Persistence and clearance of high-risk human papillomavirus and cervical dysplasia at 1 year in women living with human immunodeficiency virus: a prospective cohort study.

OBJECTIVE: Evaluate 1-year outcomes of cervical cancer screening and treatment using primary high-risk human papillomavirus (HPV) testing in women living with human immunodeficiency virus (HIV). DESIGN: Prospective cohort study. SETTING: HIV treatment centre in Botswana. POPULATION: Women living with HIV. METHODS: Participants underwent cervical cancer screening with high-risk HPV testing and triage evaluation at baseline and 1-year follow up. Excisional treatment was offered as indicated. Histopathology was the reference standard. MAIN OUTCOME MEASURES: Persistence, clearance and incidence of high-risk HPV infection; and persistence, progression, regression, cure and incidence of cervical dysplasia. RESULTS: Among 300 women screened at baseline, 237 attended follow up (79%). High-risk HPV positivity significantly decreased from 28% at baseline to 20% at 1 year (P = 0.02). High-risk HPV persistence was 46% and clearance was 54%; incidence was high at 9%. Prevalence of cervical intraepithelial neoplasia Grade 2 (CIN2) or higher was most common in participants with incident high-risk HPV (53%). CIN2 or higher was also common in those with persistent high-risk HPV (32%) and even in those who cleared high-risk HPV (30%). Of the high-risk HPV-positive participants at baseline with

Development and launch of the first obstetrics and gynaecology master of medicine residency training programme in Botswana.

BACKGROUND: Sub-Saharan Africa (SSA) faces a severe shortage of Obstetrician Gynaecologists (OBGYNs). While the Lancet Commission for Global Surgery recommends 20 OBGYNs per 100,000 population, Botswana has only 40 OBGYNs for a population of 2.3 million. We describe the development of the first OBGYN Master of Medicine (MMed) training programme in Botswana to address this human resource shortage. METHODS: We developed a 4-year OBGYN MMed programme at the University of Botswana (UB) using the Kern's approach. In-line with UB MMed standards, the programme includes clinical apprenticeship training complemented by didactic and research requirements. We benchmarked curriculum content, learning outcomes, competencies, assessment strategies and research requirements with regional and international programmes. We engaged relevant local stakeholders and developed international collaborations to support in-country subspecialty training. RESULTS: The OBGYN MMed curriculum was completed and approved by all relevant UB bodies within ten months during which time additional staff were recruited and programme financing was assured. The programme was advertised immediately; 26 candidates applied for four positions, and all selected candidates accepted. The programme was launched in January 2020 with government salary support of all residents. The clinical rotations and curricular development have been rolled out successfully. The first round of continuous assessment of residents was performed and internal programme evaluation was conducted. The national accreditation process was initiated. CONCLUSION: Training OBGYNs in-country has many benefits to health systems in SSA. Curricula can be adjusted to local resource context yet achieve international standards through thoughtful design and purposeful collaborations.

Magma flow instability and cyclic activity at soufriere hills volcano, montserrat, british west indies

Dome growth at the Soufriere Hills volcano (1996 to 1998) was frequently accompanied by repetitive cycles of earthquakes, ground deformation, degassing, and explosive eruptions. The cycles reflected unsteady conduit flow of volatile-charged magma resulting from gas exsolution, rheological stiffening, and pressurization. The cycles, over hours to days, initiated when degassed stiff magma retarded flow in the upper conduit. Conduit pressure built with gas exsolution, causing shallow seismicity and edifice inflation. Magma and gas were then expelled and the edifice deflated. The repeat time-scale is controlled by magma ascent rates, degassing, and microlite crystallization kinetics. Cyclic behavior allows short-term forecasting of timing, and of eruption style related to explosivity potential.

Primary therapy of multiple myeloma with paclitaxel (taxol).

BACKGROUND: The treatment of multiple myeloma remains unsatisfactory and new active agents are needed. Paclitaxel is effective against a variety of solid tumors and we assessed the utility against multiple myeloma. PATIENTS AND METHODS: From March 1993 to May 1994, we treated 33 patients with newly diagnosed multiple myeloma with paclitaxel given intravenously at a dose of 125 mg/m2 over 24 hours (13 patients) or at a dose of 135 mg/m2 over 3 hours (20 patients). RESULTS: Five of 33 patients responded (15%; 95% CI: 5 to 32%) with an unmaintained remission of 3-11+ months. Severe but reversible neutropenia was the major dose limiting toxicity, but myalgias and alopecia were also common. CONCLUSION: Paclitaxel was slightly active against multiple myeloma. Whether higher doses or new analogues of this agent can produce superior results requires further study.

A double-blind trial of nocturnal supplemental oxygen for sleep desaturation in patients with chronic obstructive pulmonary disease and a daytime PaO2 above 60 mm Hg.

The efficacy of nasal oxygen during sleep was evaluated in patients with COPD, episodic rapid eye movement sleep desaturation, and a daytime PaO2 greater than 60 mm Hg. The double-blind, randomized 3-yr trial used nasal oxygen versus room air in two groups of nocturnal sleep desaturating subjects. The setting was the outpatient chest clinic of a Veterans Affairs Medical Center. There were 51 patients with moderate to severe COPD, daytime PaO2 greater than or equal to 60 mm Hg: 38 with proven REM sleep desaturation and 13 without desaturation. Nocturnal oxygen at 3 L/min was delivered by concentrator to 19 desaturating subjects, and room air at 3 L/min was delivered by defective concentrator to the remaining 19 desaturating subjects. There was no gas therapy for the 13 nondesaturating subjects. The nocturnal desaturator group who received supplemental oxygen during sleep over 36 months showed a significant downward trend in pulmonary artery pressure (-3.7 mm Hg) compared with desaturating patients treated with room air (+3.9 mm Hg). Nonvascular parameters of hypoxia, such as hemoglobin and red blood cell mass, did not differ between the sham- and oxygen-treated groups. Mortality was decidedly higher in the desaturating patients compared with non-desaturating subjects, but there was no significant difference between oxygen- and sham-treated desaturating subjects. We conclude that nasal supplemental oxygen used during sleep to reverse episodic desaturation in COPD patients whose daytime PaO2 is above 60 mm Hg has a beneficial effect in reducing pulmonary artery pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Evolution of nocturnal oxyhemoglobin desaturation in patients with chronic obstructive pulmonary disease and a daytime PaO2 above 60 mm Hg.

We studied 31 clinically stable chronic obstructive pulmonary disease (COPD) patients with a PaO2 greater than or equal to 60 mm Hg using polysomnographic sleep study at baseline (between 1983 and 1986) and at a mean follow-up time of 42.5 months to examine the evolution of rapid-eye-movement (REM) sleep nocturnal oxyhemoglobin desaturation (NOD). Arterial blood gases and spirometry measured at baseline and follow-up were compared with mean nocturnal SaO2 and to other REM sleep SaO2 parameters. We postulated that the onset of NOD would be seen most frequently in those patients with marked derangements of lung mechanics and greater longitudinal deterioration in arterial blood gases. Eight of the subjects developed REM-NOD on follow-up polysomnography. The appearance of REM-NOD was not related, or only minimally so, to initial PaO2, PaCO2, or mean nocturnal SaO2. Upon follow-up, however, the onset of NOD was always associated with deterioration of daytime PaO2 and PaCO2, mainly in those patients with the most severe baseline derangement of spirometry (lung mechanics). On the other hand, one group showed equivalent deterioration in daytime PaO2 and a stable PaCO2 but had less severely deranged baseline mechanics and demonstrated a fall in mean nocturnal SaO2 only. The findings in this latter group indicate that the development of NOD is not purely a result of decreasing daytime PaO2. We conclude that the onset of REM-NOD is mainly related to a severe derangement of lung mechanics with deterioration of resting awake gas exchange (progressive hypoxemia, hypercarbia, and worsening airflow).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of positive reinforcement on hourly compliance in nasal continuous positive airway pressure users with obstructive sleep apnea.

Previous reports have described compliance with nasal continuous positive airway pressure (nCPAP) for the treatment of obstructive sleep apnea (OSA) only in terms of the number of patients able to use it beyond their initial trial night or those continuing after some home use. Because of a possible difference between the level of compliance (mean number of hours of use per 24 h) needed for symptomatic relief of OSA versus cardiovascular improvement, the level of hourly compliance in chronic nCPAP users may be important. The first part of this study prospectively examines compliance in a stable population of OSA patients already using nCPAP for 6 months to 2 yr. The second part is a prospective randomized, crossover study examining the effect of weekly (three times) then monthly (twice) positive reinforcement on hourly compliance of new nCPAP users for 3 months versus no reinforcement for 3 months. Positive reinforcement consisted of telephone discussions with the patients about the severity or complications of OSA, benefits of nCPAP, and suggestions about minimizing side effects. Using self-assessment scales, each patient reported the perceived level of improvement from the untreated to the treated condition and the prevalence and severity of side effects from the nCPAP therapy. The level of compliance in stable, chronic nCPAP users with OSA was 6.1 +/- 2.2 h/24 h (n = 9). For the new nCPAP users during the nonreinforced period, the mean compliance was 6.0 +/- 2.8 h/24 h; that during the reinforcement period was 6.0 +/- 2.7 h/24 h (NS). There was no significant correlation between perceived improvement in OSA symptoms or between the perceived side effects of nCPAP versus hourly compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Rate of oxyhemoglobin desaturation in obstructive versus nonobstructive apnea.

Preapneic thoracic gas volume (Vtg), arterial saturation (SaO2), and mixed venous oxygen saturation (SvO2), have been shown to influence the rate of SaO2 fall (dSaO2/dt) during apnea. We asked the following question: does tissue oxygen consumption (tVO2) affect the dSaO2/dt during apnea? We attempted to answer this question by comparing dSaO2/dt during obstructive apneas (high tVO2) with dSaO2/dt during nonobstructive apneas (low tVO2) in six adult baboons. Fiberoptic central venous and arterial catheters were used for continuous monitoring of SvO2, SaO2, and cardiac output. A sapphire-bearing turbine monitored minute ventilation and airflow cessation. A Respitrace and esophageal pressures were used to assess relative differences in Vtg. Obstructive apneas (30, 45, and 60-s) were created by clamping an indwelling cuffed endotracheal tube at end-expiration. Nonobstructive apneas were created by paralyzing the animals with atracurium and interrupting ventilation for periods equivalent to those of the obstructed apneas. The ventilator was adjusted to duplicate the respiratory rate, tidal volume, and relative Vtg of the spontaneously breathing animal. Mean tVO2 during spontaneous breathing was 110 ml/min (Fick method) and decreased to 90 ml/min during paralysis (p less than 0.05). The dSaO2/dt for the three apnea durations (mean, all animals), obstructive versus nonobstructed were: 0.85 and 0.74%/s (n = 6), 0.87 and 0.75%/s (n = 6), and 0.60 and 0.48%/s (n = 4), respectively. The dSaO2/dt was significantly lower during the nonobstructive apneas. We conclude that differences in VO2 during apnea may affect the dSaO2/dt and that for the same duration apnea, central apneas may show less desaturation than obstructive apneas where vigorous muscular efforts at overcoming obstruction are common.

Effect of cardiac output reduction on rate of desaturation in obstructive apnea.

The nadir of SaO2 during an obstructive apnea is dependent upon the apnea's duration and the rate of fall of saturation (dSaO2/dt). We postulated that a low Q, such as in patients with congestive heart failure with sleep apnea, or a reduction in Q, as seen in some humans during obstructive sleep apnea, might steepen dSaO2/dt. The mechanism postulated was lowering of SvO2 with increased pulmonary capillary blood oxygen uptake and faster depletion of alveolar oxygen. This study examines dSaO2/dt following the onset of apnea in eight spontaneously breathing adult baboons. Nonrepetitive obstructive apneas (30, 45, and 60 seconds) were created by clamping an indwelling cuffed endotracheal tube at the end of expiration. Following baseline measurements, the animals were given a bolus of a rapid-acting beta-adrenergic blocker followed by continuous infusion to reduce cardiac output and to limit the cardiovascular response to obstructive asphyxia. Fiberoptic catheters were used for continuous monitoring of SaO2, SvO2, and cardiac output. Esophageal pressure and relative thoracic gas volume (Respitrace) were monitored to insure equivalence of lung volume at the onset of apnea. Beta-adrenergic blockade reduced resting Q by a mean of 25 percent. The blocked vs unblocked dSaO2/dt was 0.73 vs 0.72 percent/s, 0.76 vs 0.73 percent/s, and 0.70 vs 0.71 percent/s for 30-second, 45-second, and 60-second apneas, respectively. Thus, mean dSaO2/dt for all durations of apneas was unaffected by beta-adrenergic blockade. We concluded that dSaO2/dt is not influenced by limited Q preceding or induced by obstructive asphyxia.

Atelectasis affects the rate of arterial desaturation during obstructive apnea.

Chronic hemodynamic disturbances are more profound in patients with obstructive sleep apnea when underlying lung disease with abnormal gas exchange (low arterial PO2) is present. Previous studies suggest that pulmonary gas exchange could influence the rate of fall of arterial oxygen saturation (dSaO2/dt) in obstructive sleep apnea. We postulated that abnormal gas exchange in the form of atelectasis would steepen dSaO2/dt and thereby lower nadir arterial oxyhemoglobin saturation (SaO2) for the same duration of apnea. Apneas were created by clamping an indwelling cuffed endotracheal tube at end expiration in eight spontaneously breathing adult baboons. Apneas of the same duration were then repeated during temporary endobronchial occlusion of one lobe of the lung. SaO2 and mixed venous O2 saturation were continuously monitored, and cardiac output was calculated. Worsening of pulmonary gas exchange during atelectasis was documented by an increase in calculated venous admixture from 10.5 +/- 0.8 to 25.0 +/- 0.7% (P less than 0.001). The dSaO2/dt was independent of apnea duration at 30, 45, and 60 s. During endobronchial occlusion, apnea dSaO2/dt increased 20%, and nadir SaO2 was significantly lower. Possible mechanisms for steepening of dSaO2/dt during atelectasis are discussed.

Exercise hemodynamics and gas exchange in patients with chronic obstruction pulmonary disease, sleep desaturation, and a daytime PaO2 above 60 mm Hg.

Nocturnal oxyhemoglobin desaturation (NOD) has been reported in patients with disease of the pulmonary parenchyma and/or chest wall. The resulting hypoxemia could play a role in the development of pulmonary hypertension. We have previously demonstrated a small but statistically significant difference in resting pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR) between two groups of patients with COPD of similar age, symptomatology, and degree of pulmonary dysfunction. These two groups were selected only on the basis of the presence or absence of NOD, and all had a mean daytime PaO2 at or above 60 mm Hg. The present study uses exercise to stress the pulmonary circulation of two groups of patients similar to the above. The purpose was to see if exercise can amplify underlying cardiopulmonary hemodynamic differences between NOD and non-NOD subjects. In addition, we attempted to confirm or refute previous studies which claimed that exercise desaturation correlates with NOD. Resting supine, resting upright, and upright exercise cardiopulmonary hemodynamics were measured using an indwelling right heart catheter, and arterial blood and expiratory gases were collected to assess metabolic and other gas exchange parameters. Although both groups showed increase in Ppa during exercise, the increases in systolic Ppa, mean Ppa, and driving pressure were disparately higher in subjects with NOD. Exercise desaturation was not predictive of NOD. The presence of NOD was predictive of a resting PVR greater than 120 dyne.s.cm-5, whereas mean sleep SaO2 and daytime PaO2 were unable to discriminate patients with COPD above or below this level.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary vascular hemodynamics in chronic lung disease patients with and without oxyhemoglobin desaturation during sleep.

Nonapneic, nocturnal oxyhemoglobin desaturation (NOD) during rapid-eye-movement (REM) sleep has been proposed as a predecessor and possible etiologic factor in the development of pulmonary hypertension in patients both with restrictive and obstructive chronic lung disease. The association between abnormal waking cardiopulmonary hemodynamics and NOD has not been established in patients with mild daytime hypoxemia. Gas exchange, pulmonary function, red cell mass, radionuclide gated cardiac ejection fraction, and supine cardiopulmonary hemodynamics were examined in 36 patients with chronic lung disease. All had a daytime PaO2 greater than 60 mm Hg and REM sleep-related NOD for greater than 5 minutes, to 85 percent or lower. These data were compared to those from 13 subjects with similar symptoms and objective measures of pulmonary dysfunction but without evidence of NOD. Patients with NOD showed more end organ evidence of hypoxemia and more abnormal cardiopulmonary hemodynamics than patients with similar degrees of lung disease but without NOD. The relative role of daytime vs nocturnal hypoxemia in inducing hemodynamic differences between groups cannot be determined from this study.