Substantial and sustained reduction in under-5 mortality, diarrhea, and pneumonia in Oshikhandass, Pakistan: evidence from two longitudinal cohort studies 15 years apart.

BACKGROUND: Oshikhandass is a rural village in northern Pakistan where a 1989-1991 verbal autopsy study showed that diarrhea and pneumonia were the top causes of under-5 mortality. Intensive surveillance, active community health education and child health interventions were delivered in 1989-1996; here we assess improvements in under-5 mortality, diarrhea, and pneumonia over this period and 15 years later. METHODS: Two prospective open-cohort studies in Oshikhandass from 1989 to 1996 (Study 1) and 2011-2014 (Study 2) enrolled all children under age 60 months. Study staff trained using WHO guidelines, conducted weekly household surveillance and promoted knowledge on causes and management of diarrhea and pneumonia. Information about household characteristics and socioeconomic status was collected. Hurdle models were constructed to examine putative risk factors for diarrhea and pneumonia. RESULTS: Against a backdrop of considerable change in the socioeconomic status of the community, under-5 mortality, which declined over the course of Study 1 (from 114.3 to 79.5 deaths/1000 live births (LB) between 1989 and 1996), exceeded Sustainable Development Goal 3 by Study 2 (19.8 deaths/ 1000 LB). Reductions in diarrhea prevalence (20.3 to 2.2 days/ Child Year [CY]), incidence (2.1 to 0.5 episodes/ CY), and number of bloody diarrhea episodes (18.6 to 5.2%) seen during Study 1, were sustained in Study 2. Pneumonia incidence was 0.5 episodes /CY in Study 1 and 0.2/CY in Study 2; only 5% of episodes were categorized as severe or very severe in both studies. While no individual factors predicted a statistically significant difference in diarrhea or pneumonia episodes, the combined effect of water, toilet and housing materials was associated with a significant decrease in diarrhea; higher household income was the most protective factor for pneumonia in Study 1. CONCLUSIONS: We report a 4-fold decrease in overall childhood mortality, and a 2-fold decrease in childhood morbidity from diarrhea and pneumonia in a remote rural village in Pakistan between 1989 and 2014. We conclude that significant, sustainable improvements in child health may be achieved through improved socioeconomic status and promoting interactions between locally engaged health workers and the community, but that continued efforts are needed to improve health worker training, supervision, and the rational use of medications. TRIAL REGISTRATION: Not Applicable.

A comparative assessment of irrigation and drainage characteristics for commercially available urethral catheters.

INTRODUCTION: We aimed to investigate irrigation and drainage characteristics of commercially available urethral catheters and determined which catheter offers the best flow characteristics. MATERIAL AND METHODS: Twelve different commercially available urethral catheters from three companies (Bard™, Rusch™ and Dover™) were investigated to compare their irrigation and drainage properties. Irrigation port, drainage port and overall cross-sectional areas for a 24Fr 3-way catheter was measured and compared. The maximum (Qmax) and average (Qavg) irrigation and drainage flow rates for each catheter was measured for 20-40 seconds using uroflowmetry. The primary endpoint was to determine which catheter offers optimal irrigation and drainage parameters. RESULTS: Overall cross-sectional area, irrigation port cross-sectional area, and drainage port cross-sectional area differed significantly for each 24Fr 3-way catheter assessed (p <0.001). The 24Fr 3-way Rusch Simplastic™ catheter consistently demonstrated the greatest maximal flow rate (Qmax: 5 ±0.3 ml/s) and average flow rate (Qavg: 4.6 ±0.2 ml/s) for irrigation. The 24Fr 3-way Dover™ catheter provided the greatest drainage properties (Qmax: 19.7 ±2 ml/s; Q avg: 15.9 ±5 ml/s). In the setting of continuous bladder irrigation, the 24Fr 3-way Rusch Simplastic™ catheter provided the highest irrigation rates (Qmax: 6.6 ±1.8 ml/s; Q avg: 4.6 ±0.9 ml/s). CONCLUSIONS: Three-way catheters demonstrate significant differences in their irrigation and drainage characteristics. The type of catheter selected should be based on the appropriate prioritization of efficient bladder irrigation versus efficient bladder drainage.

Prospective randomised controlled trial comparing trigone-sparing versus trigone-including intradetrusor injection of abobotulinumtoxinA for refractory idiopathic detrusor overactivity.

BACKGROUND: Botulinum toxin A is effective for treatment of idiopathic detrusor overactivity (IDO). The trigone is generally spared because of the theoretical risk of vesicoureteric reflux (VUR), although studies assessing injection sites are lacking. OBJECTIVE: Evaluate efficacy and safety of trigone-including versus trigone-sparing intradetrusor injections of abobotulinumtoxinA in patients with IDO. DESIGN, SETTING, AND PARTICIPANTS: Twenty-two patients from one centre were randomised to trigone-including or trigone-sparing injections. INTERVENTION: Injection of 500 U abobotulinumtoxinA diluted to 20ml into 20 trigone-including or trigone-sparing sites. MEASUREMENTS: The primary outcome measure was total overactive bladder symptom score (OABSS) at 6 wk. The OABSS questionnaire was completed at 0, 6, 12, and 26 wk. Baseline and postinjection urodynamic studies and micturating cystourethrograms were performed. Baseline values and subsequent time points were compared by t test. A mixed-effect model was used for repeated measures in time. RESULTS AND LIMITATIONS: For symptom scores at baseline compared with scores at 6 wk postinjection, the mean total OABSS improved from 22.4 to 8.7 (p<0.001) in the trigone-including group compared with 22.7 to 13.4 (p<0.03) in the trigone-sparing group. The difference in mean change from baseline was 4.4 points in favour of the trigone-including group (p=0.03). The total OABSS at 12 and 26 wk and the urgency subscale scores at 6, 12, and 26 wk showed significant improvement in favour of the trigone-including group. Mean postvoid residual volumes and clean intermittent self-catheterisation rates between the two groups were similar. No patients developed VUR. Performing injections under general anaesthetic was a limitation, as tolerability under local anaesthetic was not assessed. A further limitation is the lack of a trigone-only arm. CONCLUSIONS: Trigone-including injections are superior to trigone-sparing injections for the treatment of refractory IDO and did not cause VUR in this study.

Electroejaculatory stimulation for male infertility secondary to spinal cord injury: the Irish experience in National Rehabilitation Hospital.

OBJECTIVES: To examine the success rate of electroejaculatory stimulation in patients with acquired spinal injuries in a single Irish institution. The use of electroejaculatory stimulation is of benefit in patients with spinal cord injury who wish to have children. METHODS: A retrospective review of the Hospital In-Patient Enquiry scheme database and the patients' medical notes was performed. Any patient who had undergone electroejaculatory stimulation in the past 14 years was included. The quality of semen obtained and the pregnancy rate were assessed in relation to several variables, including patient age and level of spinal injury. RESULTS: From 1994 to 2008, 31 patients (29 patients with acquired spinal injury and 2 patients with a congenital spinal abnormality) had undergone electroejaculatory stimulation as a method of providing semen for assisted conception. Of the 31 patients, 6 had requested cryopreservation of their semen for future use and were therefore excluded from the pregnancy rate analysis. Of the 25 patients who had used the semen, 9 (36%) were successful in achieving pregnancy that resulted in living offspring. The semen analysis results were available for 15 patients. Three patients (one each with contaminated semen, poor semen quality, and an abandoned procedure) required testicular biopsy to extract viable sperm and subsequently achieved pregnancy. Lower spinal lesions (below T10) were associated with lower rates of pregnancy after electroejaculatory stimulation. One patient developed autonomic dysreflexia during the procedure, which was therefore abandoned. CONCLUSIONS: Electroejaculatory stimulation is an effective method of obtaining semen for reproductive purposes and is an option for fertility preservation in patients with spinal cord injury-related anejaculation.

Comparison of brown midrib sorghum-sudangrass with corn silage on lactational performance and nutrient digestibility in Holstein dairy cows.

Total mixed rations containing brown midrib sorghum-sudangrass silage (bmrSS) or corn silage (CS) at either 35 or 45% of dietary dry matter were fed to Holstein dairy cows to determine the effect on lactational performance and nutrient digestibility. Twelve cows were assigned to 1 of 4 diets in replicated 4 x 4 Latin squares with 21-d periods. In vitro 30-h neutral detergent fiber digestion, measured before the start of the trial, was 46.0% for CS and 58.3% for bmrSS. Dry matter intake was greatest when cows were fed the 35% CS (23.4 kg/d) and 45% CS (23.2 kg/d) diets, was least when cows were fed the 45% bmrSS diet (17.6 kg/d), and was intermediate when cows were fed the 35% bmrSS diet (20.1 kg/d). The bmrSS diets resulted in greater body weight gain per 21-d period but similar body condition scores compared with the CS diets. Yield of solids-corrected milk (SCM) was similar among the diets. Efficiency (SCM:dry matter intake) was 28% greater for cows fed the bmrSS than those fed the CS diets. In vivo digestibilities of organic matter and crude protein were greater for the CS diets than the bmrSS diets, but total tract digestibilities of neutral detergent fiber and starch were similar among diets. Ruminal pH was greater when cows were fed the 45% bmrSS diet (6.58), was least when cows were fed the 35% CS (6.10) and 45% CS diets (6.13), and was intermediate when cows were fed the 35% bmrSS diet (6.42). The ratio of acetate to propionate was greater for the bmrSS diets (2.77) than for the CS diets (2.41), with no difference among diets in total volatile fatty acid concentrations (122 mM). In conclusion, cows fed bmrSS had greater efficiency of SCM production, higher ruminal pH, and greater acetate to propionate ratios than cows fed CS. With these diets fed in a short-term study, bmrSS appeared to be an effective alternative to the CS hybrid when fed at either 35 or 45% of dietary dry matter.

Comparison of corn silage hybrids for yield, nutrient composition, in vitro digestibility, and milk yield by dairy cows.

A study was undertaken to compare Novartis N29-F1, a dual-purpose 90-d relative maturity corn hybrid, and Novartis NX3018, a 90-d relative maturity leafy corn silage hybrid for dry matter (DM) yield, in vitro digestibility, plant components, nutrient composition, and lactational performance by Holstein cows. The two corn hybrids were planted in replicated 15.2- x 321-m plots. Plant population and DM yield were similar between the two corn hybrids. Novartis NX3018 had higher content of crude protein and ash, a higher proportion of leaves and stalks, and a lower proportion of grain compared with Novartis N29-F1. The cob, grain, and leaves of Novartis NX3018 had higher in vitro true DM and neutral detergent fiber disappearances compared with the respective plant components of Novartis N29-F1. Thirty-eight midlactation multiparous Holstein cows (78 +/- 23.0 days in milk) producing 47.2 +/- 8.9 kg of milk per cow per day were blocked and assigned randomly to one of two total mixed ration (TMR) containing (DM basis) approximately 26% Novartis N29-F1 or Novartis NX3018 corn silage. Cows were housed in a free-stall barn and group fed ad libitum. The lactation study was conducted as a crossover design with two 28-d periods. Samples and data were collected during the final 7 d of each period. The total mixed rations were formulated using the Cornell-Penn-Miner Dairy nutrition model. Cows that were fed the total mixed rations containing Novartis NX3018 corn silage produced higher yields of milk 3.5% fat-corrected milk (FCM), milk crude protein, and milk lactose compared to cows that were fed the TMR containing Novartis N29-F1 corn silage. In conclusion, the Novartis NX3018 corn hybrid was leafier and more digestible in vitro, and when fed to dairy cows as silage, promoted higher milk yield compared with the Novartis N29-F1 corn hybrid.

Effect of corn silage hybrid on dry matter yield, nutrient composition, in vitro digestion, intake by dairy heifers, and milk production by dairy cows.

Three corn hybrids, Mycogen TMF94, Cargill F337 (which contains a brown midrib trait), and Pioneer 3861 were compared in a plot trial, an intake trial, and a lactation trial. In the plot trial, the three corn hybrids were planted in replicated 15.2 x 385-m plots. Mycogen TMF94 and Cargill F337 had lower yields of dry matter (DM), higher concentrations of neutral detergent fiber, and higher in vitro true DM disappearance compared with Pioneer 3861. Mycogen TMF94 had a higher yield of DM than Cargill F337 despite having a lower plant population. However, Cargill F337 had a higher in vitro true DM disappearance than Mycogen TMF94. In the intake trial, six individually penned Holstein heifers were blocked and assigned randomly to one of three total mixed rations containing 79% (DM basis) Mycogen TMF94, Cargill F337, or Pioneer 3861 corn silages in replicated 3 x 3 Latin squares. Heifers fed the Pioneer 3861-based TMR had lower DMI than heifers fed Mycogen TMF94 and Cargill F337-based TMR. In the lactation trial, 75 midlactation Holstein cows were blocked and assigned randomly to one of three total mixed rations containing 31% (DM basis) Mycogen TMF94, Cargill F337, or Pioneer 3861 corn silages used in the intake trial. Milk production was highest for cows fed Cargill F337-based total mixed rations. It is concluded from this study that Mycogen TMF94 was higher yielding, but less digestible, and resulted in lower milk production by lactating cows than Cargill F337. In addition, Mycogen TMF94 had higher in vitro true DM disappearance, and similar DM yield and milk production by lactating cows when compared with Pioneer 3861.

Landmarks in the development of hematopoietic cell transplantation.

The field of bone marrow transplantation has evolved over a period of 50 years. Reports of beneficial treatment of murine leukemia by irradiation and injection of marrow cells from another mouse stimulated interest in attempting to use these techniques to treat patients with leukemia. The first few bold attempts at human application were generally met with a total lack of success except for a few transplants involving identical twins. Understanding the HLA system led to the ability to select compatible sibling donors. The first successful long-term survivors were reported at the end of the 1960s. During the 1970's patients were given transplants for leukemia after failure of all other treatment. Survivals were poor, but some patients were cured. Transplantation early in the course of the disease resulted in greatly improved survival. During the 1980s improved control of infections, the use of peripheral blood as the source of stem cells, and the ability to select donors other than family members resulted in wide application of hematopoietic cell grafting.

Historic landmarks in clinical transplantation: conclusions from the consensus conference at the University of California, Los Angeles.

The transplantation of organs, cells, and tissues has burgeoned during the last quarter century, with the development of multiple new specialty fields. However, the basic principles that made this possible were established over a three-decade period, beginning during World War II and ending in 1974. At the historical consensus conference held at UCLA in March 1999, 11 early workers in the basic science or clinical practice of transplantation (or both) reached agreement on the most significant contributions of this era that ultimately made transplantation the robust clinical discipline it is today. These discoveries and achievements are summarized here in six tables and annotated with references.

Bone marrow transplantation: a review.

Bone marrow transplantation has evolved over a period of 50 years. Laboratory observations and animal studies defined the essentials of transplantation biology. The first attempts to transfer these studies to patients met with little success. The definition of the complexities of the human leukocyte antigen (HLA) system made it possible to select compatible sibling donors and more recently unrelated donors. Transplantation of stem cells from marrow, blood, or cord blood is now the treatment of choice for a variety of hematological and genetic diseases. Transplantation using less toxic preparative regimens to induce mixed chimerism makes possible an application to autoimmune diseases. Laboratory and clinical research directed toward induction of tolerance and elimination of malignant cells point the way to a wider application of hematopoietic cell transplantation in the next decade.