ames) measures chloride in fluids. For sodium chloride solutions and urine we found very good correlations between the Quantab reading and the chloride concentration as measured by chemical assay (r = 0.95 for chloride and r = 0.85 for sodium in urine). The strip gave reproducible results over the temperature range 4 to 37 degrees C. There was very little inter- and intra-observer variation in reading the strip. Although 10 to 23 min is required to complete the reaction, the strip reading is stable thereafter. We suggest that the strip could be useful in epidemiological studies of urinary sodium concentration and clinically in helping patients adhere to a low-salt diet.

Pneumatic antishock trousers.

While pneumatic antishock trousers are a useful adjunct for the initial management of hypotension, they do not replace, but can augment, fluid replacement and other resuscitative procedures. They can be applied quickly and are relatively safe when used in the manner recommended. They must not be used in a patient with congestive heart failure. Finally, it is imperative that they are not removed suddenly from the hypovolemic, hypotensive patient.